bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Hub Genes in Colorectal Adenocarcinoma by Integrated Bioinformatics
Authors: Liu Yang , Chen Lanlan , Meng Xiangbo , Ye Shujun , Ma Lianjun
Published: May 2022

An improved understanding of the molecular mechanism of colorectal adenocarcinoma is necessary to predict the prognosis and develop new target gene therapy strategies. This study aims to identify hub genes associated with colorectal adenocarcinoma and further analyze their prognostic significance. In this study, The Cancer Genome Atlas (TCGA) COAD-READ database and the gene expression profiles of GSE25070 from the Gene Expression Omnibus were collected to explore the differentially expressed genes between colorectal adenocarcinoma and normal tissues. The weighted gene co-expression network analysis (WGCNA) and differential expression analysis identified 82 differentially co-expressed genes in the collected datasets. Enrichment analysis was applied to explore the regulated signaling pathway in colorectal adenocarcinoma. In addition, 10 hub genes were identified in the protein–protein interaction (PPI) network by using the cytoHubba plug-in of Cytoscape, where five genes were further proven to be significantly related to the survival rate. Compared with normal tissues, the expressions of the five genes were both downregulated in the GSE110224 dataset. Subsequently, the expression of the five hub genes was confirmed by the Human Protein Atlas database. Finally, we used Cox regression analysis to identify genes associated with prognosis, and a 3-gene signature (CLCA1–CLCA4–GUCA2A) was constructed to predict the prognosis of patients with colorectal cancer. In conclusion, our study revealed that the five hub genes and CLCA1–CLCA4–GUCA2A signature are highly correlated with the development of colorectal adenocarcinoma and can serve as promising prognosis factors to predict the overall survival rate of patients.
Distribution of Vaginal and Gut Microbiome in Advanced Maternal Age
Authors: Huang Yuxin , Li Dianjie , Cai Wei , Zhu Honglei , Shane Mc Intyre , Liao Can , Pan Shilei
Published: May 2022

The distribution of the microbiome in women with advanced maternal age (AMA) is poorly understood. To gain insight into this, the vaginal and gut microbiota of 62 women were sampled and sequenced using the 16S rRNA technique. These women were divided into three groups, namely, the AMA (age ≥ 35 years, n = 13) group, the non-advanced maternal age (NMA) (age < 35 years, n = 38) group, and the control group (non-pregnant healthy women, age >35 years, n = 11). We found that the alpha diversity of vaginal microbiota in the AMA group significantly increased. However, the beta diversity significantly decreased in the AMA group compared with the control group. There was no significant difference in the diversity of gut microbiota among the three groups. The distributions of microbiota were significantly different among AMA, NMA, and control groups. In vaginal microbiota, the abundance of Lactobacillus was higher in the pregnant groups. Bifidobacterium was significantly enriched in the AMA group. In gut microbiota, Prevotella bivia was significantly enriched in the AMA group. Vaginal and gut microbiota in women with AMA were noticeably different from the NMA and non-pregnant women, and this phenomenon is probably related to the increased risk of complications in women with AMA.
The Design and Feasibility of the: Radial Artery Puncture Hemostasis Evaluation – RAPHE Study, a Prospective, Randomized, Multicenter Clinical Trial
Authors: Kulyassa Péter , Németh Balázs T. , Ehrenberger Réka , Ruzsa Zoltán , Szük Tibor , Fehérvári Péter , Engh Marie Anne , Becker Dávid , Merkely Béla , Édes István F.
Published: May 2022

Introduction and Aim

Radial artery approach angiography is the current gold standard for coronary status diagnostics and eventual percutaneous revascularization (PCI). Currently, application of adequate, patent hemostasis based physical torniquets are used for puncture site control, to avoid bleeding, radial artery occlusion and damage (RAO and RAD). The Radial Artery Puncture Hemostasis Evaluation (RAPHE) is a prospective, randomized, multicenter clinical trial designed to investigate new, simplified techniques of radial artery hemostasis utilizing physical compression free methods.

Methods and Results

The RAPHE study has been designed to evaluate the efficacy and safety of two non-compression based radial artery hemostasis methods: a 100% chitosan bioactive hemostatic dressing and a purpose-built radial potassium-ferrate based topical hemostasis disc. These devices will be investigated in a standalone configuration. Control group is a standard pneumatic airbladder-based compression device. A total of 600 patients will be enrolled in a three-way randomization (1:1:1) with two study and one control groups. Safety and efficacy endpoints are RAO, puncture site hematoma formation and RAD respectively, consisting of dissection, (pseudo)aneurism and/or fistula formation, measured post-procedure and at sixty days.

Conclusion

The results from this trial will provide valuable information on new, simplified methods of radial artery hemostasis options and possibly simplify post-puncture management of patients.

Clinical Trial Registration

[www.ClinicalTrials.gov], identifier [NCT04857385].
Comparative Analysis of Physical Activity Detected via an External Accelerometer and Cardiac Implantable Electronic Devices
Authors: Chen Chun-Kai , Cheng Li-Ying , Hsu Shan-Wei , Liao Min-Tsun , Ku Po-Wen , Liu Yen-Bin
Published: May 2022

Background

Physical activity (PA) has become an important health issue for decades. Cardiovascular implantable electronic devices (CIEDs) have built-in PA-recording functions. We aimed to compare PA measurements using an external accelerometer (ActiGraph GT3X+) and internal accelerometers (Abbott, Biotronik, and Medtronic CIEDs).

Methods

This was a prospective, single-center observational study. The device-measured 7-day average PA was collected, and GT3X+ -measured 7-day average PA was used as the gold-standard, including all daily observations of activity. Pearson’s correlation coefficients were used to compare the correlations between GT3X+ -measured and CIED-measured PA. Bland-Altman plots were used to analyze measurement agreement, and intraclass correlation coefficients were used to analyze reliability.

Results

In total, 720 patients treated with CIEDs were surveyed between November 2020 and April 2021, 60 of them were analyzed after patient screening by our protocol. Each manufacturer included 20 patients for the final analysis. The CIED-measured PAs of Abbott, Biotronik, and Medtronic were 3.0 ± 1.5, 2.6 ± 1.8, and 3.8 ± 2.5 h per day, respectively; the GT3X+ -measured PAs were 6.9 ± 2.8, 6.0 ± 2.4, and 6.4 ± 2.5 h per day, respectively. Moderate and significant correlations were found in patients using Abbott, Biotronik, and Medtronic CIEDs (r = 0.534, p = 0.015; r = 0.465, p = 0.039; r = 0.677, p = 0.001, respectively). Bland-Altman plots and intraclass correlation coefficients both showed a significant correlation and reliability between the average PA measured by GT3X+ and CIEDs (hours per day).

Conclusion

Although the PA recording function of CIEDs includes a single-axis accelerometer, it has a moderate correlation compared with the triaxial accelerometer of the GT3X+. However, CIEDs seem to underestimate PA for 3–4 h compared to the GT3X+.
The Seismogenic Potential of the Southernmost Ryukyu Subduction Zone as Revealed by Historical Earthquakes and Slow Slip events
Authors: Chen Sean Kuanhsiang , Wu Yih-Min , Chan Yu-Chang
Published: May 2022

The southernmost Ryukyu subduction zone may have a geodetically inferred Mw 7.5 to 8.7 megathrust earthquake in a shallow locked region, the Ryukyu fault. Paleoseismological evidence of historical earthquakes available from the last 417 years indicates that only a 1920 Mw 7.7 earthquake occurred within this magnitude range, near the downdip end of the Ryukyu fault. As slow slip events downdip the locked seismogenic zone may trigger a large subduction earthquake, we investigate how the first observed slow slip events in 2005, 2009, and 2015 initiated downdip in the Ryukyu fault interface affect the occurrence of a megathrust. We establish possible megathrust earthquake cycles from Mw 7.5 to 8.7 on the Ryukyu fault using constraints from the magnitude-frequency relation based on local historical earthquakes. This analysis shows a b value of 1.2 for magnitudes greater than Mw 7.0, which is higher than the empirical 1.0 value. This indicates that the recurrence of an event up to Mw 8.7 is longer than previously thought if the megathrust events follow the observed magnitude-frequency relation. Then, we quantify the influence of slow slip events on the triggering of a potential megathrust earthquake by calculating the static stress increase. We find that stress perturbations caused by the three slow slip events are generally consistent with the values that have triggered the large interplate earthquakes in several subduction zones. However, a large earthquake has not yet been triggered on the Ryukyu fault after a sequence of slow slip events. If the 1920 Mw 7.7 earthquake is the last rupture of the Ryukyu fault, the earthquake cycle on the Ryukyu fault is very likely in an early stage. However, this is not true if the slow slip events occur toward the end of the earthquake cycle and there has been no megathrust earthquake at the fault interface in the last 417 years, as the 2011 Mw 9.0 Tohoku earthquake. Thus, higher potential for a megathrust earthquake may occur in the southernmost Ryukyu subduction zone.
The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis
Authors: Chen Yidan , Lv Xingfei , Lin Sang , Arshad Mohammad , Dai Mengjun
Published: May 2022

Aims

This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19.

Methods

We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis.

Results

The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%.

Conclusion

Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin.

Systematic Review Registration

PROSPERO (CRD42021288200)
The Impact of Household Cooking Fuel Choice on Healthcare Expenditure in Ghana
Authors: Azorliade Dictus Atsu , Twerefou Daniel Kwabena , Dovie Delali Benjamin K.
Published: May 2022

This study investigates the impact of household cooking fuel choice on household healthcare expenditure as well as the socioeconomic and demographic factors that influence household healthcare expenditure. We employed the Tobit regression technique and data from the sixth and seventh rounds of the Ghana Living Standards Survey conducted in 2012/13 and 2016/17, respectively. The results indicate that in 2012/13, relative to households using wood as cooking fuel, households using charcoal and liquefied petroleum gas are 54.40 and 115.09 percentage points less likely to spend on healthcare services. However, the figure reduced to 28.15 and 103.25 percentage points in 2016/17 attributable possibly to a reduction in biomass energy use resulting from government liquefied petroleum gas promotion programs which helped households transition to the use of cleaner fuels. Age, education, illness reporting of the household head, total household expenditure, household size, and region of residence were found to be the determinants of household healthcare expenditure. Policy choices should focus on the use of cleaner fuel options including sustaining and extending the rural liquefied petroleum gas promotion program as well as reducing the use of dirty fuels.
How Does Agro-Tourism Integration Influence the Rebound Effect of China’s Agricultural Eco-Efficiency? An Economic Development Perspective
Authors: Jiang Guirong
Published: May 2022

Agro-tourism integration is a breakthrough to flourish rural industries and fulfill rural revitalization. Also, agricultural eco-efficiency and agro-tourism integration are closely linked, so investigating the relationship between the two is significant for realizing high-quality agro-ecological development in China. However, existing studies have ignored the impact of agro-tourism integration on agricultural eco-efficiency. For this purpose, using a dataset of 30 provincial administrative regions in China from 2001 to 2019, this paper employs the Entropy weight approach and super efficient Slack-Based Measure (SBM`) approach to measure the agro-tourism integration level and agricultural eco-efficiency, respectively. The system Generalized Method of Moments (SYS-GMM) approach is applied to investigate the effect of agro-tourism integration on agricultural eco-efficiency. The statistical results reveal that agro-tourism integration significantly contributes to agricultural eco-efficiency, which remains valid after the robustness checks are executed. There is also significant path-dependence of agro-tourism integration. Finally, agro-tourism integration significantly contributes to agricultural eco-efficiency in the eastern region, while it significantly inhibits agricultural eco-efficiency in the central-western region. Our findings suggest that policymakers not only reinforced the deep integration of agriculture and tourism to stimulate the overall rural revitalization, but also formulated agro-tourism integration policies in a differentiated and green manner to contribute to agricultural eco-efficiency growth.
COVID-19 Pandemic, Air Quality, and PM2.5 Reduction-Induced Health Benefits: A Comparative Study for Three Significant Periods in Beijing
Authors: Cai Fangfang , Yin Kedong , Hao Mengying
Published: May 2022

Previous studies have estimated the influence of control measures on air quality in the ecological environment during the COVID-19 pandemic. However, few have attached importance to the comparative study of several different periods and evaluated the health benefits of PM2.5 decrease caused by COVID-19. Therefore, we aimed to estimate the control measures' impact on air pollutants in 16 urban areas in Beijing and conducted a comparative study across three different periods by establishing the least squares dummy variable model and difference-in-differences model. We discovered that restriction measures did have an apparent impact on most air pollutants, but there were discrepancies in the three periods. The Air Quality Index (AQI) decreased by 7.8%, and SO2, NO2, PM10, PM2.5, and CO concentrations were lowered by 37.32, 46.76, 53.22, 34.07, and 19.97%, respectively, in the first period, while O3 increased by 36.27%. In addition, the air pollutant concentrations in the ecological environment, including O3, reduced significantly, of which O3 decreased by 7.26% in the second period. Furthermore, AQI and O3 concentrations slightly increased compared to the same period in 2019, while other pollutants dropped, with NO2 being the most apparent decrease in the third period. Lastly, we employed health effects and environmental value assessment methods to evaluate the additional public health benefits of PM2.5 reduction owing to the restriction measures in three periods. This research not only provides a natural experimental basis for governance actions of air pollution in the ecological environment, but also points out a significant direction for future control strategies.
Variability in Phelan-McDermid Syndrome in a Cohort of 210 Individuals
Authors: Nevado Julián , García-Miñaúr Sixto , Palomares-Bralo María , Vallespín Elena , Guillén-Navarro Encarna , Rosell Jordi , Bel-Fenellós Cristina , Mori María Ángeles , Milá Montserrat , Campo Miguel del , Barrúz Pilar , Santos-Simarro Fernando , Obregón Gabriela , Orellana Carmen , Pachajoa Harry , Tenorio Jair Antonio , Galán Enrique , Cigudosa Juan C. , Moresco Angélica , Saleme César , Castillo Silvia , Gabau Elisabeth , Pérez-Jurado Luis , Barcia Ana , Martín Maria Soledad , Mansilla Elena , Vallcorba Isabel , García-Murillo Pedro , Cammarata-Scalisi Franco , Gonçalves Pereira Natálya , Blanco-Lago Raquel , Serrano Mercedes , Ortigoza-Escobar Juan Dario , Gener Blanca , Seidel Verónica Adriana , Tirado Pilar , Lapunzina Pablo ,   Spanish PMS Working Group
Published: May 2022

Phelan-McDermid syndrome (PMS, OMIM# 606232) results from either different rearrangements at the distal region of the long arm of chromosome 22 (22q13.3) or pathogenic sequence variants in the SHANK3 gene. SHANK3 codes for a structural protein that plays a central role in the formation of the postsynaptic terminals and the maintenance of synaptic structures. Clinically, patients with PMS often present with global developmental delay, absent or severely delayed speech, neonatal hypotonia, minor dysmorphic features, and autism spectrum disorders (ASD), among other findings. Here, we describe a cohort of 210 patients with genetically confirmed PMS. We observed multiple variant types, including a significant number of small deletions (<0.5 Mb, 64/189) and SHANK3 sequence variants (21 cases). We also detected multiple types of rearrangements among microdeletion cases, including a significant number with post-zygotic mosaicism (9.0%, 17/189), ring chromosome 22 (10.6%, 20/189), unbalanced translocations (de novo or inherited, 6.4%), and additional rearrangements at 22q13 (6.3%, 12/189) as well as other copy number variations in other chromosomes, unrelated to 22q deletions (14.8%, 28/189). We compared the clinical and genetic characteristics among patients with different sizes of deletions and with SHANK3 variants. Our findings suggest that SHANK3 plays an important role in this syndrome but is probably not uniquely responsible for all the spectrum features in PMS. We emphasize that only an adequate combination of different molecular and cytogenetic approaches allows an accurate genetic diagnosis in PMS patients. Thus, a diagnostic algorithm is proposed.
Identification of Immune Infiltration-Related ceRNAs as Novel Biomarkers for Prognosis of Patients With Primary Open-Angle Glaucoma
Authors: Zhang Daowei , Wu Jiawen , Zhang Shenghai , Wu Jihong
Published: May 2022

Glaucoma is the leading cause of irreversible blindness globally; hence, relevant clinical biomarkers are necessary to enable diagnosis, early detection, and development of novel therapies. The differentially expressed genes were annotated and visualized using Gene Ontology and Kyoto Encyclopedia. In addition, a competitive endogenous ribonucleic acids network was constructed using Cytoscape, which explained the regulation of gene expression in glaucoma. The CIBERSORT algorithm was employed to analyze the immune microenvironment. We validated that the core genes could predict glaucoma occurrence and development and identified potential molecular mechanism pathways, which were associated with immune infiltration and participated in endogenous regulation networks. Our data may partially explain the pathogenesis of glaucoma and they provide potential theoretical support for targeted therapy.
Case Report: Identification Pathogenic Abnormal Splicing of BBS1 Causing Bardet–Biedl Syndrome Type I (BBS1) due to Missense Mutation
Authors: Yan Kai , Sun Yixi , Yang Yanmei , Liu Bei , Dong Minyue
Published: May 2022

Conventionally, protein features affected by missense mutation was attributed to destroy an important domain with amino acid alternation, and it was difficult to clearly specify the pathogenicity of a novel missense mutation. Nevertheless, the associations between missense mutations and abnormal splicing are nowadays increasingly reported. Rarely, some missense mutations, locating at the non-canonical splicing sites, are observed to damage the splicing process. In this study, a couple has three adverse pregnancy history that the affected fetus presented typical polydactyly, renal abnormalities, and cerebral ventriculomegaly. To identify its genetic etiology, whole-exome sequencing (WES) was performed and a missense mutation c.1339G > A was identified, which was located at the non-canonical splicing sites of theBBS1gene. Then, reverse transcription polymerase chain reaction was carried out and demonstrated extra 115bp originating from intron 13 cut into cDNA, which generated a predicted premature termination codon (PTC) in the BBS1 protein. Further expression analysis by using real-time reverse-transcribed PCR confirmed the occurrence of nonsense-mediated decay (NMD). Therefore, the pathogenicity of the missense mutation c.1339G > A was explicit and our study helped to extend the spectrum of pathogenic mutations in Bardet–Biedl syndrome type I.
The Diverse Major Histocompatibility Complex Haplotypes of a Common Commercial Chicken Line and Their Effect on Marek’s Disease Virus Pathogenesis and Tumorigenesis
Authors: Bertzbach Luca D. , Tregaskes Clive A. , Martin Rebecca J. , Deumer Undine-Sophie , Huynh Lan , Kheimar Ahmed M. , Conradie Andelé M. , Trimpert Jakob , Kaufman Jim , Kaufer Benedikt B.
Published: May 2022

The major histocompatibility complex (MHC) is crucial for appropriate immune responses against invading pathogens. Chickens possess a single predominantly-expressed class I molecule with strong associations between disease resistance and MHC haplotype. For Marek’s disease virus (MDV) infections of chickens, the MHC haplotype is one of the major determinants of genetic resistance and susceptibility. VALO specific pathogen free (SPF) chickens are widely used in biomedical research and vaccine production. While valuable findings originate from MDV infections of VALO SPF chickens, their MHC haplotypes and associated disease resistance remained elusive. In this study, we used several typing systems to show that VALO SPF chickens possess MHC haplotypes that include B9, B9:02, B15, B19 and B21 at various frequencies. Moreover, we associate the MHC haplotypes to MDV-induced disease and lymphoma formation and found that B15 homozygotes had the lowest tumor incidence while B21 homozygotes had the lowest number of organs with tumors. Finally, we found transmission at variable levels to all contact birds except B15/B21 heterozygotes. These data have immediate implications for the use of VALO SPF chickens and eggs in the life sciences and add another piece to the puzzle of the chicken MHC complex and its role in infections with this oncogenic herpesvirus.
Finite Element and Artificial Neural Network Modeling of FRP-RC Columns Under Axial Compression Loading
Authors: Isleem Haytham F. , Tayeh Bassam A. , Abid Muhammad , Iqbal Mudassir , Mohamed Abdeliazim M. , Sherbiny Mohammed Galal El
Published: May 2022

The use of fiber-reinforced polymer (FRP) bars to overcome the corrosion problems in various reinforced concrete structures is now well documented in the literature. As a result, the currently available design guidelines such as North American design codes allow for using the FRP bars as alternative materials to steel bars to be incorporated into the concrete structures. In practice, hollow-core concrete columns (HCCs) are widely accepted to make a lightweight structure and reduce its cost. Due to the lack of laboratory tests, engineers may not perform a safe design of HCCs with internal FRP bars. Therefore, the presented paper has endeavored to numerically and theoretically explore using the FRP bars and spirals as internal reinforcement for HCCs and investigate the effects of several test parameters. Using the current version of Finite Element Analysis (FEA) ABAQUS (3DS, 2014), a total of 116 HCCs were simulated based on 29 specimens experimentally tested by the researchers which acted as control specimens for the FE model. The complex structural response of concrete was reasonably determined using the concrete damaged plasticity model (CDPM) and the mechanical response of the FRP rebars are considered to behave linearly up to failure with no yielding stage. The calibrated FE model can provide an excellent portrayal of the HCCs’ response. Based on the database obtained from laboratory and simulation, several Artificial Neural Network (ANN) models were further provided to predict the confined compressive load of GFRP-RC HCCs at different loading stages.
Seasonal Influenza Vaccination at a German University Hospital: Distinguishing Barriers Between Occupational Groups
Authors: Peschke Martin , Hagel Stefan , Rose Norman , Pletz Mathias W. , Steiner Andrea
Published: May 2022

The annual influenza vaccination has been officially recommended for medical staff in Germany since 1988. Nevertheless, the vaccination rate among medical staff is still low. The present study deals with the influenza vaccination rate of staff at a German University hospital over time as well as with the reasons that led to a positive vaccination decision and the barriers to acceptance of vaccination. For this purpose, the staff members received questionnaires in which they were asked about influenza vaccination and the reasons for or against vaccination. In addition, the questionnaire contains information on gender, age group, occupational group and presence of a chronic co-morbidity. Logistic regression analysis was used to investigate which of these predictors most strongly influenced the vaccination decision. It was shown that the reasons for or against vaccination differ significantly between the occupational groups and that the occupational group affiliation has the greatest influence on the vaccination decision in the comparison of the investigated predictors. In order to achieve a positive influence on vaccination acceptance, future measures should focus on increasing confidence in vaccination and on increasing the perception of risk from influenza illness. The findings may contribute to future targeted strategies to increase vaccination rates and suggest occupational group-specific interventions.
Evaluation of Patients With Cognitive Impairment Due to Suspected Idiopathic Normal-Pressure Hydrocephalus at Medical Centers for Dementia: A Nationwide Hospital-Based Survey in Japan
Authors: Kazui Hiroaki , Hashimoto Mamoru , Takeda Shigetoshi , Chiba Yasuji , Goto Tokiko , Fuchino Katsuhiro
Published: May 2022

Objective

Treatment of idiopathic normal-pressure hydrocephalus (iNPH) requires collaboration between dementia specialists and neurosurgeons. The role of dementia specialists is to differentiate patients with iNPH from patients with other dementia diseases and to determine if other dementia diseases are comorbid with iNPH. We conducted a nationwide hospital-based questionnaire survey on iNPH in medical centers for dementia (MCDs).

Methods

We developed a questionnaire to assess how physicians in MCDs evaluate and treat patients with cognitive impairment due to suspected iNPH and the difficulties these physicians experience in the evaluation and treatment of patients. The questionnaire was sent to all 456 MCDs in Japan.

Results

Questionnaires from 279 MCDs were returned to us (response rate: 61.2%). Patients underwent cognitive tests, evaluation of the triad symptoms of iNPH, and morphological neuroimaging examinations in 96.8, 77.8, and 98.2% of the MCDs, respectively. Patients with suspected iNPH were referred to other hospitals (e.g., hospitals with neurosurgery departments) from 78.9% of MCDs, and cerebrospinal fluid (CSF) tap test was performed in 44 MCDs (15.8%). iNPH guidelines (iNPHGLs) and disproportionately enlarged subarachnoid space hydrocephalus (DESH), a specific morphological finding, were used and known in 39.4% and 38% of MCDs, respectively. Logistic regression analysis with “Refer the patient to other hospitals (e.g., hospitals with neurosurgery departments) when iNPH is suspected.” as the response variable and (a) using the iNPHGLs, (b) knowledge of DESH, (c) confidence regarding DESH, (d) difficulty with performing brain magnetic resonance imaging, (e) knowledge of the methods of CSF tap test, (f) absence of physician who can perform lumbar puncture, and (g) experience of being told by neurosurgeons that referred patients are not indicated for shunt surgery as explanatory variables revealed that the last two factors were significant predictors of patient referral from MCDs to other hospitals.

Conclusion

Sufficient differential or comorbid diagnosis using CSF tap test was performed in a few MCDs. Medical care for patients with iNPH in MCDs may be improved by having dementia specialists perform CSF tap tests and share the eligibility criteria for shunt surgery with neurosurgeons.
Reversible Suppression of Fear Memory Recall by Transient Circadian Arrhythmia
Authors: Steiger Athreya , Farfan Julia , Fisher Nathan , Heller H. Craig , Fernandez Fabian-Xosé , Ruby Norman F.
Published: May 2022

We tested the hypothesis that a temporary period of circadian arrhythmia would transiently impair recall of an aversive memory in Siberian hamsters (Phodopus sungorus). Unlike mice or rats, circadian arrhythmia is easily induced in this species by a one-time manipulation of their ambient lighting [i.e., the disruptive phase shift (DPS) protocol]. Hamsters were conditioned to associate footshocks with a shock chamber (context) and with a predictive auditory tone (cue), and then exposed to the DPS protocol. Following DPS, animals either became arrhythmic (ARR), reentrained to the light-dark cycle (ENT), or became arrhythmic for < 14 days before their circadian locomotor rhythms spontaneously recovered and reentrained (ARR-ENT). Tests for contextual memory showed that freezing was decreased 9–10 days post-DPS when both ARR and ARR-ENT groups were arrhythmic. Once ARR-ENT animals reentrained (day 41), however, freezing was elevated back to Pre-DPS levels and did not differ from those observed in ENT hamsters. ENT animals maintained high levels of freezing at both time points, whereas, freezing remained low in ARR hamsters. In contrast to contextual responses, cued responses were unaffected by circadian arrhythmia; all three groups exhibited elevated levels of freezing in response to the tones. The differential impact of circadian arrhythmia on contextual versus cued associative memory suggests that arrhythmia preferentially impacts memory processes that depend on the hippocampus.
Bitter Orange (Citrus aurantium L.) Intake Before Submaximal Aerobic Exercise Is Safe for Cardiovascular and Autonomic Systems in Healthy Males: A Randomized Trial
Authors: Benjamim Cicero Jonas R. , Júnior Francisco Welington de Sousa , Porto Andrey Alves , Rocha Élida Mara B. , Santana Milana D. , Garner David M. , Valenti Vitor E. , Bueno Júnior Carlos Roberto
Published: May 2022

Background

There are still no studies of the cardiovascular safety of the isolated use of Citrus aurantium in aerobic submaximal exercise.

Objective

To evaluate the effect of C. aurantium supplementation on the recovery of cardiorespiratory and autonomic parameters following a session of submaximal aerobic exercise.

Methods

Twelve healthy male adults achieved a crossover, randomized, double-blind, and placebo-controlled trial. C. aurantium (600 mg, p-synephrine at 30% amount [180 mg]) or placebo (600 mg of starch) were ingested 90 min before evaluation in randomized days. We evaluated systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), heart rate (HR) and, HR variability indexes at Rest and during 60 min of recovery from exercise.

Results

Citrus aurantium ingestion accelerated the reduction in SBP after exercise, anticipated the return of vagal modulation of the heart after exercise via the HF (ms2), pNN50 (%), and 2 UV% indices. Moreover, rushed the output of sympathetic modulation after exercise via the 0V% index. No unfavorable cardiovascular effects were achieved for HR, DBP, PP, and MAP parameters.

Conclusions

Citrus aurantium was shown to be safe for the cardiovascular and autonomic systems alongside submaximal aerobic exercise in healthy males.
Complications of Endoscopic Skull Base Surgery for Sellar and Parasellar Tumors in Pediatric Population; Neurosurgical Perspectives
Authors: Yang Jeyul , Kim Yong Hwy , Phi Ji Hoon , Kim Seung-Ki , Wang Kyu-Chang
Published: May 2022

Background

Advances in surgical techniques based on in-depth anatomical knowledge of the skull base have broadened the indications for endoscopic skull base surgery (ESS) with the advantage of wide and direct surgical exposure while minimizing invasiveness. However, the low incidence of the indicated diseases and narrow surgical corridors in children have limited the popularization of ESS. In addition, surgical complications and preventive interventions are not yet well known. Therefore, we retrospectively investigated the complications and prevention methods of ESS in children with a comprehensive review.

Methods

We retrospectively analyzed the medical records of pediatric patients who underwent ESS for sellar and parasellar tumors at Seoul National University Children’s Hospital from July 2010 to December 2020. Visual and endocrine status, extent of resection, complications, and recurrences were investigated depending on the pathology of the tumor. In addition, a comprehensive literature review regarding the complications of pediatric ESS was performed.

Results

A total of 98 patients were enrolled. The median age of the patients was 12 years, and 52 patients were male. Preoperative visual disturbance was found in 53 patients, anterior pituitary function deficit in 69, and diabetes insipidus in 32. Gross total resection was attempted in 67 patients and achieved in 62 (93%). Biopsy and cyst fenestration were the goals of surgery in 26 patients, and all were achieved as planned. Regarding outcomes, visual disturbance worsened in two patients (2%), endocrine status was aggravated in 34 (35%) patients, and new-onset diabetes insipidus occurred in 27 (41%) patients. The overall surgical complication rate (other than aggravation of visual or endocrine status) was 17%. Postoperative meningitis (12%) was the most common complication, followed by cerebrospinal fluid leakage (2%), vasospasm, hemorrhage and infarction. By pathological diagnosis, craniopharyngioma had the highest complication rate of 29%. All but one patient with postoperative hemorrhage showed no permanent deficits.

Conclusion

ESS in children is feasible and relatively safe. More attention and different postoperative management protocols are required in children to avoid complications, especially in craniopharyngiomas. However, the complications can be mostly managed conservatively without permanent neurologic deficits.
Gastrointestinal Endoscopy Performed by Gastroenterologists: Opportunistic Screening Strategy for Newly Diagnosed Head and Neck Cancers
Authors: Yang Chih-Wei , Chu Yueng-Hsiang , Chen Hsin-Chien , Huang Wei-Chen , Chen Peng-Jen , Chang Wei-Kuo
Published: May 2022

Aim

Approximately 66% of head and neck cancers are diagnosed at an advanced stage. This prospective study aimed to detect newly diagnosed head and neck cancers using regular upper gastrointestinal (UGI) endoscopy with oral-pharynx-larynx examination.

Methods

A total of 2,849 patients underwent UGI endoscopy with an additional oral-pharynx-larynx examination. Patients aged < 20 years, those who were pregnant, had a history of head and neck cancers, were undergoing emergency endoscopy, and had a poor laryngopharyngeal view were excluded. The symptoms, incidence, location, pathology, and stage of malignant neoplasms were investigated.

Results

A total of 2,720 patients were enrolled. Endoscopically observable 23 abnormal findings (0.85%) included 18 (0.66%) benign lesions and 5 (0.18%) newly diagnosed malignant neoplasms. Notably, 4 (80%) of 5 patients with malignant neoplasms were diagnosed at an early stage (Stage 0, I, and II).

Conclusions

UGI endoscopy with oral-pharynx-larynx examination can achieve opportunistic head neck cancer screening and is recommended for every patient in endoscopy units.
Management of Metastatic Endometrial Cancer: Physicians’ Choices Beyond the First Line. A MITO Survey
Authors: Giannone Gaia , Castaldo Daniele , Tuninetti Valentina , Scotto Giulia , Turinetto Margherita , Valsecchi Anna Amela , Bartoletti Michele , Mammoliti Serafina , Artioli Grazia , Mangili Giorgia , Salutari Vanda , Lorusso Domenica , Cormio Gennaro , Zamagni Claudio , Savarese Antonella , Di Maio Massimo , Ronzino Graziana , Pisano Carmela , Pignata Sandro , Valabrega Giorgio
Published: May 2022

Background

Endometrial cancer (EC) therapeutic and diagnostic approaches have been changed by the development of a new prognostic molecular classification, the introduction of dostarlimab in microsatellite instability (MSI) high pre-treated advanced EC patients with further expected innovation deriving from lenvatinib plus pembrolizumab regardless MSI status. How this is and will be translated and embedded in the clinical setting in Italy is not known; this is why we developed Multicentre Italian Trials in Ovarian cancer and gynaecologic malignancies (MITO) survey on the current practice and expected future changes in EC.

Methods

We designed a self-administered, multiple-choice online questionnaire available only for MITO members for one month, starting in April 2021.

Results

75.6% of the respondents were oncologists with a specific focus on gynaecologic malignancies and 73.3% of the respondents declared the availability of clinical trials in second line treatment for advanced EC. The therapeutic algorithm in second line was heterogeneous, being the most frequent choice administering anthracyclines followed by endocrine therapy or enrolling in clinical trials. While more than half of the clinicians declared that they performed the molecular classification, only six/45 respondents (13.3%) ran all the tests needed for it. On the other hand, 80% of them declared regular assessment of MSI status with IHC as recommended. The therapeutic approach in MSI high advanced EC patients has changed since dostarlimab approval. Indeed the most frequent choice in second line has been chemotherapy (53.3%) before its availability, while dostarlimab has been preferred in more than three-fourths of the cases (75.6%) after its approval. As for MSS patients, 77.8% of clinicians would choose lenvatinib plus pembrolizumab for them in second line once approved.

Conclusions

Despite the selected sample of respondents from Italian MITO centres showing good knowledge of diagnostic and therapeutic innovations in EC, these are not fully implemented in everyday clinics, except for MSI status assessment.
Clinical Outcomes and Prognostic Analysis of 101 Patients of Central Neurocytoma: A 10-Year Treatment Experience at a Single Institution
Authors: Xie Qiongxuan , Xie Bin , Ou Ludi , Wang Min , Tang Ziqing , He Yuxiang , Yang Xiaoyu , Hong Jidong , Lyu Zhiping , Wei Rui
Published: May 2022

Objective

Central neurocytoma (CN) is a rare type of tumor that currently lacks an optimal treatment protocol. This study aimed to explore the clinical outcomes of CN in a cohort of 101 patients and identify prognostic factors associated with multiple treatment modalities.

Methods

This monocentric study retrospectively analyzed the clinical data of 101 CN patients who underwent surgical resection. The patients were followed up, and their overall survival (OS) and progression-free survival (PFS) were calculated.

Results

For the entire cohort, the 5- and 10-year OS rates were 88.7% and 82.8%, respectively, and the 5- and 10-year PFS rates were 86.5% and 64.9%, respectively. Of the 82 (81.19%) patients with CN who underwent gross total resection (GTR), 28 (28/82, 34.1%) also received radiotherapy (RT). Of the 19 (18.81%) patients with CN who underwent subtotal resection (STR), 11 (11/19, 57.9%) also received RT or stereotactic radiosurgery (SRS). Compared to STR, GTR significantly improved the 5-year OS (92.4% vs. 72.4%, P=0.011) and PFS (92.4% vs. 60.4%, P=0.009) rates. Radiotherapy did not affect OS in the GTR group (p=0.602), but it had a statistically significant effect on OS in the STR group (P<0.001). However, the OS (P=0.842) and PFS (P=0.915) in the STR plus radiotherapy group were comparable to those in the GTR alone group. Compared to STR alone, STR plus radiotherapy improved the 5-year PFS rate from 25% to 75% in patients with atypical CN (P=0.004). Cox regression models and a competing risk model showed that the removal degree and radiotherapy were independent prognostic factors for survival. With improvements in modern radiotherapy techniques, severe radiotherapy toxicity was not observed.

Conclusion

Our findings support the use of GTR whenever possible. Radiotherapy can improve the prognosis of patients who undergo STR, especially in atypical CNs having a higher tendency to relapse. Close imaging follow-up is necessary. Our findings will help clinicians to select optimal, individualized treatment strategies to improve OS and PFS for patients with CN.
Finite-Size Scaling on a Digital Quantum Simulator Using Quantum Restricted Boltzmann Machine
Authors: Khalid Bilal , Sureshbabu Shree Hari , Banerjee Arnab , Kais Sabre
Published: May 2022

The critical point and the critical exponents for a phase transition can be determined using the Finite-Size Scaling (FSS) analysis. This method assumes that the phase transition occurs only in the infinite size limit. However, there has been a lot of interest recently in quantum phase transitions occurring in finite size systems such as a single two-level system interacting with a single bosonic mode e.g., in the Quantum Rabi Model (QRM). Since these phase transitions occur at a finite system size, the traditional FSS method is rendered inapplicable for these cases. For cases like this, we propose an alternative FSS method in which the truncation of the system is done in the Hilbert space instead of the physical space. This approach has previously been used to calculate the critical parameters for stability and symmetry breaking of electronic structure configurations of atomic and molecular systems. We calculate the critical point for the quantum phase transition of the QRM using this approach. We also provide a protocol to implement this method on a digital quantum simulator using the Quantum Restricted Boltzmann Machine algorithm. Our work opens up a new direction in the study of quantum phase transitions on quantum devices.
Cancer and Associated Therapies Impact the Skeletal Muscle Proteome
Authors: E. L. Dillon , T. J. Wright , A. R. Filley , A. B. Pulliam , K. M. Randolph , C. P. Danesi , C. R. Gilkison , J. E. Wiktorowicz , K. V. Soman , R. J. Urban , M Sheffield-Moore
Published: May 2022

Introduction: Both cancer and cancer associated therapies (CAT; including chemotherapy or concurrent chemoradiation) disrupt cellular metabolism throughout the body, including the regulation of skeletal muscle mass and function. Adjunct testosterone therapy during standard of care chemotherapy and chemoradiation modulates CAT-induced dysregulation of skeletal muscle metabolism and protects lean body mass during CAT. However, the extent to which the skeletal muscle proteome is altered under these therapeutic conditions is unknown.

Objective: We probed the skeletal muscle proteome of cancer patients as an ancillary analysis following a randomized, double-blind, placebo-controlled phase II trial investigating the effect of adjunct testosterone on body composition in men and women with advanced cancers undergoing CAT.

Methods: Men and women diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care CAT were administered an adjunct 7 weeks treatment of weekly intramuscular injections of either 100 mg testosterone (CAT+T, n = 7; 2M/5F) or placebo/saline (CAT+P, n = 6; 4M/2F). Biopsies were performed on the vastus lateralis before (PRE) and after (POST) the 7 weeks treatment. Extracted proteins were separated with 2-dimensional gel electrophoresis (2DE), and subjected to analyses of total protein abundance, phosphorylation and S-nitrosylation. Proteoforms showing significant 1.5 fold differences (t-test p ≤ 0.05) between PRE and POST timepoints were identified by mass spectroscopy (MS), and lists of altered proteins were subjected to Gene Set Enrichment Analysis (GSEA) to identify affected pathways.

Results: A total of 756 distinct protein spots were identified. Of those spots, 102 were found to be altered in terms of abundance, phosphorylation, or S-nitrosylation, and identified by mass spectroscopy analysis to represent 58 unique proteins. Among the biological processes and pathways identified, CAT+P predominantly impacted metabolic processes, cell assembly, oxygen transport, and apoptotic signaling, while CAT+T impacted transcription regulation, muscle differentiation, muscle development, and contraction.

Conclusion: Cancer and CAT significantly altered the skeletal muscle proteome in a manner suggestive of loss of structural integrity, reduced contractile function, and disrupted metabolism. Proteomic analysis suggests that the addition of adjunct testosterone minimized the structural and contractile influence of cancer and its associated therapies.
Development and Validation of a Mechanistic, Weather-Based Model for Predicting Puccinia graminis f. sp. tritici Infections and Stem Rust Progress in Wheat
Authors: Salotti Irene , Bove Federica , Rossi Vittorio
Published: May 2022

Stem rust (or black rust) of wheat, caused by Puccinia graminis f. sp. tritici (Pgt), is a re-emerging, major threat to wheat production worldwide. Here, we retrieved, analyzed, and synthetized the available information about Pgt to develop a mechanistic, weather-driven model for predicting stem rust epidemics caused by uredospores. The ability of the model to predict the first infections in a season was evaluated using field data collected in three wheat-growing areas of Italy (Emilia-Romagna, Apulia, and Sardinia) from 2016 to 2021. The model showed good accuracy, with a posterior probability to correctly predict infections of 0.78 and a probability that there was no infection when not predicted of 0.96. The model’s ability to predict disease progress during the growing season was also evaluated by using published data obtained from trials in Minnesota, United States, in 1968, 1978, and 1979, and in Pennsylvania, United States, in 1986. Comparison of observed versus predicted data generated a concordance correlation coefficient of 0.96 and an average distance between real data and the fitted line of 0.09. The model could therefore be considered accurate and reliable for predicting epidemics of wheat stem rust and could be tested for its ability to support risk-based control of the disease.