bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase II Study Evaluating the Interest to Combine UCPVax, a Telomerase CD4 TH1-Inducer Cancer Vaccine, and Atezolizumab for the Treatment of HPV Positive Cancers: VolATIL Study
Authors: Rebucci-Peixoto Magali , Vienot Angélique , Adotevi Olivier , Jacquin Marion , Ghiringhelli Francois , de la Fouchardière Christelle , You Benoit , Maurina Tristan , Kalbacher Elsa , Bazan Fernando , Meynard Guillaume , Clairet Anne-Laure , Fagnoni-Legat Christine , Spehner Laurie , Bouard Adeline , Vernerey Dewi , Meurisse Aurélia , Kim Stefano , Borg Christophe , Mansi Laura
Published: July 2022

Background

There is a strong rational of using anti–programmed cell death protein-1 and its ligand (anti–PD-1/L1) antibodies in human papillomavirus (HPV)–induced cancers. However, anti–PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti–PD-1/L1 is therefore of interest. Combining anti–PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non–small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers.

Methods

Patients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously.

Discussion

Anti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti–PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials.

Clinical Trial Registration

https://www.clinicaltrials.gov/, identifier NCT03946358.
The functions of long noncoding RNAs on regulation of F-box proteins in tumorigenesis and progression
Authors: Xia Lu , Chen Jingyun , Huang Min , Mei Jie , Lin Min
Published: July 2022

Accumulated evidence has revealed that F-box protein, a subunit of SCF E3 ubiquitin ligase complexes, participates in carcinogenesis and tumor progression via targeting its substrates for ubiquitination and degradation. F-box proteins could be regulated by cellular signaling pathways and noncoding RNAs in tumorigenesis. Long noncoding RNA (lncRNA), one type of noncoding RNAs, has been identified to modulate the expression of F-box proteins and contribute to oncogenesis. In this review, we summarize the role and mechanisms of multiple lncRNAs in regulating F-box proteins in tumorigenesis, including lncRNAs SLC7A11-AS1, MT1JP, TUG1, FER1L4, TTN-AS1, CASC2, MALAT1, TINCR, PCGEM1, linc01436, linc00494, GATA6-AS1, and ODIR1. Moreover, we discuss that targeting these lncRNAs could be helpful for treating cancer via modulating F-box protein expression. We hope our review can stimulate the research on exploration of molecular insight into how F-box proteins are governed in carcinogenesis. Therefore, modulation of lncRNAs is a potential therapeutic strategy for cancer therapy via regulation of F-box proteins.
Traditional Chinese Medicine in Treating Children With Coronavirus Disease 2019: A Scoping Review
Authors: Duan Naifan , Liu Bin , Li Xiaona , Xiong Yibai , Li Li , Ma Yan , Lu Cheng
Published: July 2022

Coronavirus disease 2019 (COVID-19) is currently widely spread across the world. Traditional Chinese Medicine (TCM) plays an important role in the overall treatment process. As a special group of population, the treatment outcome of children with COVID-19 has attracted much attention. Our study summarizes the current situation of TCM treatment of children with COVID-19. The results showed that TCM displayed a positive role in the treatment process, and that no significant adverse reactions were found. Our findings provide analytical evidence for the efficacy and safety of TCM participation in the treatment of COVID-19 in children.
Case Report: Prenatal Diagnosis of Nemaline Myopathy
Authors: Liu Dongmei , Yu Jiali , Wang Xin , Yang Yang , Yu Li , Zeng Shi , Zhang Ming , Xu Ganqiong
Published: July 2022

Nemaline myopathy (NM) is a rare, hereditary heterogeneous myopathy. Fetal NM has a more severe disease course and a poorer prognosis and is usually lethal during the first few months of life. Hence, early prenatal diagnosis is especially important for clinical interventions and patient counseling. We report the case of a fetus with NM due to KLHL40 gene variation leading to arthrogryposis multiplex congenita (AMC). The ultrasonography and histopathology results revealed an enhanced echo intensity and decreased muscle thickness, which may be novel features providing early clues for the prenatal diagnosis of NM. Moreover, to our knowledge, this article is the first report to describe a case of NM associated with complex congenital heart disease (CHD).
Global trends in pediatric burn injuries and care capacity from the World Health Organization Global Burn Registry
Authors: Jordan Kelly C. , Di Gennaro Jane L. , von Saint André-von Arnim Amélie , Stewart Barclay T.
Published: July 2022

Background

Burn injuries are a major cause of death and disability globally. The World Health Organization (WHO) launched the Global Burn Registry (GBR) to improve understanding of burn injuries worldwide, identify prevention targets, and benchmark acute care. We aimed to describe the epidemiology, risk factors, and outcomes of children with burns to demonstrate the GBR's utility and inform needs for pediatric burn prevention and treatment.

Methods

We performed descriptive analyses of children age ≤ 18 years in the WHO GBR. We also described facility-level capacity. Data were extracted in September of 2021.

Results

There were 8,640 pediatric and adult entries from 20 countries. Of these, 3,649 (42%) were children (0–18 years old) from predominantly middle-income countries. The mean age was 5.3 years and 60% were boys. Children aged 1–5 years comprised 62% (n = 2,279) of the cohort and mainly presented with scald burns (80%), followed by flame burns (14%). Children >5 years (n = 1,219) more frequently sustained flame burns (52%) followed by scald burns (29%). More than half of pediatric patients (52%) sustained a major burn (≥15% total body surface area) and 48% received surgery for wound closure during the index hospitalization. Older children had more severe injuries and required more surgery. Despite the frequency of severe injuries, critical care capacity was reported as “limited” for 23% of pediatric patients.

Conclusions

Children represent a large proportion of people with burn injuries globally and often sustain major injuries that require critical and surgical intervention. However, critical care capacity is limited at contributing centers and should be a priority for healthcare system development to avert preventable death and disability. This analysis demonstrates that the GBR has the potential to highlight key epidemiological characteristics and hospital capacity for pediatric burn patients. To improve global burn care, addressing barriers to GBR participation in low- and low-middle-income countries would allow for greater representation from a diversity of countries, regions, and burn care facilities.
In Vitro Evaluation of Antioxidant, Anticancer, and Anti-Inflammatory Activities of Ethanolic Leaf Extract of Adenium obesum
Authors: Alshehri Ahmad , Ahmad Afza , Tiwari Rohit Kumar , Ahmad Irfan , Alkhathami Ali G. , Alshahrani Mohammad Y. , Asiri Mohammed A. , Almeleebia Tahani M. , Saeed Mohd , Yadav Dharmendra Kumar , Ansari Irfan Ahmad
Published: July 2022

Adenium obesum commonly known as “desert rose” belongs to the family Apopcynaceae and has previously been reported for its anti-influenza, antimicrobial, and cytotoxic efficacies and well-known for their ethno-medicinal applications. In the present study, ethanolic extracts of A. obesum (AOE) were analyzed by gas chromatography-mass spectrometry (GC–MS) to identify the important phytochemical compounds. The GC–MS analysis of AOE detected the presence of 26 phytochemical compounds. This plant is traditionally used for the treatment of various diseases. In this report, the antioxidant, anti-inflammatory, and anticancer activities of ethanolic leaf extract from A. obesum (AOE) were studied. The antioxidant potential of ethanolic extract of AOE was examined by different antioxidant assays, such as antioxidant capacity by the DPPH, ABTS, superoxide, hydroxyl radical scavenging, and lipid peroxidation inhibition assays. The antioxidant activities of various reaction mixtures of AOE were compared with a reference or standard antioxidant (ascorbic acid). In addition, we also evaluated the anticancer activity of AOE, and it was observed that AOE was found to be cytotoxic against A549 lung cancer cells. It was found that AOE inhibited the viability of A549 lung cancer cells by inducing nuclear condensation and fragmentation. Furthermore, ethanolic AOE demonstrated the anti-inflammatory potential of AOE in murine alveolar macrophages (J774A.1) as an in vitro model system. AOE showed its potential in reducing the levels of inflammatory mediators including the proinflammatory cytokines and TNF-α. The results obtained in the present investigation established the antioxidant, anticancer, and anti-inflammatory potency of AOE, which may account for subsequent studies in the formulation of herbal-based medicine.
Natural Phenylethanoid Supplementation Alleviates Metabolic Syndrome in Female Mice Induced by High-Fructose Diet
Authors: Zhan Xiujun , He Mingshuai , Pei Jierong , Fan Wenjing , Mwangi Charity Ngina , Zhang Peng , Chai Xin , Jiang Miaomiao
Published: July 2022

Tyrosol (T), hydroxytyrosol (H), and salidroside (S) are typical phenylethanoids and also powerful dietary antioxidants. This study aimed at evaluating the influence of three natural phenylethanoids, which are dietary phenylethanoids of natural origins, on reversing gut dysbiosis and attenuating nonalcoholic fatty liver features of the liver induced by metabolic syndrome (MetS) mice. C57BL/6J female mice induced with high-fructose diet were established and administrated with salidroside, tyrosol, and hydroxytyrosol for 12 weeks, respectively. Biochemical analysis showed that S, T, and H significantly improved glucose metabolism and lipid metabolism, including reduced levels of total cholesterol insulin (INS), uric acid, low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (ALT). Histopathological observation of the liver confirmed the protective effects of S, T, and H against hepatic steatosis, which were demonstrated by the results of metabolomic analysis, such as the improvement in glycolysis, purine metabolism, bile acid, fatty acid metabolism, and choline metabolism. Additionally, 16S rRNA gene sequence data revealed that S, T, and H could enhance the diversity of gut microbiota. These findings suggested that S, T, and H probably suppress lipid accumulation and have hepatoprotective effects and improve intestinal microflora disorders to attenuate metabolic syndromes.
DYRK1a Inhibitor Mediated Rescue of Drosophila Models of Alzheimer’s Disease-Down Syndrome Phenotypes
Authors: Zhu Bangfu , Parsons Tom , Stensen Wenche , Mjøen Svendsen John S. , Fugelli Anders , Hodge James J. L.
Published: July 2022

Alzheimer’s disease (AD) is the most common neurodegenerative disease which is becoming increasingly prevalent due to ageing populations resulting in huge social, economic, and health costs to the community. Despite the pathological processing of genes such as Amyloid Precursor Protein (APP) into Amyloid-β and Microtubule Associated Protein Tau (MAPT) gene, into hyperphosphorylated Tau tangles being known for decades, there remains no treatments to halt disease progression. One population with increased risk of AD are people with Down syndrome (DS), who have a 90% lifetime incidence of AD, due to trisomy of human chromosome 21 (HSA21) resulting in three copies of APP and other AD-associated genes, such as DYRK1A (Dual specificity tyrosine-phosphorylation-regulated kinase 1A) overexpression. This suggests that blocking DYRK1A might have therapeutic potential. However, it is still not clear to what extent DYRK1A overexpression by itself leads to AD-like phenotypes and how these compare to Tau and Amyloid-β mediated pathology. Likewise, it is still not known how effective a DYRK1A antagonist may be at preventing or improving any Tau, Amyloid-β and DYRK1a mediated phenotype. To address these outstanding questions, we characterised Drosophila models with targeted overexpression of human Tau, human Amyloid-β or the fly orthologue of DYRK1A, called minibrain (mnb). We found targeted overexpression of these AD-associated genes caused degeneration of photoreceptor neurons, shortened lifespan, as well as causing loss of locomotor performance, sleep, and memory. Treatment with the experimental DYRK1A inhibitor PST-001 decreased pathological phosphorylation of human Tau [at serine (S) 262]. PST-001 reduced degeneration caused by human Tau, Amyloid-β or mnb lengthening lifespan as well as improving locomotion, sleep and memory loss caused by expression of these AD and DS genes. This demonstrated PST-001 effectiveness as a potential new therapeutic targeting AD and DS pathology.
Comparative Pharmacokinetics and Local Tolerance of Tenofovir Alafenamide (TAF) From Subcutaneous Implant in Rabbits, Dogs, and Macaques
Authors: Gatto G. J. , Krovi A. , Li L. , Massud I. , Holder A. , Gary J. , Mills P. , Mitchell J. , Luecke E. , Demkovich Z. R. , Heneine W. , García-Lerma J. G. , Marzinke M. A. , Brand R. M. , Dobard C. W. , Johnson L. M. , Van Der Straten A.
Published: July 2022

The administration of antiretrovirals (ARVs) for HIV pre-exposure prophylaxis (PrEP) is highly efficacious and may benefit from new long-acting (LA) drug delivery approaches. This paper describes a subcutaneous, reservoir-style implant for the LA delivery of tenofovir alafenamide (TAF) and documents the preclinical assessment of implant safety and pharmacokinetics (PK) in New Zealand White (NZW) rabbits (3 groups ofn= 5), beagle dogs (2 groups ofn= 6), and rhesus macaques (2 groups ofn= 3). Placebo implants were placed in rabbits (n= 10) and dogs (n= 12). Implant parameters, including selection of the TAF form, choice of excipient, and PCL formulation were tuned to achieve targeted concentrations of the active anabolite of TAF, tenofovir diphosphate (TFV-DP), within peripheral blood mononuclear cells (PBMCs) and mucosal tissues relevant to HIV transmission. Sustained concentrations of TFV-DP in PBMCs over 100 fmol/106cells were achieved in all animal species indicating that the implants effectively delivered TAF for 3–6 months. Unlike placebo implants without TAF, all active implants resulted in local adverse events (AEs) proximal to the implant ranging in severity from mild to moderate and included dermal inflammation and necrosis across all species. Despite these AEs, the implant performed as designed and achieved a constant drug release profile, supporting the continued development of this drug delivery platform.
Maternal Methamphetamine Exposure Influences Behavioral Sensitization and Nucleus Accumbens DNA Methylation in Subsequent Generation
Authors: Dong Nan , Zhu Jie , Wang Rui , Wang Shuai , Chen Yanjiong , Wang Changhe , Goh Eyleen L.K , Chen Teng
Published: July 2022

The deleterious effects of methamphetamine (METH) exposure extend beyond abusers, and may potentially impact the vulnerability of their offspring in developing addictive behaviors. Epigenetic signatures have been implicated in addiction, yet the characteristics to identify prenatal METH abuse to offspring addiction risk remains elusive. Here, we used escalating doses of METH-exposed mouse model in F0 female mice before and during pregnancy to simulate the human pattern of drug abuse and generated METH-induced behavioral sensitization to investigate the addictive behavior in offspring mice. We then utilized whole genome-bisulfite sequencing (WGBS) to investigate the methylation signature of nucleus accumbens (NAc) in male METH-sensitized mice. Interestingly, male but not female offspring exhibited an enhanced response to METH-induced behavioral sensitization. Additionally, the METH-exposed group of male mice underwent a more comprehensive wave of epigenome remodeling over all genomic elements compared with unexposed groups due to drug exposure history. 104,219 DMCs (METH-SAL vs. SAL-SAL) induced by prenatal METH-exposure were positively correlated with that of postnatal METH-exposure (38,570, SAL-METH vs. SAL-SAL). Moreover, 4,983 DMCs induced by pre- and postnatal METH exposure (METH-METH vs. SAL-METH) were negatively correlated with that of postnatal METH exposure, and 371 commonly changed DMCs between the two comparison groups also showed a significantly negative correlation and 86 annotated genes functionally enriched in the pathways of neurodevelopment and addiction. Key annotated genes included Kirrel3, Lrpprc, and Peg3, implicated in neurodevelopmental processes, were down-regulated in METH-METH group mice compared with the SAL-METH group. Taken together, we render novel insights into the epigenetic correlation of drug exposure and provide evidence for epigenetic characteristics that link maternal METH exposure to the intensity of the same drug-induced behavioral sensitization in adult offspring.
Dynamics of Non-Newtonian Tangent Hyperbolic Liquids Conveying Tiny Particles on Objects with Variable Thickness when Lorentz Force and Thermal Radiation are Significant
Authors: Nadeem Muhammad , Siddique Imran , Ali Rifaqat , Riahi Mohamed Kamel , Mousa Abd Allah A. , Khan Ilyas , Hafeez Hafiza Mariyam , Azam Muhammad
Published: July 2022

The flow via needle has prominent applications in the modern world such as nano-wires, microstructure electric gadgets, microsensors, surgical instruments and biological treatments. The present investigation focuses on boundary layer heat, flow, and mass transfer of MHD tangent hyperbolic fluid (conveying tiny particles) via a thin needle under the impacts of activation energy, non-constant thermal conductivity, heat source, and nonlinear thermal radiation. In the description of the Buongiorno model, the significant features of Brownian motion and thermophoresis have been included. Adopting appropriate transformations to the given problem specified by the set of partial differential equations yields the dimensionless form of ordinary differential equations After that, these obtained ODEs are solved numerically via MATLAB bvp4c. A comparative result with previous findings is conducted. Physical parameters’ impact on flow rate, heat, and concentration is exhibited and explained in depth. The main findings of this study are that flow patterns reduce as the magnetic parameter and the Weissenberg number grow. Higher values of Brownian motion, heat source/sink, nonlinear radiation, and thermophoretic parameter improve the thermal profile. Moreover, the rate of heat transfer for the variable property case is significantly improved. Concentration profiles reduce as the thermophoresis parameter and chemical reaction parameter grow but improve as the activation energy and Brownian motion parameter rise. The percentage increase in Sherwood number is 35.07 and 5.44 when the thermophoresis takes input in the range 0 ≤ Nt ≤ 0.2 and activation energy parameters 0 ≤ E ≤ 0.2. The Weissenberg number and power-law index parameters are all designed to boost the Sherwood number.
Self-Assembly in Mixtures of Charged Lobed Particles
Authors: Srivastava Arpita , Rocha Brunno C. , Vashisth Harish
Published: July 2022

We report coarse-grained Langevin dynamics simulations of homogeneous mixtures of lobed colloidal particles with opposite charges. We show that dumbbell, trigonal planar, tetrahedral, square planar, trigonal bipyramidal, and octahedral shaped particles form distinct self-assemblies including chains, sheets, crystalline, and spherical structures. The dumbbell and square planar particles predominantly form chains and sheets while other particles form network-like self-assembled morphologies. At higher temperatures and lower charges, non-planar particles form three-dimensional aggregates. We further report on packing arrangements of particles which lead to differences in porosities within self-assembled morphologies. Our results show that the trigonal planar particles form larger porous structures. The self-assembled structures that we report are potentially useful in designing porous biomaterials for biomedical applications.
Three-Dimensional Virtual Optical Clearing With Cycle-Consistent Generative Adversarial Network
Authors: Chen Jiajia , Du Zhenhong , Si Ke
Published: July 2022

High-throughput deep tissue imaging and chemical tissue clearing protocols have brought out great promotion in biological research. However, due to uneven transparency introduced by tissue anisotropy in imperfectly cleared tissues, fluorescence imaging based on direct chemical tissue clearing still encounters great challenges, such as image blurring, low contrast, artifacts and so on. Here we reported a three-dimensional virtual optical clearing method based on unsupervised cycle-consistent generative adversarial network, termed 3D-VoCycleGAN, to digitally improve image quality and tissue transparency of biological samples. We demonstrated the good image deblurring and denoising capability of our method on imperfectly cleared mouse brain and kidney tissues. With 3D-VoCycleGAN prediction, the signal-to-background ratio (SBR) of images in imperfectly cleared brain tissue areas also showed above 40% improvement. Compared to other deconvolution methods, our method could evidently eliminate the tissue opaqueness and restore the image quality of the larger 3D images deep inside the imperfect cleared biological tissues with higher efficiency. And after virtually cleared, the transparency and clearing depth of mouse kidney tissues were increased by up to 30%. To our knowledge, it is the first interdisciplinary application of the CycleGAN deep learning model in the 3D fluorescence imaging and tissue clearing fields, promoting the development of high-throughput volumetric fluorescence imaging and deep learning techniques.
Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity
Authors: Favrais Geraldine , Bokobza Cindy , Saliba Elie , Chalon Sylvie , Gressens Pierre
Published: July 2022

Preterm birth before the gestational age of 32 weeks is associated with the occurrence of specific white matter damage (WMD) that can compromise the neurological outcome. These white matter abnormalities are embedded in more global brain damage defining the encephalopathy of prematurity (EoP). A global reduction in white matter volume that corresponds to chronic diffuse WMD is the most frequent form in contemporary cohorts of very preterm infants. This WMD partly results from alterations of the oligodendrocyte (OL) lineage during the vulnerability window preceding the beginning of brain myelination. The occurrence of prenatal, perinatal and postnatal events in addition to preterm birth is related to the intensity of WMD. Systemic inflammation is widely recognised as a risk factor of WMD in humans and in animal models. This review reports the OL lineage alterations associated with the WMD observed in infants suffering from EoP and emphasizes the role of systemic inflammation in inducing these alterations. This issue is addressed through data on human tissue and imaging, and through neonatal animal models that use systemic inflammation to induce WMD. Interestingly, the OL lineage damage varies according to the inflammatory stimulus, i.e., the liposaccharide portion of the E.Coli membrane (LPS) or the proinflammatory cytokine Interleukin-1β (IL-1β). This discrepancy reveals multiple cellular pathways inducible by inflammation that result in EoP. Variable long-term consequences on the white matter morphology and functioning may be speculated upon according to the intensity of the inflammatory challenge. This hypothesis emerges from this review and requires further exploration.
Acute effects of mixed circuit training on hemodynamic and cardiac autonomic control in chronic hemiparetic stroke patients: A randomized controlled crossover trial
Authors: Fonseca Guilherme F. , Midgley Adrian W. , Billinger Sandra A. , Michalski André C. , Costa Victor A. B. , Monteiro Walace , Farinatti Paulo , Cunha Felipe A.
Published: July 2022

Objectives:To investigate whether a single bout of mixed circuit training (MCT) can elicit acute blood pressure (BP) reduction in chronic hemiparetic stroke patients, a phenomenon also known as post-exercise hypotension (PEH).

Methods:Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and a single bout of MCT on separate days and in a randomized counterbalanced order. The MCT included 10 exercises with 3 sets of 15-repetition maximum per exercise, with each set interspersed with 45 s of walking. Systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), cardiac output (Q), systemic vascular resistance (SVR), baroreflex sensitivity (BRS), and heart rate variability (HRV) were assessed 10 min before and 40 min after CTL and MCT. BP and HRV were also measured during an ambulatory 24-h recovery period.

Results:Compared to CTL, SBP (∆-22%), DBP (∆-28%), SVR (∆-43%), BRS (∆-63%), and parasympathetic activity (HF; high-frequency component: ∆-63%) were reduced during 40 min post-MCT (p< 0.05), while Q (∆35%), sympathetic activity (LF; low-frequency component: ∆139%) and sympathovagal balance (LF:HF ratio: ∆145%) were higher (p< 0.001). In the first 10 h of ambulatory assessment, SBP (∆-7%), MAP (∆-6%), and HF (∆-26%) remained lowered, and LF (∆11%) and LF:HF ratio (∆13%) remained elevated post-MCTvs.CTL (p< 0.05).

Conclusion:A single bout of MCT elicited prolonged PEH in chronic hemiparetic stroke patients. This occurred concurrently with increased sympathovagal balance and lowered SVR, suggesting vasodilation capacity is a major determinant of PEH in these patients. This clinical trial was registered in the Brazilian Clinical Trials Registry (RBR-5dn5zd), available athttps://ensaiosclinicos.gov.br/rg/RBR-5dn5zd.

Clinical Trial Registration:https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd, identifier RBR-5dn5zd
Pentatricopeptide Repeat Gene-Mediated Mitochondrial RNA Editing Impacts on Rice Drought Tolerance
Authors: Luo Zhi , Xiong Jie , Xia Hui , Wang Lei , Hou Guihua , Li Zhaoyang , Li Jing , Zhou Hengling , Li Tianfei , Luo Lijun
Published: July 2022

Mitochondrial RNA editing plays crucial roles in the plant development and environmental adaptation. Pentatricopeptide repeat (PPR) genes, which are involved in the regulating mitochondrial RNA editing, are potential gene resources in the improvement of rice drought tolerance. In this study, we investigated genome-wide mitochondrial RNA editing in response to drought between upland and lowland rice. Responses of mitochondrial RNA editing to drought exhibit site-specific and genotype-specific patterns. We detected 22 and 57 ecotype-differentiated editing sites under well-watered and drought-treated conditions, respectively. Interestingly, the RNA editing efficiency was positively correlated with many agronomic traits, while it was negatively correlated with drought tolerance. We further selected two mitochondrial-localized PPR proteins, PPR035 and PPR406, to validate their functions in drought tolerance. PPR035 regulated RNA editing at rps4-926 and orfX-406, while PPR406 regulated RNA editing at orfX-355. The defectiveness in RNA editing at these sites had no apparent penalties in rice respiration and vegetative growth. Meanwhile, the knockout mutants of ppr035 and ppr406 show enhanced drought- and salt tolerance. PPR035 and PPR406 were under the balancing selection in upland rice and highly differentiated between upland and lowland rice ecotypes. The upland-dominant haplotypes of PPR035 and PPR406 shall contribute to the better drought tolerance in upland rice. They have great prospective in the improvement of rice drought tolerance.
Two-Phase Conceptual Framework of Phosphatase Activity and Phosphorus Bioavailability
Authors: Manzoor Aamir , Dippold Michaela A. , Loeppmann Sebastian , Blagodatskaya Evgenia
Published: July 2022

The activity of extracellular phosphatases is a dynamic process controlled by both plant roots and microorganisms, which is responsible for the mineralization of soil phosphorus (P). Plants regulate the availability of soil P through the release of root mucilage and the exudation of low-molecular weight organic acids (LMWOAs). Mucilage increases soil hydraulic conductivity as well as pore connectivity, both of which are associated with increased phosphatase activity. The LMWOAs, in turn, stimulate the mineralization of soil P through their synergistic effects of acidification, chelation, and exchange reactions. This article reviews the catalytic properties of extracellular phosphatases and their interactions with the rhizosphere interfaces. We observed a biphasic effect of root metabolic products on extracellular phosphatases, which notably altered their catalytic mechanism. In accordance with the proposed conceptual framework, soil P is acquired by both plants and microorganisms in a coupled manner that is characterized by the exudation of their metabolic products. Due to inactive or reduced root exudation, plants recycle P through adsorption on the soil matrix, thereby reducing the rhizosphere phosphatase activity. The two-phase conceptual framework might assist in understanding P-acquisition (substrate turnover) and P-restoration (phosphatase adsorption by soil) in various terrestrial ecosystems.
Pathophysiology and transcriptomic analysis of Picea koraiensis inoculated by bark beetle-vectored fungus Ophiostoma bicolor
Authors: Liu Ya , Zhou Qinzheng , Wang Zheng , Wang Huiming , Zheng Guiheng , Zhao Jiaping , Lu Quan
Published: July 2022

Ophiostomatoid fungi exhibit a complex relationship with bark beetles; exhausting of host tree defenses is traditionally regarded as one of the key benefits provided to beetle vectors. Ophiostoma bicolor is one of the dominant species of the mycobiota associated with Ips genus bark beetles which infect the spruce trees across the Eurasian continent. Host spruce trees resist fungal invasion through structural and inducible defenses, but the underlying mechanisms at the molecular level, particularly with respect to the interaction between bark beetle-associated fungi and host trees, remain unclear. The aim of this study was to observe the pathological physiology and molecular changes in Picea koraiensis seedlings after artificial inoculation with O. bicolor strains (TS, BH, QH, MX, and LWQ). This study showed that O. bicolor was a weakly virulent pathogen of spruce, and that the virulent of the five O. bicolor strains showed differentiation. All O. bicolor strains could induce monoterpenoid release. A positive correlation between fungal virulence and release of monoterpenoids was observed. Furthermore, the release rate of monoterpenoids peaked at 4 days post-inoculation (dpi) and then decreased from 4 to 90 dpi. Transcriptomic analysis at 4 dpi showed that many plant-pathogen interaction processes and mitogen-activated protein kinase (MAPK) metabolic processes were activated. The expression of monoterpenoid precursor synthesis genes and diterpenoid synthesis genes was upregulated, indicating that gene expression regulated the release rate of monoterpenoids at 4 dpi. The enriched pathways may reveal the immune response mechanism of spruce to ophiostomatoid fungi. The dominant O. bicolor possibly induces the host defense rather than defense depletion, which is likely the pattern conducted by the pioneers of beetle-associated mycobiota, such as Endoconidiophora spp.. Overall, these results facilitate a better understanding of the interaction mechanism between the dominant association of beetles and the host at the molecular level.
Kernel principal component analysis and differential non-linear feature extraction of pesticide residues on fruit surface based on surface-enhanced Raman spectroscopy
Authors: Shi Guolong , Shen Xinyi , Ren Huan , Rao Yuan , Weng Shizhuang , Tang Xianghu
Published: July 2022

Surface-enhanced Raman spectroscopy (SERS) has attracted much attention because of its high sensitivity, high speed, and simple sample processing, and has great potential for application in the field of pesticide residue detection. However, SERS is susceptible to the influence of a complex detection environment in the detection of pesticide residues on the surface of fruits, facing problems such as interference from the spectral peaks of detected impurities, unclear dimension of effective correlation data, and poor linearity of sensing signals. In this work, the enhanced raw data of the pesticide thiram residues on the fruit surface using gold nanoparticle (Au-NPs) solution are formed into the raw data set of Raman signal in the IoT environment of Raman spectroscopy principal component detection. Considering the non-linear characteristics of sensing data, this work adopts kernel principal component analysis (KPCA) including radial basis function (RBF) to extract the main features for the spectra in the ranges of 653∼683 cm−1, 705∼728 cm−1, and 847∼872 cm−1, and discusses the effects of different kernel function widths (σ) to construct a qualitative analysis of pesticide residues based on SERS spectral data model, so that the SERS spectral data produce more useful dimensionality reduction with minimal loss, higher mean squared error for cross-validation in non-linear scenarios, and effectively weaken the interference features of detecting impurity spectral peaks, unclear dimensionality of effective correlation data, and poor linearity of sensing signals, reflecting better extraction effects than conventional principal component analysis (PCA) models.
Environmental threat in France: Two studies testing the effect of threatening messages on system justification and environmental denial
Authors: Labarre Hélène , Felonneau Marie-Line
Published: July 2022

Climate change consequences are affecting our entire political, economic and social system. At a psychological level, it represents a large number of threatening events that we have to deal with. In the scientific literature, there is an active debate about the inconsistent effects of environmental threatening messages. One explanation for this inconsistency is that people respond differently to a threat, depending on some psychological dispositions. Indeed, studies on system justification theory showed that when people with a right political orientation are exposed to a threat to their system, they show a motivation to defend it. Although those tendencies have been linked to environmental denial, there is a lack of experimental studies testing the direct effect of environmental threat, especially in European context. We address this issue with two experiments in which we highlighted the environmental threat for one’s system (Study 1, N = 144) and for the continuity of one’s habits (Study 2, N = 148) in a French sample. The design was the same for both studies: three types of video-clips were presented to participants (i.e., control, neutral and threat) and we measured general system justification, environmental denial and political orientation. Our results showed no significant effect of our threat manipulation in both studies. However, they support that a right political orientation in France positively predicts system justification tendencies in study 1 and environmental denial in study 2. Findings are discussed through theoretical and methodological implications.
Why take the risk? Exploring the psychosocial determinants of floodwater driving
Authors: Benjamin Shauntelle , Parsons Melissa , Apthorp Deborah , Lykins Amy D.
Published: July 2022

As anthropogenic climate change progresses, there is an increasing need for individuals to make appropriate decisions regarding their approach to extreme weather events. Natural hazards are involuntary risk environments (e.g., flooded roads); interaction with them cannot be avoided (i.e., a decision must be made about how to engage). While the psychological and sociocultural predictors of engagement with voluntary risks (i.e., risk situations that are sought out) are well-documented, less is known about the factors that predict engagement with involuntary risk environments. This exploratory study assessed whether mental health (depression, anxiety, and stress symptoms), personality traits, and cultural worldviews combine to predict engagement with involuntary risk, using the situation of floodwater driving. An Australian sample (N = 235) was assessed via questionnaire and scenario measures. Results were analyzed in a binomial logistic regression assessing which individual factors predicted decision-making in a proxy floodwater driving scenario. Agreeableness and gender were individually significant predictors of floodwater driving intention, and four factors (named “affect,” “progressiveness,” “insightfulness,” and “purposefulness”) were derived from an exploratory factor analysis using the variables of interest, though only two (“progressiveness” and “insightfulness”) predicted floodwater driving intention in an exploratory binomial logistic regression. The findings highlight the need for further research into the differences between voluntary and involuntary risk. The implication of cultural worldviews and personality traits in interaction with mental health indicators on risk situations is discussed.
Bioimpedance Body Measures and Serum Lipid Levels in Masculine Depression
Authors: von Zimmermann Claudia , Brückner Lena , Mühle Christiane , Weinland Christian , Kornhuber Johannes , Lenz Bernd
Published: July 2022

Background

Major depressive disorder (MDD) is a main reason for suicide, and serum lipids are involved in both affective disorders and related suicidal behavior. Moreover, masculine depression has been suggested as a subtype of depression with an increased risk for suicide. Here, we studied the relationship between body measures, serum lipids, suicidal thoughts, and masculine depression.

Methods

Depressed patients (44% women) were divided by a sex-separated median-split into a group of 81 “patients with masculine depression” (mean age ± standard error: 36.4 ± 1.6 years) and a group of 82 “patients with non-masculine depression” (age 45.7 ± 1.6 years) according to the Male Depression Risk Scale. We compared body measures, serum lipid levels, and past suicidal ideation between these groups and explored differences between these groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years).

Results

Patients with masculine depression did not significantly differ from patients with non-masculine depression in any of the body measures, lipid markers, or suicidal thoughts. Compared to healthy controls, both patient groups showed significantly higher body fat (B[masculine depression] = 0.041 and B[non–masculine depression] = 0.050), lower high-density lipoprotein (HDL) cholesterol (B = –0.045 and –0.044), and a higher risk for suicidal thoughts (B = 3.927 and 2.663) than healthy controls. Suicidal thoughts were significantly associated with lower low-density lipoprotein (LDL)/HDL ratios (B = –0.455) in patients with depression and with higher LDL cholesterol levels (B = 0.020) in healthy controls subjects.

Limitation

Correlational study design and focus on in-patients.

Conclusion

In the studied cohort, masculine depression was not significantly associated with the analyzed parameters of body measures, serum lipids, or suicidal thoughts in in-patients with depression.
Threshold effects of body mass index on cognitive function and heterogeneity by sex and cardiovascular risk factors
Authors: Kim Young-Joo , Yeom Hyun-E
Published: July 2022

Background

Disclosing the underlying relationship between body mass index (BMI) and cognitive decline is imperative for cognitive impairment prevention and early detection. Empirical studies have indicated the risk of abnormal BMI leading to cognitive impairment. However, the relative risk of underweight or overweight on cognitive function is obscure. This study investigated the asymmetric causal effect of BMI on cognitive decline below and above an unknown threshold and the heterogeneity in the threshold level and the magnitude of the threshold effect due to sex and cardiovascular risk factors.

Methods

This study used 2010–2018 panel data from the Korean Longitudinal Study of Aging that assessed sociodemographic and health-related trends in Korean middle-aged to older population. A generalized method of moments estimator of the panel threshold model was applied to estimate the potential nonlinear pattern between BMI and cognitive function.

Results

There was a threshold effect in the relationship between BMI and cognitive function. An increase in BMI below the threshold was associated with higher cognitive function, whereas a further increase in BMI above the threshold led to cognitive decline. The nonlinear pattern between BMI and cognitive function differed by sex and cardiovascular risk appearing more distinctively within men or the cardiovascular risk group.

Conclusions

The detrimental impact of being underweight or overweight on cognitive function is heterogeneous by sex or cardiovascular risk. For obese men or individuals with cardiovascular risk factors, maintaining adequate BMI should be highlighted to help prevent cognitive decline.
Spending and Hospital Stay for Melanoma in Hunan, China
Authors: Ke Xinchen , Lin Wenrui , Li Daishi , Zhao Shuang , Chen Mingliang , Xiao Yi , Chen Xiang , Shen Minxue , Su Juan
Published: July 2022

Objective

This study aimed to describe the economic burden of Chinese patients with melanoma in Hunan province of China, and to investigate the factors for hospitalization spending and length of stay (LOS) in patients undergoing melanoma surgery.

Methods

Data was extracted from the Chinese National Health Statistics Network Reporting System database in Hunan province during 2017–2019. Population and individual statistics were presented, and nonparametric tests and quantile regression were used to analyze the factors for spending and LOS.

Result

A total of 2,644 hospitalized patients with melanoma in Hunan were identified. During 2017–2019, the total hospitalization spending was $5,247,972, and out-of-pocket payment (OOP) was $1,817,869, accounting for 34.6% of the total expenditure. The median spending was $1,123 [interquartile range (IQR): $555–2,411] per capita, and the median LOS was 10 days (IQR: 5–18). A total of 1,104 patients who underwent surgery were further analyzed. The non-parametric tests and quantile regression showed that women were associated with less spending and LOS than men. In general, patients aged 46–65 and those with lesions on the limbs had higher hospitalization costs and LOS than other subgroups.

Conclusion

Melanoma causes heavy economic burdens on patients in Hunan, such that the median spending is close to 60% of the averagely annual disposable income. Middle-aged men patients with melanoma on the limbs present the highest financial burden of melanoma.
Differences in HIV, STI and Other Risk Factors Among Younger and Older Male Sex Workers Who Have Sex With Men in Nairobi, Kenya
Authors: Muraguri Nicholas , Okal Jerry O. , Temmerman Marleen , Mukoko Dunstan , Musyoki Helgar K. , Gichangi Peter
Published: July 2022

Introduction

Previous surveys of male sex workers (MSW) in sub-Saharan Africa have not fully documented the HIV and sexually transmitted infections (STIs) rates and vulnerabilities by age category.

Methods

The bio-behavioral survey of MSW in Nairobi, Kenya, utilized respondent-driven sampling to recruit MSW. Structured interviews captured MSW's behavioral aspects, and biological tests for HIV and other STIs.

Results

Analysis of the two age categories, 18–24 years (younger MSW) and 25 years and above (older MSW), shows that of all participants, a significantly higher proportion of younger MSW (59.6% crude, 69.6% RDS-adjusted) were recruited compared to older MSW (40.4% crude, 30.4% RDS-adjusted, P < 0.001). Young male sex workers were more likely to report multiple sexual partnerships in the last 12 months and had multiple receptive anal intercourses (RAI) acts in the last 30 days than older MSW: 0–2 RAI acts (20.6 vs. 8.6%, P = 0.0300), 3–5 RAI acts (26.3 vs. 11.5, P < 0.001), and >5 RAI acts (26.3 vs. 11.5%, P < 0.01). Furthermore, younger MSW were significantly more likely to have 3–5 insertive anal intercourse (IAI) with a regular male sex partner in the last 30 days than older MSW (24.3 vs. 8.0%, P < 0.01). Younger MSW were also more likely to report other STIs [28.5% (95% CI: 19.1–40.4%)] than older MSW [19.0% (95% CI: 7.7–29.2%)]. However, older MSWs were more likely to be infected with HIV than younger MSW (32.3 vs. 9.9 %, P < 0.01).

Conclusions

Owing to the high risk sexual behaviors, HIV and STIs risks among younger and older MSW, intensified and targeted efforts are needed on risk reduction campaigns and expanded access to services.
Luteal phase support in fresh and frozen embryo transfers
Authors: Greenbaum Shirley , Athavale Ahlad , Hershko Klement Anat , Bentov Yaakov
Published: July 2022

Context

Luteal phase support (LPS) has become an essential component of IVF protocols following both fresh and frozen embryo transfers, yet there is still controversy with regards to the optimal protocol of LPS to enhance treatment outcome.

Search strategy

A search via PubMed for all the selected topics was limited to publications from the past 10 years and to English language. We subsequently searched the reference lists of retrieved articles. Where available, RCTs were chosen over non-randomized studies. Here we provide an updated review of the current literature on various issues relating to LPS, in both fresh and frozen embryo transfers. The timing of LPS initiation as well as the route of administration and dosing are discussed for both fresh and frozen transfers. A separate discussion for frozen thawed embryo transfer in natural cycles and non-ovulatory cycles is presented.

Conclusions

We present data that supports the use of Progesterone LPS in fresh and frozen embryo transfers. No benefits were found to the addition of hCG or estradiol to progesterone LPS in fresh transfers, however GnRH agonist may have a role. IM Progesterone was not advantageous over vaginal progesterone in fresh transfers but was superior in frozen transfers. The timing of LPS introduction, the interval to embryo transfer, as well as the serum concentration of progesterone, have significant effects on the success of the treatment.