bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Lung Immune Prognostic Index in Non-Small Cell Lung Cancer Patients Treated With Systemic Therapy: A Retrospective Study and Meta-Analysis
Authors: Huang Litang , Han Hedong , Zhou Li , Chen Xi , Xu Qiuli , Xie Jingyuan , Zhan Ping , Chen Si , Lv Tangfeng , Song Yong
Published: June 2021

The lung immune prognostic index (LIPI) has been shown to be an important prognostic marker for various tumors. However, the prognostic value of LIPI among non-small cell lung cancer (NSCLC) patients treated with systemic therapy remains controversial. We aimed to evaluate survival status according to LIPI among NSCLC patients receiving different forms of systemic therapy at our institution. We also performed a meta-analysis of articles from PubMed and Embase to illustrate this question. For our cohort, we found that good LIPI was associated with better overall survival (OS) among 91 patients on immunotherapy, 329 patients on targeted therapy, and 570 patients on chemotherapy. For the meta-analysis, a total of eight studies with 8,721 patients were included. Pooled results showed that a higher LIPI (those with 1 or 2 factors) was associated with poor overall progression-free survival (PFS) (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.45−1.71) and OS (HR, 2.01; 95% CI, 1.75−2.31). Subgroup analyses showed that a higher LIPI was related to poor survival among patients prescribed different systemic therapies: immunotherapy (OS HR, 2.50; 95% CI, 1.99–3.13; PFS HR, 1.77; 95% CI, 1.56–2.01), chemotherapy (OS HR, 1.58; 95% CI, 1.34–1.86; PFS HR, 1.38; 95% CI, 1.23–1.55), and targeted therapy (OS HR; 2.15, 95% CI, 1.57–2.96; PFS HR, 1.60; 95% CI, 1.25–2.06). The study shows that the LIPI is a clinically significant prognostic factor for NSCLC patients receiving systemic therapy.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420209009.
Senescence-Induced Chemoresistance in Triple Negative Breast Cancer and Evolution-Based Treatment Strategies
Authors: Chakrabarty Anindita , Chakraborty Shayantani , Bhattacharya Ranjini , Chowdhury Goutam
Published: June 2021

Triple negative breast cancer (TNBC) is classically treated with combination chemotherapies. Although, initially responsive to chemotherapies, TNBC patients frequently develop drug-resistant, metastatic disease. Chemotherapy resistance can develop through many mechanisms, including induction of a transient growth-arrested state, known as the therapy-induced senescence (TIS). In this paper, we will focus on chemoresistance in TNBC due to TIS. One of the key characteristics of senescent cells is a complex secretory phenotype, known as the senescence-associated secretory proteome (SASP), which by prompting immune-mediated clearance of senescent cells maintains tissue homeostasis and suppresses tumorigenesis. However, in cancer, particularly with TIS, senescent cells themselves as well as SASP promote cellular reprograming into a stem-like state responsible for the emergence of drug-resistant, aggressive clones. In addition to chemotherapies, outcomes of recently approved immune and DNA damage-response (DDR)-directed therapies are also affected by TIS, implying that this a common strategy used by cancer cells for evading treatment. Although there has been an explosion of scientific research for manipulating TIS for prevention of drug resistance, much of it is still at the pre-clinical stage. From an evolutionary perspective, cancer is driven by natural selection, wherein the fittest tumor cells survive and proliferate while the tumor microenvironment influences tumor cell fitness. As TIS seems to be preferred for increasing the fitness of drug-challenged cancer cells, we will propose a few tactics to control it by using the principles of evolutionary biology. We hope that with appropriate therapeutic intervention, this detrimental cellular fate could be diverted in favor of TNBC patients.
Predicting Severe Radiation Esophagitis in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Definitive Chemoradiotherapy: Construction and Validation of a Model Based in the Clinical and Dosimetric Parameters as Well as Inflammatory Indexes
Authors: Yu Yilin , Zheng Hongying , Liu Lingyun , Li Hui , Zheng Qunhao , Wang Zhiping , Wu Yahua , Li Jiancheng
Published: June 2021

Objective

Radiation esophagitis (RE) is common in patients treated with radiotherapy (RT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aim to construct a nomogram predicting the severe RE (grade ≥2) in patients with ESCC receiving definitive chemoradiotherapy (dCRT).

Materials and Methods

Logistic regression was performed to evaluate the risk factors in predicting RE. Nomogram was built based on the multivariate analysis result. The model was validated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analyses (DCA). Spearman correlation analysis was used to evaluate the correlation between inflammation indexes.

Results

A total of 547 patients with stage II–IVA ESCC treated with dCRT from the retrospective study were included. Two hundred and thirty-two of 547 patients (42.4%) developed grade ≥2 RE. Univariate analysis indicated that gender (p = 0.090), RT dose (p < 0.001), targeted therapy (p = 0.047), tumor thickness (p = 0.013), lymphocyte-monocyte ratio (LMR, p = 0.016), neutrophil-lymphocyte ratio (NLR, p < 0.001), and platelet-lymphocyte ratio (PLR, p < 0.001) were the significant factors for a higher incidence of RE. In multivariate analysis, RT dose [p < 0.001; odds ratio (OR), 4.680; 95% confidence interval (CI), 2.841–6.709], NLR (p < 0.001; OR, 0.384; 95% CI, 0.239–0.619), and PLR (p < 0.001; OR, 3.539; 95% CI: 2.226–5.626) were independently associated grade ≥2 RE and were involved in the nomogram. ROC curves showed the AUC of the nomogram was 0.714 (95% CI, 0.670–0.757), which was greater than each factor alone (RT dose: 0.615; NLR: 0.596; PLR: 0.590). Calibration curves showed good consistency between the actual observation and the predicted RE. DCA showed satisfactory positive net benefits of the nomogram among most threshold probabilities.

Conclusions

The study demonstrated that RT dose, NLR, and PLR were independent risk factors for grade ≥2 RE in patients with locally advanced ESCC receiving dCRT. A predictive model including all these factors was built and performed better than it based on each separately. Further validation in large patient populations is still warranted.
Case Report: Durvalumab-Associated Encephalitis in Extensive-Stage Small Cell Lung Carcinoma
Authors: Shionoya Yosuke , Hattori Akito , Hanada Taro , Fujino Michihiro
Published: June 2021

In recent years, the clinical importance of immunotherapy has been demonstrated in the treatment of extensive-stage small-cell lung cancer (ES-SCLC). However, immune checkpoint inhibitors (ICIs) have been shown to cause immune-related adverse events (irAEs), including autoimmune encephalitis. Here, we describe th treatment of a patient with ES-SCLC who developed immune-related encephalitis. A 68-year-old Japanese woman with ES-SCLC treated with carboplatin plus etoposide plus durvalumab 20 days earlier was admitted to our hospital with a high fever and anorexia. Her symptoms gradually worsened over time, and she had a headache daily and showed reduced levels of consciousness. An electroencephalogram showed diffuse slow waves, and there was a slight increase in cell counts and an increase in protein levels in the cerebrospinal fluid. The patient was diagnosed with durvalumab-associated encephalitis. Her symptoms improved immediately after steroid pulse therapy. Following steroid pulse therapy, oral prednisolone (1 mg/kg) was administered, and then, the dose was gradually reduced. Subsequently, treatment with carboplatin plus etoposide without durvalumab was restarted. In conclusion, this study shows the efficacy of steroid therapy in the treatment of durvalumab-induced encephalitis in ES-SCLC.
HER2 Positivity in Histological Subtypes of Salivary Gland Carcinoma: A Systematic Review and Meta-Analysis
Authors: Egebjerg Kristian , Harwood Cecilie Dupont , Woller Nina Claire , Kristensen Claus Andrup , Mau-Sørensen Morten
Published: June 2021

Background

HER2 aberrations in salivary gland carcinomas (SGC) as well as benefit of HER2 directed therapy have been reported in small studies. However, reliable estimates of the prevalence of HER2 positivity in SGC and its various histological subtypes are lacking.

Objective

To assess the prevalence of HER2 positivity in histological subtypes of salivary gland carcinomas (SGC).

Methods

Studies were identified by a systematic review of the literature. Data on in situ hybridization (ISH) and immunohistochemistry (IHC) were extracted to derive pooled prevalence estimates calculated by a random effects model. Characteristics of the studies were extracted for subgroup analysis.

Results

Fifty studies including 3372 patients were identified, providing data on sixteen histological subtypes. Based on the meta-analysis, the estimated prevalence of HER2 positivity were 43% (95% CI: 36% – 51%) in salivary duct carcinoma (SDC), 39% (95% CI: 32% – 45%) in carcinoma ex pleomorphic adenoma (CEP), 17% (95% CI: 7.5% – 33%) in squamous cell carcinoma (SCC), 13% (95% CI: 7.6% – 21%) in adenocarcinoma NOS (ADC), 6.7% (95% CI: 0.17%-32%) in poorly differentiated carcinoma, 5.5% (95% CI: 2.9% – 9.6%) in mucoepidermoid carcinoma, 4.3% (95% CI: 1.4% – 13%) in myoepithelial carcinoma, 1.8% (95% CI: 0.04%-9.6%) in epithelial-myoepithelial carcinoma, 0.45% (95% CI: 0.0097% – 18%) in acinic cell carcinoma and 0.15% (0.037% – 5.4%) in adenoid cystic carcinoma. Estimates for five additional subtypes were assessed.

Conclusion

Prevalence of HER 2 positivity in SGC varies greatly based on histological subtype, with SDC, CEP, SCC, and ADC displaying the highest rates.
Clinical Implementation of Automated Treatment Planning for Rectum Intensity-Modulated Radiotherapy Using Voxel-Based Dose Prediction and Post-Optimization Strategies
Authors: Zhong Yang , Yu Lei , Zhao Jun , Fang Yingtao , Yang Yanju , Wu Zhiqiang , Wang Jiazhou , Hu Weigang
Published: June 2021

Purpose

This study aims to demonstrate the feasibility of clinical implementation of automated treatment planning (ATP) using voxel-based dose prediction and post-optimization strategies for rectal cancer on uRT (United Imaging Healthcare, Shanghai, China) treatment planning system.

Methods

A total of 180 previously treated rectal cancer cases were enrolled in this study, including 160 cases for training, 10 for validation and 10 for testing. Using CT image data, planning target volumes (PTVs) and contour delineation of the organs at risk (OARs) as input and three-dimensional (3D) dose distribution as output, a 3D-Uet DL model was developed. Based on the voxel-wise prediction dose distribution, intensity-modulated radiation therapy (IMRT) plans were then generated automatedly using post-optimization strategies, including a complex clinical dose target metrics homogeneity index (HI) and conformation index (CI). To evaluate the performance of the proposed ATP approach, the dose-volume histogram (DVH) parameters of OARs and PTV and the 3D dose distributions of the plan were compared with those of manual plans.

Results

By combining clinical post-optimization strategies, the automatically generated treatment plan can achieve better homogeneous PTV coverage and dose sparing for OARs except the mean dose for femoral-head compared with the use of the mean square error objective function alone. Compared with the manual plan, no statistically significant differences in HI, CI or global maximum dose were found. The manual plans perform slightly better than plans with post-optimization strategies in other dosimetric indexes, but these plans are still within clinical requirements.

Conclusions

With the help of clinical post-optimization strategies, the proposed new ATP solution can generate IMRT plans that are within clinically acceptable levels and comparable to plans manually generated by dosimetrists.
Influenza vs. COVID-19: Comparison of Clinical Characteristics and Outcomes in Pediatric Patients in Mexico City
Authors: Laris-González Almudena , Avilés-Robles Martha , Domínguez-Barrera Clemen , Parra-Ortega Israel , Sánchez-Huerta José Luis , Ojeda-Diezbarroso Karla , Bonilla-Pellegrini Sergio , Olivar-López Víctor , Chávez-López Adrián , Jiménez-Juárez Rodolfo
Published: June 2021

Introduction: Respiratory viruses are among the leading causes of disease and death among children. Co-circulation of influenza and SARS-CoV2 can lead to diagnostic and management difficulties given the similarities in the clinical picture.

Methods: This is a cohort of all children hospitalized with SARS-CoV2 infection from March to September 3rd 2020, and all children admitted with influenza throughout five flu-seasons (2013–2018) at a pediatric referral hospital. Patients with influenza were identified from the clinical laboratory database. All hospitalized patients with confirmed SARS-CoV2 infection were followed-up prospectively.

Results: A total of 295 patients with influenza and 133 with SARS-CoV2 infection were included. The median age was 3.7 years for influenza and 5.3 years for SARS-CoV2. Comorbidities were frequent in both groups, but they were more common in patients with influenza (96.6 vs. 82.7%, p < 0.001). Fever and cough were the most common clinical manifestations in both groups. Rhinorrhea was present in more than half of children with influenza but was infrequent in those with COVID-19 (53.6 vs. 5.8%, p < 0.001). Overall, 6.4% percent of patients with influenza and 7.5% percent of patients with SARS-CoV2 infection died. In-hospital mortality and the need for mechanical ventilation among symptomatic patients were similar between groups in the multivariate analysis.

Conclusions: Influenza and COVID-19 have a similar picture in pediatric patients, which makes diagnostic testing necessary for adequate diagnosis and management. Even though most cases of COVID-19 in children are asymptomatic or mild, the risk of death among hospitalized patients with comorbidities may be substantial, especially among infants.
Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling
Authors: Moreno-Corona Nidia , Chentout Loïc , Poggi Lucie , Thouenon Romane , Masson Cecile , Parisot Melanie , Mouel Lou Le , Picard Capucine , André Isabelle , Cavazzana Marina , Perrin Laurence , Durandy Anne , Azarnoush Saba , Kracker Sven
Published: June 2021

Activated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene responsible for an alternative splice product and a shortened protein. The clinical presentation of APDS2 patients is highly variable, ranging from mild to profound combined immunodeficiency features as massive lymphoproliferation, increased susceptibility to bacterial and viral infections, bronchiectasis, autoimmune manifestations, and occurrence of cancer. Non-immunological features such as growth retardation and neurodevelopmental delay have been reported for APDS2 patients. Here, we describe a patient suffering from an APDS2 associated with a Smith–Magenis syndrome (SMS), a complex genetic disorder affecting, among others, neurological manifestations and review the literature describing neurodevelopmental impacts in APDS2 and other PIDs/monogenetic disorders associated with dysregulated PI3K signaling.
Concentration-dependent alpha1-Adrenoceptor Antagonism and Inhibition of Neurogenic Smooth Muscle Contraction by Mirabegron in the Human Prostate
Authors: Huang Ru , Liu Yuhan , Ciotkowska Anna , Tamalunas Alexander , Waidelich Raphaela , Strittmatter Frank , Stief Christian G. , Hennenberg Martin
Published: June 2021

Introduction: Mirabegron is available for treatment of storage symptoms in overactive bladder, which may be improved by β3-adrenoceptor-induced bladder smooth muscle relaxation. In addition to storage symptoms, lower urinary tract symptoms in men include obstructive symptoms attributed to benign prostatic hyperplasia, caused by increased prostate smooth muscle tone and prostate enlargement. In contrast to the bladder and storage symptoms, effects of mirabegron on prostate smooth muscle contraction and obstructive symptoms are poorly understood. Evidence from non-human smooth muscle suggested antagonism of α1-adrenoceptors as an important off-target effect of mirabegron. As α1-adrenergic contraction is crucial in pathophysiology and medical treatment of obstructive symptoms, we here examined effects of mirabegron on contractions of human prostate tissues and on proliferation of prostate stromal cells.

Methods: Contractions were induced in an organ bath. Effects of mirabegron on proliferation, viability, and cAMP levels in cultured stromal cells were examined by EdU assays, CCK-8 assays and enzyme-linked immunosorbent assay.

Results: Mirabegron in concentrations of 5 and 10 μM, but not 1 µM inhibited electric field stimulation-induced contractions of human prostate tissues. Mirabegron in concentrations of 5 and 10 µM shifted concentration response curves for noradrenaline-, methoxamine- and phenylephrine-induced contractions to the right, including recovery of contractions at high concentrations of α1-adrenergic agonists, increased EC50 values, but unchanged Emax values. Rightshifts of noradrenaline concentration response curves and inhibition of EFS-induced contractions were resistant to L-748,337, l-NAME, and BPIPP. 1 µM mirabegron was without effect on α1-adrenergic contractions. Endothelin-1- and U46619-induced contractions were not affected or only inhibited to neglectable extent. Effects of mirabegron (0.5–10 µM) on proliferation and viability of stromal cells were neglectable or small, reaching maximum decreases of 8% in proliferation assays and 17% in viability assays. Mirabegron did not induce detectable increases of cAMP levels in cultured stromal cells.

Conclusion: Mirabegron inhibits neurogenic and α1-adrenergic human prostate smooth muscle contractions. This inhibition may be based on antagonism of α1-adrenoceptors by mirabegron, and does not include activation of β3-adrenoceptors and requires concentrations ranging 50-100fold higher than plasma concentrations reported from normal dosing. Non-adrenergic contractions and proliferation of prostate stromal cells are not inhibited by mirabegron.
MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression
Authors: Cao Xuefeng , Zhang Zheng , Wang Yu , Shan Weichao , Wang Ruiting , Mao Shufang , Ding Shi , Pang Chong , Li Baoqun , Zhou Jian , Guo Xiaoyan , Guo Na , Li Cui , Liang Jing , Ma Wenya , Liu Yu , Zhao Liang
Published: June 2021

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hypertrophy by angiotensin II (Ang II), and found that miR-27a-3p and hypertrophy-related genes were up-regulated. Further studies showed that miR-27a-3p-inhibitor can alleviate myocardial hypertrophy and electrical remodeling. Moreover, luciferase assay confirmed that miR-27a-3p could regulate the expression of downstream Hoxa10 at the transcriptional level by targeting at its 3′UTR. At the same time, the protein expression of Hoxa10 was significantly reduced in Ang II-treated cardiomyocytes. Furthermore, overexpression of Hoxa10 can reverse myocardial hypertrophy and electrical remodeling induced by Ang II in cardiomyocytes. Finally, we found that Hoxa10 positively regulated the expression of potassium channel protein Kv4.3 which was down-regulated in hypertrophic cardiomyocytes. Taken together, our results revealed miR-27a-3p/Hoxa10/Kv4.3 axis as a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which provided a new target for clinical prevention and treatment of cardiac hypertrophy and heart failure.
The Effect of a Novel Serine Protease Inhibitor on Inflammation and Intestinal Permeability in a Murine Colitis Transfer Model
Authors: Van Spaendonk Hanne , Ceuleers Hannah , Smet Annemieke , Berg Maya , Joossens Jurgen , Van der Veken Pieter , Francque Sven M. , Lambeir Anne-Marie , De Man Joris G. , De Meester Ingrid , Augustyns Koen , De Winter Benedicte Y.
Published: June 2021

Background: A protease/antiprotease disbalance is observed in inflammatory bowel diseases (IBD). We therefore studied the effect of the novel serine protease inhibitor UAMC-00050 on intestinal inflammation and permeability in a chronic colitis T cell transfer mouse model to get further insight into the regulation of T cell-mediated immunopathology.

Methods: Colitis was induced in severe combined immunodeficient (SCID) mice, by the adoptive transfer of CD4+CD25−CD62L+ T cells. Animals were treated intraperitoneally (i.p.) 2x/day with vehicle or UAMC-00050 (5 mg/kg) from week 2 onwards. Colonic inflammation was assessed by clinical parameters, colonoscopy, macroscopy, microscopy, myeloperoxidase activity and cytokine expression levels. At week 4, 4 kDa FITC-dextran intestinal permeability was evaluated and T helper transcription factors, protease-activated receptors and junctional proteins were quantified by RT-qPCR.

Results: Adoptive transfer of CD4+CD25−CD62L+ T cells resulted in colonic inflammation and an altered intestinal permeability. The serine protease inhibitor UAMC-00050 ameliorated both the inflammatory parameters and the intestinal barrier function. Furthermore, a decrease in colonic mRNA expression of Tbet and PAR4 was observed in colitis mice after UAMC-00050 treatment.

Conclusion: The beneficial effect of UAMC-00050 on inflammation was apparent via a reduction of Tbet, IFN-γ, TNF-α, IL-1β and IL-6. Based on these results, we hypothesize a pivotal effect of serine protease inhibition on the Th1 inflammatory profile potentially mediated via PAR4.
Patient and Payer Preferences for Additional Value Criteria
Authors: Jakab Ivett , Whittington Melanie D. , Franklin Elizabeth , Raiola Susan , Campbell Jonathan D. , Kaló Zoltán , McQueen R. Brett
Published: June 2021

Background: Defining the value of healthcare is an elusive target, and depends heavily on the decision context and stakeholders involved. Cost-utility analysis and the quality-adjusted life year (QALY) have become the method and value definition of choice for traditional value judgements in coverage and pricing decisions. Other criteria that may influence value are often not measured and therefore omitted from value assessments, or are only used to qualitatively contextualize assessments. The objective of this study was to engage two key stakeholders; patients and payers to elicit and rank the importance of additional value criteria, potentially assessed in Multiple Criteria Decision Analysis (MCDA).

Methods: This study consisted of a focus group with cancer patients (n = 7), including follow-up questions through an electronic survey, and in-depth phone interviews with payers (n = 5).

Results: For payers, value equated either with criteria that provided tangible benefits (from their perspective) such as new treatment options that respond to serious unmet need. For patients, population-level value equated to options that would potentially benefit them in the future and the value of hope. However, these criteria were seen by payers as difficult to measure and incorporate into objective decision making.

Limitations: The findings from this study are primarily limited due to generalizability. Due to the small sample size, it was outside the scope of this study to calculate a weight for each criterion that could be used as part of a quantitative MCDA.

Conclusion: MCDA, with particular attention to qualitative aspects, is an avenue to incorporate these additional criteria into value assessments, as well as provide an opportunity for reflecting the patient’s preferences in assessing the value of a treatment.
Application of Machine Learning in Pulmonary Function Assessment Where Are We Now and Where Are We Going?
Authors: Giri Paresh C. , Chowdhury Anand M. , Bedoya Armando , Chen Hengji , Lee Hyun Suk , Lee Patty , Henriquez Craig , MacIntyre Neil R. , Huang Yuh-Chin T.
Published: June 2021

Analysis of pulmonary function tests (PFTs) is an area where machine learning (ML) may benefit clinicians, researchers, and the patients. PFT measures spirometry, lung volumes, and carbon monoxide diffusion capacity of the lung (DLCO). The results are usually interpreted by the clinicians using discrete numeric data according to published guidelines. PFT interpretations by clinicians, however, are known to have inter-rater variability and the inaccuracy can impact patient care. This variability may be caused by unfamiliarity of the guidelines, lack of training, inadequate understanding of lung physiology, or simply mental lapses. A rules-based automated interpretation system can recapitulate expert’s pattern recognition capability and decrease errors. ML can also be used to analyze continuous data or the graphics, including the flow-volume loop, the DLCO and the nitrogen washout curves. These analyses can discover novel physiological biomarkers. In the era of wearables and telehealth, particularly with the COVID-19 pandemic restricting PFTs to be done in the clinical laboratories, ML can also be used to combine mobile spirometry results with an individual’s clinical profile to deliver precision medicine. There are, however, hurdles in the development and commercialization of the ML-assisted PFT interpretation programs, including the need for high quality representative data, the existence of different formats for data acquisition and sharing in PFT software by different vendors, and the need for collaboration amongst clinicians, biomedical engineers, and information technologists. Hurdles notwithstanding, the new developments would represent significant advances that could be the future of PFT, the oldest test still in use in clinical medicine.
TRP Channel Agonists Activate Different Afferent Neuromodulatory Mechanisms in Guinea Pig Urinary Bladder
Authors: Daugherty Stephanie L. , Beckel Jonathan M. , Kim Kyoungeun A. , Freeman Bruce A. , Liu Jiaxin , Wang Shaoyong , de Groat William C. , Zhang Xiulin
Published: June 2021

Activation of TRP channels expressed in urinary bladder afferent nerves and urothelium releases neurotransmitters that influence bladder function. Experiments were undertaken to examine the mechanisms underlying effects of TRPA1 (allyl isothiocyanate, AITC), TRPV1 (capsaicin, CAPS), and TRPC (oleoyl-2-acetyl-sn-glycerol, OAG) agonists on guinea pig bladder activity. Effects of these agonists were compared with effects of nitro-oleic acid (OA-NO2), an electrophilic nitro-fatty acid, known to activate TRPV1, TRPA1 or TRPC channels in sensory neurons. AITC (100 μM) increased (231%) area of spontaneous bladder contractions (SBCs) an effect reduced by a TRPA1 antagonist (HC3-03001, HC3, 10 μM) and reversed to inhibition by indomethacin (INDO, 500 nM) a cyclooxygenase inhibitor. The post-INDO inhibitory effect of AITC was mimicked (39% depression) by calcitonin gene-related peptide (CGRP, 100 nM) and blocked by a CGRP antagonist (BIBN, 25 μM). CAPS (1 μM) suppressed SBCs by 30% in 81% of strips, an effect blocked by a TRPV1 antagonist (diarylpiperazine, 1 μM) or BIBN. SBCs were suppressed by OA-NO2 (30 μM, 21% in 77% of strips) or by OAG (50 μM, 30%) an effect blocked by BIBN. OA-NO2 effects were not altered by HC3 or diarylpiperazine. OA-NO2 also induced excitation in 23% of bladder strips. These observations raise the possibility that guinea pig bladder is innervated by at least two types of afferent nerves: [1] Type A express TRPA1 receptors that induce the release of prostaglandins and excite the detrusor, [2] Type B express TRPV1, TRPA1 and TRPC receptors and release CGRP that inhibits the detrusor.
Leptin and Melanocortin Signaling Mediates Hypertension in Offspring From Female Rabbits Fed a High-Fat Diet During Gestation and Lactation
Authors: Lim Kyungjoon , Burke Sandra L. , Marques Francine Z. , Jackson Kristy L. , Gueguen Cindy , Sata Yusuke , Armitage James A. , Head Geoffrey A.
Published: June 2021

Maternal high-fat diet in rabbits leads to hypertension and elevated renal sympathetic nerve activity (RSNA) in adult offspring but whether this is due to adiposity or maternal programming is unclear. We gave intracerebroventricular (ICV) and ventromedial hypothalamus (VMH) administration of leptin-receptor antagonist, α-melanocyte-stimulating hormone (αMSH), melanocortin-receptor antagonist (SHU9119), or insulin-receptor (InsR) antagonist to conscious adult offspring from mothers fed a high-fat diet (mHFD), control diet (mCD), or mCD offspring fed HFD for 10d (mCD10d, to deposit equivalent fat but not during development). mHFD and mCD10d rabbits had higher mean arterial pressure (MAP, +6.4 mmHg, +12.1 mmHg, p < 0.001) and RSNA (+2.3 nu, +3.2 nu, p < 0.01) than mCD, but all had similar plasma leptin. VMH leptin-receptor antagonist reduced MAP (−8.0 ± 3.0 mmHg, p < 0.001) in mCD10d but not in mHFD or mCD group. Intracerebroventricular leptin-receptor antagonist reduced MAP only in mHFD rabbits (p < 0.05). Intracerebroventricular SHU9119 reduced MAP and RSNA in mHFD but only reduced MAP in the mCD10d group. VMH αMSH increased RSNA (+85%, p < 0.001) in mHFD rabbits but ICV αMSH increased RSNA in both mHFD and mCD10d rabbits (+45%, +51%, respectively, p < 0.001). The InsR antagonist had no effect by either route on MAP or RSNA. Hypothalamic leptin receptor and brain-derived neurotrophic factor (BDNF) mRNA were greater in mHFD compared with mCD rabbits and mCD10d rabbits. In conclusion, the higher MAP in mHFD and mCD10d offspring was likely due to greater central leptin signaling at distinct sites within the hypothalamus while enhanced melanocortin contribution was common to both groups suggesting that residual body fat was mainly responsible. However, the effects of SHU9119 and αMSH on RSNA pathways only in mHFD suggest a maternal HFD may program sympatho-excitatory capacity in these offspring and that this may involve increased leptin receptor and BDNF expression.
Physiological and Proteomic Responses to Drought in Leaves of Amygdalus mira (Koehne) Yü et Lu
Authors: Xu Liping , Hu Yanbo , Jin Guangze , Lei Pei , Sang Liqun , Luo Qiuxiang , Liu Zhi , Guan Fachun , Meng Fanjuan , Zhao Xiyang
Published: June 2021

Various environmental stresses strongly influence plant development. Among these stresses is drought, which is a serious threat that can reduce agricultural productivity and obstruct plant growth. Although the mechanism of plants in response to drought has been studied extensively, the adaptive strategies of Amygdalus mira (Koehne) Yü et Lu grown in drought and rewatered habitats remain undefined. Amygdalus mira from the Tibetan Plateau has outstanding nutritional and medicinal values and can thrive in extreme drought. In this study, the physiological and proteomic responses in leaves of A. mira were investigated during drought and recovery period. The changes in plant growth, photosynthesis, enzymes, and non-enzymatic antioxidant under drought and rewatering were also analyzed in leaves. Compared with controls, A. mira showed stronger adaptive and resistant characteristics to drought. In addition, the proteomic technique was also used to study drought tolerance mechanisms in A. mira leaves. Differentially expressed proteins were identified using mass spectrometry. Accordingly, 103 proteins involved in 10 functional categories: cytoskeleton dynamics, energy metabolism, carbohydrate metabolism, photosynthesis, transcription and translation, transport, stress and defense, molecular chaperones, other materials metabolism, and unknown function were identified. These results showed that an increase of stress-defense-related proteins in leaves after drought treatment contributed to coping with drought. Importantly, A. mira developed an adaptive mechanism to scavenge reactive oxygen species (ROS), including enhancing antioxidant enzyme activities and non-enzymatic antioxidant contents, reducing energy, and adjusting the efficiency of gas exchanges. These results may help to understand the acclimation of A. mira to drought.
Alternative Oxidase Inhibition Impairs Tobacco Root Development and Root Hair Formation
Authors: Liu Yang , Yu Lu-Lu , Peng Ye , Geng Xin-Xin , Xu Fei
Published: June 2021

Alternative oxidase (AOX) is the terminal oxidase of the mitochondrial respiratory electron transport chain in plant cells and is critical for the balance of mitochondrial hemostasis. In this study, the effect of inhibition of AOX with different concentrations of salicylhydroxamic acid (SHAM) on the tobacco root development was investigated. We show here that AOX inhibition significantly impaired the development of the main root and root hair formation of tobacco. The length of the main root of SHAM-treated tobacco was significantly shorter than that of the control, and no root hairs were formed after treatment with a concentration of 1 mM SHAM or more. The transcriptome analysis showed that AOX inhibition by 1 mM SHAM involved in the regulation of gene expression related to root architecture. A total of 5,855 differentially expressed genes (DEGs) were obtained by comparing SHAM-treated roots with control. Of these, the gene expression related to auxin biosynthesis and perception were significantly downregulated by 1 mM SHAM. Similarly, genes related to cell wall loosening, cell cycle, and root meristem growth factor 1 (RGF1) also showed downregulation on SHAM treatment. Moreover, combined with the results of physiological measurements, the transcriptome analysis demonstrated that AOX inhibition resulted in excessive accumulation of reactive oxygen species in roots, which further induced oxidative damage and cell apoptosis. It is worth noting that when indoleacetic acid (20 nM) and dimethylthiourea (10 mM) were added to the medium containing SHAM, the defects of tobacco root development were alleviated, but to a limited extent. Together, these findings indicated that AOX-mediated respiratory pathway plays a crucial role in the tobacco root development, including root hair formation.
Respiration, Rather Than Photosynthesis, Determines Rice Yield Loss Under Moderate High-Temperature Conditions
Authors: Li Guangyan , Chen Tingting , Feng Baohua , Peng Shaobing , Tao Longxing , Fu Guanfu
Published: June 2021

Photosynthesis is an important biophysical and biochemical reaction that provides food and oxygen to maintain aerobic life on earth. Recently, increasing photosynthesis has been revisited as an approach for reducing rice yield losses caused by high temperatures. We found that moderate high temperature causes less damage to photosynthesis but significantly increases respiration. In this case, the energy production efficiency is enhanced, but most of this energy is allocated to maintenance respiration, resulting in an overall decrease in the energy utilization efficiency. In this perspective, respiration, rather than photosynthesis, may be the primary contributor to yield losses in a high-temperature climate. Indeed, the dry matter weight and yield could be enhanced if the energy was mainly allocated to the growth respiration. Therefore, we proposed that engineering smart rice cultivars with a highly efficient system of energy production, allocation, and utilization could effectively solve the world food crisis under high-temperature conditions.
Accessing Ancestral Origin and Diversity Evolution by Net Divergence of an Ongoing Domestication Mediterranean Olive Tree Variety
Authors: Sales Hélia , Šatović Zlatko , Alves Mara Lisa , Fevereiro Pedro , Nunes João , Vaz Patto Maria Carlota
Published: June 2021

Olea europaea ‘Galega vulgar’ variety is a blend of West and Central Mediterranean germplasm with cultivated-wild admixture characteristics. ‘Galega vulgar’ is known for its high rusticity and superior-quality olive oil, being the main Portuguese variety with high impact for bioeconomy. Nevertheless, it has been replaced by higher-yielding and more adapted to intensive production foreign varieties. To clarify the potential ancestral origin, genetic diversity evolution, and existing genetic relationships within the national heritage of ‘Galega vulgar’, 595 trees, belonging to ancient and centenary age groups and prospected among ten traditional production regions, were characterized using 14 SSR markers after variety validation by endocarp measurements. Ninety-five distinguishable genets were identified, revealing the presence of a reasonable amount of intra-genetic and morphological variability. A minimum spanning tree, depicting the complete genealogy of all identified genets, represented the ‘Galega vulgar’ intra-varietal diversity, with 94% of the trees showing only a two-allele difference from the most frequent genet (C001). Strong correlations between the number of differentiating alleles from C001, the clonal size, and their net divergence suggested an ancestral monoclonal origin of the ‘Galega vulgar’, with the most frequent genet identified as the most likely origin of all the genets and phenotypic diversification occurring through somatic mutations. Genetic erosion was detected through the loss of some allele combinations across time. This work highlights the need to recover the lost diversity in this traditional olive variety by including ancient private genets (associated with potential adaptation traits) in future breeding programs and investing in the protection of these valuable resources in situ by safeguarding the defined region of origin and dispersion of ‘Galega vulgar’. Furthermore, this approach proved useful on a highly diverse olive variety and thus applicable to other diverse varieties due either to their intermediate nature between different gene pools or to the presence of a mixture of cultivated and wild traits (as is the case of ‘Galega vulgar’).
How Should Athletes Coping With COVID-19: Focus on Severity and Psychological Support
Authors: Han Qi , Li Xueyang , Wang Zhenghanxiao
Published: June 2021

Objective: Athletes are suffering from many uncertainties and hope to achieve the best possible position under the current circumstances of this global coronavirus disease (COVID-19) pandemic. In this study, we aimed to address the severity and psychological support for athletes with COVID-19.

Methods: We extracted public data and news reports of the up-to-date first seven cases of elite athletes with COVID-19 confirmed in China and made psychological recommendations based on scientific evidence.

Results: The severity and mortality in athletes who tested positive to COVID-19 are mild and extremely low. The included cases from different sports are two soccer players, two athletes from ice hockey, and three from fencing. In this study, we adapted well-recognized psychological questionnaires, improvised it for athletes to use under the COVID-19 pandemic, and also provided recommended psychological support.

Conclusion: The severity and mortality in Chinese athletes contracted with COVID-19 are mild and low with zero death. Psychological support of any kind from nurses, team medical staff, psychologists, family, and friends through social media and telecommunication should be adopted and can be of great help.
Mindfully Reframing the Psychological Impact of the COVID-19 Outbreak Through a Social Media Community for Students: A Pragmatic Study
Authors: Pagnini Francesco , Bonalda Elisa , Montrasi Eleonora , Toselli Elena , Antonietti Alessandro
Published: June 2021

The COVID-19 outbreak and the restrictions that have been enforced by the health authorities are having a profound psychological impact on the population. Many people, including the students, faced forced modifications to their daily lives and this prompted the need for scalable strategies to promote resilience. We designed an online community intervention for psychology students and recent alumni aimed to promote functional coping strategies through openness and cognitive flexibility. This psycho-educational intervention was delivered through a private group on social media (Facebook) during the acute phase of the lockdown period and it involved the publication of exercises and quick lectures. Contents were posted regularly and members of the community were invited to share their comments. The posts included stimuli that promote open and flexible reflections on the current situation. The overall aim of this group was a cognitive reframing on the epidemic effects, promoting creative and flexible thinking. We ran a thematic analysis of the interactions and we collected qualitative feedback at the end of the intervention. The participants' comments dealt with changes in their perspectives, sharing discomfort, encouragement and support, and building a sense of community. Post-intervention comments were highly satisfied and confirmed the helpfulness of the intervention to promote flexibility and openness, eventually helping to manage the negative emotions related to the COVID-19 outbreak. This study provides preliminary evidence that an online psycho-educational community stimulating flexibility and openness can help to reframe the negative psychological impact of the outbreak, improving their management.
Teacher Online Informal Learning as a Means to Innovative Teaching During Home Quarantine in the COVID-19 Pandemic
Authors: Yu Haiqin , Liu Ping , Huang Xiaoqing , Cao Yuxi
Published: June 2021

The home quarantine in the COVID-19 pandemic has created challenges for teaching across the world and called for innovative teaching, as well as teachers' learning. Given the rapid development of teachers' online learning and teaching, identifying effective ways to facilitate innovative teaching under such challenging conditions is a critical issue. Although researchers have realized that workplace informal learning (IL) increasingly reveals its potential value to individual development, the relationship between IL and innovation has been under-explored. The purpose of this study was to evaluate the impact of IL on innovative teaching, through the mediating roles of three types of teaching-related efficacy, with a particular focus on college teachers and online context. A sample of 479 Chinese college teachers was randomly selected to participate in the survey. The results showed that teachers' online IL in pandemic improved their personal teaching efficacy and ICT efficacy (information and communication technology efficacy), and then facilitated their innovative teaching without differences of gender and teaching-age effect. Whereas, general teaching efficacy was not a mediator between online IL and innovative teaching. Hence, we proposed a can-do motivating model of teacher efficacy in fostering innovative teaching through informal learning. It implies three properties of teachers' online IL: social interaction, autonomous learning and novelty-seeking. It also revealed that innovative teaching can be driven in COVID-19 pandemic, mainly by learning domain-specific knowledge and skills, thus enhancing personal teaching efficacy and ICT efficacy in online teaching context.
A Validation Study of the Work Need Satisfaction Scale for Korean Working Adults
Authors: Kim Ji-Hye , Yoo Kieun , Lee Seran , Lee Ki-Hak
Published: June 2021

This study aimed to verify the reliability and validity of the Korean version of the Work Need Satisfaction Scale for working adults, based on the psychology of working theory. A total of 589 working adults in Korea responded to the online survey. Of these respondents, 339 were used for exploratory factor analysis and 250 for confirmatory factor analysis. In Stage 1, we translated all items into Korean, back-translated them into English, and then verified the accuracy of the translation. Exploratory factor analysis revealed the 5-factor structure of the Korean version of the Work Need Satisfaction Scale reflecting those of the original scale (survival needs, social contribution needs, autonomy, relatedness, and competence). The scale showed good internal consistency. In Stage 2, confirmatory factor analysis was conducted, and the results indicated that there were no significant differences between a correlational model, a higher-order model, and a higher-order self-determination needs model. Thus, we offered a higher-order self-determination needs model, which had better model fit and was consistent with the original scale and the psychology of working theoretical framework. In addition, convergent and discriminant validity were supported by correlation estimates of the Korean version of the Work Need Satisfaction Scale, and the concurrent validity showed that the Korean version of the Work Need Satisfaction Scale had a significant proportion of explained variance for outcomes. The findings support the conclusion that this study established strong internal consistency and validity for the Korean version of the Work Need Satisfaction Scale. Thus, the scale is unique and meaningful for measuring need satisfaction in work settings in Korea.
Implementing Collaborative Writing in Chinese EFL Classrooms: Voices From Tertiary Teachers
Authors: Zheng Yao , Yu Shulin , Lee Icy
Published: June 2021

While collaborative writing has been increasingly investigated in educational research, little is known about whether and how it is adopted as a pedagogical activity in classroom contexts. This exploratory study investigated EFL teachers' perceptions of the implementation of collaborative writing in Chinese tertiary institutions. The analysis of in-depth interviews with 31 EFL teachers from 13 institutions in the People's Republic of China and their teaching materials reveals mismatches between their perceptions and practices, as well as their perceptions and knowledge. While the teachers perceived collaborative writing as valuable and feasible, more than half of them were not using it, and their perceptions were not supported by sound teacher knowledge. Practical implications are provided for implementing collaborative writing in classroom contexts.
Cross-Language Influences in the Processing of Multiword Expressions: From a First Language to Second and Back
Authors: Du Lingli , Elgort Irina , Siyanova-Chanturia Anna
Published: June 2021

The present study investigated cross-language influences in the processing of binomial expressions (knife and fork), from a first language (L1) to a second language (L2) and from L2 to L1. Two groups of unbalanced bilinguals (Chinese/L1-English/L2 and English/L1-Chinese/L2) and a control group of English monolinguals performed a visual lexical decision task that incorporated unmasked priming. To assess cross-language influences, we used three types of expressions: congruent binomials (English binomials that have translation equivalents in Chinese), English-only binomials, and Chinese-only binomials translated into English. Lexical decision latencies to the last word (fork) in a binomial (knife and fork) were compared with response latencies to the same word in a matched control phrase (spoon and fork). We found that (1) Chinese-English bilinguals showed a significant priming effect for congruent binomials but no facilitation for English-only binomials, (2) English–Chinese bilinguals showed a trend toward priming for congruent binomials, which did not reach statistical significance, and no priming for English-only binomials, (3) English monolinguals showed comparable priming for congruent and English-only binomials. With respect to the Chinese-only binomials, none of the three participant groups showed priming for translated Chinese-only binomials over controls. These findings suggest that L1 influences the processing of L2 binomials, and that there may be some cross-linguistic influence in the opposite direction, i.e., from L2 to L1, although to a lesser extent.