bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct cortico-muscular coupling between step and stance leg during reactive stepping responses
Authors: Stokkermans Mitchel , Solis-Escalante Teodoro , Cohen Michael X. , Weerdesteyn Vivian
Published: March 2023

Balance recovery often relies on successful stepping responses, which presumably require precise and rapid interactions between the cerebral cortex and the leg muscles. Yet, little is known about how cortico-muscular coupling (CMC) supports the execution of reactive stepping. We conducted an exploratory analysis investigating time-dependent CMC with specific leg muscles in a reactive stepping task. We analyzed high density EEG, EMG, and kinematics of 18 healthy young participants while exposing them to balance perturbations at different intensities, in the forward and backward directions. Participants were instructed to maintain their feet in place, unless stepping was unavoidable. Muscle-specific Granger causality analysis was conducted on single step- and stance-leg muscles over 13 EEG electrodes with a midfrontal scalp distribution. Time-frequency Granger causality analysis was used to identify CMC from cortex to muscles around perturbation onset, foot-off and foot strike events. We hypothesized that CMC would increase compared to baseline. In addition, we expected to observe different CMC between step and stance leg because of their functional role during the step response. In particular, we expected that CMC would be most evident for the agonist muscles while stepping, and that CMC would precede upregulation in EMG activity in these muscles. We observed distinct Granger gain dynamics over theta, alpha, beta, and low/high-gamma frequencies during the reactive balance response for all leg muscles in each step direction. Interestingly, between-leg differences in Granger gain were almost exclusively observed following the divergence of EMG activity. Our results demonstrate cortical involvement in the reactive balance response and provide insights into its temporal and spectral characteristics. Overall, our findings suggest that higher levels of CMC do not facilitate leg-specific EMG activity. Our work is relevant for clinical populations with impaired balance control, where CMC analysis may elucidate the underlying pathophysiological mechanisms.
Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer’s disease
Authors: Wijesinghe Printha , Whitmore Clayton A. , Campbell Matthew , Li Charles , Tsuyuki Miranda , To Eleanor , Haynes Justin , Pham Wellington , Matsubara Joanne A.
Published: March 2023

Introduction

Ergothioneine (Ergo) is a naturally occurring dietary antioxidant. Ergo uptake is dependent on the transporter, organic cation transporter novel-type 1 (OCTN1) distribution. OCTN1 is highly expressed in blood cells (myeloid lineage cells), brain and ocular tissues that are likely predisposed to oxidative stress. Ergo may protect the brain and eye against oxidative damage and inflammation, however, the underlying mechanism remains unclear. Amyloid beta (Aβ) clearance is a complex process mediated by various systems and cell types including vascular transport across the blood–brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Impaired Aβ clearance is a major cause for Alzheimer’s disease (AD). Here we investigated neuroretinas to explore the neuroprotective effect of Ergo in a transgenic AD mouse model.

Methods

Age-matched groups of Ergo-treated 5XFAD, non-treated 5XFAD, and C57BL/6J wildtype (WT controls) were used to assess Ergo transporter OCTN1 expression and Aβ load along with microglia/macrophage (IBA1) and astrocyte (GFAP) markers in wholemount neuroretinas (n = 26) and eye cross-sections (n = 18). Immunoreactivity was quantified by fluorescence or by semi-quantitative assessments.

Results and discussion

OCTN1 immunoreactivity was significantly low in the eye cross-sections of Ergo-treated and non-treated 5XFAD vs. WT controls. Strong Aβ labeling, detected in the superficial layers in the wholemounts of Ergo-treated 5XFAD vs. non-treated 5XFAD reflects the existence of an effective Aβ clearance system. This was supported by imaging of cross-sections where Aβ immunoreactivity was significantly low in the neuroretina of Ergo-treated 5XFAD vs. non-treated 5XFAD. Moreover, semi-quantitative analysis in wholemounts identified a significantly reduced number of large Aβ deposits or plaques, and a significantly increased number of IBA1(+)ve blood-derived phagocytic macrophages in Ergo-treated 5XFAD vs. non-treated 5XFAD. In sum, enhanced Aβ clearance in Ergo-treated 5XFAD suggests that Ergo uptake may promote Aβ clearance possibly by blood-derived phagocytic macrophages and via perivascular drainage.
Investigating behavioral phenotypes related to autism spectrum disorder in a gene-environment interaction model of Cntnap2 deficiency and Poly I:C maternal immune activation
Authors: Haddad Faraj L. , De Oliveira Cleusa , Schmid Susanne
Published: March 2023

Introduction

Autism Spectrum Disorder (ASD) has been associated with a wide variety of genetic and environmental risk factors in both human and preclinical studies. Together, findings support a gene-environment interaction hypothesis whereby different risk factors independently and synergistically impair neurodevelopment and lead to the core symptoms of ASD. To date, this hypothesis has not been commonly investigated in preclinical ASD models. Mutations in the Contactin-associated protein-like 2 (Cntnap2) gene and exposure to maternal immune activation (MIA) during pregnancy have both been linked to ASD in humans, and preclinical rodent models have shown that both MIA and Cntnap2 deficiency lead to similar behavioral deficits.

Methods

In this study, we tested the interaction between these two risk factors by exposing Wildtype, Cntnap2+/–, and Cntnap2–/– rats to Polyinosinic: Polycytidylic acid (Poly I:C) MIA at gestation day 9.5.

Results

Our findings showed that Cntnap2 deficiency and Poly I:C MIA independently and synergistically altered ASD-related behaviors like open field exploration, social behavior, and sensory processing as measured through reactivity, sensitization, and pre-pulse inhibition (PPI) of the acoustic startle response. In support of the double-hit hypothesis, Poly I:C MIA acted synergistically with the Cntnap2–/– genotype to decrease PPI in adolescent offspring. In addition, Poly I:C MIA also interacted with the Cntnap2+/– genotype to produce subtle changes in locomotor hyperactivity and social behavior. On the other hand, Cntnap2 knockout and Poly I:C MIA showed independent effects on acoustic startle reactivity and sensitization.

Discussion

Together, our findings support the gene-environment interaction hypothesis of ASD by showing that different genetic and environmental risk factors could act synergistically to exacerbate behavioral changes. In addition, by showing the independent effects of each risk factor, our findings suggest that ASD phenotypes could be caused by different underlying mechanisms.
Addressing the unmet needs of patients with BRAF-mutated melanoma in Latin America: Expert perspective
Authors: Salman Pamela , de Melo Andreia Cristina , Rico-Restrepo Mariana , Rodriguez Jeronimo , Russi Andrea , Schmerling Rafael Aron , Zambrano Angela , Cinat Gabriela
Published: March 2023

Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF-status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF-mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma’s time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment.
Latency of breast cancer stigma during survivorship and its influencing factors: A qualitative study
Authors: Melhem Samar J. , Nabhani-Gebara Shereen , Kayyali Reem
Published: March 2023

Introduction

Breast cancer diagnosis and treatment have been shown in studies to have a negative impact on patients’ physical, psychological, and social well-being, as well as overall quality of life. Psychologically, it’s linked to sadness, anxiety, and demoralisation. Stigma contributes to the hidden burden of breast cancer as a chronic illness. Research on the elements that breast cancer survivors encounter as influences on stigma associated to the disease is lacking. Based on the lived experiences of breast cancer survivors, this study sought to investigate the factors that lead to the manifestations of both self- and public breast cancer stigma.

Methods

Individual semi-structured interviews with 24 patients diagnosed with breast cancer were performed, followed by five focus groups with 25 patients diagnosed with breast cancer. Interviews were verbatim transcribed and analysed using thematic framework analysis.

Results

Two major themes have emerged from the data: a) Breast cancer stigma among breast cancer survivors, highlighting the various manifestations of stigma and the variables that influence them; including disease-related factors, patients’ views of cancer, public perceptions of breast cancer, family and interpersonal dynamics, and b) Stigma resilience and empowerment, emphasising the necessity of sociocultural transformation and coping strategies to preserve resilience.

Conclusions

To improve the well-being of breast cancer survivors, practitioners and health policymakers should be aware of the breast cancer stigma that underpins patients’ emotional and behavioural outlooks and its potential consequences on patients’ quality of life. They need to develop interventions to address the different stages of cancer stigma taking into consideration sociocultural influences, norms, and beliefs.
Cost-effectiveness evaluation based on two models of first-line atezolizumab monotherapy and chemotherapy for advanced non-small cell lung cancer with high-PDL1 expression
Authors: Zhang Chuan , Liu Yue , Tan Jing , Tian Panwen , Li Weimin
Published: March 2023

Background

Atezolizumab may provide clinical benefits to patients with advanced non-small cell lung cancer (NSCLC). However, the price of atezolizumab is relatively high, and its economic outcomes have remained unclear. In this study, we used two models to examine the cost-effectiveness of initial atezolizumab monotherapy versus chemotherapy for patients with PD-L1 high-expressing EGFR and ALK wild-type advanced NSCLC in the context of the Chinese healthcare system.

Methods

Partitioned Survival model and Markov model were performed to evaluate the cost-effectiveness of first-line single-agent atezolizumab versus platinum-based chemotherapy for patients with advanced NSCLC with PD-L1 high-expressing EGFR and ALK wild-type disease. Clinical outcomes and safety information were obtained from the most recent data from the IMpower110 trial, while cost and utility values were obtained from Chinese hospitals and relevant literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed to explore model uncertainty. Scenario analyses were also conducted for the Patient Assistance Program (PAP) and various provinces in China.

Results

In the Partitioned Survival model, the total cost of atezolizumab was $145,038, providing 2.92 LYs and 2.39 QALYs, while the total cost of chemotherapy was $69,803, providing 2.12 LYs and 1.65 QALYs. The ICER for atezolizumab versus chemotherapy was $102,424.83/QALY; in the Markov model, the ICER was $104,806.71/QALY. Atezolizumab was not cost-effective at the WTP threshold of three times China’s per capita gross domestic product (GDP). Sensitivity analysis showed that the cost of atezolizumab, the utility of PFS, and the discount rate had a significant impact on ICER; PAP significantly reduced ICER, but atezolizumab was still not cost-effective in China.

Conclusion

First-line monotherapy with atezolizumab for patients with PD-L1 high-expressing EGFR and ALK wild-type advanced NSCLC was estimated to be less cost-effective than chemotherapy in terms of the Chinese healthcare system; offering PAP increased the likelihood that atezolizumab would be cost-effective. In some areas of China with higher levels of economic development, atezolizumab was likely to be cost-effective. To improve the cost-effectiveness of atezolizumab, drug prices would need to be reduced.
Case report: A case of complete clinical response in a patient experiencing high microsatellite instability unresectable colon cancer being treated with a PD-L1 inhibitor after interstitial pneumonia
Authors: Wang Luo , Mou Haibo , Hou Xuehua , Liao Qin
Published: March 2023

Immune checkpoint inhibitors (ICI) have dramatically transformed the treatment landscape for metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) or high microsatellite instability (MSI-H). Envafolimab, a novel programmed death-1 ligand 1 (PD-L1) inhibitor, has been reported to be efficient and safe for the management of advanced MSI-H/dMMR solid tumors. Here, we report the case of a 35-year-old female patient with MSI-H/dMMR mCRC who was treated with envafolimab following mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) plus bevacizumab. While suffering from interstitial pneumonia after chemotherapy, the patient achieved a complete clinical response with the use of envafolimab without additional adverse events. Thus, PD-L1 inhibitors may be potential candidates for treating patients with MSI-H/dMMR mCRC.
NTRK fusion protein expression is absent in a large cohort of diffuse large B-cell lymphoma
Authors: Ghandili Susanne , Dierlamm Judith , Bokemeyer Carsten , von Bargen Clara Marie , Weidemann Sören Alexander
Published: March 2023

Background

Even though two NTRK-targeting drugs are available for the treatment of irresectable, metastatic, or progressive NTRK-positive solid tumors, less is known about the role of NTRK fusions in lymphoma. For this reason, we aimed to investigate if NTRK fusion proteins are expressed in diffuse large B-cell lymphoma (DLBCL) by systemic immunohistochemistry (IHC) screening and additional FISH analysis in a large cohort of DLBCL samples according to the ESMO Translational Research and Precision Medicine Working Group recommendations for the detection of NTRK fusions in daily practice and clinical research.

Methods

A tissue microarray of 92 patients with the diagnosis of DLBCL at the University Hospital Hamburg between 2020 and 2022 was built. The clinical data were taken from patient records. Immunohistochemistry for Pan-NTRK fusion protein was performed and positive staining was defined as any viable staining. For FISH analysis only results with quality 2 and 3 were evaluated.

Results

NTRK immunostaining was absent in all analyzable cases. No break apart was detectable by FISH.

Conclusion

Our negative result is consistent with the very sparse data existing on NTRK gene fusions in hematologic neoplasms. To date, only a few cases of hematological malignancies have been described in which NTRK-targeting drugs may provide a potential therapeutic agent. Even though NTRK fusion protein expression was not detectable in our sample cohort, performing systemic screenings for NTRK fusions are necessary to define further the role of NTRK fusions not only in DLBCL but in a multitude of lymphoma entities as long as the lack of reliable data exists.
New therapeutics for soft tissue sarcomas: Overview of current immunotherapy and future directions of soft tissue sarcomas
Authors: Seong Gyuhee , D’Angelo Sandra P.
Published: March 2023

Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a ‘cold’, non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.
Advanced lung cancer inflammation index predicts survival outcomes of hepatocellular carcinoma patients receiving immunotherapy
Authors: Li Qian , Ma Fei , Wang Ju feng
Published: March 2023

Objective

We evaluate the predictive significance of the Advanced Lung Cancer Inflammation Index (ALI) in patients with advanced hepatocellular carcinoma (HCC) following therapy with immune checkpoint drugs.

Methods

In 2018-2020, 98 patients with advanced hepatocellular carcinoma who were treated with immune checkpoint inhibitors at our hospital were compiled. Using the receiver operating characteristic (ROC) curve, the appropriate cut-off point for ALI was determined. Kaplan-Meier analysis, the Cox proportional hazards model, and Nomogram plots highlighted the relationship between ALI and overall survival (OS). The model was validated using calibration plots, receiver operating characteristic curves (ROC), and decision curve analysis (DCA), which was performed on 52 patient sets by external validation.

Results

The AUC for ALI was 0.663. The best cutoff value was 36.5, with a median overall survival (OS) of 473 days for patients with ALI≤ 36.5 and 611 days for those with ALI > 36.5. Univariate analysis revealed that the presence or absence of local treatment, alpha-fetoprotein (AFP), and ALI were prognostic factors; LASSO regression analysis identified four candidate variables. Multifactorial COX analysis revealed that high ALI was an independent prognostic factor for overall survival in both groups (HR = 0.411; 95% CI: 0.244-0.651; P<0.001). In addition, the Nomogram model that included ALI was able to predict the success of immunotherapy in patients with advanced liver cancer more accurately.

Conclusion

ALI is a novel prognostic marker in immunotherapy-treated patients with advanced hepatocellular cancer.
Diaphragmatic ultrasound and patent ductus arteriosus in the newborn: A retrospective case series
Authors: Dassios Theodore , Arattu Thodika Fahad M. S. , Nanjundappa Mahesh , Williams Emma , Bell Aaron J. , Greenough Anne
Published: March 2023

Background

Patent ductus arteriosus (PDA) and diaphragmatic dysfunction are frequently seen in newborn infants but their relationship remains unknown. We aimed to use point of care ultrasound to compare diaphragmatic kinetics in infants with a PDA compared to in those without a PDA.

Methods

M-mode ultrasonography was used to measure the mean inspiratory velocity (VI) in newborn infants with and without a haemodynamically significant PDA admitted in the Neonatal Unit at King's College Hospital during a three month period.

Results

Seventeen diaphragmatic ultrasound studies were reviewed from 14 infants with a median (IQR) gestational age of 26.1 (25.8–30.6) weeks, birth weight of 780 (660–1385) gr at a postnatal age of 18 (14–34) days. Eight scans had evidence of a PDA. The median (IQR) VI was significantly lower in scans with a PDA [1.01 (0.78–1.86) cm/s] compared to the ones without a PDA [3.21 (2.80–3.59) cm/s, p < 0.001]. The median (IQR) gestational age was lower in infants with a PDA [25.8 (25.6–27.3) weeks] compared to infants without a PDA [29.0 (26.1–35.1) weeks, p = 0.007]. Using multivariable linear regression analysis the VI was independently associated with a PDA (adjusted p < 0.001) but not with the gestational age (adjusted p = 0.659).

Conclusions

Patent ductus arteriosus was associated with a lower mean inspiratory velocity in neonates and this effect was independent of gestational age.
Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development
Authors: Ayoun Alsoud Rami , Svensson Robin J. , Svensson Elin M. , Gillespie Stephen H. , Boeree Martin J. , Diacon Andreas H. , Dawson Rodney , Aarnoutse Rob E. , Simonsson Ulrika S. H.
Published: March 2023

Biomarkers are quantifiable characteristics of biological processes. In Mycobacterium tuberculosis, common biomarkers used in clinical drug development are colony forming unit (CFU) and time-to-positivity (TTP) from sputum samples. This analysis aimed to develop a combined quantitative tuberculosis biomarker model for CFU and TTP biomarkers for assessing drug efficacy in early bactericidal activity studies. Daily CFU and TTP observations in 83 previously patients with uncomplicated pulmonary tuberculosis after 7 days of different rifampicin monotherapy treatments (10–40 mg/kg) from the HIGHRIF1 study were included in this analysis. The combined quantitative tuberculosis biomarker model employed the Multistate Tuberculosis Pharmacometric model linked to a rifampicin pharmacokinetic model in order to determine drug exposure-response relationships on three bacterial sub-states using both the CFU and TTP data simultaneously. CFU was predicted from the MTP model and TTP was predicted through a time-to-event approach from the TTP model, which was linked to the MTP model through the transfer of all bacterial sub-states in the MTP model to a one bacterial TTP model. The non-linear CFU-TTP relationship over time was well predicted by the final model. The combined quantitative tuberculosis biomarker model provides an efficient approach for assessing drug efficacy informed by both CFU and TTP data in early bactericidal activity studies and to describe the relationship between CFU and TTP over time.
PBPK-based dose finding for sildenafil in pregnant women for antenatal treatment of congenital diaphragmatic hernia
Authors: Macente Julia , Nauwelaerts Nina , Russo Francesca M. , Deprest Jan , Allegaert Karel , Lammens Bart , Hernandes Bonan Rodolfo , Turner Jessica M. , Kumar Sailesh , Diniz Andrea , Martins Frederico S. , Annaert Pieter
Published: March 2023

Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known as Revatio® and approved for the treatment of pulmonary arterial hypertension. Maternal administration of sildenafil during pregnancy is being evaluated for antenatal treatment of several conditions, including the prevention of pulmonary hypertension in fetuses with congenital diaphragmatic hernia. However, determination of a safe and effective maternal dose to achieve adequate fetal exposure to sildenafil remains challenging, as pregnancy almost always is an exclusion criterion in clinical studies. Physiologically-based pharmacokinetic (PBPK) modelling offers an attractive approach for dose finding in this specific population. The aim of this study is to exploit physiologically-based pharmacokinetic modelling to predict the required maternal dose to achieve therapeutic fetal exposure for the treatment congenital diaphragmatic hernia. A full-PBPK model was developed for sildenafil and N-desmethyl-sildenafil using the Simcyp simulator V21 platform, and verified in adult reference individuals, as well as in pregnant women, taking into account maternal and fetal physiology, along with factors known to determine hepatic disposition of sildenafil. Clinical pharmacokinetic data in mother and fetus were previously obtained in the RIDSTRESS study and were used for model verification purposes. Subsequent simulations were performed relying either on measured values for fetal fraction unbound (fu = 0.108) or on values predicted by the simulator (fu = 0.044). Adequate doses were predicted according to the efficacy target of 15 ng/mL (or 38 ng/mL) and safety target of 166 ng/mL (or 409 ng/mL), assuming measured (or predicted) fu values, respectively. Considering simulated median profiles for average steady state sildenafil concentrations, dosing regimens of 130 mg/day or 150 mg/day (administered as t.i.d.), were within the therapeutic window, assuming either measured or predicted fu values, respectively. For safety reasons, dosing should be initiated at 130 mg/day, under therapeutic drug monitoring. Additional experimental measurements should be performed to confirm accurate fetal (and maternal) values for fu. Additional characterization of pharmacodynamics in this specific population is required and may lead to further optimization of the dosing regimen.
The effect of transcutaneous electrical stimulation of the submental area on the cardiorespiratory response in normal and awake subjects
Authors: Alsharifi Abdulaziz , Kaltsakas Georgios , Pengo Martino F. , Parati Gianfranco , Serna-Pascual Miquel , Rafferty Gerrard , Steier Joerg
Published: March 2023

Background: Electrical stimulation has recently been introduced to treat patients with Obstructive sleep apnoea There are, however, few data on the effects of transcutaneous submental electrical stimulation (TES) on the cardiovascular system. We studied the effect of TES on cardiorespiratory variables in healthy volunteers during head-down-tilt (HDT) induced baroreceptor loading.

Method: Cardiorespiratory parameters (blood pressure, heart rate, respiratory rate, tidal volume, airflow/minute ventilation, oxygen saturation, and end-tidal CO2/O2 concentration) were recorded seated, supine, and during head-down-tilt (50) under normoxic, hypercapnic (FiCO2 5%) and poikilocapnic hypoxic (FiO2 12%) conditions. Blood pressure (BP) was measured non-invasively and continuously (Finapres). Gas conditions were applied in random order. All participants were studied twice on different days, once without and once with TES.

Results: We studied 13 healthy subjects (age 29 (12) years, six female, body mass index (BMI) 23.23 (1.6) kg·m−2). A three-way ANOVA indicated that BP decreased significantly with TES (systolic: p = 4.93E-06, diastolic: p = 3.48E-09, mean: p = 3.88E-08). Change in gas condition (systolic: p = 0.0402, diastolic: p = 0.0033, mean: p = 0.0034) and different postures (systolic: 8.49E-08, diastolic: p = 6.91E-04, mean: p = 5.47E-05) similarly impacted on BP control. When tested for interaction, there were no significant associations between the three different factors electrical stimulation, gas condition, or posture, except for an effect on minute ventilation (gas condition/posture p = 0.0369).

Conclusion: Transcutaneous electrical stimulation has a substantial impact on the blood pressure. Similarly, postural changes and variations in inspired gas impact on blood pressure control. Finally, there was an interaction between posture and inspired gases that affects minute ventilation. These observations have implications on our understanding of integrated cardiorespiratory control, and may prove beneficial for patients with SDB who are assessed for treatment with electrical stimulation.
Microgravity and the intervertebral disc: The impact of space conditions on the biomechanics of the spine
Authors: Marfia Giovanni , Guarnaccia Laura , Navone Stefania Elena , Ampollini Antonella , Balsamo Melissa , Benelli Francesca , Gaudino Chiara , Garzia Emanuele , Fratocchi Claudia , Di Murro Claudia , Ligarotti Gianfranco Kim , Campanella Carmelo , Landolfi Angelo , Perelli Pietro , Locatelli Marco , Ciniglio Appiani Giuseppe
Published: March 2023

The environmental conditions to which astronauts and other military pilots are subjected represent a unique example for understanding and studying the biomechanical events that regulate the functioning of the human body. In particular, microgravity has shown a significant impact on various biological systems, such as the cardiovascular system, immune system, endocrine system, and, last but not least, musculoskeletal system. Among the potential risks of flying, low back pain (LBP) has a high incidence among astronauts and military pilots, and it is often associated with intervertebral disc degeneration events. The mechanisms of degeneration determine the loss of structural and functional integrity and are accompanied by the aberrant production of pro-inflammatory mediators that exacerbate the degenerative environment, contributing to the onset of pain. In the present work, the mechanisms of disc degeneration, the conditions of microgravity, and their association have been discussed in order to identify possible molecular mechanisms underlying disc degeneration and the related clinical manifestations in order to develop a model of prevention to maintain health and performance of air- and space-travelers. The focus on microgravity also allows the development of new proofs of concept with potential therapeutic implications.
The effects of sampling and instrument orientation on LiDAR data from crop plots
Authors: Khorsandi Azar , Tanino Karen , Noble Scott D.
Published: March 2023

Wheat is one of the most widely consumed grains in the world and improving its yield, especially under severe climate conditions, is of great importance to world food security. Phenotyping methods can evaluate plants according to their different traits, such as yield and growth characteristics. Assessing the vertical stand structure of plants can provide valuable information about plant productivity and processes, mainly if this trait can be tracked throughout the plant’s growth. Light Detection And Ranging (LiDAR) is a method capable of gathering three-dimensional data from wheat field trials and is potentially suitable for providing non-destructive, high-throughput estimations of the vertical stand structure of plants. The current study considers LiDAR and focuses on investigating the effects of sub-sampling plot data and data collection parameters on the canopy vertical profile (CVP). The CVP is a normalized, ground-referenced histogram of LiDAR point cloud data representing a plot or other spatial domain. The effects of sub-sampling of plot data, the angular field of view (FOV) of the LiDAR and LiDAR scan line orientation on the CVP were investigated. Analysis of spatial sub-sampling effects on CVP showed that at least 144000 random points (600 scan lines) or an area equivalent to three plants along the row were adequate to characterize the overall CVP of the aggregate plot. A comparison of CVPs obtained from LiDAR data for different FOV showed that CVPs varied with the angular range of the LiDAR data, with narrow ranges having a larger proportion of returns in the upper canopy and a lower proportion of returns in the lower part of the canopy. These findings will be necessary to establish minimum plot and sample sizes and compare data from studies where scan direction or field of view differ. These advancements will aid in making comparisons and inform best practices for using close-range LiDAR in phenotypic studies in crop breeding and physiology research.
CRISPR/Cas9-mediated mutagenesis of the susceptibility gene OsHPP04 in rice confers enhanced resistance to rice root-knot nematode
Authors: Huang Qiuling , Lin Borong , Cao Yuqing , Zhang Yu , Song Handa , Huang Chunhui , Sun Tianling , Long Changwen , Liao Jinling , Zhuo Kan
Published: March 2023

CRISPR crops carrying a mutation in susceptibility (S) genes provide an effective strategy for controlling plant disease, because they could be ‘transgene-free’ and commonly have more broad-spectrum and durable type of resistance. Despite their importance, CRISPR/Cas9-mediated editing of S genes for engineering resistance to plant-parasitic nematode (PPN) disease has not been reported. In this study, we employed the CRISPR/Cas9 system to specifically induce targeted mutagenesis of the S gene rice copper metallochaperone heavy metal-associated plant protein 04 (OsHPP04), and successfully obtained genetically stable homozygous rice mutants with or without transgenic elements. These mutants confer enhanced resistance to the rice root-knot nematode (Meloidogyne graminicola), a major plant pathogenic nematode in rice agriculture. Moreover, the plant immune responses triggered by flg22, including reactive oxygen species burst, defence-related genes expression and callose deposition, were enhanced in the ‘transgene-free’ homozygous mutants. Analysis of rice growth and agronomic traits of two independent mutants showed that there are no obvious differences between wild-type plants and mutants. These findings suggest that OsHPP04 may be an S gene as a negative regulator of host immunity and genetic modification of S genes through the CRISPR/Cas9 technology can be used as a powerful tool to generate PPN resistant plant varieties.
Genome-wide identification and expression analysis of the response regulator gene family in alfalfa (Medicago sativa L.) reveals their multifarious roles in stress response
Authors: Qiang Yuqin , He Xiaojuan , Li Zhen , Li Siqi , Zhang Jia , Liu Tao , Tursunniyaz Mamateliy , Wang Xinyu , Liu Zhipeng , Fang Longfa
Published: March 2023

As important components of the two-component regulatory system, response regulatory proteins (RRPs) play a crucial role in histidine phosphorylation-mediated signal transduction in response to environmental fluctuations. Accumulating evidence has revealed that RRPs play important roles in plant growth and stress response. However, the specific functions of RR genes (RRs) in cultivated alfalfa remain ambiguous. Therefore, in this study, we identified and characterized the RR family genes in the alfalfa genome using bioinformatics methods. Our analysis revealed 37 RRs in the alfalfa genome of Zhongmu No.1 that were unevenly distributed on the chromosomes. Cis-elements analysis revealed the involvement of RRs in responses to light, stress, and various plant hormones. Expression analysis of RRs in different tissues revealed their distinct tissue expression patterns. These findings provide preliminary insights into the roles of RRs in plant responses to abiotic stress, which can be used to improve the stress tolerance of autotetraploid-cultivated alfalfa plants via genetic engineering.
TaBAS1 encoding a typical 2-Cys peroxiredoxin enhances salt tolerance in wheat
Authors: Xiao Guilian , Zhao Mingming , Liu Qinghua , Zhou Junzhi , Cheng Zhaohui , Wang Qiannan , Xia Guangmin , Wang Mengcheng
Published: March 2023

Efficient antioxidant enzymatic system contributes to salt tolerance of plants via avoiding ROS over-accumulation. Peroxiredoxins are crucial components of the reactive oxygen species (ROS) scavenging machinery in plant cells, but whether they offer salt tolerance with potential for germplasm improvement has not been well addressed in wheat. In this work, we confirmed the role of a wheat 2-Cys peroxiredoxin gene TaBAS1 that was identified through the proteomic analysis. TaBAS1 overexpression enhanced the salt tolerance of wheat at both germination and seedling stages. TaBAS1 overexpression enhanced the tolerance to oxidative stress, promoted the activities of ROS scavenging enzymes, and reduced ROS accumulation under salt stress. TaBAS1 overexpression promoted the activity of ROS production associated NADPH oxidase, and the inhibition of NADPH oxidase activity abolished the role of TaBAS1 in salt and oxidative tolerance. Moreover, the inhibition of NADPH-thioredoxin reductase C activity erased the performance of TaBAS1 in the tolerance to salt and oxidative stress. The ectopic expression of TaBAS1 in Arabidopsis exhibited the same performance, showing the conserved role of 2-Cys peroxiredoxins in salt tolerance in plants. TaBAS1 overexpression enhanced the grain yield of wheat under salt stress but not the control condition, not imposing the trade-offs between yield and tolerance. Thus, TaBAS1 could be used for molecular breeding of wheat with superior salt tolerance.
Impact of cultural intelligence on the cross-cultural adaptation of international students in China: The mediating effect of psychological resilience
Authors: Chu Kequn , Zhu Fengshu
Published: March 2023

Introduction

Cultural intelligence can affect the cross-cultural adaptation of international students in China, but the mechanism of its influence is still unclear. This study examines the mediating effect of the psychological resilience of international students in China in the process of cultural intelligence affecting cross-cultural adaptation. We used the cultural intelligence scale, psychological resilience scale, and cross-cultural adaptation scale to measure 624 foreign students in China.

Results

(1) There is a significant positive correlation between the cultural intelligence, psychological resilience, and cross-cultural adaptation of international students in China. (2) Resilience plays a mediating effect in the influence of the cultural intelligence of international students in China on cross-cultural adaptation.

Conclusion

The cultural intelligence of international students in China can directly affect their cross-cultural adaptation and can also affect their cross-cultural adaptation through the mediating effect of psychological resilience.
Implementing EMI in Chinese music classes: Students’ perceived benefits and challenges
Authors: Su Pengcheng , Kong Jiayin
Published: March 2023

Recognizing the opportunities and problems of using English as a medium of instruction (EMI) enables teachers, students, and educational administrators to capitalize on the opportunities and mitigate the problems. Considering this, many researchers worldwide have explored the opportunities and problems of EMI courses. Yet, the advantages and disadvantages of implementing EMI in Chinese academic contexts have rarely been investigated. To fill this gap, the present research evaluated the benefits and challenges of implementing EMI in Chinese music classes. To accomplish this, a researcher-made scale was distributed among 74 Chinese music students. The thematic analysis of participants’ responses revealed that using English as a means of teaching and learning benefited Chinese music students in some ways. However, as the results of the thematic analysis indicated, Chinese music students experienced some serious challenges in EMI courses because of their limited English proficiency. Finally, the limitations, pedagogical implications, and future research directions are thoroughly explained.
Effects of a games-based physical education lesson on cognitive function in adolescents
Authors: Gilbert Luke M. , Dring Karah J. , Williams Ryan A. , Boat Ruth , Sunderland Caroline , Morris John G. , Nevill Mary E. , Cooper Simon B.
Published: March 2023

Despite the importance of physical education (PE) lessons for physical activity in adolescents, the acute cognitive responses to PE lessons have not been explored; a gap in the literature that this study addresses. Following familiarisation, 76 (39 female) adolescents (12.2 ± 0.4 y) completed two trials (60 min games-based PE lesson and 60 min academic lesson) separated by 7-d in a counterbalanced, crossover design. Attention, executive function, working memory, and perception were assessed 30 min before, immediately post, and 45 min post-lesson in both trials. Participants were split into high-and low-fit groups based on a gender-specific median split of distance run on the multi-stage fitness test. Furthermore, participants were split into high and low MVPA groups based on a gender-specific median split of MVPA time (time spent >64% HR max) during the PE lesson. Overall, a 60 min games-based PE lesson had no effect on perception, working memory, attention, or executive function in adolescents (all p > 0.05) unless MVPA time is high. The physical activity-cognition relationship was moderated by MVPA, as working memory improved post-PE lesson in adolescents who completed more MVPA during their PE lesson (time*trial*MVPA interaction, p < 0.05, partial η2 = 0.119). Furthermore, high-fit adolescents displayed superior cognitive function than their low-fit counterparts, across all domains of cognitive function (main effect of fitness, all p < 0.05, partial η2 0.014–0.121). This study provides novel evidence that MVPA time moderates the cognitive response to a games-based PE lesson; and emphasises that higher levels of fitness are beneficial for cognitive function in adolescents.
Assessing manifestations of bossing in the context of personality traits of business managers
Authors: Stefko Robert , Birknerova Zuzana , Zbihlejova Lucia , Nebesky Lubomir
Published: March 2023

Introduction

Abusive supervision or bossing represents a specific form of mobbing as a long-term, systematic negative action by superiors toward subordinates.

Methods

From the point of view of the operationalization of this construct, the original BOSSm18 methodology is presented in the paper in the context of the B5 methodology, which enables specification of personality traits in terms of the original Big Five concept.

Results

Based on the research dataset of 636 business managers, the paper presents the results of the basic psychometric parameters of the methodology and the content specification of the extracted factors. The research findings support a multidimensional understanding of the bossing construct.

Discussion

The limiting factors of the interpretation and generalization of the results relate to the consideration of cultural contexts and situational conditions of perception of bossing manifestations.
The paradoxical effects of professional stereotypes on the quality of care by interprofessional teams: The contingent effects of team faultlines, team stereotypes, and championship behaviors
Authors: Sheffer Hilel Galia , Drach-Zahavy Anat , Endevelt Ronit
Published: March 2023

Background

Despite calls for interprofessional teamwork to ensure quality care in healthcare settings, interprofessional teams do not always perform effectively. There is evidence that professional stereotypes inhibit effective interprofessional teamwork, but they haven’t been explored as a phenomenon that impacts team’s performance and quality of care.

Objectives

To focus on professional stereotypes emerging in interprofessional teams and examine the contingency effects of interprofessional team’s faultlines, professional stereotypes, and leader’s championship behaviors on team’s quality of care.

Methods

A cross-sectional nested sample of 59 interprofessional teams and 284 professionals, working in geriatric long-term-care facilities in Israel. Additionally, five to seven of the residents of each facility were randomly sampled to obtain the outcome variable. Data collection employed a multisource (interprofessional team members), multimethod (validated questionnaires and data from residents’ health records) strategy.

Results

The results indicated that faultlines are not directly harmful to team’s quality of care; instead, they are likely to impact quality of care only when team stereotypes emerge. Furthermore, whereas teams typified by high professional stereotypes require person-oriented championship leadership, for teams typified by low team stereotypes, championship leadership harms the quality of care they provide.

Conclusion

These findings have implications for handling interprofessional teams. Practically, leaders must be well-educated to better analyze team members’ needs and maintain the appropriate leadership style.
The influence of children’s emotional comprehension on peer conflict resolution strategies
Authors: Cao Yanfei , Wang Haowei , Lv Yaojian , Xie Dongjie
Published: March 2023

Peer conflicts commonly happen in children’s daily interaction, and strategies they employed to deal with the conflicts have an impact on peer conflict resolution. It has been illustrated that children’s understanding of emotion plays an important role in social communication. However, there is little research focusing on the relation between emotional comprehension and peer conflict resolution strategies. In this study, 90 children of 3 to 6 finished the Test of Emotional Comprehension, and their preschool teachers were required to complete the Conflict Resolution Strategy Questionnaire, which scored each child’s conflict resolution strategies. The results showed that: (a) the preference of conflict resolution strategies differed in age, and girls tended to adopt positive strategies; (b) children’s emotional comprehension grew with age; and (c) children’s conflict resolution strategies and emotional comprehension were closely related. Children’s emotional comprehension can positively predict the overall conflict resolution strategies and negatively predicted negative strategies, whereas mental emotional comprehension can positively predict positive strategies. The factors affecting children’s emotional comprehension and conflict resolution strategies, and their relationship were discussed in depth.
The structure and evaluation of educational research skills and accomplishments among rural teachers: Data from China
Authors: Feng Luo , Yuxiang Yao , Lihua Qiu
Published: March 2023

The practice of educational research by rural teachers is highly valued and very important for their professional development and for the revitalization of rural education. This study explored the components of educational research activities among rural teachers (Study 1). Based on the results, a regional norm for Hunan province was formulated, and discriminant criteria were developed for the evaluation of educational research skills and accomplishments among rural teachers (Study 2). In Study 1, data from 892 Chinese rural teachers working at compulsory education schools in Hunan Province (a representative province in central China), divided into two samples, were found to support the constructs included in the measurement instrument. Exploratory and confirmatory factor analyses of the 33 items of the Rural Teachers’ Educational Research Self-rating Scale identified a first-order model with three factors: educational research on basic educational activities (BEA), educational research involving the creation of an educational community (CEC), and educational research involving the refinement and popularization of educational theory (RPE). Based on the results of Study 1, in Study 2, a set of norms for educational research skills and accomplishments among rural teachers was formulated based on the data from Hunan Province. This norm can serve as a reference standard for the evaluation of rural teachers’ educational research skills and accomplishments. The components of rural teachers’ educational research activities are discussed, and suggestions for the formulation of education policies are provided.