bluuebunny/crossref_metadata_2025 huggingface dataset:
DOTA Conjugate of Bisphosphonate and PSMA-Inhibitor: A Promising Combination for Therapy of Prostate Cancer Related Bone Metastases
Authors: Grus Tilmann , Lahnif Hanane , Bausbacher Nicole , Miederer Matthias , Rösch Frank
Published: June 2022

Prostate cancer (PCa) is one of the most common cancer types worldwide. 90% of men with late stage PCa will develop bone metastases. Since the expression level of PSMA (prostate-specific membrane antigen) in bone metastases can vary significantly, a compound is being searched for which accumulates in bone metastases independently of PSMA level. With DOTA-L-Lys(SA.Pam)-PSMA-617, we present a compound that, in addition to a PSMA inhibitor as a target vector, also contains a bisphosphonate that is established as a bone tracer and thus combines the advantages of PSMA targeting and bone targeting. This is a class of small molecules combining targeting of two different targets with the potential advantages for treatment of biologically heterogeneous bone metastasis from prostate cancer. The molecule can be labeled with lutetium-177 and used for the therapy of PCa-related bone metastases. DOTA-L-Lys(SA.Pam)-PSMA-617 was synthesized and radiolabelled in 1 M ammonium acetate buffer pH 5.5 at 95°C. Different amounts of precursor were evaluated. Complex stability was evaluated in three different media. LogD7.4 value was evaluated via the determination of the equilibrium distribution in a PBS/n-octanol mixture. A hydroxyapatite binding assay was used to evaluate the potential binding to bone metastases. In vitro affinity was determined and Ki value was evaluated. To evaluate the binding potential in mice, ex vivo biodistribution studies were carried out in LNCaP tumor-bearing Balb/c mice. [177Lu]Lu-labeling of DOTA-L-Lys(SA.Pam)-PSMA-617 showed quantitative RCY within 10 min and high complex stability over 14 days. The lipophilicity of the labeled compound was similar to the lipophilicity of the reference compound [177Lu]Lu-PSMA-617 and showed an excellent and selective HAP binding of 98.2 ± 0.11%. With a Ki of 42.3 ± 7.7 nM PSMA binding affinity is lower in comparison to [177Lu]Lu-PSMA-617. First ex vivo biodistribution studies with LNCaP tumor-bearing Balb/c mice showed a PSMA dependent tumor accumulation of 4.2 ± 0.7%ID/g and a femur accumulation of 3.4 ± 0.4%ID/g. [177Lu]Lu-DOTA-L-Lys(SA.Pam)-PSMA-617 is a promising compound for therapy of PCa related bone and tissue metastases. Accumulation on the bone metastases via two mechanisms also enables the treatment of bone metastases that show little or no PSMA expression.
Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience
Authors: Brown Andrea , Buss Elizabeth J. , Chin Christine , Liu Gaotong , Lee Shing , Rao Roshni , Taback Brett , Wiechmann Lisa , Horowitz David , Choi Julie C. , Katz Leah M. , Connolly Eileen P.
Published: June 2022

Purpose/Objective

We present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines.

Materials/Methods

We identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time.

Results

237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 – 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%.

Conclusion

There is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.
Hymeglusin Enhances the Pro-Apoptotic Effects of Venetoclax in Acute Myeloid Leukemia
Authors: Zhou Cheng , Wang Zhiqin , Yang Shuanghui , Li Huan , Zhao Liang
Published: June 2022

Venetoclax is used for the priority treatment of elderly patients with acute myeloid leukemia (AML). Resistance or intolerance to venetoclax offsets its clinical benefits in some patients. Combination strategies with other drugs are promising alternatives to overcome the current complications associated with venetoclax use. Hymeglusin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1), regulates the mevalonate pathway, which is vital for AML growth and chemosensitivity. The effects of the combination of venetoclax and hymeglusin on AML were explored in this study. The correlations between HMGCS1 and apoptosis-related genes were analyzed using the Gene Expression Profiling Interactive Analysis 2 and The Cancer Genome Atlas databases. Apoptosis and cell viability were detected in HL-60 and KG-1 cells after treatment with gradient concentrations of venetoclax or hymeglusin. The transcriptomic profiles of HL-60 and KG-1 cells were compared via RNA-Seq analysis. The effects of venetoclax and hymeglusin on apoptosis were validated in primary cells. The results showed that HMGCS1 expression was closely associated with apoptosis-related genes based on the data from large clinical databases. B cell lymphoma (BCL)-2 expression was elevated in AML and negatively associated with overall survival. Hymeglusin decreased BCL2 expression levels in HL-60 and KG-1 cells. Venetoclax and hymeglusin inhibited cell viability in both cell lines, but induced apoptosis in HL-60 cells. This discrepancy in sensitivity to hymeglusin may be attributed to the positive increase in the expression levels of HMGCS1 and multiple upregulated pro-leukemia genes in KG-1 cells. Combination treatment with venetoclax and hymeglusin significantly increased the apoptotic rates compared to single-agent treatment in both AML cell lines and primary AML cells. Furthermore, the combination strategy did not result in remarkably enhanced toxicity in normal mononuclear cells. Collectively, hymeglusin enhanced the effects of venetoclax on apoptosis. This combination strategy showed enhanced antileukemic activity with acceptable toxicity in AML.
Prognostic Impact of Serum CRP Level in Head and Neck Squamous Cell Carcinoma
Authors: Zhang Yaoting , Gu Dongsheng
Published: June 2022

Objective

This study evaluated the association of pretreatment serum C-reactive protein (CRP) level with prognosis in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

Within a single-center retrospective study, HNSCC patients receiving treatment between 2014 and 2016 were analyzed regarding the prognostic value of CRP serum levels. X-Tile software was used to determine the optimal cutoff value of serum CRP level. The log-rank test and Kaplan–Meier method were used to assess the effects of CRP level on prognosis in patients with HNSCC. Univariate and multivariate analyses (enter method) using a Cox proportional hazards model were utilized to identify prognostic indicators of progression-free survival (PFS) as the primary outcome and overall survival (OS) as the secondary outcome.

Results

A total of 221 patients with HNSCC were assessed for eligibility, and 208 cases were included in the analysis. The HNSCC patients in the low-group (CRP ≤11.3 mg/L) showed better survival than those in the high-group (CRP > 11.3 mg/L). The univariate and multivariate analyses showed that N1-3 stage and a high serum CRP level (>11.3 mg/L) were unfavorable prognostic factors for PFS and OS in patients with HNSCC.

Conclusion

Serum CRP level is an independent prognostic marker for patients with HNSCC. CRP level could be regarded as a novel prognostic factor for HNSCC patients.
Challenges and Opportunities for Immunoprofiling Using a Spatial High-Plex Technology: The NanoString GeoMx® Digital Spatial Profiler
Authors: Hernandez Sharia , Lazcano Rossana , Serrano Alejandra , Powell Steven , Kostousov Larissa , Mehta Jay , Khan Khaja , Lu Wei , Solis Luisa M.
Published: June 2022

Characterization of the tumor microenvironment through immunoprofiling has become an essential resource for the understanding of the complex immune cell interactions and the assessment of biomarkers for prognosis and prediction of immunotherapy response; however, these studies are often limited by tissue heterogeneity and sample size. The nanoString GeoMx® Digital Spatial Profiler (DSP) is a platform that allows high-plex profiling at the protein and RNA level, providing spatial and temporal assessment of tumors in frozen or formalin-fixed paraffin-embedded limited tissue sample. Recently, high-impact studies have shown the feasibility of using this technology to identify biomarkers in different settings, including predictive biomarkers for immunotherapy in different tumor types. These studies showed that compared to other multiplex and high-plex platforms, the DSP can interrogate a higher number of biomarkers with higher throughput; however, it does not provide single-cell resolution, including co-expression of biomarker or spatial information at the single-cell level. In this review, we will describe the technical overview of the platform, present current evidence of the advantages and limitations of the applications of this technology, and provide important considerations for the experimental design for translational immune-oncology research using this tissue-based high-plex profiling approach.
Elevated Serum Alpha-Fetoprotein Is a Significant Prognostic Factor for Patients with Gastric Cancer: Results Based on a Large-Scale Retrospective Study
Authors: Zhan Zhouwei , Chen Bijuan , Yu Jiami , Zheng Jingxian , Zeng Yi , Sun Mingyao , Peng Li , Guo Zengqing , Wang Xiaojie
Published: June 2022

Objectives

The aim of this work is to study the clinicopathological features and prognostic factors of serum alpha-fetoprotein (AFP)–positive gastric cancer (GC).

Methods

A cohort study including 2,318 patients with GC who underwent radical surgery from January 2008 to December 2015 was retrospectively analyzed. Patients were divided into two groups according to preoperative serum AFP values: 191 patients with AFP-positive GC (AFP > 20 ng/ml, 8.24%) and 2,127 patients with AFP-negative GC (AFP ≤ 20 ng/ml, 91.76%). The clinicopathological features and prognostic factors were explored.

Results

Compared with AFP-negative GC, AFP-positive GC had higher rates of liver metastasis, lymph node metastasis, venous invasion, and nerve invasion (all P < 0.05). The 5-year OS, DFS, and mLMFS of AFP-positive GC were shorter than AFP-negative GC (55.00% vs. 45.04%, P < 0.001; 39.79% vs. 34.03%, P < 0.001; 13.80 months vs. 16.25 months, P = 0.002). In whole cohort, multivariate analysis found that serum AFP levels (positive vs. negative), pT stage, pN stage, nerve invasion (yes or no), and venous invasion (yes or no) were independent prognostic factors. Serum AFP levels (20–300 ng/ml vs. 300–1,000 ng/ml vs. >1,000 ng/ml), pT stage, pN stage, and venous invasion (yes or no) were independent prognostic factors in AFP-positive GC.

Conclusion

Liver metastases and venous invasion are more likely to occur in AFP-positive GC and lead to poor prognosis. Serum AFP level is an independent prognostic factor in patients with GC. As the level of AFP increases, the prognosis becomes worse.
Diagnostic-Therapeutic Pathway and Outcomes of Early Stage NSCLC: a Focus on EGFR Testing in the Real-World
Authors: Pasello Giulia , Lorenzi Martina , Pretelli Giulia , Comacchio Giovanni Maria , Pezzuto Federica , Schiavon Marco , Buja Alessandra , Frega Stefano , Bonanno Laura , Guarneri Valentina , Calabrese Fiorella , Rea Federico
Published: June 2022

Background

Osimertinib is considered the standard-of-care for previously-untreated EGFR mutant advanced non-small cell lung cancer (NSCLC). Oncogene driver screening in early NSCLC is not standard practice. A real-world study has been designed in order to investigate the optimal testing frequency and timing for EGFR mutations in early NSCLC in clinical practice.

Patients and Methods

The present observational, retrospective study evaluated the real-world diagnostic-therapeutic pathway and clinical outcomes of 225 patients with stage I-III NSCLC, with particular reference to the EGFR-mutant subgroup.

Results

Prior to surgery, 101 patients had undergone a diagnostic biopsy; EGFR mutational analysis was available in 56 (55%) patients and 12 patients (21%) had a cancer harboring an EGFR mutation. Among surgical specimens, reflex EGFR test was performed in 181 (80%) of 225 and 35 cases (19%) were EGFR mutant. The majority of patients had not received adjuvant chemotherapy (N=174, 77%) or adjuvant radiotherapy (N=201, 89%). Of 49 (22%) patients experiencing disease relapse, 26 (53%) received first-line systemic treatment. All EGFR-mutant relapsed patients (N=6, 12.2%) received an EGFR-TKI. Median overall survival (OS) and relapse-free survival for the entire population were not reached. Multivariate analysis for OS confirmed a significant correlation with age, female gender, EGFR status, necrosis score, perineural invasion, and relapsed disease. EGFR test costs represented 1.6-2.4% of the total costs of management per patient (€34,340).

Conclusions

Our results suggest that the frequency of EGFR mutations in early stage (I-III) NSCLC is similar to that of advanced stages. Reflex EGFR testing in all early-stage NSCLC at diagnosis or after surgery appears to be a valid tool to give patients the chance to benefit from targeted adjuvant treatment.
Androgens in Patients With Luminal B and HER2 Breast Cancer Might Be a Biomarker Promoting Anti-PD-1 Efficacy
Authors: Li Peng , Yuan Wenhui , Wu Ruan , Zeng Chuqian , Li Ke , Lu Ligong
Published: June 2022

Endocrine therapy is considered as an effective strategy for estrogen and progestogen receptor (ER and PR)-positive breast cancer (BRCA) patients, whereas resistance to these agents is the major cause of BRCA mortality in women. Immune checkpoint receptor (ICR) blockade is another approach to treat BRCA, but the response rate of this approach for non-triple-negative breast cancer (non-TNBC) is relatively low. Recently, the androgen receptor (AR) has been identified as a tumor suppressor in ER-positive BRCA; however, the relationship between the levels of androgens and ICRs on T cells in BRCA is unclear. We observed that testosterone and dihydrotestosterone (DHT) in patients with HER2 and Luminal B were significantly lower than those in healthy controls, and the expression of AR has significant correlation with overall survival (OS) advantage for Luminal B patients. Moreover, testosterone and DHT were positively correlated with the PD-1 expression on Vδ1+ T cells in HER2 and Luminal B patients. These results suggest a potential approach of combining androgens with PD-1 blockade for treating HER2 and Luminal B breast cancer.
Performance Evaluation of the Deep Learning Based Convolutional Neural Network Approach for the Recognition of Chest X-Ray Images
Authors: Sharma Sandhya , Gupta Sheifali , Gupta Deepali , Rashid Junaid , Juneja Sapna , Kim Jungeun , Elarabawy Mahmoud M.
Published: June 2022

Recent advancement in the field of deep learning has provided promising performance for the analysis of medical images. Every year, pneumonia is the leading cause for death of various children under the age of 5 years. Chest X-rays are the first technique that is used for the detection of pneumonia. Various deep learning and computer vision techniques can be used to determine the virus which causes pneumonia using Chest X-ray images. These days, it is possible to use Convolutional Neural Networks (CNN) for the classification and analysis of images due to the availability of a large number of datasets. In this work, a CNN model is implemented for the recognition of Chest X-ray images for the detection of Pneumonia. The model is trained on a publicly available Chest X-ray images dataset having two classes: Normal chest X-ray images and Pneumonic Chest X-ray images, where each class has 5000 Samples. 80% of the collected data is used for the purpose to train the model, and the rest for testing the model. The model is trained and validated using two optimizers: Adam and RMSprop. The maximum recognition accuracy of 98% is obtained on the validation dataset. The obtained results are further compared with the results obtained by other researchers for the recognition of biomedical images.
Plasma Signaling Factors in Patients With Langerhans Cell Histiocytosis (LCH) Correlate With Relative Frequencies of LCH Cells and T Cells Within Lesions
Authors: Mitchell Jenée , Kvedaraite Egle , von Bahr Greenwood Tatiana , Lourda Magda , Henter Jan-Inge , Berzins Stuart P. , Kannourakis George
Published: June 2022

Langerhans cell histiocytosis (LCH) lesions contain an inflammatory infiltrate of immune cells including myeloid-derived LCH cells. Cell-signaling proteins within the lesion environment suggest that LCH cells and T cells contribute majorly to the inflammation. Foxp3+ regulatory T cells (Tregs) are enriched in lesions and blood from patients with LCH and are likely involved in LCH pathogenesis. In contrast, mucosal associated invariant T (MAIT) cells are reduced in blood from these patients and the consequence of this is unknown. Serum/plasma levels of cytokines have been associated with LCH disease extent and may play a role in the recruitment of cells to lesions. We investigated whether plasma signaling factors differed between patients with active and non-active LCH. Cell-signaling factors (38 analytes total) were measured in patient plasma and cell populations from matched lesions and/or peripheral blood were enumerated. This study aimed at understanding whether plasma factors corresponded with LCH cells and/or LCH-associated T cell subsets in patients with LCH. We identified several associations between plasma factors and lesional/circulating immune cell populations, thus highlighting new factors as potentially important in LCH pathogenesis. This study highlights plasma cell-signaling factors that are associated with LCH cells, MAIT cells or Tregs in patients, thus they are potentially important in LCH pathogenesis. Further study into these associations is needed to determine whether these factors may become suitable prognostic indicators or therapeutic targets to benefit patients.
Risk Factors for Benign Convulsions With Mild Gastroenteritis
Authors: Fang Cuiyun , Fan Wei , Zhang Chunsheng , Yang Yi
Published: June 2022

Objective

To investigate the risk factors for benign convulsions with mild gastroenteritis (CwG) and provide a basis for the early identification and diagnosis.

Method

We selected children with CwG and acute gastroenteritis in the same period who attended the pediatric department of the Liyang People's Hospital from June 2018 to June 2021. A retrospective analysis of the general data, clinical characteristics, and laboratory test results of the two groups was performed. Finally, we conducted a multifactorial logistic regression analysis to derive the risk factors for CwG.

Results

A total of 82 children were included in the CwG and 93 children were included in the acute gastroenteritis group. Univariate analysis showed no significant differences in gender, age, vomiting, diarrhea, neutrophil, lymphocyte, hemoglobin, platelets, and serum calcium. Statistically significant differences were found in onset season, rotavirus, white blood cells, aspartate aminotransferase, alanine transaminase, serum sodium, and uric acid. Finally, multifactorial logistic regression analysis showed rotavirus (OR, 3.042, 95% CI, 1.116–8.289, p = 0.030), serum sodium (OR, 0.811, 95% CI, 0.684–0.962, p = 0.016) and uric acid (OR, 1.018, 95% CI, 1.012–1.024, p = 0.000) to be independent risk factors.

Conclusion

Characteristics of gastroenteritis symptoms such as vomiting and diarrhea cannot be used to predict the onset of CwG. Rotavirus is an independent risk factor for CwG, and decreased serum sodium and increased uric acid can be used as early warning indicators for CwG.
Mitigation of Ionizing Radiation-Induced Gastrointestinal Damage by Insulin-Like Growth Factor-1 in Mice
Authors: Pejchal Jaroslav , Tichy Ales , Kmochova Adela , Fikejzlova Lenka , Kubelkova Klara , Milanova Marcela , Lierova Anna , Filipova Alzbeta , Muckova Lubica , Cizkova Jana
Published: June 2022

Purpose: Insulin-like growth factor-1 (IGF-1) stimulates epithelial regeneration but may also induce life-threatening hypoglycemia. In our study, we first assessed its safety. Subsequently, we examined the effect of IGF-1 administered in different dose regimens on gastrointestinal damage induced by high doses of gamma radiation.

Material and methods: First, fasting C57BL/6 mice were injected subcutaneously with IGF-1 at a single dose of 0, 0.2, 1, and 2 mg/kg to determine the maximum tolerated dose (MTD). The glycemic effect of MTD (1 mg/kg) was additionally tested in non-fasting animals. Subsequently, a survival experiment was performed. Animals were irradiated (60Co; 14, 14.5, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously at 1 mg/kg 1, 24, and 48 h after irradiation. Simultaneously, mice were irradiated (60Co; 12, 14, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously under the same regimen. Jejunum and lung damage were assessed 84 h after irradiation. Finally, we evaluated the effect of six different IGF-1 dosage regimens administered subcutaneously on gastrointestinal damage and peripheral blood changes in mice 6 days after irradiation (60Co; 12 and 14 Gy; shielded head). The regimens differed in the number of doses (one to five doses) and the onset of administration (starting at 1 [five regimens] or 24 h [one regimen] after irradiation).

Results: MTD was established at 1 mg/kg. MTD mitigated lethality induced by 14 Gy and reduced jejunum and lung damage caused by 12 and 14 Gy. However, different dosing regimens showed different efficacy, with three and four doses (administered 1, 24, and 48 h and 1, 24, 48, and 72 h after irradiation, respectively) being the most effective. The three-dose regimens supported intestinal regeneration even if the administration started at 24 h after irradiation, but its potency decreased.

Conclusion: IGF-1 seems promising in the mitigation of high-dose irradiation damage. However, the selected dosage regimen affects its efficacy.
Efficacy of Resveratrol in Experimental Subarachnoid Hemorrhage Animal Models: A Stratified Meta-Analysis
Authors: Tan Jiahe , Song Rui , Luo Siyue , Fu Wenqiao , Ma Yinrui , Zheng Lian , He Zhaohui
Published: June 2022

Background: Subarachnoid hemorrhage (SAH) is a serious neurosurgical emergency with extremely high morbidity and mortality rates. Resveratrol (RES), a natural polyphenolic phytoalexin, is broadly presented in a wide variety of plants. Previous research had reasonably revealed its neuroprotective effects on experimental SAH animal models to some extent. But the results were more controversial. Therefore, we conducted a meta-analysis to evaluate the evidence on the effectiveness of RES in improving outcomes in SAH animal models.

Methods: A systematic literature review was conducted in PubMed, EMBASE, and Web of Science databases to incorporate experimental control studies on the efficacy of RES on SAH models into our research. The standardized mean difference (SMD) was used to compare the brain water content (BWC) and neurological score (NS) between the treatment and control groups.

Results: Overall, 16 articles published from 2014 to 2022 met the inclusion criteria. The meta-analysis of BWC showed a significant difference in favor of RES treatment (SMD: −1.026; 95% CI: −1.380, −0.672; p = 0.000) with significant heterogeneity (Q = 84.97; I2 = 60.0%; p = 0.000). Further stratified analysis was performed for methodological differences, especially dosage, time of treatments, and time-point of outcome assessment. The meta-analysis of NS showed a significant difference in favor of RES treatment (SMD: 1.342; 95% CI: 1.089, 1.595; p = 0.000) with low heterogeneity (Q = 25.58; I2 = 17.9%; p = 0.223).

Conclusion: Generally, RES treatment showed an improvement in both pathological and behavioral outcomes in SAH animal models. The results of this study may provide a reference for preclinical and clinical studies in the future to some extent, with great significance for human health.
A Computational Framework to Characterize the Cancer Drug Induced Effect on Aging Using Transcriptomic Data
Authors: Zhao Yueshan , Wang Yue , Yang Da , Suh Kangho , Zhang Min
Published: June 2022

Cancer treatments such as chemotherapies may change or accelerate aging trajectories in cancer patients. Emerging evidence has shown that “omics” data can be used to study molecular changes of the aging process. Here, we integrated the drug-induced and normal aging transcriptomic data to computationally characterize the potential cancer drug-induced aging process in patients. Our analyses demonstrated that the aging-associated gene expression in the GTEx dataset can recapitulate the well-established aging hallmarks. We next characterized the drug-induced transcriptomic changes of 28 FDA approved cancer drugs in brain, kidney, muscle, and adipose tissues. Further drug-aging interaction analysis identified 34 potential drug regulated aging events. Those events include aging accelerating effects of vandetanib (Caprelsa®) and dasatinib (Sprycel®) in brain and muscle, respectively. Our result also demonstrated aging protective effect of vorinostat (Zolinza®), everolimus (Afinitor®), and bosutinib (Bosulif®) in brain.
Curcumin, thymoquinone, and 3, 3′-diindolylmethane combinations attenuate lung and liver cancers progression
Authors: Saddiq Amna A. , El-Far Ali H. , Mohamed Abdullah Shymaa Abdullah , Godugu Kavitha , Almaghrabi Omar A. , Mousa Shaker A.
Published: June 2022

Cancer can develop due to abnormal cell proliferation in any body’s cells, so there are over a hundred different types of cancer, each with its distinct behavior and response to treatment. Therefore, many studies have been conducted to slow cancer progression and find effective and safe therapies. Nutraceuticals have great attention for their anticancer potential. Therefore, the current study was conducted to investigate the anticancer effects of curcumin (Cur), thymoquinone (TQ), and 3, 3′-diindolylmethane (DIM) combinations on lung (A549) and liver (HepG2) cancer cell lines’ progression. Results showed that triple (Cur + TQ + DIM) and double (Cur + TQ, Cur + DIM, and TQ + DIM) combinations of Cur, TQ, and DIM significantly increased apoptosis with elevation of caspase-3 protein levels. Also, these combinations exhibited significantly decreased cell proliferation, migration, colony formation activities, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (AKT) protein levels with S phase reduction. Triple and double combinations of Cur, TQ, and DIM hindered tumor weight and angiogenesis of A549 and HepG2 implants in the chorioallantoic membrane model. Interestingly, Cur, TQ, and DIM combinations are considered promising for suppressing cancer progression via inhibiting tumor angiogenesis. Further preclinical and clinical investigations are warranted.
The Reduced Adaptability of H-Reflex Parameters to Postural Change With Deficiency of Foot Plantar Sensitivity
Authors: Sun Mengzi , Lewis Kelsey , Choi Jung Hun , Zhang Fangtong , Qu Feng , Li Li
Published: June 2022

Purpose: The project was to examine the influence of peripheral neuropathy (PN) severity on the relationship between Hoffmann-reflex (H-reflex) and postures.

Methods: A total of 34 participants were recruited. H-reflex (H/M ratio and H-index) during prone, standing, and the heel-contact phase of walking was tested, along with foot sole sensitivity.

Results: The participants were divided into three groups based on the severity of the foot sole sensitivity deficit: control, less (LA), and more (MA) affected with both feet 5.07 monofilament test scores ranging 10, 0–5, and 6–9, respectively. A significant group by the posture interaction was observed in the H/M ratio (F3.0, 41.9 = 2.904, p = 0.046, ηp2 = 0.172). In the control group, the H/M ratio of prone (22 ± 7%) was greater than that of the standing (13 ± 3%, p = 0.013) and heel-contact phase (10 ± 2%, p = 0.004). In the MA group, the H/M ratio of standing (13 ± 3%) was greater than that of the heel-contact phase (8 ± 2%, p = 0.011). The H-index was significantly different among groups (F2,28 = 5.711, p = 0.008, and ηp2= 0.290). Post hoc analysis showed that the H-index of the control group (80.6 ± 11.3) was greater than that of the LA (69.8 ± 12.1, p = 0.021) and MA groups (62.0 ± 10.6, p = 0.003).

Conclusion: In a non-PN population, the plantar sensory input plays an important role in maintaining standing postural control, while as for the PN population with foot sole sensitivity deficiency, type Ⅰ afferent fibers reflex loop (H-reflex) contributes more to the standing postural control. The H-index parameter is an excellent method to recognize the people with and without PN but not to distinguish the severity of PN with impaired foot sole sensitivity.
New Perspectives on Sex Steroid and Mineralocorticoid Receptor Signaling in Cardiac Ischemic Injury
Authors: Bienvenu Laura A. , Bell James R. , Weeks Kate L. , Delbridge Lea M. D. , Young Morag J.
Published: June 2022

The global burden of ischemic heart disease is burgeoning for both men and women. Although advances have been made, the need for new sex-specific therapies targeting key differences in cardiovascular disease outcomes in men and women remains. Mineralocorticoid receptor directed treatments have been successfully used for blood pressure control and heart failure management and represent a potentially valuable therapeutic option for ischemic cardiac events. Clinical and experimental data indicate that mineralocorticoid excess or inappropriate mineralocorticoid receptor (MR) activation exacerbates ischemic damage, and many of the intracellular response pathways activated in ischemia and subsequent reperfusion are regulated by MR. In experimental contexts, where MR are abrogated genetically or mineralocorticoid signaling is suppressed pharmacologically, ischemic injury is alleviated, and reperfusion recovery is enhanced. In the chronic setting, mineralocorticoid signaling induces fibrosis, oxidative stress, and inflammation, which can predispose to ischemic events and exacerbate post-myocardial infarct pathologies. Whilst a range of cardiac cell types are involved in mineralocorticoid-mediated regulation of cardiac function, cardiomyocyte-specific MR signaling pathways are key. Selective inhibition of cardiomyocyte MR signaling improves electromechanical resilience during ischemia and enhances contractile recovery in reperfusion. Emerging evidence suggests that the MR also contribute to sex-specific aspects of ischemic vulnerability. Indeed, MR interactions with sex steroid receptors may differentially regulate myocardial nitric oxide bioavailability in males and females, potentially determining sex-specific post-ischemic outcomes. There is hence considerable impetus for exploration of MR directed, cell specific therapies for both women and men in order to improve ischemic heart disease outcomes.
A Shorter-Bout of HIIT Is More Effective to Promote Serum BDNF and VEGF-A Levels and Improve Cognitive Function in Healthy Young Men
Authors: Li Qing , Zhang Li , Zhang Zhengguo , Wang Yuhan , Zuo Chongwen , Bo Shumin
Published: June 2022

Objective: The aim of this study was to investigate the effects of single bouts of high-intensity interval training (HIIT) with different duration on serum brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor-A (VEGF-A) levels and cognitive function in healthy young men.

Methods: Twelve healthy young men were participated in two HIIT treatments (20 min HIIT and 30 min HIIT) in a random order. BDNF, VEGF-A, cortisol, testosterone, blood lactic acid were measured and cognitive function was assessed by Stroop test (CWST) and Digital Span test (DST) before, immediately after, and 30 min after HIIT.

Results: 20 and 30 min HIIT increased BLa (both p < 0.01), cortisol (20 min HIIT: p < 0.05; 30 min HIIT: p < 0.01), and testosterone (both p < 0.05) levels immediately when compared with their baselines. While BLa and cortisol were significantly higher in 30 min HIIT group than in 20 min HIIT group. Moreover, BDNF concentration (p < 0.01), DST-F (p < 0.01) and DST-B (p < 0.05) were increased and response time of Stroop was decreased immediately after HIIT only in 20 min HIIT group. VEGF-A concentration was increased immediately after HIIT in both groups (p < 0.01), but after 30 min recovery, it was returned to the baseline in the 20 min HIIT group and was lower than the baseline in 30 min HIIT group (p < 0.05).

Conclusion: Twenty minutes HIIT is more effective than 30 minutes HIIT for promoting serum levels of BDNF and VEGF-A as well as cognitive function in healthy young men.
Application of Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Distress Syndrome Caused by Pneumocystis jirovecii Pneumonia Following Kidney Transplantation: A Case Series
Authors: Wang Hong-Yu , Li Yi-Hao , Zhang Si-Sen , Jiang Xin , Niu Xing-Guo , Qian Xin-Ling , Liu Cong-Yan
Published: June 2022

Objective: To investigate the application effect of extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) caused by Pneumocystis jirovecii pneumonia (PJP) after kidney transplantation.

Methods: This is a case series on 10 kidney transplant recipients with severe ARDS caused by PJP at the People’s Hospital of Zhengzhou, who were enrolled as the case group. A total of 17 cases of PJP diagnosed with severe ARDS without ECMO were selected as the control group. The timing and mode of ECMO support and treatment complications were summarized. The primary aim of this study was mortality and secondary was imaging and complications.

Results: The enrolled patients’ oxygenation index before the start of ECMO ranged from 25 to 92, and the time from admission to the start of ECMO was 1–17 days, with an average of 5.56 days. In the case group, one patient died of hemorrhagic shock due to abdominal hemorrhage, but the other nine patients were successfully weaned from ECMO. Of these patients, one died due to sepsis following weaning. The survival rate in the case group was 80.0% (8/10), and the survival rate in the control group was 35.29% (6/17). The vein–vein ECMO support time in the nine successfully weaned patients in the case group ranged from 131 to 288 h, with an average of 215.5 h. Of the eight patients who survived, deterioration of renal function after transplantation occurred in two patients, but no fatal complications occurred.

Conclusion: Overall, Patients with severe ARDS caused by postoperative PJP infection following kidney transplantation have a poor prognosis. The mortality was lower in patients who were treated with ECMO compared to standard care.
Phylogeographical Pattern and Population Evolution History of Indigenous Elymus sibiricus L. on Qinghai-Tibetan Plateau
Authors: Han Mengli , Zhang Jingxue , Li Daxu , Sun Shengnan , Zhang Changbing , Zhang Chuanjie , Yan Lijun , Guan Yongzhuo , Chen Lili , Guo Yuxia , You Minghong , Gou Wenlong , Li Xinrui , Yan Jiajun , Bai Shiqie , Yan Xuebing
Published: June 2022

Elymus sibiricus L. is a perennial allotetraploid belonging to Triticeae of Poaceae,ElymusL., as the type species of genusElymusL. The existing geographical distribution pattern and genetic spatial structure ofE. sibiricuson Qinghai–Tibetan Plateau (QTP) are not yet clear. In this study, population genetic structure and demography history of 216 individuals from 44E. sibiricuspopulations on QTP were studied used specific-locus amplified fragment sequencing (SLAF-seq). The result of genetic diversity showed that there was no single genetic diversity center was observed across allE. sibiricuspopulations. The results of genetic variation showed that 44 populations were clearly divided into the following three groups: Qinghai Plateau (Group I), South Tibet (Group II), and Hengduan Mountains (Group III). From the three analyses of AMOVA, Mantel test and Treemix, strong genetic differentiation across all populations and low genetic differentiation among populations within three groups. Molecular dating indicated thatE. sibiricusdiverged at 16.08 Ma (during the early Miocene) can be linked to the Himalayan Motion stage of QTP uplift. It is speculated that the reasons affecting the current phylogeographical pattern are as follows: (1) The environmental changes due to the uplift of the QTP; (2) The geographic distance between the populations (Groups I and III are close in geographic distance, and gene flow are frequent); (3) Geographical barriers (the Tanggula and Bayangela Mountains between Groups I and II). This study provides new evidence and historical perspective to the future exploration of the evolution and geographic distribution pattern ofElymusL.
Analysis of Physiological Variations and Genetic Architecture for Photosynthetic Capacity of Japanese Soybean Germplasm
Authors: Shamim Mohammad Jan , Kaga Akito , Tanaka Yu , Yamatani Hiroshi , Shiraiwa Tatsuhiko
Published: June 2022

The culmination of conventional yield improving parameters has widened the margin between food demand and crop yield, leaving the potential yield productivity to be bridged by the manipulation of photosynthetic processes in plants. Efficient strategies to assess photosynthetic capacity in crops need to be developed to identify suitable targets that have the potential to improve photosynthetic efficiencies. Here, we assessed the photosynthetic capacity of the Japanese soybean mini core collection (GmJMC) using a newly developed high-throughput photosynthesis measurement system “MIC-100” to analyze physiological mechanisms and genetic architecture underpinning photosynthesis. K-means clustering of light-saturated photosynthesis (Asat) classified GmJMC accessions into four distinct clusters with Cluster2 comprised of highly photosynthesizing accessions. Genome-wide association analysis based on the variation of Asat revealed a significant association with a single nucleotide polymorphism (SNP) on chromosome 17. Among the candidate genes related to photosynthesis in the genomic region, variation in expression of a gene encoding G protein alpha subunit 1 (GPA1) showed a strong correlation (r = 0.72, p < 0.01) with that of Asat. Among GmJMC accessions, GmJMC47 was characterized by the highest Asat, stomatal conductance (gs), stomatal density (SDensity), electron transfer rate (ETR), and light use efficiency of photosystem II (Fv’/Fm′) and the lowest non-photochemical quenching [NPQ(t)], indicating that GmJMC47 has greater CO2 supply and efficient light-harvesting systems. These results provide strong evidence that exploration of plant germplasm is a useful strategy to unlock the potential of resource use efficiencies for photosynthesis.
Understanding the Impact of Green Human Resource Management Practices and Dynamic Sustainable Capabilities on Corporate Sustainable Performance: Evidence From the Manufacturing Sector
Authors: Khaskhely Mahvish Kanwal , Qazi Sarah Wali , Khan Naveed R. , Hashmi Tooba , Chang Asma Abdul Rahim
Published: June 2022

Pakistan ranks as the eighth most vulnerable country on the 2021 global climate change vulnerability index. Partially, this perilous position is attributed to unsustainable practices in the large-scale manufacturing sector since its contribution to carbon emission is among the highest in the economy. These serious environmental challenges impede the attainment of sustainable development goals that concern responsible consumption and production. In manufacturing organizations, there are an ongoing debate regarding sustainable human resource management (HRM) determinants, which can promote sustainable performance. In this regard, green human resource management (GHRM) practices and dynamic sustainable capabilities are significant components as they have a unique role in transforming corporations into sustainable organizations. However, there is a dearth of evidence regarding the impact of individual GHRM practices, such as green recruitment and selection, green pay and reward, and sustainable capabilities like monitoring and re-configuration, in improving the corporate environmental and social performance. Hence, an empirical investigation regarding the association among these macro-level components with the corporate environmental and social performance through partial least squares structural equation modeling (PLS-SEM) is conducted. The findings inferred from 396 employees affiliated with six large-scale industries substantiate the main hypotheses of this study. It is empirically confirmed that GHRM and dynamic sustainable capabilities significantly and positively impact corporate sustainable performance. This research contributes to the literature by employing dynamic capabilities approach and a dynamic resource-based view (RBV) to explicate how corporations can benefit from the interplay of sustainable capabilities and GHRM functions. Hence, in the absence of a significant predictive model, this research is the first of its kind to isolate macro-level antecedents of sustainable HRM to find their impact on corporate sustainable performance in a developing country context. The study recommends that the management should prioritize the acquisition of monitoring capabilities and hiring environmentally conscious employees to achieve social equity and ecological conservation goals.
Research on the Public Opinion Guidance Mechanism of Major Public Health Incidents
Authors: Wang Yuqi , Wu Rui , Zeng Jun , Xue Peiyi
Published: June 2022

Public opinion guidance plays a crucial role in the management of major public health incidents, and thus, exploring its mechanism is conducive to the comprehensive governance of social security. This study conducts a case study on the anti-pandemic public opinion guidance and analyzes the public opinion representation and the internal mechanism of public opinion guidance in the context of the COVID-19 in China. The findings suggest that the public opinion on the COVID-19 manifested a three-stage progressive and stable tendency and witnessed the strength of China, specifically, benefiting from the systematic and complete integration and release mechanism for anti-pandemic information, the three-dimensional mechanism for the dissemination of knowledge related to pandemic prevention and health, the innovative disclosure mechanism for precise information, and diversified channels for international public opinion guidance. The guidance mechanism proposed in this study provides significant suggestions for the public opinion guidance of global major public health incidents in future.
Teacher Becoming Curriculum Designer: Professional Teaching and Learning in China’s Early Childhood Education
Authors: Tian Xiaoming , Bao Li , Li Tianxin , Gu Yue
Published: June 2022

The Curriculum Design Coherence Model (CDC Model) was created as a universal curriculum design method to connect disciplinary knowledge to teachers’ expertise in a bid to promote professional teaching and learning. However, research into how the CDC Model has been adopted and localized in the Chinese educational context is scarce. This article focuses on the application and impact of the CDC Model on the resulting teaching practices in China’s Early Childhood Education (ECE) settings. The data collected through a focus group discussion with 21 teachers from a model kindergarten at the municipal level in China reveals that the CDC Model has increased the teachers’ professionalism by promoting their curriculum initiative, forging curriculum knowledge orientation, strengthening the conceptual structure within the kindergarten-developed curriculum, and enhancing the coordination between the curricula of the different courses offered by the kindergarten. This positive influence has also helped the teachers bridge their disagreement on curriculum content and pedagogy and overcome some difficulties in using the CDC Model. The study has implications for revitalizing the value of disciplinary knowledge and for viewing ECE teachers as active professional agents in ECE curriculum design and teaching.
Does Imagery Ability Matter for the Relationship Between Temperament and Self-Confidence in Team and Individual Sport Disciplines?
Authors: Budnik-Przybylska Dagmara , Huzarska Izabela , Karasiewicz Karol
Published: June 2022

The main purpose of our study was to investigate the relationship among temperamental traits, a general tendency to use imagery, and self-confidence in sport. The specific aim was to verify if general imagery mediates the relationship between temperament and self-confidence in sport, but also with respect to individual and team sport disciplines. The study involved 144 athletes aged 19–25 years (75 men and 69 women) with different lengths of training (from 1 month to 18 years) and presented different sports levels: international (n = 12), national (n = 46), and recreational (n = 86). They also represented individual (n = 73) and team (n = 68) sports. The Imagination in Sport Questionnaire (ISQ), Trait Sports Confidence Inventory (TSCI-PL), and Temperament Questionnaire (EAS) were all completed by the participants. Results indicate that self-confidence is explained in about 13% by temperament and general imagery, but only general imagery (b = 0.22; p < 0.05) and negative axes of the temperament—emotionality (b = –0.26; p < 0.05). The test of the indirect effect of the negative axes of the temperament on self-confidence through general imagery, conducted by Preacher and Hayes bootstrapping procedure, revealed significant mediation [b = 0.37; 95% CI = (0.09; 0.68); R2Med = 0.46] suggesting that about 46% of variance explained in self-confidence by emotionality is related to general imagery. The other 3% of variance explained in self-confidence by the positive temperament axes is related to general imagery, however, it was insignificant. The general imagery explains the relationship between emotionality and self-confidence only in individual sports athletes.