bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifestyle and Socioeconomic Transition and Health Consequences of Breast Cancer in the East Asia Region, From 1990 to 2019
Authors: Mubarik Sumaira , Cao Jinhong , Wang Fang , Hussain Syeda Rija , Liu Qing , Wang Suqing , Liu Yan , Yu Chuanhua
Published: April 2022

Background

Due to its higher prevalence and heterogeneity, female breast cancer (BC) is the widest disease throughout the world. We sought to assess the epidemiological and sociodemographic transitions of BC and to identify the potential risk factors attributed to burden of BC in East Asia.

Methods

At the regional level of East Asia and at a national level of East Asian countries, we investigated the burden of the incidence of female BC, mortality, and disability-adjusted life years (DALYs) in 2019 and assessed the epidemiological, socioeconomic, and health-linked disparities in incidence of BC and mortality over a 30-year period. The changes in BC’s mortality and DALYs between 1990 and 2019, attributable to varying risk factors, were evaluated in different age groups.

Results

In 2019, the incidence of and mortality from and DALYs of BC were estimated to be 382,321 (95% UI: 303,308–477,173) incidence cases [age-standardized rate (ASR) of 35.69 per 100,000; 28.32–44.54], 98,162 (79,216–120,112) deaths (ASR of 9.12; 7.36–11.13), and 3,024,987 (2,477, 984–3,659,370) DALYs with an ASR of 282.15 (230.81–341.19) in 2019. It was also observed that out of four most representative locations of East Asia, two (China and Japan) showed more than 60% increase in age-standardized incidence rate between 1990 and 2019. While only Japan females showed a significant rise of 15.3% (95% UI: 2.3–28) in ASR of death and 12.6% (95% UI: 0.5–26.9) in ASR of DALYs between 1990 and 2019. Inclusively, 88 and 81% variations were explained in the incidence of BC and death due to change in sociodemographic index (SDI) in 2019, in East Asia. The highest positive percent changes in death and DALYs between 1990 and 2019 were attributable to high body mass index (BMI), high fasting plasma glucose (FPG), and alcohol consumption in East Asia.

Conclusion

The burden of death and disability from female BC is the result of multiple risk factors, mainly due to behavioral and metabolic risk factors. The increase of the incidence is related to the westernized lifestyle and diet habits and the improvement of screening and diagnosis techniques in the recent years, whereas the increase in DALYs is mainly attributed to high BMI, high FPG, alcohol use, and high diet in red meat.
Refeeding Syndrome and Its Related Factors in Critically Ill Coronavirus Disease 2019 Patients: A Prospective Cohort Study
Authors: Vahdat Shariatpanahi Zahra , Vahdat Shariatpanahi Maryam , Shahbazi Erfan , Shahbazi Shaahin
Published: April 2022

Background and Aim

Malnutrition and its complications is usually neglected in critically ill COVID-19 patients. We conducted the present study to investigate the prevalence of refeeding syndrome and its related factors in this group of patients.

Methods

In this prospective cohort study, 327 patients were assessed for being at risk and developing refeeding syndrome. The criteria was ASPEN consensus recommendations for refeeding syndrome released in 2020. Malnutrition was assessed based on global leadership initiative on malnutrition (GLIM) criteria. The relation between actual protein, calorie intake, and refeeding syndrome was also evaluated via cox regression model. The data concerning calorie and protein intake were gathered for 5 days after initiating feeding. The daily protein and calorie intake were divided by kilogram body weight in order to calculate the actual protein (g/kg/day) and energy (kcal/kg/day) intake.

Results

Among the subjects, 268 (82%) were at risk of refeeding syndrome and 116 (36%) got involved in this syndrome. Malnutrition, according to the GLIM criteria, was found in 193 (59%) of the subjects. In the at-risk population, the risk of refeeding syndrome was reduced by 90% with the rise in protein intake (CI; 0.021–0.436, P = 0.002), increased by 1.04 times with the increase in age (CI; 1.032–1.067, P < 0.001), and by 1.19 times with the rise in the days from illness onset to admission (CI; 1.081–1.312, P < 0.001) in adjusted cox model analysis.

Conclusion

The incidence of refeeding syndrome is relatively high, which threatens the majority of critically ill COVID-19 patients. Increased protein intake was found to reduce the occurrence of refeeding syndrome.
Mediterranean Diet Patterns in Relation to Lung Cancer Risk: A Meta-Analysis
Authors: Du Hongzhen , Cao Tengrui , Lu Xuning , Zhang Tianfeng , Luo Bin , Li Zengning
Published: April 2022

Background

We systematically quantified the currently inconclusive association between Mediterranean diet patterns and the risk of lung cancer.

Methods

We searched the PubMed, Cochrane, Database of Abstracts of Reviews of Effects (DARE) and Web of Science electronic databases to identify relevant articles published before October 2021. We used the Newcastle–Ottawa scale to assess the quality of the published research and a random-effects model to estimate the aggregate hazard ratios and 95% CIs. As a result of significant heterogeneity, we performed subgroup analysis, meta-regression analysis, and sensitivity analysis. Where data were available, we also performed a dose–response analysis.

Results

Nine articles were included in the meta-analysis. The meta-analysis showed that there was a significant negative correlation between Mediterranean diet patterns and the risk of lung cancer in the general population with a hazard ratio of 0.82, a 95% CI of 0.74–0.92, and a high heterogeneity (I2 = 59.9%, P < 0.05). As a result of the significant heterogeneity, we conducted subgroup analysis, meta-regression analysis, and sensitivity analysis and found that the study design was the source of the heterogeneity. Subgroup analysis and sensitivity analysis showed that the final results did not change very much, the sensitivity was low and the results were relatively stable. The dose–response relationship showed that, based on the lowest Mediterranean diet score (0 points), for every three-point increase, the risk of lung cancer was reduced by 9%.

Conclusion

The evidence in this meta-analysis shows that there is a significant negative correlation between Mediterranean diet patterns and the risk of lung cancer, suggesting that Mediterranean diets are a protective factor in lung cancer.
Vitamin A Status Is More Commonly Associated With Symptoms and Neurodevelopment in Boys With Autism Spectrum Disorders—A Multicenter Study in China
Authors: Yang Ting , Chen Li , Dai Ying , Jia Feiyong , Hao Yan , Li Ling , Zhang Jie , Wu Lijie , Ke Xiaoyan , Yi Mingji , Hong Qi , Chen Jinjin , Fang Shuanfeng , Wang Yichao , Wang Qi , Jin Chunhua , Chen Jie , Li Tingyu
Published: April 2022

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and show a striking male bias in prevalence. Vitamin A (VA) is essential for brain development, and abnormalities in its metabolite retinoic acid are associated with the pathophysiology of ASD. This national multicenter study was conducted to investigate the relationship between serum VA level and core symptoms in ASD children and whether there are still sex differences.

Method

A total of 1,300 children with ASD and 1,252 typically-developing (TD) controls aged 2–7 years old from 13 cities in China were enrolled in this study. The symptoms of children with ASD were evaluated by the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS). The neurodevelopmental level of the children was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). The serum level of VA was measured by high-performance liquid chromatography (HPLC).

Results

The serum VA level in children with ASD was significantly lower than that in TD children, especially in boys with ASD. Furthermore, VA levels in male children with ASD were lower than those in female children with ASD. In addition, we found that serum VA level was negatively correlated the SRS, CARS and communication warming behavior of CBNS-R2016 scores in boys with ASD. In terms of developmental quotients, serum VA level was positively associated with the general quotient, language quotient, gross motor quotient and personal-social quotient of boys with ASD, but no difference was found in girls with ASD.

Conclusions

ASD children, especially boys, have lower serum VA levels than TD children. Moreover, serum VA status is more commonly associated with clinical symptoms and neurodevelopment in boys with ASD.
A Cocoa Diet Can Partially Attenuate the Alterations in Microbiota and Mucosal Immunity Induced by a Single Session of Intensive Exercise in Rats
Authors: Ruiz-Iglesias Patricia , Massot-Cladera Malén , Rodríguez-Lagunas Maria J. , Franch Àngels , Camps-Bossacoma Mariona , Castell Margarida , Pérez-Cano Francisco J.
Published: April 2022

Background

Following intensive sports events, a higher rate of upper respiratory tract infections and the appearance of gastrointestinal symptomatology have been reported. We aimed to evaluate the effect of a cocoa-enriched diet on the cecal microbiota and mucosal immune system of rats submitted to high-intensity acute exercise, as well as to elucidate the involvement of cocoa fiber in such effects.

Methods

Wistar rats were fed either a standard diet, a diet containing 10% cocoa providing 5% fiber and a diet containing only 5% cocoa fiber. After 25 days, half of the rats of each diet performed an exhaustion running test. Sixteen hours later, samples were obtained to assess, among others, the cecal microbiota and short chain fatty acids (SCFAs) composition, mesenteric lymph nodes (MLNs) and Peyer’s patches (PPs) lymphocyte composition, and immunoglobulin (Ig) content in salivary glands.

Results

The intake of cocoa, partially due to its fiber content, improved the SCFA production, prevented some changes in PPs and in MLNs lymphocyte composition and also decreased the production of proinflammatory cytokines. Cocoa diet, contrary to cocoa fiber, did not prevent the lower salivary IgM induced by exercise.

Conclusion

A cocoa dietary intake can partially attenuate the alterations in microbiota and mucosal immunity induced by a single session of intensive exercise.
A Machine Learning-Modified Novel Nomogram to Predict Perioperative Blood Transfusion of Total Gastrectomy for Gastric Cancer
Authors: Zhang Jiawen , Jiang Linhua , Zhu Xinguo
Published: April 2022

Background

Perioperative blood transfusion reserves are limited, and the outcome of blood transfusion remains unclear. Therefore, it is important to prepare plans for perioperative blood transfusions. This study aimed to establish a risk assessment model to guide clinical patient management.

Methods

This retrospective comparative study involving 513 patients who had total gastrectomy (TG) between January 2018 and January 2021 was conducted using propensity score matching (PSM). The influencing factors were explored by logistic regression, correlation analysis, and machine learning; then, a nomogram was established.

Results

After assessment of the importance of factors through machine learning, blood loss, preoperative controlling nutritional status (CONUT), hemoglobin (Hb), and the triglyceride–glucose (TyG) index were considered as the modified transfusion-related factors. The modified model was not considered to be different from the original model in terms of performance, but is simpler. A nomogram was created, with a C-index of 0.834, and the decision curve analysis (DCA) demonstrated good clinical benefit.

Conclusions

A nomogram was established and modified with machine learning, which suggests the importance of the patient’s integral condition. This emphasizes that caution should be exercised regarding transfusions, and, if necessary, preoperative nutritional interventions or delayed surgery should be implemented for safety.
Prognostic Factors and Nomogram Construction for First Local Recurrent Retroperitoneal Sarcoma Following Surgical Resection: A Single Asian Cohort of 169 Cases
Authors: Zhuang Aobo , Lu Weiqi , Fang Yuan , Ma Lijie , Xu Jing , Wang Jiongyuan , Tong Hanxing , Zhang Yong
Published: April 2022

Objective

This study aimed to explore the prognostic factors for first local recurrent retroperitoneal soft tissue sarcoma (FLR-RPS) and construct predictive nomograms in the Asian population.

Methods

In a single Asian sarcoma center, data of patients with FLR-RPS were retrospectively analyzed from January 2011 to September 2020. We developed and internally validated prognostic factors determined by the Cox regression model, as well as nomograms for predicting recurrence-free survival (RFS) and overall survival (OS). The concordance index and calibration curve were used to determine the nomogram’s discriminative and predictive ability.

Results

With 169 patients, the median follow-up duration was 48 months and the 5-year OS rate was 60.9% (95% confidence interval (CI), 51.9%–69.9%). OS was correlated with chemotherapy at the time of initial surgery and tumor grading. The 5-year cumulative local recurrence rate and distant metastasis rate were 75.9% (95% CI, 67.5%–84.3%) and 10.1% (95% CI, 4.2%–16.0%), respectively, and the length of the disease-free interval following the primary operation was associated with disease recurrence. The 6-year OS and cumulative recurrence rate after surgery in our cohort were comparable with those in the TARPSWG cohort, but the proportion of local recurrence was higher (80.4% vs. 59.0%), and distant metastasis was less common (10.1% vs. 14.6%). In this study, two nomogram prediction models were established, which could predict the 1-, 2-, and 5-year OS and RFS, and the concordance indices were 0.74 and 0.70, respectively. The calibration plots were excellent.

Conclusions

For the FLR-RPS patients, some can still achieve an ideal prognosis. The treatment of FLR-RPS in Asian populations can be aided by the predictive model established in this study.
TGF-β1 Promotes Autophagy and Inhibits Apoptosis in Breast Cancer by Targeting TP63
Authors: Wang Yichao , Lu Hongsheng , Wang Zhongrong , Li Yueguo , Chen Xiaoying
Published: April 2022

Background

Breast cancer (BC) is a prevalent female cancer, which has high morbidity and mortality. However, the pathogenesis of BC has not been fully elucidated. Studies have shown that TGF-β1 plays an important role in regulating the balance between autophagy and apoptosis of tumor. We aim to clarify the specific mechanism of autophagy and apoptosis in breast cancer maintaining the tumor microenvironment.

Methods

The clinical characteristics of 850 BC patients were retrieved from the TCGA database. Differentially expressed autophagy-related genes (DEARGs) between tumor and normal tissues were obtained by the Wilcox test. Through Cox proportional hazard regression analysis, the prognostic risk model was constructed and verified by the ROC curve. We used MDC staining, colony formation assay, CCK-8, flow cytometric analysis to confirm the importance of TGF-β1 on the autophagy and apoptosis of breast cancer cells. Furthermore, western blot was performed to determine the relative expression of protein. The Kaplan-Meier Plotter database was utilized to identify the prognostic value of TP63.

Results

We successfully constructed a prognostic risk model of breast cancer and screened out an autophagy-related prognostic gene -TP63. We predicted that TGF-β1 and TP63 have a binding site in the JASPAR database as expected. Additionally, TGF-β1 promoted autophagy and inhibited apoptosis of breast cancer cells by inhibiting the expression of TP63.

Conclusion

Our study demonstrated that the molecular mechanism of TGF-β/TP63 signaling in regulating autophagy and apoptosis of breast cancer and provided a potential prognostic marker in breast cancer.
Mucinous Tubular and Spindle Cell Carcinoma of the Kidney: A Study of Clinical, Imaging Features and Treatment Outcomes
Authors: Xu Xiaofeng , Zhong Jing , Zhou Xiumin , Wei Zhifeng , Xia Qiuyuan , Huang Pengfei , Shi Changjie , Da Jianping , Tang Chaopeng , Cheng Wen , Ge Jingping
Published: April 2022

Purpose

To describe the clinical, imaging, pathological features and oncologic outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney.

Patients and Methods

Twenty-two cases of MTSCC were pathologically identified between January 2004 and April 2021 at our institution. The clinical and imaging findings, pathological features, treatment methods and outcomes of the patients were reviewed.

Results

These cases included 17 women and 5 men, with a median age at diagnosis of 52.5 years. On contrast-enhanced CT, MTSCC was less enhanced than the adjacent renal parenchyma. Tumor attenuation values were 33.3 ± 6.8HU, 44.0 ± 9.1HU, 54.4 ± 13.9HU and 67.1 ± 11.8HU in the non-contrast, corticomedullary, nephrographic and excretory phases of CT, respectively. Contrast-enhanced ultrasonography and MRI also showed hypovascular features of the masses. On MRI, the tumors were isointense on T1-weighted images and slightly hypo- or hyperintense on T2-weighted images. Diffusion-weighted imaging revealed a low apparent diffusion coefficient of the tumor. The patients were managed with laparoscopic partial nephrectomy (n=5), radical nephrectomy (n=16), or robotic-assisted laparoscopic partial nephrectomy (n=1). The median follow-up time was 59.5 months. All the patients were free of local recurrence or distant metastasis.

Conclusions

MTSCC is generally indolent and has favorable outcomes. The imaging features of MTSCC are generally hypovascular, which is significantly different from clear cell renal cell carcinoma. However, it is still difficult to distinguish MTSCC from other hypovascular renal tumors preoperatively because their imaging features overlap. Further studies are essential to fully characterize the features of this rare RCC variant.
A Bibliometric Analysis of the Landscape of Pediatric Liver Transplantation
Authors: Shi Lei , Zhou Jie , Jiang Chenyi , Dai Wanbing , Yu Weifeng , Xia Qiang , Su Diansan
Published: April 2022

Background

Nowadays, pediatric liver transplantation (PLT) has become an effective strategy for treating various acute or chronic end-stage liver diseases and inherited metabolic diseases. Many experts have already concluded the current challenges and future directions of PLT. However, no detailed analysis of the publication landscape has substantiated these proposed opinions.

Methods

This study presents a bibliometric review of the articles related to PLT between 1997 and 2020. A total of 3,084 publications were analyzed mainly by CiteSpace and VOSviewer.

Results

The field of PLT has evolved gradually in the past two decades. Articles increased at an average rate of 97 articles every 4 years. University of Pittsburgh (PITT) is the most prolific institution. The three most productive regions are North America, Europe, and East Asia. Currently, interdisciplinary studies on PLT are scarce. The main goal of PLT has shifted from survival rates to long-term outcome. The quality of life, living donor liver transplantation (LDLT), immunological biomarkers, perioperative hemodynamic management, expanding the indications of PLT, etc. are parts of the emerging research fronts. In the past two decades, articles that contain potentials that may lead to transformative discoveries are scarce, and obvious deficits can be seen in the field of new therapies.

Conclusions

Long-term outcome and good quality of life represent the principal direction of work concerning PLT. Deficits in new therapies align with the shortage of intellectual milestones, which indicate possible subsequent intellectual milestones may occur as innovations in therapies such as new immunosuppression therapies or liver cell transplantation.
Case Report: Testicular Torsion in Unilateral Supernumerary Testis
Authors: Xiaofei Lu , Benzhang Zhou
Published: April 2022

Supernumerary testis (SNT), or polyorchidism, is a rare congenital anomaly of the genitourinary tract, described as the presence of more than two testicles. Testicular torsion (TT) in unilateral SNT is extremely rare. We report a case of unilateral SNT in a 16-year-old boy accompanied by TT, which was diagnosed preoperatively based on the outcomes of physical examination and ultrasound and confirmed intraoperatively. We opted for orchiectomy of this SNT because of the long-time hypoperfusion. And as for the normal testis, orchidopexy was performed. His clinical presentation subsided after surgery, and the patient was discharged 3 days later.
Mupirocin Promotes Wound Healing by Stimulating Growth Factor Production and Proliferation of Human Keratinocytes
Authors: Twilley Danielle , Reva Oleg , Meyer Debra , Lall Namrita
Published: April 2022

Mupirocin has been reported for its role in the treatment of infected wounds through its antibacterial activity, however the role of mupirocin in promoting wound healing via alternative mechanisms has not been extensively evaluated. This study aimed to evaluate the potential effect of mupirocin to promote wound healing, not only through its antibacterial activity but by increasing human keratinocyte proliferation and growth factor production. In the scratch assay, using human keratinocytes (HaCat), mupirocin (at 0.1 and 0.2 mM) significantly increased wound closure compared to the vehicle control. Cell viability, measured from the scratch assay, verified the increase in wound closure, where mupirocin at both concentrations showed higher cell viability compared to the vehicle control. In addition, mupirocin at 0.1 mM significantly stimulated the production of hepatocyte growth factor and M-CSF in HaCat cells, whereas at 0.2 mM, PDGF-AA and EPO were increased. The findings of this study suggest that mupirocin, which is commonly used as an antibacterial agent for the treatment of wounds, also facilitates the wound healing process by stimulating the proliferation of human keratinocytes and enhancing the production of several growth factors involved in wound healing. This is the first report on the effect of mupirocin on growth factors expressed by human keratinocytes as well as the stimulation of keratinocyte proliferation.
A Triple High Throughput Screening for Extracellular Vesicle Inducing Agents With Immunostimulatory Activity
Authors: Shukla Nikunj M. , Sato-Kaneko Fumi , Yao Shiyin , Pu Minya , Chan Michael , Lao Fitzgerald S. , Sako Yukiya , Saito Tetsuya , Messer Karen , Hayashi Tomoko , Cottam Howard B. , Corr Maripat , Carson Dennis A.
Published: April 2022

Extracellular vesicles (EVs) play an important role in intercellular communication and regulation of cells, especially in the immune system where EVs can participate in antigen presentation and may have adjuvant effects. We aimed to identify small molecule compounds that can increase EV release and thereby enhance the immunogenicity of vaccines. We utilized a THP-1 reporter cell line engineered to release EV-associated tetraspanin (CD63)-Turbo-luciferase to quantitatively measure EVs released in culture supernatants as a readout of a high throughput screen (HTS) of 27,895 compounds. In parallel, the cytotoxicity of the compounds was evaluated by PrestoBlue dye assay. For screening immunostimulatory potency, we performed two additional independent HTS on the same compound library using NF-κB and interferon-stimulated response element THP-1 reporter cell lines. Hit compounds were then identified in each of the 3 HTS’s, using a “Top X″ and a Gaussian Mixture Model approach to rule out false positive compounds and to increase the sensitivity of the hit selection. Thus, 644 compounds were selected as hits which were further evaluated for induction of IL-12 in murine bone-marrow derived dendritic cells (mBMDCs) and for effects of cell viability. The resulting 130 hits were then assessed from a medicinal chemistry perspective to remove compounds with functional group liabilities. Finally, 80 compounds were evaluated as vaccine adjuvants in vivo using ovalbumin as a model antigen. We analyzed 18 compounds with adjuvant activity for their ability to induce the expression of co-stimulatory molecules on mBMDCs. The full complement of data was then used to cluster the compounds into 4 distinct biological activity profiles. These compounds were also evaluated for quantitation of EV release and spider plot overlays were generated to compare the activity profiles of compounds within each cluster. This tiered screening process identified two compounds that belong to the 4-thieno-2-thiopyrimidine scaffold with identical screening profiles supporting data reproducibility and validating the overall screening process. Correlation patterns in the adjuvanticity data suggested a role for CD63 and NF-κB pathways in potentiating antigen-specific antibody production. Thus, our three independent cell-based HTS campaigns led to identification of immunostimulatory compounds that release EVs and have adjuvant activity.
Applications of Machine Learning to Improve the Clinical Viability of Compton Camera Based in vivo Range Verification in Proton Radiotherapy
Authors: Polf Jerimy C. , Barajas Carlos A. , Peterson Stephen W. , Mackin Dennis S. , Beddar Sam , Ren Lei , Gobbert Matthias K.
Published: April 2022

We studied the application of a deep, fully connected Neural Network (NN) to process prompt gamma (PG) data measured by a Compton camera (CC) during the delivery of clinical proton radiotherapy beams. The network identifies 1) recorded “bad” PG events arising from background noise during the measurement, and 2) the correct ordering of PG interactions in the CC to help improve the fidelity of “good” data used for image reconstruction. PG emission from a tissue-equivalent target during irradiation with a 150 MeV proton beam delivered at clinical dose rates was measured with a prototype CC. Images were reconstructed from both the raw measured data and the measured data that was further processed with a neural network (NN) trained to identify “good” and “bad” PG events and predict the ordering of individual interactions within the good PG events. We determine if NN processing of the CC data could improve the reconstructed PG images to a level in which they could provide clinically useful information about the in vivo range and range shifts of the proton beams delivered at full clinical dose rates. Results showed that a deep, fully connected NN improved the achievable contrast to noise ratio (CNR) in our images by more than a factor of 8x. This allowed the path, range, and lateral width of the clinical proton beam within a tissue equivalent target to easily be identified from the PG images, even at the highest dose rates of a 150 MeV proton beam used for clinical treatments. On average, shifts in the beam range as small as 3 mm could be identified. However, when limited by the amount of PG data measured with our prototype CC during the delivery of a single proton pencil beam (∼1 × 109 protons), the uncertainty in the reconstructed PG images limited the identification of range shift to ∼5 mm. Substantial improvements in CC images were obtained during clinical beam delivery through NN pre-processing of the measured PG data. We believe this shows the potential of NNs to help improve and push CC-based PG imaging toward eventual clinical application for proton RT treatment delivery verification.
Airway Pressure Release Ventilation With Time-Controlled Adaptive Ventilation (TCAV™) in COVID-19: A Community Hospital’s Experience
Authors: Rola Philippe , Daxon Benjamin
Published: April 2022

Santa Cabrini Ospedale, a community hospital in Montreal, Canada, used the airway pressure release ventilation following a time-controlled adaptive ventilation (APRV-TCAV™) approach for several patients in the first wave of the coronavirus disease 2019 (COVID-19) outbreak in the spring of 2021. Based on favorable patient responses, it became the primary mode of invasive mechanical ventilation—from initiation through extubation—during the second and third waves of COVID-19. In this article, we describe our success with APRV-TCAV™ over more conventional modes and protocols and look at three cases that aptly demonstrate our experience. We then outline several risks with our approach and the lessons learned from our experience. While we generally saw improvement in patients’ clinical course with APRV-TCAV™, there are inherent risks with this approach that others must prepare for if they attempt to implement it in their practice.
Metatranscriptomic Analysis of Corals Inoculated With Tolerant and Non-Tolerant Symbiont Exposed to High Temperature and Light Stress
Authors: Yuyama Ikuko , Higuchi Tomihiko , Mezaki Takuma , Tashiro Hisako , Ikeo Kazuho
Published: April 2022

Algal symbionts of corals can influence host stress resistance; for example, in the Pacific Ocean, whereas Cladocopium (C-type) is generally dominant in corals, Durusdinium (D-type) is found in more heat-resistant corals. Thus, the presence of D-type symbiont likely increases coral heat tolerance, and this symbiotic relationship potentially provides a hint to increase the stress tolerance of coral–algal symbioses. In this study, transcriptome profiles of Cladocopium- and Durusdinium-harboring Acropora solitaryensis (C-coral and D-coral, respectively) and algal photosystem functioning (Fv/Fm) under bleaching conditions (high temperature and light stress) were compared. Stress treatment caused algal photoinhibition that the Fv/Fm value of Symbiodiniaceae was immediately reduced. The transcriptome analysis of corals revealed that genes involved in the following processes were detected: endoplasmic reticulum (ER) stress, mitophagy, apoptosis, endocytosis, metabolic processes (acetyl-CoA, chitin metabolic processes, etc.), and the PI3K-AKT pathway were upregulated, while DNA replication and the calcium signaling pathway were downregulated in both C- and D-corals. These results suggest that unrepaired DNA and protein damages were accumulated in corals under high temperature and light stress. Additionally, some differentially expressed genes (DEGs) were specific to C- or D-corals, which includes genes involved in transient receptor potential (TRP) channels and vitamin B metabolic processes. Algal transcriptome analysis showed the increased expression of gene encoding photosystem and molecular chaperone especially in D-type symbiont. The transcriptome data imply a possible difference in the stress reactions on C-type and D-type symbionts. The results reveal the basic process of coral heat/light stress response and symbiont-type-specific coral transcriptional responses, which provides a perspective on the mechanisms that cause differences in coral stress tolerance.
Automating Pitted Red Blood Cell Counts Using Deep Neural Network Analysis: A New Method for Measuring Splenic Function in Sickle Cell Anaemia
Authors: Nardo-Marino Amina , Braunstein Thomas H. , Petersen Jesper , Brewin John N. , Mottelson Mathis N. , Williams Thomas N. , Kurtzhals Jørgen A. L. , Rees David C. , Glenthøj Andreas
Published: April 2022

The spleen plays an important role in the body’s defence against bacterial infections. Measuring splenic function is of interest in multiple conditions, including sickle cell anaemia (SCA), where spleen injury occurs early in life. Unfortunately, there is no direct and simple way of measuring splenic function, and it is rarely assessed in clinical or research settings. Manual counts of pitted red blood cells (RBCs) observed with differential interference contrast (DIC) microscopy is a well-validated surrogate biomarker of splenic function. The method, however, is both user-dependent and laborious. In this study, we propose a new automated workflow for counting pitted RBCs using deep neural network analysis. Secondly, we assess the durability of fixed RBCs for pitted RBC counts over time. We included samples from 48 children with SCA and 10 healthy controls. Cells were fixed in paraformaldehyde and examined using an oil-immersion objective, and microscopy images were recorded with a DIC setup. Manual pitted RBC counts were performed by examining a minimum of 500 RBCs for pits, expressing the proportion of pitted RBCs as a percentage (%PIT). Automated pitted RBC counts were generated by first segmenting DIC images using a Zeiss Intellesis deep learning model, recognising and segmenting cells and pits from background. Subsequently, segmented images were analysed using a small ImageJ macro language script. Selected samples were stored for 24 months, and manual pitted RBC counts performed at various time points. When comparing manual and automated pitted RBC counts, we found the two methods to yield comparable results. Although variability between the measurements increased with higher %PIT, this did not change the diagnosis of asplenia. Furthermore, we found no significant changes in %PIT after storing samples for up to 24 months and under varying temperatures and light exposures. We have shown that automated pitted RBC counts, produced using deep neural network analysis, are comparable to manual counts, and that fixed samples can be stored for long periods of time without affecting the %PIT. Automating pitted RBC counts makes the method less time consuming and results comparable across laboratories.
Sevoflurane and Hypercapnia Blunt the Physiological Variability of Spontaneous Breathing: A Comparative Interventional Study
Authors: Balogh Adam L. , Sudy Roberta , Petak Ferenc , Habre Walid , Dos Santos Rocha Andre
Published: April 2022

Background: Although spontaneous breathing is known to exhibit substantial physiological fluctuation that contributes to alveolar recruitment, changes in the variability of the respiratory pattern following inhalation of carbon dioxide (CO2) and volatile anesthetics have not been characterized. Therefore, we aimed at comparing the indices of breathing variability under wakefulness, sleep, hypercapnia and sedative and anesthetic concentrations of sevoflurane.

Methods: Spontaneous breathing pattern was recorded on two consecutive days in six rabbits using open whole-body plethysmography under wakefulness and spontaneous sleep and following inhalation of 5% CO2, 2% sevoflurane (0.5 MAC) and 4% (1 MAC) sevoflurane. Tidal volume (VT), respiratory rate (RR), minute ventilation (MV), inspiratory time (TI) and mean inspiratory flow (VT/TI) were calculated from the pressure fluctuations in the plethysmograph. Means and coefficients of variation were calculated for each measured variable. Autoregressive model fitting was applied to estimate the relative contributions of random, correlated, and oscillatory behavior to the total variance.

Results: Physiological sleep decreased MV by lowering RR without affecting VT. Hypercapnia increased MV by elevating VT. Sedative and anesthetic concentrations of sevoflurane increased VT but decreased MV due to a decrease in RR. Compared to the awake stage, CO2 had no effect on VT/TI while sevoflurane depressed significantly the mean inspiratory flow. Compared to wakefulness, the variability in VT, RR, MV, TI and VT/TI were not affected by sleep but were all significantly decreased by CO2 and sevoflurane. The variance of TI originating from correlated behavior was significantly decreased by both concentrations of sevoflurane compared to the awake and asleep conditions.

Conclusions: The variability of spontaneous breathing during physiological sleep and sevoflurane-induced anesthesia differed fundamentally, with the volatile agent diminishing markedly the fluctuations in respiratory volume, inspiratory airflow and breathing frequency. These findings may suggest the increased risk of lung derecruitment during procedures under sevoflurane in which spontaneous breathing is maintained.
Synergy Between Dietary Quercetin and Vitamin E Supplementation in Aged Hen’s Diet Improves Hatching Traits, Embryo Quality, and Antioxidant Capacity of Chicks Hatched From Eggs Subjected to Prolonged Storage
Authors: Amevor Felix Kwame , Cui Zhifu , Du Xiaxia , Ning Zifan , Deng Xun , Xu Dan , Wu Youhao , Cao Xueqing , Wei Shuo , Shu Gang , Han Xue , Tian Yaofu , Li Diyan , Wang Yan , Zhang Yao , Du Xiaohui , Zhu Qing , Zhao Xiaoling
Published: April 2022

The current study aims to investigate the effects of the synergy between quercetin and vitamin E in aged hen’s diet on hatchability and antioxidant levels of the embryo and newly hatched chicks from prolonged storage eggs. A total of 400 breeder laying hens of 65 weeks of age were selected and randomly divided into 4 groups. Birds were fed a basal diet alone (Control), and basal diets supplemented with quercetin (Q) (0.4 g/kg) and vitamin E (VE) (0.2 g/kg) alone and their combination (0.4 g/kg Q + 0.2 g/kg VE) for 14 weeks, respectively, to determine their effects on yolk antioxidant status, fertility, embryonic mortality, hatchability, antioxidant status of embryonic tissues, as well as the antioxidant status of the newly hatched chicks. The results showed that the hen’s dietary Q + VE increased the yolk weight, as well as increased the antioxidant status of the egg yolk (p < 0.05). Compared with the control group, the supplementation of Q + VE significantly increased the hatchability of set-fertile eggs and decreased early embryonic mortality in eggs stored for 7 and 14 days, respectively (p < 0.05), and also improved the antioxidant capacity of the embryos obtained from eggs stored for 14 days (before incubation) (p < 0.05). Moreover, Q + VE increased the levels of SOD, GSH-Px, T-AOC, T-SOD, and CAT in the liver, heart, and pectoral muscle of the embryo, 1-day-old and 14-day-old chicks (p < 0.05), as well as upregulated the antioxidant related genes (GPx-1, GPx-2, GPx-4, DIO-1, and SOD-1) in the liver of the embryo, 1-day-old and 14-day-old chicks hatched from 14-days storage eggs (p < 0.05). Meanwhile, the MDA levels were decreased by the Q + VE in the embryo and post-hatched chicks (p < 0.05). In conclusion, these findings suggested that maternal dietary Q + VE exerts beneficial synergistic effects on the antioxidant capacity of the egg yolk, embryo, and chicks during prolong egg storage, therefore, Q + VE could be used as a dietary measure to enhance hatchability and chick quality in poultry production.
A Whole Leaf Comparative Study of Stomatal Conductance Models
Authors: Sakurai Gen , Miklavcic Stanley J.
Published: April 2022

We employed a detailed whole leaf hydraulic model to study the local operation of three stomatal conductance models distributed on the scale of a whole leaf. We quantified the behavior of these models by examining the leaf-area distributions of photosynthesis, transpiration, stomatal conductance, and guard cell turgor pressure. We gauged the models' local responses to changes in environmental conditions of carbon dioxide concentration, relative humidity, and light irradiance. We found that a stomatal conductance model that includes mechanical processes dependent on local variables predicts a spatial variation of physiological activity across the leaf: the leaf functions of photosynthesis and transpiration are not uniformly operative even when external conditions are uniform. The gradient pattern of hydraulic pressure which is needed to produce transpiration from the whole leaf is derived from the gradient patterns of turgor pressures of guard cells and epidermal cells and consequently leads to nonuniform spatial distribution patterns of transpiration and photosynthesis via the mechanical stomatal model. Our simulation experiments, comparing the predictions of two versions of a mechanical stomatal conductance model, suggest that leaves exhibit a more complex spatial distribution pattern of both photosynthesis and transpiration rate and more complex dependencies on environmental conditions when a non-linear relationship between the stomatal aperture and guard cell and epidermal cell turgor pressures is implemented. Our model studies offer a deeper understanding of the mechanism of stomatal conductance and point to possible future experimental measurements seeking to quantify the spatial distributions of several physiological activities taking place over a whole leaf.
Comparative Analyses of 3,654 Plastid Genomes Unravel Insights Into Evolutionary Dynamics and Phylogenetic Discordance of Green Plants
Authors: Yang Ting , Sahu Sunil Kumar , Yang Lingxiao , Liu Yang , Mu Weixue , Liu Xin , Strube Mikael Lenz , Liu Huan , Zhong Bojian
Published: April 2022

The plastid organelle is essential for many vital cellular processes and the growth and development of plants. The availability of a large number of complete plastid genomes could be effectively utilized to understand the evolution of the plastid genomes and phylogenetic relationships among plants. We comprehensively analyzed the plastid genomes of Viridiplantae comprising 3,654 taxa from 298 families and 111 orders and compared the genomic organizations in their plastid genomic DNA among major clades, which include gene gain/loss, gene copy number, GC content, and gene blocks. We discovered that some important genes that exhibit similar functions likely formed gene blocks, such as the psb family presumably showing co-occurrence and forming gene blocks in Viridiplantae. The inverted repeats (IRs) in plastid genomes have doubled in size across land plants, and their GC content is substantially higher than non-IR genes. By employing three different data sets [all nucleotide positions (nt123), only the first and second codon positions (nt12), and amino acids (AA)], our phylogenomic analyses revealed Chlorokybales + Mesostigmatales as the earliest-branching lineage of streptophytes. Hornworts, mosses, and liverworts forming a monophylum were identified as the sister lineage of tracheophytes. Based on nt12 and AA data sets, monocots, Chloranthales and magnoliids are successive sister lineages to the eudicots + Ceratophyllales clade. The comprehensive taxon sampling and analysis of different data sets from plastid genomes recovered well-supported relationships of green plants, thereby contributing to resolving some long-standing uncertainties in the plant phylogeny.
Identification of Veratrum Species in Pimacao Based on ITS2 Sequences and Steroidal Alkaloids by a Pseudo-Targeted Metabolomics Method
Authors: Lu Qinwei , Wang Shuaiyao , Yin Zili , Chen Qinsheng , He Xingchao , Wang Qi , Hu Qingyu , Gu Yu , Tang Huiru , Xie Hui
Published: April 2022

Pimacao is a traditional Chinese folk medicine and is the main component of the famous Chinese herbal remedy “Yunnan Baiyao” for its significant analgesic activity in the treatment of wounds. Due to increases in consumption, its wild population is now difficult to find, and adulterant from the same genus has occurred. However, this is challenging to distinguish the species of Veratrum in Pimacao using dried roots and rhizomes or medicinal powder. ITS2 sequences and steroidal alkaloids by the non-targeted and pseudo-targeted metabolomics methods were taken advantage of establishing an effective identification method. Based on the ITS2 sequence, metabolite profiling of steroidal alkaloids and morphological characteristics, the classification of two distinct subspecies in V. mengzeanum has been reinforced. In addition, the new subspecies V. mengzeanum subsp. phuwae was collected in China for the first time. The ITS2 sequence could be used in the identification of V. taliense, V. mengtzeanum, V. stenophyllum, and V. nigrum, but is insufficient for intraspecific identification. Simultaneously, 147 variables were labeled by non-targeted analysis accomplished utilizing an ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UPLC-ESI-QE-Orbitrap-MS) system consisting of an Orbitrap QE HF-X. Followed by a pseudo-targeted analysis method developed for the Qtrap 6500-plus mass spectrometry system coupled with an ESI source, 29 labeled steroidal alkaloids detected by the MRM mode could distinguish between four species. Notably, 25 labeled steroidal alkaloids could distinguish between three closely related species. These have the potential to be used as markers for identification. Furthermore, there were several variables with statistical differences between two subspecies of V. mengtzeanum and populations of V. taliense, V. mengtzeanum, and V. stenophyllum.
Allocation Strategies of Carbon, Nitrogen, and Phosphorus at Species and Community Levels With Recovery After Wildfire
Authors: Song Zhaopeng , Wang Xuemei , Liu Yanhong , Luo Yiqi , Li Zhaolei
Published: April 2022

Plant stoichiometry and nutrient allocation can reflect a plant’s adaptation to environmental nutrient changes. However, the allocation strategies of carbon (C), nitrogen (N), and phosphorus (P) between leaf and fine root in response to wildfire have been poorly studied. Our primary objective was to elucidate the trade-off of elemental allocation between above- and belowground parts in response to the soil nutrient changes after a wildfire. We explored the allocation sloping exponents of C, N, and P between leaf and fine root at the species and community levels at four recovery periods (year 2, 10, 20, and 30) after moderately severe wildfire and one unburned treatment in boreal forests in Great Xing’an Mountains, northeast China. Compared with the unburned treatment, leaf C concentration decreased and fine root C increased at year 2 after recovery. The leaf N concentration at year 10 after recovery was higher than that of unburned treatment. Plant growth tended to be limited by P concentration at year 10 after recovery. Nutrient allocation between leaf and fine root differed between species and community levels, especially in the early recovery periods (i.e., 2 and 10 years). At the community level, the nutrient concentrations of the leaf changed more as compared to that of the fine root at year 2 after recovery when the fine root nutrients changed more than those of the leaf. The different C, N, and P allocation strategies advanced the understanding of plant adaptation to soil nutrient changes during the postfire ecosystem restoration.
Dual Roles of OsGH3.2 in Modulating Rice Root Morphology and Affecting Arbuscular Mycorrhizal Symbiosis
Authors: Liu Cheng-Chen , Liu Ying-Na , Cheng Jian-Fei , Guo Rui , Tian Li , Wang Bin
Published: April 2022

Several angiosperm GRETCHEN HAGEN 3 (GH3) genes, including tomato SlGH3.4 and rice OsGH3.2 are induced during arbuscular mycorrhizal (AM) symbiosis, but their functions remain largely unclear. Recently, tomato SlGH3.4 was suggested to negatively regulate arbuscule incidence via decreasing auxin levels in colonized cells. In this study, by acquiring rice OsGH3.2pro:β-glucuronidase (GUS) transgenic plants and generating Osgh3.2 mutants via CRISPR/Cas9 technique, the roles of OsGH3.2 in modulating rice root morphology and affecting AM symbiosis were investigated through time course experiments. Unlike SlGH3.4, OsGH3.2 showed asymbiotic expression in rice young lateral roots, and its mutation resulted in a “shallow” root architecture. Such root morphological change was also observed under symbiotic condition and it likely promoted AM fungal colonization, as the mutants exhibited higher colonization levels and arbuscule incidence than wild-type at early stages. Similar to SlGH3.4, OsGH3.2 showed symbiotic expression in cortical cells that have formed mature arbuscules. At late stages of symbiosis, Osgh3.2 mutants showed elongated cortical cells and larger arbuscules than wild-type, indicating elevated auxin level in the colonized cells. Together, these results revealed both asymbiotic and symbiotic roles of OsGH3.2 in modulating rice root architecture and controlling auxin levels in arbusculated cells, which further affected colonization rate and arbuscule phenotype.