bluuebunny/crossref_metadata_2025 huggingface dataset:
A Retrospective Evaluation of the Retrosigmoidal Approach for Petroclival Meningioma Surgery and Prognostic Factors Affecting Clinical Outcome
Authors: Masalha Waseem , Heiland Dieter Henrik , Steiert Christine , Krueger Marie T. , Schnell Daniel , Scheiwe Christian , Grosu Anca-L. , Schnell Oliver , Beck Juergen , Grauvogel Juergen
Published: April 2022

Introduction

Petroclival meningioma (PCM) remains a major neurosurgical challenge. There are still controversial strategic treatment concepts about surgical approach, the extent of resection, and postoperative radiotherapy. We aimed to evaluate prognostic factors influencing the progression-free survival (PFS) rates of PCM, with a particular focus on the retrosigmoidal approach, the role of the extent of resection, and postoperative radiotherapy.

Methods

Eighty-nine patients with complete follow-up data were included. All patients were operated on via a retrosigmoidal approach, of whom 19 underwent gross total resection (GTR) and 70 underwent subtotal resection (STR). In the subgroups of tumors with infiltration of the cavernous sinus, 41 patients received near total resection (NTR) and 24 STR. Thirty-one patients received postoperative radiotherapy of the residual tumor and 58 were treated with surgery alone. Kaplan–Meier analyses and Cox regression were used to identify significant factors associated with treatment.

Results

GTR (p=0.0107) and postoperative radiotherapy (p=0.014) were associated with significantly improved PFS. Even the subgroup analysis of extended PCM with infiltration of the cavernous sinus (CS) showed an advantage for PFS after near total resection (NTR) (p=0.0017). The additional radiotherapy of the residual tumor in the CS in this subgroup also showed a beneficial effect on PFS (p=0.012).

Conclusion

The extension of surgical resection remains the most important prognostic factor in relation to oncological outcomes. However, the GTR of extended PCM with infiltration of the CS is associated with significant neurological morbidity and requires additional adjuvant therapy concepts. Postoperative radiotherapy is an important element in the treatment of the residual tumor after surgery.
Nivolumab Combined With Ipilimumab Treatment Induced Hypophysitis and Immune-Mediated Liver Injury in Advanced Esophageal Squamous Cell Carcinoma: A Case Report
Authors: Feng Yi , Li Chengyang , Ji Yuan , Liu Ying , Gan Lu , Yu Yiyi , Liu Tianshu
Published: April 2022

Immune checkpoint inhibitors (ICIs) have transformed the treatment in malignancies because of the impact on reactivating the immune cells to kill tumor cells. Because anti-CTLA-4 antibody and anti-PD-1 antibody (or anti-PD-L1 antibody) work in different ways, they have synergistic effects when used in combination in many cancers. However, it has been found that a strong immune response may lead to more serious and multi-system immune-related adverse events (irAE). We describe an advanced esophageal squamous cell carcinoma patient who received nivolumab combined with ipilimumab resulting in hypophysitis and immune-mediated liver injury. He was enrolled into a CheckMate 648 global, multicenter, randomized phase 3 Clinical Trial (CTR20171227) investigating the combined potency of nivolumab and ipilimumab in the treatment of patients with advanced esophageal squamous cell carcinoma and admitted to our center (site 0200). The patient developed hypophysitis and immune-related hepatitis rapidly after ICIs therapy, leading to the interruption of anti-tumor therapy. Then the patient developed Herpes zoster and recurrence of tuberculosis after treatment of irAEs with glucocorticoids. We report this case in the hope that doctors need to have sufficient knowledge and attention to the occurrence of irAE during the anti-immune combination therapy and actively intervene as soon as possible to obtain better anti-tumor effects and less harm to patients.
Atypical Teratoid Rhabdoid Tumor: A Possible Oriented Female Pathology?
Authors: Baiano Cinzia , Della Monica Rosa , Franca Raduan Ahmed , Del Basso De Caro Maria Laura , Cavallo Luigi Maria , Chiariotti Lorenzo , Ius Tamara , Jouanneau Emmanuel , Somma Teresa
Published: April 2022

Atypical teratoid rhabdoid tumor is a rare lesion that occurs mainly in children can be supratentorial or infratentorial and it accounts for 1-2% of pediatric brain tumors and over 10% of central nervous system (CNS) tumors in infants, with a male preponderance up to 3 years of age, more than 50% of these occur in the cerebellum. In this report we describe four new cases of sellar AT/RTs underwent endoscopic endonasal approach and different adjuvant therapies. Our aim is to report the clinical, radiological and pathological features of these rare lesions, focusing on the possibility to perform an early diagnosis and appropriate therapeutic strategy.
Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response
Authors: Doescher Johannes , von Witzleben Adrian , Boukas Konstantinos , Weissinger Stephanie E. , Thomas Gareth J. , Laban Simon , Thomas Jaya , Hoffmann Thomas K. , Ottensmeier Christian H.
Published: April 2022

Chemoradiotherapy (CRT) is a standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Unfortunately, not all patients respond to this therapy and require further treatment, either salvage surgery or palliative therapy. The addition of immunotherapy to CRT is currently being investigated and early results describe a mixed response. Therefore, it is important to understand the impact of CRT on the tumor microenvironment (TME) to be able to interpret the results of the clinical trials. Paired biopsies from 30 HNSCC patients were collected before and three months after completion of primary CRT and interrogated for the expression of 1392 immune- and cancer-related genes. There was a relevant difference in the number of differentially expressed genes between the total cohort and patients with residual disease. Genes involved in T cell activation showed significantly reduced expression in these tumors after therapy. Furthermore, gene enrichment for several T cell subsets confirmed this observation. The analysis of tissue resident memory T cells (TRM) did not show a clear association with impaired response to therapy. CRT seems to lead to a loss of T cells in patients with incomplete response that needs to be reversed. It is not clear whether the addition of anti-PD-1 antibodies alone to CRT can prevent treatment failure, as no upregulation of the targets was measurable in the TME.
Is Persistent Post-COVID Headache Associated With Protein-Protein Interactions Between Antibodies Against Viral Spike Protein and CGRP Receptor?: A Case Report
Authors: Özkan Esra , Celebi Özlem , Keskin Özlem , Gursoy Attila , Gürsoy-Özdemir Yasemin
Published: April 2022

Background

After the acute pandemic of coronavirus disease 2019 (COVID-19), a wide variety of symptoms are identified under the term post-COVID syndrome, such as persistent headache. Post-COVID headache can be presented in a broad spectrum like headache attributed to systemic infection, chronification of already existing primary headache, or long-lasting, and also late-onset new daily persistent headache. Still, little is known about the pathophysiology of post-COVID headache, but activation of the trigeminovascular system may be one of the players.

Case Report

Here, we present a case with a severe, long-lasting post-COVID headache and its sudden cessation with calcitonin gene-related peptide (CGRP) monoclonal antibody treatment.

Conclusion

In our previous protein mimicry study, we have pointed at mimicry of virus spike protein and CGRP receptors. This mechanism may enlighten the current, common, and yet unsolved post-COVID headache cases.
Health Equity and Disparities in ROP Care: A Need for Systematic Evaluation
Authors: Ndukwe Tochukwu , Cole Emily , Scanzera Angelica C. , Chervinko Margaret A. , Chiang Michael F. , Campbell John Peter , Chan Robison Vernon Paul
Published: April 2022

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disorder that can have devastating visual sequelae if not managed appropriately. From an ophthalmology standpoint, ROP care is complex, since it spans multiple care settings and providers, including those in the neonatal intensive care unit (NICU), step down nurseries, and the outpatient clinic setting. This requires coordination and communication between providers, ancillary staff, and most importantly, effective communication with the patient's family members and caregivers. Often, factors related to the social determinants of health play a significant role in effective communication and care coordination with the family, and it is important for ophthalmologists to recognize these risk factors. The aim of this article is to (1) review the literature related to disparities in preterm birth outcomes and infants at risk for ROP; (2) identify barriers to ROP care and appropriate follow up, and (3) describe patient-oriented solutions and future directions for improving ROP care through a health equity lens.
Improving Pediatric/Neonatology Residents' Newborn Resuscitation Skills With a Digital Serious Game: DIANA
Authors: Bardelli Serena , Del Corso Giulio , Ciantelli Massimiliano , Del Pistoia Marta , Lorenzoni Francesca , Fossati Nicoletta , Scaramuzzo Rosa T. , Cuttano Armando
Published: April 2022

Background

Serious games, and especially digital game based learning (DGBL) methodologies, have the potential to strengthen classic learning methodology in all medical procedures characterized by a flowchart (e.g., neonatal resuscitation algorithm). However, few studies have compared short- and long-term knowledge retention in DGBL methodologies with a control group undergoing specialist training led by experienced operators. In particular, resident doctors' learning still has limited representation in simulation-based education literature.

Objective

A serious computer game DIANA (DIgital Application in Newborn Assessment) was developed, according to newborn resuscitation algorithm, to train pediatric/neonatology residents in neonatal resuscitation algorithm knowledge and implementation (from procedure knowledge to ventilation/chest compressions rate). We analyzed user learning curves after each session and compared knowledge retention against a classic theoretical teaching session.

Methods

Pediatric/neonatology residents of the Azienda Ospedaliera Universitaria Pisana (AOUP) were invited to take part in the study and were split into a game group or a control group; both groups were homogeneous in terms of previous training and baseline scores. The control group attended a classic 80 min teaching session with a neonatal trainer, while game group participants played four 20 min sessions over four different days. Three written tests (pre/immediately post-training and at 28 days) were used to evaluate and compare the two groups' performances.

Results

Forty-eight pediatric/neonatology residents participated in the study. While classic training by a neonatal trainer demonstrated an excellent effectiveness in short/long-term knowledge retention, DGBL methodology proved to be equivalent or better. Furthermore, after each game session, DGBL score improved for both procedure knowledge and ventilation/chest compressions rate.

Conclusions

In this study, DGBL was as effective as classic specialist training for neonatal resuscitation in terms of both algorithm memorization and knowledge retention. User appreciation for the methodology and ease of administration, including remotely, support the use of DGBL methodologies for pediatric/neonatology residents education.
Acute Retinal Necrosis: Clinical Features, Diagnostic Pitfalls, Treatment, and Outcome of an Insidious Disease in Children. Case Report and Review of the Literature
Authors: Mapelli Chiara , Milella Paolo , Donà Caterina , Nassisi Marco , Osnaghi Silvia , Viola Francesco , Agostoni Carlo , Minoia Francesca , Filocamo Giovanni
Published: April 2022

Objective

This study aims to explore clinical features, diagnostic work-up, treatment, and outcomes of pediatric patients with acute retinal necrosis (ARN), and to propose a standardized management of this condition in childhood.

Methods

Clinical manifestations, diagnostic work-up, and treatment of three pediatric cases with ARN were analyzed. Furthermore, a review of the literature was performed from January 1990 to November 2021, focused on 1) clinical presentation; 2) differential diagnosis, including both infectious and non-infectious conditions; 3) key role of diagnostic techniques; and 4) currently available treatments.

Results

Data from 72 children with ARN (69 from literature and 3 from our center) were analyzed. The most frequent presenting symptoms were red eye resistant to topical treatment (57%) and altered vision (58%), 25 patients had bilateral involvement. In 30% a known history of herpetic infection was reported. PCR testing on anterior chamber and/or vitreous sampling was performed in 46 cases (64%) and was diagnostic in 88% of them, with herpes simplex virus (HSV) 2 being the most frequently identified pathogen (57%). All patients underwent systemic antiviral therapy (16% only oral); adjunctive intravitreal injections were performed in 21% of them.

Conclusions

ARN is a rare but severe ocular infection presenting as a panuveitis with occlusive retinal vasculitis and peripheral retinal necrosis. Varicella-zoster virus and HSV 1–2 are most frequently implicated. Due to a high incidence of rhegmatogenous retinal detachment and optic atrophy, ARN has a poor prognosis with a potentially severe impact on visual function. Although a prompt recognition is crucial to prevent complications, ARN diagnosis in children is still challenging.
Effect of Metformin on Myocardial Injury Induced by Hepatic Ischemia-Reperfusion in Rats
Authors: An Wen , Kang Ju-Seop
Published: April 2022

Background: There is no effective medication for treatment or prevention of hepatic ischemia-reperfusion (HIR) injury caused by liver transplantation and hepatectomy. This study aimed to investigate the therapeutic effects of metformin on HIR injury and related myocardial injury in rats.

Methods: Wistar male rats were randomly divided into four groups: sham group, ischemia-reperfusion group, and IR group treated with metformin 150 mg/kg and 100 mg/kg. Wistar male rats were administered metformin 150 mg/kg, 100 mg/kg or saline 30 min pre-operative and underwent 15 min ischemia and 6 h reperfusion (n = 4).

Results: Metformin significantly alleviates the injury caused by HIR. Administration of metformin resulted in a significant reduction in the serum levels of alanine transaminase and aspartate transaminase and the activity of malondialdehyde, creatine kinase-MB, and lactate dehydrogenase but maintained high catalase and superoxide dismutase activity. Metformin significantly inhibited the IR-induced elevation of tumor necrosis factor-α in liver and heart tissue.

Conclusion: Metformin can alleviate hepatic and myocardial injury induced by IR by inhibiting oxidative stress.
NUSAP1 Could be a Potential Target for Preventing NAFLD Progression to Liver Cancer
Authors: Zeng Taofei , Chen Guanglei , Qiao Xinbo , Chen Hui , Sun Lisha , Ma Qingtian , Li Na , Wang Junqi , Dai Chaoliu , Xu Feng
Published: April 2022

Background: Non-alcoholic fatty liver disease (NAFLD) has gradually emerged as the most prevalent cause of chronic liver diseases. However, specific changes during the progression of NAFLD from non-fibrosis to advanced fibrosis and then hepatocellular carcinoma (HCC) are unresolved. Here, we firstly identify the key gene linking NAFLD fibrosis and HCC through analysis and experimental verification.

Methods: Two GEO datasets (GSE89632, GSE49541) were performed for identifying differentially expressed genes (DEGs) associated with NAFLD progression from non-fibrosis to early fibrosis and eventually to advanced fibrosis. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis, protein-protein interaction (PPI) network were integrated to explore the potential function of the DEGs and hub genes. The expression of NUSAP1 was confirmed in vivo and in vitro NAFLD models at mRNA and protein level. Then, cell proliferation and migration under high fat conditions were verified by cell counting kit-8 (CCK-8) and wound-healing assays. The lipid content was measured with Oil Red O staining. Finally, the analysis of clinical survival curves was performed to reveal the prognostic value of the crucial genes among HCC patients via the online web-tool GEPIA2 and KM plotter.

Results: 5510 DEGs associated with non-fibrosis NAFLD, 3913 DEGs about NAFLD fibrosis, and 739 DEGs related to NAFLD progression from mild fibrosis to advanced fibrosis were identified. Then, a total of 112 common DEGs were found. The result of enrichment analyses suggested that common DEGs were strongly associated with the glucocorticoid receptor pathway, regulation of transmembrane transporter activity, peroxisome, and proteoglycan biosynthetic process. Six genes, including KIAA0101, NUSAP1, UHRF1, RAD51AP1, KIF22, and ZWINT, were identified as crucial candidate genes via the PPI network. The expression of NUSAP1 was validated highly expressed in vitro and vivo NAFLD models at mRNA and protein level. NUSAP1 silence could inhibit the ability of cell proliferation, migration and lipid accumulation in vitro. Finally, we also found that NUSAP1 was significantly up-regulated at transcriptional and protein levels, and associated with poor survival and advanced tumor stage among HCC patients.

Conclusion: NUSAP1 may be a potential therapeutic target for preventing NAFLD progression to liver cancer.
Herbal Medicine for the Treatment of Anorexia in Children: A Systematic Review and Meta-Analysis
Authors: Lee Boram , Kwon Chan-Young , Lee Sun Haeng , Chang Gyu Tae
Published: April 2022

Background: Anorexia is a common obstacle to adequate nutrition in childhood, a critical period for physical growth. East Asian traditional medicine treatment modalities including herbal medicine (HM) a re considered an attractive therapeutic option, especially in East Asian countries. The purpose of this systematic review was to comprehensively examine the efficacy and safety of HM for anorexia in children.

Methods: A total of 12 electronic databases from their inception date to June 2021 were searched for randomized controlled trials (RCTs) assessing the efficacy of HM for the treatment of anorexia in children. The primary outcome was an improvement in anorexia clinical symptoms after treatment. In this meta-analysis, continuous and binary outcomes were assessed, and the data are presented as the mean difference or standardized mean difference and risk ratio (RR) with their 95% confidence intervals (CIs). The risk of bias and quality of evidence were assessed using the Cochrane Collaboration’s risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluations tool.

Results: A total of 205 RCTs were included. A comparison of HM with placebo revealed that the total effective rate based on anorexia symptom improvement was significantly higher in the HM group (RR 1.58, 95% CI 1.34, 1.85). In comparison with controls, HM as monotherapy or adjunctive therapy to dietary supplements or conventional medications led to significant improvements in anorexia symptoms, body measurements, levels of blood biomarkers related to gastrointestinal function, and nutrition indices, with a lower recurrence rate of anorexia. No serious adverse events related to HM were reported. The risk of bias of the included studies was generally unclear, and the quality of evidence was generally low to moderate.

Conclusion: Our study showed that HM could improve clinical symptoms, some anthropometric outcomes, and some biological markers related to appetite and growth in children with anorexia. However, considering the high risk of bias of the included studies and the heterogeneity of the HMs used, future research should focus on the use of standardized HMs and the implementation of methodologically robust clinical trials.

Systematic Review Registration: https://www.crd.york.ac.uk/prosperodisplay_record.php?ID=CRD42021274376, identifier CRD42021274376
Challenging T > MIC Using Meropenem vs. Escherichia coli and Pseudomonas aeruginosa
Authors: Nussbaumer-Pröll A. , Eberl S. , Kurdina E. , Schmidt L. , Zeitlinger M.
Published: April 2022

Objective: For meropenem 40%T > MIC is associated with optimal killing of P. aeruginosa and E. coli. However, it is unknown how the distribution of %T > MIC through a treatment day impacts the antimicrobial effect in vitro. Therefore, we investigated the in vitro antibiotic activity of meropenem, precisely if 40%T > MIC is achieved in one single long period (single dose), 2 × 20% periods (dosing-bid), or 3 × 13.3% (dosing t.i.d.) thereby keeping the overall period of T > MIC constant.

Material/Methods: Time kill curves (TKC) with P. aeruginosa-ATCC-27853 and E. coli-ATCC-25922 and five clinical isolates each were implemented over 24 h in CAMHB with concentrations from 0.25×MIC-32×MIC. Periods over and under MIC were simulated by centrifugation steps (discarding supernatant and refilling with fresh CAMHB). Double and triple dosing involved further addition and removal of antibiotic. Complementary growth controls (GC) with and without centrifugation steps were done and the emergence of phenotypical resistance was evaluated (repeated MIC-testing after antibiotic administration).

Results: No impact of centrifugation on bacterial growth was seen. TKC with P. aeruginosa showed the best killing in the triple dosage, followed by the double and single dose. In multiple regimens at least a concentration of 4×MIC was needed to achieve a recommended 2-3 log10 killing. Likewise, a reduction of E. coli was best within the three short periods. Contrary to the TKCs with P. aeruginosa we could observe that after the inoculum reached a certain CFU/mL (≥10^8), no further addition of antibiotic could achieve bacterial killing (identified as the inoculum effect). For P. aeruginosa isolates resistance appeared within all regimens, the most pronounced was found in the 40%T > MIC experiments indicating that a single long period might accelerate the emergence of resistance. Contrary, for E. coli no emergence of resistance was found.

Conclusion/Outlook: We could show that not solely the %T > MIC is decisive for an efficient bacterial eradication in vitro, but also the distribution of the selected %T > MIC. Thus, dividing the 40%T > MIC in three short periods requested lowers antibiotic concentrations to achieve efficient bacterial killing and reduces the emergence of resistance in P. aeruginosa isolates. The distribution of the %T > MIC did impact the bacterial eradication of susceptible pathogens in vitro and might play an even bigger role in infections with intermediate or resistant pathogens.
Dexmedetomidine Alleviates Intracerebral Hemorrhage-Induced Anxiety-Like Behaviors in Mice Through the Inhibition of TRPV4 Opening
Authors: An Ping , Zhao Xiao-Chun , Liu Man-Jia , You Yu-Qing , Li Jing-Ya , Gong He-Song
Published: April 2022

Post-stroke anxiety severely affects recovery in patients with intracerebral hemorrhage (ICH). Dexmedetomidine (Dex), a highly selective alpha 2 adrenal receptor (α2-AR) agonist, was recently found to exert an excellent protective effect against mental disorders including anxiety. The transient receptor potential vanilloid 4 (TRPV4) channel is involved in a series of diseases such as asthma, cancer, anxiety, and cardiac hypertrophy. This study examines whether Dex improved ICH-induced anxiety via the inhibition of TRPV4 channel opening. A rodent model of moderate ICH in the basal ganglia was established using autologous blood injection (20 μl). Mice were treated with Dex (25 μg/kg, intraperitoneal injection) every day for 3 days post-ICH. GSK1016790A (1 μmol/2 μl), an agonist of TRPV4, was administered via the left lateral ventricle. Thirty days post-ICH, post-stroke anxiety was evaluated by elevated plus-maze and open-field tests. Following behavioral tests, superoxide dismutase (SOD), malondialdehyde (MDA), astrocytic activation, and A1-and A2-type astrocytes were determined. Primary astrocytes were exposed to hemin to simulate ICH in vitro. Compared with sham-treated mice, Dex administration ameliorates ICH-induced decreases of distance and time in the open-arm, reduces distance and time in the central zone, increases astrocytic activation and A1-type astrocytes, elevates MDA content, downregulates total SOD contents, and decreases A2-type astrocytes. However, GSK1016790A partially reversed the neuroprotective effects of Dex. In addition, Dex significantly inhibited hemin-induced astrocytic activation in vitro. Dex improves ICH-induced anxiety-like behaviors in mice, and the mechanism might be associated with the inhibition of TRPV4-channel opening.
Periodic Flow of Non-Newtonian Fluid Over a Uniformly Heated Block With Thermal Plates: A Hybrid Mesh-Based Study
Authors: Hussain Majeed Afraz , Mahmood Rashid , Hamadneh Nawaf N. , Siddique Imran , Khan Ilyas , Alshammari Nawa
Published: April 2022

In this work, we analyze the characteristics of periodic flows in non-isothermal viscous fluid over a heated block in the presence of thermal plates at Reynolds number (Re=100). The unsteady, incompressible Navier–Stokes (NS) equations with suitable initial and boundary data in 2D are executed by the finite element technique using a highly refined hybrid mesh. The temporal discretization is performed by an implicit stable backward differencing in time and a stable choice of finite elements from the finite element library for spatial discretization. The discrete nonlinear system arising from this discretization is linearized by Newton’s method and then solved through a direct linear solver PARDISO. For this forced convective study, the range of dimensionless parameters, namely, the Prandtl number (Pr) and power law index (n), are varied from 1 to 10 and 0.6 to 1.4 with a low Grashof number varying as (1≤Gr≤10) to produce a forced convection regime, respectively. For the authentication, we have compared our results with the literature at a similar configuration. After simulation, the results accomplished in the velocity profile, pressure, isotherm contours, drag and lift coefficients (trajectory motion), average Nusselt number (Nuavg), etc. are considered. For convergence of solution at low shear rate (n<1), crosswind stabilization (CWS) function has been incorporated. It is observed that Nuavg becomes oscillatory for the shear-thinning case (n<1), while for the shear-thickening cases (n>1), it converges to a single value. Furthermore, the drag (CD) and lift (CL) coefficients are more pronounced for shear-thinning cases (n<1) as compared with shear-thickening cases (n>1).
Short-Term Beat-to-Beat QT Variability Appears Influenced More Strongly by Recording Quality Than by Beat-to-Beat RR Variability
Authors: Toman Ondřej , Hnatkova Katerina , Šišáková Martina , Smetana Peter , Huster Katharina M. , Barthel Petra , Novotný Tomáš , Andršová Irena , Schmidt Georg , Malik Marek
Published: April 2022

Increases in beat-to-beat variability of electrocardiographic QT interval duration have repeatedly been associated with increased risk of cardiovascular events and complications. The measurements of QT variability are frequently normalized for the underlying RR interval variability. Such normalization supports the concept of the so-called immediate RR effect which relates each QT interval to the preceding RR interval. The validity of this concept was investigated in the present study together with the analysis of the influence of electrocardiographic morphological stability on QT variability measurements. The analyses involved QT and RR measurements in 6,114,562 individual beats of 642,708 separate 10-s ECG samples recorded in 523 healthy volunteers (259 females). Only beats with high morphology correlation (r > 0.99) with representative waveforms of the 10-s ECG samples were analyzed, assuring that only good quality recordings were included. In addition to these high correlations, SDs of the ECG signal difference between representative waveforms and individual beats expressed morphological instability and ECG noise. In the intra-subject analyses of both individual beats and of 10-s averages, QT interval variability was substantially more strongly related to the ECG noise than to the underlying RR variability. In approximately one-third of the analyzed ECG beats, the prolongation or shortening of the preceding RR interval was followed by the opposite change of the QT interval. In linear regression analyses, underlying RR variability within each 10-s ECG sample explained only 5.7 and 11.1% of QT interval variability in females and males, respectively. On the contrary, the underlying ECG noise contents of the 10-s samples explained 56.5 and 60.1% of the QT interval variability in females and males, respectively. The study concludes that the concept of stable and uniform immediate RR interval effect on the duration of subsequent QT interval duration is highly questionable. Even if only stable beat-to-beat measurements of QT interval are used, the QT interval variability is still substantially influenced by morphological variability and noise pollution of the source ECG recordings. Even when good quality recordings are used, noise contents of the electrocardiograms should be objectively examined in future studies of QT interval variability.
Genome-Wide Identification of TLP Gene Family and Their Roles in Carya cathayensis Sarg in Response to Botryosphaeria dothidea
Authors: Li Peipei , Xu Yifan , Wang Ketao , Guo Wenlei , Gu Yujie , Lyu Shiheng , Huang Jianqin , Lin Haiping , Huang Chunying , Xu Zhen , Li Yan
Published: April 2022

Hickory (Carya cathayensis) is a critical tree species of the genus Carya from the Juglandaceae family that contains nutrient-rich nuts. Due to large-scale soil degradation, the pests and diseases of hickory are becoming more and more serious. Thaumatin-like proteins (TLPs) are vital proteins involved in the complex defense process of plant pathogens. In this study, 40 CcTLP genes were identified genome-widely and phylogenetically grouped into three subfamilies. The sequence of CcTLPs had a conservative pattern, such as eight stable disulfide bonds, REDDD, and G-X-[GF]-X-C-X-T-[GA]-D-C-X(1,2)-G-X-(2,3)-C structure. In total, 57 cis-elements related to stress-responsive, light-responsive, phytohormone-responsive, and plant-responsive were discovered. Under salicylate (SA), methyl jasmonate (MeJA), and ethephon (ETH) treatments, the expressions of CcTLP28, CcTLP29, CcTLP30, CcTLP31, CcTLP32, CcTLP33, CcTLP37, CcTLP38, and CcTLP39 had different patterns. This is an indication that most of the TLP genes were upregulated by SA and downregulated by MeJA. Notably, seven TLP genes were significantly upregulated under the Botryosphaeria dothidea inoculation, especially CcTLP31, with an over 20-fold change. Nine genes were shown by subcellular localization analysis to be located at the plasma membrane and cytoplasm. The knowledge of the disease-resistant function of the CcTLP family in hickory is promoted by these results. A foundation reference for the molecular breeding of this plant in the future is provided by our findings.
A Moderated Mediation Model of Wellbeing and Competitive Anxiety in Male Marathon Runners
Authors: Jaenes Jose C. , Alarcón David , Trujillo Manuel , Méndez-Sánchez María del Pilar , León-Guereño Patxi , Wilczyńska Dominika
Published: April 2022

Running marathons is an increasingly popular activity with an ever-increasing number of events and participants. Many participants declare that they pursue a variety of goals by running, namely, the maintenance of good health, the development of strength and improvement of fitness, the management of emotions, and the achievement of resilience and psychological wellbeing (PWB). The research has examined marathon running, like many other sports, and has studied various factors that reduce athletic performance, such as the experience of anxiety, and that enhance such performance, such as an increase in general wellbeing. This article reports the results of a study on the experience of competitive anxiety among 238 male marathon runners who participated in Seville’s (Spain) 26th Marathon race on February 23, 2020, and investigates the relationship between anxiety and key dimensions of wellbeing as measured by the Spanish-adapted 20-item PWB Scale. We hypothesized that participating athletes who rated high on the dimensions of PWB would experience lower levels of competitive anxiety with respect to this race. We also proposed that PWB would function as a mediating factor with respect to the experience of anxiety. The results show, as hypothesized, that marathon running enhances wellbeing and reduces anxiety. The data showed significant negative correlations between four of five wellbeing dimensions and the three types of anxiety measured, namely, somatic anxiety, worry, and concentration-impairing anxiety. Other findings supported our hypothesis that wellbeing, as measured, functions as a mediating factor for the moderation of competitive anxiety. Generalization of these findings is limited by the fact that the low number of female participants recruited did not permit valid statistical analyses in this respect. It is known that both anxiety and wellbeing are subjects to variation by gender. The future inclusion of male and female subjects in equivalent studies will undoubtedly add valuable information concerning the dynamics of anxiety and wellbeing. The implications of these findings and the limitations of the study will be discussed.
Scholarship Policies of International Students in Chinese Universities: A Brand Perception Perspective
Authors: Wang Nuo
Published: April 2022

China has carried out a series of higher education reforms in the past decades. One of the most important parts of the reforms is the internationalization progress of Chinese universities. Despite being a developing country, China offers globally competitive scholarships to international students. However, surprisingly, little research has touched on how international students view China’s high scholarship policies, leaving an important and intriguing question underexplored. Therefore, this paper attempts to fill the literature gap by investigating international students’ brand perceptions of Chinese universities that provide high scholarships. Moreover, we reveal the process of their judgments through identifying the mediating role of perceived quality. A set of two experimental studies provide convergent support for these propositions. Theoretically, the findings of this paper contribute to the literature on higher education reforms, scholarship policies, and branding. In terms of practice, the research results offer implications to policy makers, education professionals, and students.
Preliminary Evidence That the Short Allele of 5-HTTLPR Moderates the Association of Psychiatric Symptom Severity on Suicide Attempt: The Example in Obsessive-Compulsive Disorder
Authors: Harika-Germaneau Ghina , Lafay-Chebassier Claire , Langbour Nicolas , Thirioux Bérangère , Wassouf Issa , Noël Xavier , Jaafari Nemat , Chatard Armand
Published: April 2022

Background

The severity of symptoms represents an important source of distress in patients with a psychiatric disease. However, the extent to which this endogenous stress factor interacts with genetic vulnerability factors for predicting suicide risks remains unclear.

Methods

We evaluated whether the severity of symptoms interacts with a genetic vulnerability factor (the serotonin transporter gene-linked promoter region variation) in predicting the frequency of lifetime suicide attempts in patients with a psychiatric disease. Symptom severity and 5-HTTLPR polymorphism were collected from a sample of 95 patients with obsessive-compulsive disorder (OCD). Lifetime suicide attempt was the primary outcome, and antecedent of multiple suicide attempts was the secondary outcome.

Results

The gene-by-symptoms interaction was associated with an excess risk of suicide attempts (OR = 4.39, 95CI[1.44, 13.38], p < 0.009) and of multiple suicide attempts (OR = 4.18, 95CI[1.04, 16.77], p = 0.043). Symptom severity (moderate, severe, or extreme) was associated with an approximately five-fold increase in the odds of a lifetime suicide attempt in patients carrying one or two copies of the short allele of 5-HTTLPR. No such relationship was found for patients carrying the long allele.

Conclusion

This study provides preliminary evidence for the gene-by-stress interaction on suicide attempt when stress is operationalized as symptom severity. Progress in suicide research may come from efforts to investigate the gene-by-symptoms interaction hypothesis in a variety of diseases.
Alter Game: A Study Protocol on a Virtual “Serious Game” for Relapse Prevention in Patients With Gambling Disorder
Authors: Giordano Rosaria , Donati Maria Anna , Zamboni Lorenzo , Fusina Francesca , Primi Caterina , Lugoboni Fabio
Published: April 2022

Cognitive behavioral therapy (CBT) is the most successful protocol in gambling disorder (GD) treatment. However, it presents some weaknesses, especially concerning relapse prevention (RP). RP is one of the most important therapeutic steps, aiming at managing cravings and to avoid future relapse increasing perceived self-efficacy. Encouraging results come from the blending of psychotherapy and virtual reality (VR), containing gambling cues. The goal of Alter Game (approved by the Ethical Commission, Prot. No. 69346) is verifying the efficacy of an innovative psychological treatment for GD based on the integration of traditional CBT therapy and an immersive VR cue exposure therapy using a serious virtual game, which is a game designed for purposes other than entertainment. RP in virtual cue-exposure therapy allows pathological gamblers to manage the urge to gamble and to avoid relapse by becoming aware of which internal and external triggers are related to craving. We hypothesize that the integrated intervention will be more effective than simple CBT with regard to self-efficacy, craving, and gambling-related distortions. Four virtual ecological environments were developed, and a virtual app, Exludo, interfaced with a computerized multiparametric acquisition system for biofeedback, was created. A sample of about 60 patients aged between 18 and 65 with GD referring to the Addiction Medicine Unit of Verona (Rossi Hospital) will be recruited. Patients will be randomly assigned to the CBT group (16 CBT sessions) or the CBT + VR group (8 CBT sessions + 8 VR cue-exposure therapy sessions). The MCMI-III, the BIS-11, and the SOGS will be used to evaluate inclusion and exclusion criteria, while the Gambling Related Cognitions Scale and the Multidimensional Gambling Self-Efficacy Scale will be used to verify changes as a function of the treatment. Craving will be evaluated through VAS, and psychophysiological variables will be assessed through biofeedback. A pre-test/post-test experimental design with a 1-month follow-up will be conducted. This study will examine an innovative psychotherapeutic protocol for GD treatment, and it will help in identifying new virtual tools to increase the efficacy of traditional therapeutic approaches that could also be applied to treat other addictions.
Mental Health Challenges, Parenting Stress, and Features of the Couple Relationship in Parents of Children With Fragile X Syndrome
Authors: Potter Sarah Nelson , Harvey Danielle J. , Sterling Audra , Abbeduto Leonard
Published: April 2022

Background

Individuals with fragile X syndrome (FXS) have significant delays in cognition and language, as well as anxiety, symptoms of autism spectrum disorder, and challenging behaviors such as hyperactivity and aggression. Biological mothers of children with FXS, who are themselvesFMR1premutation or full mutation carriers, are at elevated risk for mental health challenges in addition to experiencing stress associated with parenting a child with significant disabilities. However, little is known about fathers in these families, including the ways in which parental well-being influences the mother-father relationship and the impact of child characteristics on paternal and couple functioning.

Method

The current study examined features of, and relationships between, parental well-being, couple well-being, and child functioning in 23 families of young boys with FXS. Mothers and fathers independently completed multiple questionnaires about their individual well-being, couple functioning, and child behavior. One parent per family also completed an interview about the child’s adaptive skills.

Results

Results suggest that both mothers and fathers in these families experience clinically significant levels of mental health challenges and elevated rates of parenting stress relative to the general population. Findings also indicate that the couples’ relationship may be a source of strength that potentially buffers against some of the daily stressors faced by these families. Additionally, parents who reported less parenting stress had higher couples satisfaction and dyadic coping. Finally, parents of children with less severe challenging behaviors exhibited fewer mental health challenges, less parenting stress, and higher levels of both couples satisfaction and dyadic coping. Parents of children with higher levels of adaptive behavior also reported less parenting stress and higher couples satisfaction.

Conclusion

Overall, this study provides evidence that families of children with FXS need access to services that not only target improvements in the child’s functioning, but also ameliorate parental stress. Family-based services that include both mothers and fathers would lead to better outcomes for all family members.
Clergy's Viewpoint Change Toward Mental Health and Stigma on Mental Illness: A Short Course Training
Authors: Taghva Arsia , Noorbala Ahmad Ali , Khademi Mojgan , Shahriari Alireza , Nasr Esfahani Mahdi , Asadi Ali , Mohsenifar Jafar , Yousefifard Ali , Abolhassani Moussa , Bolhari Jafar , Hajebi Ahmad , Rahnejat Amir Mohsen , Shahed-haghghadam Haleh
Published: April 2022

Background

As stigma is one of the main barriers in promoting the mental health, the present study was designed with the purpose of reviewing clergy's viewpoint regarding the effect of mental health workshops on these barriers.

Methods

For this study, by order of Iran's Health Ministry, a questionnaire was designed to examine the clergy's viewpoint related to mental illnesses and the consequent stigma. Ten faculty members and psychiatrists confirmed the questionnaire's validity after some modifications. In this research, 30 members of the clergy from the main religious city in Iran's “Qom” Seminary attended the training workshops for 2 days. The data obtained from the clergy's responses were analyzed using the SPSS software (ver.16) and descriptive and analytical tests. Also, the significance level was considered p < 0.05 in all tests. The results exhibited that the mean and standard deviation (Mean ± SD) of the clergy's attitude domain and awareness before the workshop was 1.90 ± 26.30 and 8.31 ± 1.64, respectively. Also, average and standard deviation (Mean ± SD) of their attitude domain and awareness after the workshop was 1.95 ± 29.73 and 1.18 ± 10.70, respectively.

Discussion

The present study, which was designed to examine the clergy's viewpoint toward mental illnesses and the consequent stigma in the most considerable religious base in the country, illustrated that one strategy for reducing mental illness stigma in religious communities can be by holding training sessions to promote the clergy's awareness of and attitude toward mental health.

Conclusion

There was a significant statistical difference between their awareness and attitude scores before and after the workshop (p < 0.01). In the present research, the awareness and attitude of clergy toward mental health and stigma due to mental illness was relatively good and significantly increased by holding the workshop.
Stimulating Sunscreen Use Among Outdoor Construction Workers: A Pilot Study
Authors: Keurentjes Anne J. , Kezic Sanja , Rustemeyer Thomas , Hulshof Carel T. J. , van der Molen Henk F.
Published: April 2022

Background

Outdoor workers (OW) receive a higher dose of ultraviolet radiation (UVR) compared to indoor workers (IW) which increases the risk of non-melanoma skin cancer (NMSC). Regular sunscreen use reduces the NMSC risk, however, adequate sun-safety behavior among OW is poor. The main objective was to conduct method- and intervention-related elements of a future intervention trial among OW, based on providing sunscreen and assessing sunscreen use on group- and individual level.

Methods

This pilot study was conducted at a construction site in the Netherlands from May-August 2021. Nine dispensers with sunscreen (SPF 50+) were installed at the worksite. OW (n = 67) were invited to complete two (cross-sectional) questionnaires on sun-safety behavior, before and after providing sunscreen. Stratum corneum (SC) samples for the assessment of UV-biomarkers were collected from the forehead and behind the ear from 15 OW and 15 IW. The feasibility of the following elements was investigated: recruitment, (loss to) follow-up, outcome measures, data collection, and acceptability of the intervention.

Results

The first questionnaire was completed by 27 OW, the second by 17 OW. More than 75 percent of the OW were aware of the risks of sun exposure, and 63% (n = 17) found sunscreen use during worktime important. The proportion of OW never applying sunscreen in the past month was 44.4% (n = 12) before, and 35.3% (n = 6) after providing sunscreen. A majority of OW (59.3%, n = 16) found sunscreen provision encouraging for sunscreen use, the dispensers easy to use (64.7%, n = 17) and placed in practical spots (58.8%, n = 18). Collecting SC-samples was fast and easy, and several UV-biomarkers showed higher levels for sun-exposed compared to less exposed body parts. There was no significant difference in UV-biomarker levels between OW and IW.

Conclusions

This pilot study revealed low sunscreen use among OW despite providing sunscreen, overall satisfaction with the sunscreen, and the sufficient awareness of the risks of UVR-exposure. Collecting SC-samples at the workplace is feasible and several UV-biomarkers showed to be promising in assessing UVR-exposure. The low participation rate and high loss to follow-up poses a challenge for future intervention studies.