bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Architecture of Morphing Wing Based on Hyperelastic Materials and Metastructures With Tunable Stiffness
Authors: Xiao Liping , Zhao Haifeng , Xu Zhao , Li Xiaoyu , Shen Chengcheng , Wang Ke , Zhang Lu
Published: February 2022

Morphing wings with the ability of shape changing may enlarge the flight envelop of air vehicles. This is particularly important for small-scale aircrafts demanding maneuverability and adaptability in dynamic environments. However, to design a shape-changing mechanism suitable for small drones is very challenging due to extreme requirements raised by dimensional constraint, actuating limits, and weight restriction in Micro Air Vehicles (MAVs). A novel design method of morphing wings is proposed for small-scale aircrafts in this paper. The morphing wing is composed of a heterogeneous architecture, including three components: a longitudinal spar with pneumatic actuators, chordwise stiffening ribs with cable-driven metastructures, and a compliant skin. Through employing both pneumatic networks with hyperelastic behavior and modified pantographic metastructures with tunable stiffness, structural deformation along both spanwise and chordwise. Mechanical behaviors of this morphing wing were investigated thoroughly by theorical analysis, numerical verification, and experimental validation. Theorical predictions agree well with the results of 3D Finite Element Method (FEM). With optimal design determined through design of experiment (DOE) and FEM, prototyped morphing wings were fabricated accordingly. The aerodynamic performance was examined by a wind tunnel test with a Particle Image Velocimetry (PIV) instrument. Results demonstrate the efficiency and capacity of this morphing wing to adjust aerodynamic layout of aircraft in a low-speed airflow environment. This proposed design provides a promising solution applicable to small-scale aircrafts with morphing wings.
Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings
Authors: Au Hau Kiu Edna , Isalan Mark , Mielcarek Michal
Published: February 2022

Adeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles to drive long-term transgene expression in gene therapy. While animal studies have shown promising results, the translatability of AAVs into clinical settings has been partly limited due to their restricted gene packaging capacities, off-target transduction, and immunogenicity. In this study, we analysed over two decades of AAV applications, in 136 clinical trials. This meta-analysis aims to provide an up-to-date overview of the use and successes of AAVs in clinical trials, while evaluating the approaches used to address the above challenges. First, this study reveals that the speed of novel AAV development has varied between therapeutic areas, with particular room for improvement in Central Nervous System disorders, where development has been slow. Second, the lack of dose-dependent toxicity and efficacy data indicates that optimal dosing regimes remain elusive. Third, more clinical data on the effectiveness of various immune-modulation strategies and gene editing approaches are required to direct future research and to accelerate the translation of AAV-mediated gene therapy into human applications.
Refining a Protocol for Faecal Microbiota Engraftment in Animal Models After Successful Antibiotic-Induced Gut Decontamination
Authors: Amorim Nadia , McGovern Emily , Raposo Anita , Khatiwada Saroj , Shen Sj , Koentgen Sabrina , Hold Georgina , Behary Jason , El-Omar Emad , Zekry Amany
Published: February 2022

Background

There is mounting evidence for the therapeutic use of faecal microbiota transplant (FMT) in numerous chronic inflammatory diseases. Germ free mice are not always accessible for FMT research and hence alternative approaches using antibiotic depletion prior to FMT in animal studies are often used. Hence, there is a need for standardising gut microbiota depletion and FMT methodologies in animal studies. The aim of this study was to refine gut decontamination protocols prior to FMT engraftment and determine efficiency and stability of FMT engraftment over time.

Methods

Male C57BL/6J mice received an antibiotic cocktail consisting of ampicillin, vancomycin, neomycin, and metronidazole in drinking water for 21 days ad libitum. After antibiotic treatment, animals received either FMT or saline by weekly oral gavage for 3 weeks (FMT group or Sham group, respectively), and followed up for a further 5 weeks. At multiple timepoints throughout the model, stool samples were collected and subjected to bacterial culture, qPCR of bacterial DNA, and fluorescent in-situ hybridisation (FISH) to determine bacterial presence and load. Additionally, 16S rRNA sequencing of stool was used to confirm gut decontamination and subsequent FMT engraftment.

Results

Antibiotic treatment for 7 days was most effective in gut decontamination, as evidenced by absence of bacteria observed in culture, and reduced bacterial concentration, as determined by FISH as well as qPCR. Continued antibiotic administration had no further efficacy on gut decontamination from days 7 to 21. Following gut decontamination, 3 weekly doses of FMT was sufficient for the successful engraftment of donor microbiota in animals. The recolonised animal gut microbiota was similar in composition to the donor sample, and significantly different from the Sham controls as assessed by 16S rRNA sequencing. Importantly, this similarity in composition to the donor sample persisted for 5 weeks following the final FMT dose.

Conclusions

Our results showed that 7 days of broad-spectrum antibiotics in drinking water followed by 3 weekly doses of FMT provides a simple, reliable, and cost-effective methodology for FMT in animal research.
ELP6 and PLIN5 Mutations Were Probably Prognostic Biomarkers for Patients With Gastric Cancer
Authors: Di Ji , Chai Yan , Yang Xin , Dong Haibin , Jiang Bo , Ji Faxiang
Published: February 2022

Purpose

Gastric cancer (GC) is the fifth leading cancer around world. And prognosis of patients with GC is still undesirable. Our study aimed to explore potential prognostic biomarkers for patients with GC.

Methods

The clinical samples were collected from the Qinghai University Affiliated Hospital, which were subjected to the whole exome sequencing (WES). The other GC-related data were obtained from The Cancer Genome Atlas (TCGA) database. Cross analyses were done to determine the candidate genes. And the final mutated genes were determined by survival analyses, univariate and multivariate Cox regression analyses. CIBERSORT and GSEA were used for immune cell infiltration analysis and functional enrichment, respectively.

Results

After cross analyses, 160 candidate-mutated genes were identified. And mutated ELP6 and PLIN5 were significantly independently correlated with the overall survival (OS) of patients with GC. Patients with GC with ELP6 and PLIN5 mutations had worse and better prognosis, respectively. Totally 5 types of immune cells were significantly differentially infiltrated in wild-type and mutated ELP6 and PLIN5 GC samples. In mutated ELP6 and PLIN5 GC samples, totally 7 and 11 pathways were significantly enriched, respectively.

Conclusions

The ELP6 and PLIN5 mutations were probably prognostic biomarkers for patients with GC.
Dry Eye Disease in Patients With Schizophrenia: A Case-Control Study
Authors: Chen Qiankun , Wei Zhengjiang , Wang Leying , Xu Xizhan , Wei Zhenyu , Zheng Panpan , Cao Kai , Zhang Zijun , Chen Kexin , Liang Qingfeng
Published: February 2022

Objective

To evaluate the clinical features and inflammatory cytokines of dry eye disease (DED) in patients with schizophrenia.

Methods

This is a case-control study. The modified self-rating depression scale (M-SDS) and the ocular surface disease index (OSDI) were used to evaluate the symptoms of depression and DED, respectively. Lipid layer thickness (LLT), partial blink rate (PBR), meibomian gland loss (MGL), tear break-up time (TBUT), corneal fluorescein staining, Schirmer I-test, and eyelid margin abnormalities were also measured. A multiplex ELISA Quantibody array was used to detect the inflammatory cytokines in the tears of all participants.

Results

Forty schizophrenic patients and 20 control subjects were included. The mean age was 45.0 ± 9.5 years (range, 22–63 years) in schizophrenic patients and 45.4 ± 16.2 years (range, 23–76 years) in controls (P = 0.914). The ratio of male to female was 1.1 in schizophrenic patients and 1.0 in controls (P = 0.914). Ten women (52.6%) with schizophrenia and 2 (20%) in the control group (P = 0.096) were menopausal or post-menopausal. The OSDI [0.0 (0.0–4.2) vs. 7.3 (2.1–14.6)] and TBUT [4.5 (3.0–6.0) vs. 10.0 (3.5–11.0)] were significantly lower in patients with schizophrenia than in controls (P = 0.003 and P = 0.009, respectively). The rate of MGL [36.5 (17.5–47.5) vs. 8.5 (0.0–17.5)] increased in schizophrenic patients (P < 0.001). Among pro-inflammatory cytokines, the levels of interleukin (IL)-1α, IL-6, IL-11, IL-12A, IL-15, IL-17A, and granulocyte colony-stimulating factor (G-CSF) in tears were elevated in the schizophrenia group (all P < 0.01). Most of the chemokines examined were at increased levels in the tears of schizophrenics (all P < 0.05). The levels of matrix metalloproteinases-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) were also higher in the schizophrenic patients (all P < 0.001). The concentrations of IL-1Ra, tissue-inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in the schizophrenia group were decreased (all P < 0.001). In schizophrenic patients, the level of CCL2 in tears was positively correlated with OSDI (R = 0.34, P = 0.03). The increasing TIMP-1 and decreasing IL-5 were correlated with increasing LLT (R = 0.33, P = 0.035; R = −0.35, P = 0.027, respectively). The level of ICAM-1 was then positively correlated with partial blink rate (PBR) (R = 0.33, P = 0.035). There was a negative correlation between IL-8 and the Schirmer I-test (R = −0.41, P = 0.009).

Conclusions

Patients with schizophrenia were more likely to experience asymptomatic DED, with mild symptoms and obvious signs. The inflammatory cytokines in the tears of schizophrenic patients differed greatly from that of non-schizophrenic patients.
Correlation Between Fe/S/As Speciation Transformation and Depth Distribution of Acidithiobacillus ferrooxidans and Acidiphilium acidophilum in Simulated Acidic Water Column
Authors: Zhou Yu-hang , Wang Can , Liu Hong-chang , Xue Zhen , Nie Zhen-yuan , Liu Yue , Wan Jiao-li , Yang Yu , Shu Wen-sheng , Xia Jin-lan
Published: February 2022

It is well known that speciation transformations of As(III) vs. As(V) in acid mine drainage (AMD) are mainly driven by microbially mediated redox reactions of Fe and S. However, these processes are rarely investigated. In this study, columns containing mine water were inoculated with two typical acidophilic Fe/S-oxidizing/reducing bacteria [the chemoautotrophic Acidithiobacillus (At.) ferrooxidans and the heterotrophic Acidiphilium (Aph.) acidophilum], and three typical energy substrates (Fe2+, S0, and glucose) and two concentrations of As(III) (2.0 and 4.5 mM) were added. The correlation between Fe/S/As speciation transformation and bacterial depth distribution at three different depths, i.e., 15, 55, and 105 cm from the top of the columns, was comparatively investigated. The results show that the cell growth at the top and in the middle of the columns was much more significantly inhibited by the additions of As(III) than at the bottom, where the cell growth was promoted even on days 24–44. At. ferrooxidans dominated over Aph. acidophilum in most samples collected from the three depths, but the elevated proportions of Aph. acidophilum were observed in the top and bottom column samples when 4.5 mM As(III) was added. Fe2+ bio-oxidation and Fe3+ reduction coupled to As(III) oxidation occurred for all three column depths. At the column top surfaces, jarosites were formed, and the addition of As(III) could lead to the formation of the amorphous FeAsO4⋅2H2O. Furthermore, the higher As(III) concentration could inhibit Fe2+ bio-oxidation and the formation of FeAsO4⋅2H2O and jarosites. S oxidation coupled to Fe3+ reduction occurred at the bottom of the columns, with the formations of FeAsO4⋅2H2O precipitate and S intermediates. The formed FeAsO4⋅2H2O and jarosites at the top and bottom of the columns could adsorb to and coprecipitate with As(III) and As(V), resulting in the transfer of As from solution to solid phases, thus further affecting As speciation transformation. The distribution difference of Fe/S energy substrates could apparently affect Fe/S/As speciation transformation and bacterial depth distribution between the top and bottom of the water columns. These findings are valuable for elucidating As fate and toxicity mediated by microbially driven Fe/S redox in AMD environments.
Co-Overexpression of GRK5/ACTC1 Correlates With the Clinical Parameters and Poor Prognosis of Epithelial Ovarian Cancer
Authors: Liu Longyang , Lv Jin , Lin Zhongqiu , Ning Yingxia , Li Jing , Liu Ping , Chen Chunlin
Published: February 2022

Background: The prognosis of epithelial ovarian cancer (EOC) is poor, and the present prognostic predictors of EOC are neither sensitive nor specific.

Objective: The aim of this study was to search the prognostic biomarkers of EOC and to investigate the expression of G protein-coupled receptor kinase 5 (GRK5) and actin alpha cardiac muscle 1 (ACTC1) in EOC tissues (both paraffin-embedded and fresh-frozen tissues) and to explore their association with clinicopathological parameters and prognostic value in patients with EOC.

Methods: A total of 172 paraffin-embedded cancer tissues of EOC patients diagnosed and operated at the memorial hospital of Sun Yat-sen University between December 2009 and March 2017 and 41 paratumor tissues were collected and the expression of GRK5 and ACTC1 was examined using immunohistochemistry. Furthermore, 16 fresh-frozen EOC tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, between August 2013 and November 2019 and subjected to reverse-transcription quantitative PCR analysis to detect the mRNA expression of GRK5 and ACTC1.

Results: The expression of GRK5 and ACTC1 was both higher in cancer tissues than in paratumor tissues. GRK5 expression was positively correlated with ACTC1 expression. In addition, GRK5, ACTC1, and GRK5/ACTC1 expression was associated with the recurrence-free survival and overall survival of EOC patients. Furthermore, multivariate logistic regression analysis indicated that GRK5+/ACTC1+ co-expression, intestinal metastasis, postoperative chemotherapy, platinum resistance, and hyperthermic intraperitoneal chemotherapy were independent prognostic factors of EOC.

Conclusion: GRK5 and ACTC1 are both upregulated in EOC compared with those in paratumor tissues. The co-expression of GRK5+/ACTC1+ rather than GRK5 or ACTC1 is an independent prognostic biomarker of EOC.
PcrA Dissociates RecA Filaments and the SsbA and RecO Mediators Counterbalance Such Activity
Authors: Carrasco Begoña , Moreno-del Álamo María , Torres Rubén , Alonso Juan Carlos
Published: February 2022

PcrA depletion is lethal in wild-type Bacillus subtilis cells. The PcrA DNA helicase contributes to unwinding RNA from the template strand, backtracking the RNA polymerase, rescuing replication-transcription conflicts, and disassembling RecA from single-stranded DNA (ssDNA) by poorly understood mechanisms. We show that, in the presence of RecA, circa one PcrA/plasmid-size circular ssDNA (cssDNA) molecule hydrolyzes ATP at a rate similar to that on the isolated cssDNA. PcrA K37A, which poorly hydrolyses ATP, fails to displace RecA from cssDNA. SsbA inhibits and blocks the ATPase activities of PcrA and RecA, respectively. RecO partially antagonizes and counteracts the negative effect of SsbA on PcrA- and RecA-mediated ATP hydrolysis, respectively. Conversely, multiple PcrA molecules are required to inhibit RecA·ATP-mediated DNA strand exchange (DSE). RecO and SsbA poorly antagonize the PcrA inhibitory effect on RecA·ATP-mediated DSE. We propose that two separable PcrA functions exist: an iterative translocating PcrA monomer strips RecA from cssDNA to prevent unnecessary recombination with the mediators SsbA and RecO balancing such activity; and a PcrA cluster that disrupts DNA transactions, as RecA-mediated DSE.
Risk Factors and Prognosis in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis Requiring Prolonged Mechanical Ventilation
Authors: Lin Jingfang , Xiang Qu , Liu Xu , Li Jinmei
Published: February 2022

Background

Mechanical ventilation (MV) is commonly used in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients with serious conditions. However, little is known about the potential risk factors and long-term outcomes of anti-NMDAR encephalitis requiring MV, especially prolonged MV.

Methods

The data collected prospectively from 305 patients with anti-NMDAR encephalitis were retrospectively reviewed. The functional outcome was assessed using a modified Rankin scale (mRS) every 3 months.

Results

We identified 62 (20.3%) patients who required MV. The most common reasons for MV were decreased consciousness and/or status epilepticus (SE). Among 60 patients analyzed, 27 patients required prolonged MV (>15 days). Prolonged MV primarily was based on the younger age, coma, tumor, and severe pneumonia. During the follow-up (median: 28 months, range: 3–87 months), 77% of patients required MV that exhibited a good outcome. In univariate analysis, prolonged MV, higher levels of C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were found to be associated with poor neurological outcome at 6 months. Although the prolonged MV group exhibited a longer time to achieve a good outcome as compared to the short MV group (median duration 6 months vs. 3 months, p = 0.004), no significant difference was observed between the two groups about long-term outcomes.

Conclusion

It is important to recognize that most anti-NMDAR encephalitis patients who required MV will achieve a favorable long-term outcomes, despite the longer duration of MV. Our results may help clinicians in the ventilator management of severe anti-NMDAR encephalitis patients.
Clinicopathological Features, Prognostic Factors and Survival in Patients With Pancreatic Cancer Bone Metastasis
Authors: Ren Ying , Wang Shicheng , Wu Bo , Wang Zhan
Published: February 2022

Purpose

The purpose of this study is to reveal the clinicopathological features and identify risk factors of prognosis among patients with pancreatic cancer bone metastasis (PCBM).

Patients and Methods

Patients with PCBM were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Independent predictors for survival of those patients were determined by the univariate and multivariate Cox regression analysis. Forest plots were drawn by GraphPad 8.0.1 and used to visually display the results of multivariate analysis.

Results

We identified 2072 eligible PCBM patients, of which 839 patients (40.5%) were female. Patients with age >60 years accounted for 70.6%. Multivariable Cox regression analysis indicated that age, pathological type, chemotherapy, liver metastasis, lung metastasis, and marital status were independent prognostic factors for both overall survival (OS) and cancer-specific survival (CSS). Kaplan–Meier survival curves showed that for patients with PCBM, age ≤60 years, non-ductal adenocarcinoma type, chemotherapy, no liver metastasis, no lung metastasis, and married status were correlated with increased survival. This population-based study showed that 1-year OS and CSS were 13.6% and 13.7%, respectively.

Conclusion

The present study identified six independent predictors of prognosis in PCBM, including age, pathological type, chemotherapy, liver metastasis, lung metastasis, and marital status. Knowledge of these survival predictors is helpful for clinicians to accelerate clinical decision process and design personalized treatment for patients with PCBM.
The Role of the CDK4/6 Inhibitor Ribociclib in Locally Advanced and Oligometastatic Hormone Receptor Positive, Her2 Negative, Advanced Breast Cancer: Case Series and Review of the Literature
Authors: Botticelli Andrea , Fabbri Agnese , Roberto Michela , Alesini Daniele , Cirillo Alessio , D’Auria Giuliana , Krasniqi Eriseld , Marrucci Eleonora , Muratore Margherita , Pantano Francesco , Pizzuti Laura , Portarena Ilaria , Rossi Rosalina , Scagnoli Simone , Marchetti Paolo
Published: February 2022

The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors to endocrine therapy has remarkably improved the outcome of patients affected with hormone receptor positive (HR+), human epidermal grow factor receptor 2 negative (HER2 -) advanced breast cancer (ABC). Ribociclib showed to be effective across most subgroups, regardless of the number and the site of metastasis. Up to 10% of patients with ABC, reported an oligometastatic condition, recently defined as a slow-volume metastatic disease with limited number and size of metastatic lesions (up to 5 and not necessarily in the same organ), potentially amenable for local treatment, aimed at achieving a complete remission status. Despite the wide use of CDK4/6 inhibitors in HR+, HER2-, ABC treatment, data regarding both locally advanced, inoperable disease and oligometastatic conditions are still poor. We reported a review and case series of HR+, HER2-, ABC patients treated with ribociclib as first-line therapy, for a locally advanced and oligometastatic conditions, reporting an impressive response and good safety profile.
Lack of Cardiotoxicity Endpoints in Prospective Trials Involving Chest Radiation Therapy: A Review of Registered, Latter-Phase Studies
Authors: Prasad Rahul N. , Miller Eric D. , Addison Daniel , Bazan Jose G.
Published: February 2022

Background

Chest radiation therapy (RT) has been associated with increased cardiac morbidity and mortality in numerous studies including the landmark Darby study published in 2013 demonstrating a linear increase in cardiac mortality with increasing mean heart radiation dose. However, the extent to which cardiotoxicity has been incorporated as an endpoint in prospective RT studies remains unknown.

Methods

We queried clincaltrials.gov to identify phase II/III trials in lung, esophageal, lymphoma, mesothelioma, thymoma, or breast cancer from 1/1/2006-2/1/2021 enrolling greater than 100 patients wherein chest RT was delivered in at least one treatment arm. The primary endpoint was the rate of inclusion of cardiotoxicity as a specific primary or secondary endpoint in the pre- (enrollment started prior to 1/1/2014) versus post-Darby era using the Chi-square test (p<0.05 considered significant). We also analyzed clinical trial factors associated with the inclusion of cardiotoxicity as an endpoint using logistic regression analysis.

Results

In total, 1,822 trials were identified, of which 256 merited inclusion. 32% were for esophageal, 31% lung, 28% breast, and 7% lymphoma/thymoma/mesothelioma cancers, respectively. 5% (N=13) included cardiotoxicity as an endpoint: 6 breast cancer, 3 lung cancer, 3 esophageal cancer, and 1 lymphoma study. There was no difference in the inclusion of cardiotoxicity endpoints in the pre-Darby versus post-Darby era (3.9% vs. 5.9%, P=0.46). The greatest absolute increase in inclusion of cardiotoxicity as an endpoint was seen for lung cancer (0% vs. 6%, p=0.17) and breast cancer (5.7% vs. 10.8%, p=0.43) studies, though these increases remained statistically non-significant. We found no clinical trial factors associated with the inclusion of cardiotoxicity as an endpoint.

Conclusions

Among prospective trials involving chest RT, cardiotoxicity remains an uncommon endpoint despite its prevalence as a primary source of toxicity following treatment. In order to better characterize cardiac toxicities, future prospective studies involving chest RT should include cardiotoxicity endpoints.
Effects of Concomitant Antibiotics Use on Immune Checkpoint Inhibitor Efficacy in Cancer Patients
Authors: Jiang Shuai , Geng Shuai , Chen Qian , Zhang Chen , Cheng Mengfei , Yu Yang , Zhang Shuo , Shi Ning , Dong Mei
Published: February 2022

Objective

Immune checkpoint inhibitors (ICIs) have changed the outcomes of a variety of cancers in an unprecedented manner. Gut microbiome plays a crucial regulatory role in the antineoplastic therapy of ICIs, which can be influenced by antibiotic (ABX) administration. In this efficacy evaluation, we aimed to clarify the correlations of ABX administration with the survival of cancer patients receiving ICIs treatment.

Method

The eligible literatures were searched using PubMed, Cochrane Library, Web of Science, and Clinical trials.gov databases before Nov 2021. The correlations of ABX administration with progression-free survival (PFS) and overall survival (OS) were determined using Hazard ratios (HRs) coupled with 95% confidence intervals (CIs).

Results

A total of 12 studies enrolling 6010 cancer patients receiving ICIs treatment were included in this efficacy evaluation. ABX administration was significantly correlated worse PFS (HR=1.60, 95%CI=1.33-1.92, P<0.00001) and OS (HR=1.46, 95%CI=1.32-1.61, P<0.00001). Similar results were found in the subgroup analysis of non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and melanoma.

Conclusions

ABX use during ICIs treatment of cancer may significantly shorten PFS and OS. ABX should be used cautiously in cancer patients receiving ICIs. However, further validations are still essential due to existing publication bias.
Impact of Obesity on Major Surgical Outcomes in Ovarian Cancer: A Meta-Analysis
Authors: Cai Benshuo , Li Kang , Li Gang
Published: February 2022

Background

The impact of obesity on the surgical outcomes in patients after primary ovarian cancer surgery is unclear. We aimed at conducting a meta-analysis to evaluate the associations between obesity and major surgical outcomes in ovarian cancer patients.

Method

Embase, PubMed and Web of Science databases were searched for eligible studies. Study-specific relative risks (RR) were pooled using fixed effect model when little evidence of heterogeneity was detected, otherwise random effect model was employed.

Results

Twelve eligible studies were identified. The pooled incidence rates of all complications were 38% (95% CI: 29%, 47%) for obese patients and 27% (95% CI: 18%, 36%) for non-obese patients. Compared with the non-obese patients, there was a significantly increased risk of all complications in obese patients after ovarian cancer surgery, with a pooled RR of 1.75 (95% CI: 1.26, 2.43). For advanced (stages III–IV) ovarian cancer, the pooled RR of all complications was 1.55 (95% CI: 1.07, 2.24). Obese patients after ovarian cancer surgery were at higher risks of wound complication (pooled RR: 7.06, 95% CI: 3.23, 15.40) and infection (pooled RR: 1.94, 95% CI: 1.47, 2.55) compared with non-obese patients. Such increased risk was not observed for other major complications, namely, venous thromboembolism, ileus and organ failure. Hospital stay days between obese patients and non-obese patients were similar (Standardized Mean Difference: −0.28, 95% CI: −0.75, 0.19). The rates of optimal debulking (pooled RR: 0.96, 95% CI: 0.90, 1.03), readmission/return to operation room (pooled RR: 1.20, 95% CI: 0.56, 2.57) and 30-day mortality (pooled RR: 0.95, 95% CI: 0.54, 1.66) were also comparable between obese patients and non-obese patients.

Conclusion

Obesity is associated with an increased risk of postoperative complications, especially wound complications and infection after primary ovarian cancer surgery. Obesity may not affect their optimal debulking rates and 30-day mortality in patients undergoing ovarian cancer surgery. Besides, to improve surgical outcomes, an advanced minimally invasive robotic approach seems to be feasible for the treatment of obese patients with ovarian cancer.
Epidemiology of Hypoxic Community-Acquired Pneumonia in Children Under 5 Years of Age: An Observational Study in Northern India
Authors: Awasthi Shally , Rastogi Tuhina , Pandey Anuj Kumar , Roy Chittaranjan , Mishra Kripanath , Verma Neelam , Kumar Chandra Bhushan , Jain Pankaj Kumar , Yadav Rajesh , Chauhan Abhishek , Mohindra Namita , Shukla Ram Chandra , Agarwal Monika , Pandey Chandra Mani , Kohli Neera
Published: February 2022

Background

Community-acquired pneumonia (CAP) is the leading cause of under-five mortality in India. An increased risk of mortality has been reported in cases of hypoxic pneumonia.

Methods

The primary objective of this study was to assess the proportion of children aged 2–59 months, hospitalized with hypoxic CAP, as well as socio-demographic, clinical, and radiological features associated with it. The secondary objective was to determine the risk of mortality among hospitalized cases of hypoxic CAP. This prospective, observational study was conducted in four districts of Northern India, between January 2015 and April 2021. A hospital-based surveillance network was established. Inclusion criteria were as follows: (a) child between 2 and 59 months, (b) hospitalization with symptoms of WHO-defined CAP, (c) resident of project district, (d) illness of <14 days, and (e) child had neither been hospitalized for this illness nor recruited previously. Children whose chest x-rays (CXRs) were either unavailable/un-interpretable and those that received any dose of pneumococcal conjugate vaccine-13 were excluded. Hypoxic pneumonia was defined as oxygen saturation <90% on pulse oximetry or requiring oxygen supplementation during hospital stay.

Results

During the study period, 71.9% (7,196/10,006) children of severe pneumonia were eligible for inclusion, of whom 35.9% (2,580/7,196) were having hypoxic pneumonia. Female gender and use of biomass fuel for cooking increased the odds of hypoxic CAP. Clinical factors like wheezing, pallor, tachypnea, low pulse volume, presence of comorbidity, general danger signs, severe malnutrition, and radiological finding of primary end-point pneumonia ± other infiltrates (PEP±OI) also increased the odds of hypoxic CAP in a conditional logistic regression model. Adjusted odds ratio for mortality with hypoxia was 2.36 (95% CI: 1.42–3.92).

Conclusion

Almost one-third of cases hospitalized with severe CAP had hypoxia, which increased chances of mortality. Besides known danger signs, certain newer clinical signs such as pallor and wheezing as well as PEP+OI were associated with hypoxic CAP. Therefore, objective assessment of oxygen saturation must be done by pulse oximetry in all cases of CAP at the time of diagnosis.
Case Report: Persistency Pneumococcal Polysaccharide in Cerebrospinal Fluid During a Post Pneumococcal Chronic Aseptic Meningitis: Coincidental or (Auto-)Inflammatory Embers
Authors: Ladeveze Manon , Dumont Yann , Boursier G. , Batteux Frederic , Mahe Perrine , Bensimon Borrull Aurelie , Sarrabay Guillaume , Bollore Karine , Tuaillon Edouard , Godreuil Sylvain , Jeziorski Eric
Published: February 2022

We report the case of a 9-months-old boy that has presented a steroid-dependent post-pneumococcal chronic aseptic meningitis was associated with persistence of pneumococcal cell wall components in cerebrospinal fluid during more than 20 months. Suggesting that this antigenic persistence could be involved in post-infectious manifestations through innate immunity response.
Polyadenylated Telomeric Noncoding RNA Functions as a Pivotal Therapeutic Target of Anti-Ageing to Stabilize Telomere Length of Chromosomes Via Collaborating With Zscan4c
Authors: Xu Xiaojuan , Chen Zhengju , Wu Wei , Tian Xiaohe
Published: February 2022

Telomeres are closely associated with the development of cell aging. Shortening or erosion of telomeres will cause cell mortality, suggesting that the maintenance of telomere integrity facilitates cell anti-senescence. However, the mechanism of how to keep the telomere length remains fragmentary. Here, we found that polyadenylated telomeric noncoding RNA (TERRA) can promote the self-renewal when overexpressed in mouse embryonic stem cells (mESCs), implying that TERRA with polyadenylation is critical for mESC maintenance. Further studies revealed that TERRA with a polyadenylated tail plays an important role in the sustenance of telomere length. High-throughput sequencing and quantitative real-time PCR show that zinc finger and SCAN domain containing 4C (Zscan4c) may be a potential target of TERRA. Zscan4c is negatively regulated by TERRA and collaborates with TERRA to stabilize the telomere length of chromosomes in mESCs. Our study not only identifies TERRA as a potential novel factor of telomere length regulation and uncovers the new molecular mechanism of cell anti-aging, but also indicates that Zscan4c could be a key therapeutic target candidate for therapy in dysfunctional chromosome diseases. These data will expand our understanding of the cell fate regulatory network and will be beneficial to drug discovery and theragnostics for antiaging and anticancer therapy in the future.
Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy
Authors: Honma O. , Watanabe C. , Fukuchimoto H. , Kashiwazaki J. , Tateba M. , Wagatsuma S. , Ogata K. , Maki K. , Sonou H. , Shiga K. , Otsuka E. , Hiruta M. , Hirasawa Y. , Hosonuma M. , Murayama M. , Narikawa Y. , Toyoda H. , Tsurui T. , Kuramasu A. , Kin M. , Kubota Y. , Sambe T. , Horiike A. , Ishida H. , Shimada K. , Umeda M. , Tsunoda T. , Yoshimura K.
Published: February 2022

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire.

Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet’s content and quality, respondents’ satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale.

Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet.

Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.
Systemic Administration of Tempol, a Superoxide Dismutase Mimetic, Augments Upper Airway Muscle Activity in Obese Zucker Rats
Authors: Baby Santhosh M. , Tanner Lisa H. , Discala Joseph F. , Gruber Ryan B. , Hsieh Yee-Hsee , Lewis Stephen J.
Published: February 2022

Obstructive sleep apnea (OSA) is characterized by repetitive partial/complete collapse of the pharynx during sleep, which results in apnea/hypopnea leading to arterial oxygen desaturations and arousals. Repetitive apnea/hypopnea-arousal episodes cause hypoxia/reoxygenation cycles, which increase free radical generation and oxidative stress that cause motor/sensory nerve impairments and muscle damage. We hypothesize that antioxidants may protect and/or reverse from oxidative stress-induced damage in OSA patients. To understand the acute protective effects of antioxidants on respiratory muscles, we studied the systemic effects of a membrane permeable superoxide dismutase mimetic, Tempol, on genioglossus (EMGGG) and diaphragmatic (EMGDIA) electro-myographic activities, hypoglossal motoneuron (HMN) nerve activity and cardiorespiratory parameters (mean arterial blood pressure, heart rate) in adult isoflurane-anesthetized obese Zucker rats (OZR) and age-matched lean Zucker rats (LZR). Tempol dose-dependently (1–100 mg/kg) increased EMGGGwithout changing EMGDIAin OZR and LZR. Tempol increased respiratory rate and tidal volume in OZR and LZR. Tempol (1–25 mg/kg) dose-dependently increased HMN nerve activity in healthy Sprague Dawley rats. Tempol (100 mg/kg) increased EMGGGoutput by 189% in OZR and 163% in LZR. With respect to mechanisms of effect, Tempol (100 mg/kg) did not augment EMGGGafter bilateral HMN transection in Sprague Dawley rats. Although future studies are warranted, available data suggest that in addition to its antioxidant and antihypertensive properties, Tempol can selectively augment EMGGGthrough modulating HMN and this effect may prevent collapsibility and/or improve stability of the upper airway pharyngeal dilator muscles during episodes of partial and/or complete collapse of the upper airway in OSA human subjects.
An Unmatched Radio Frequency Chain for Low-Field Magnetic Resonance Imaging
Authors: Harper Joshua R. , Zárate Cristhian , Krauch Federico , Muhumuza Ivan , Molina Jorge , Obungoloch Johnes , Schiff Steven J.
Published: February 2022

Magnetic Resonance Imaging (MRI) is a safe and versatile diagnostic tool for intracranial imaging, however it is also one of the most expensive and specialized making it scarce in low- to middle-income countries (LMIC). The affordability and portability of low-field MRI offers the potential for increased access to brain imaging for diseases like Hydrocephalus in LMIC. In this tutorial style work, we show the design of a low powered and low cost radio frequency chain of electronics to be paired with a previously reported prepolarized low-field MRI for childhood hydrocephalus imaging in sub-Saharan Africa where the incidence of this condition is high. Since the Larmor frequency for this system is as low as 180 kHz, we are able to minimize the impedance of the transmit coil to 5 ohms rather than match to 50 ohms as is traditionally the case. This reduces transmit power consumption by a factor of 10. We also show the use of inexpensive and commonly available animal enclosure fencing (“chicken wire”) as a shield material at this frequency and compare to more traditional shield designs. These preliminary results show that highly portable and affordable low-field MRI systems could provide image resolution and signal-to-noise sufficient for planning hydrocephalus treatment in areas of the world with substantial resource limitations. Employment of these technologies in sub-Saharan Africa offers a cost-effective, sustainable approach to neurological diagnosis and treatment planning in this disease burdened region.
Effects of Dietary Phenylalanine and Tyrosine Supplements on the Chronic Stress Response in the Seabream (Sparus aurata)
Authors: Salamanca Natalia , Moreno Oscar , Giráldez Inmaculada , Morales Emilio , de la Rosa Ignacio , Herrera Marcelino
Published: February 2022

The increase of aquaculture production is associated with a growing interest in improving physiological status and welfare in fish. For this reason, the search for strategies for mitigating stress has been intensified, with one of these strategies being food supplementation with different amino acids (AA). The objective of this study was to evaluate the effects of dietary phenylalanine (Phe) and tyrosine (Tyr) supplements on the endocrine and physiological state of seabreams (Sparus aurata) subjected to chronic stress. The fish were stocked at 30 fish/tank in a recirculation aquatic system, fed one control diet and two diets supplemented with 5% Phe or Tyr for 90 days. Blood was drawn from 10 fish per tank every 30 days, and the weight and length were measured every 15 days. At the end of the experiment, length/weight of the fish were measured, and they were sacrificed for the extraction of blood, head kidney, liver, and brain. Classic plasma stress markers (glucose, lactate, proteins, and cortisol), as well as hormones derived from Phe and Tyr (adrenaline, norepinephrine, and dopamine) and the accumulation of AA were analyzed. Fish fed with diets supplemented with Phe or Tyr showed a reduction in various stress markers and physiological parameters. In addition, the stress condition favored a mobilization of AA toward the tissues, especially in supplemented diets, so this excess of AA could be used as an energy substrate to cope with stress.
Autonomic Regulation of the Goldfish Intact Heart
Authors: Bazmi Maedeh , Escobar Ariel L.
Published: February 2022

Autonomic regulation plays a central role in cardiac contractility and excitability in numerous vertebrate species. However, the role of autonomic regulation is less understood in fish physiology. Here, we used Goldfish as a model to explore the role of autonomic regulation. A transmural electrocardiogram recording showed perfusion of the Goldfish heart with isoproterenol increased the spontaneous heart rate, while perfusion with carbamylcholine decreased the spontaneous heart rate. Cardiac action potentials obtained via sharp microelectrodes exhibited the same modifications of the spontaneous heart rate in response to isoproterenol and carbamylcholine. Interestingly, the duration of the cardiac action potentials lengthened in the presence of both isoproterenol and carbamylcholine. To evaluate cardiac contractility, the Goldfish heart was perfused with the Ca2+ indicator Rhod-2 and ventricular epicardial Ca2+ transients were measured using Pulsed Local Field Fluorescence Microscopy. Following isoproterenol perfusion, the amplitude of the Ca2+ transient significantly increased, the half duration of the Ca2+ transient shortened, and there was an observable increase in the velocity of the rise time and fall time of the Ca2+ transient, all of which are compatible with the shortening of the action potential induced by isoproterenol perfusion. On the other hand, carbamylcholine perfusion significantly reduced the amplitude of the Ca2+ transient and increased the half duration of the Ca2+ transient. These results are interesting because the effect of carbamylcholine is opposite to what happens in classically used models, such as mouse hearts, and the autonomic regulation of the Goldfish heart is strikingly similar to what has been observed in larger mammalian models resembling humans.
Longer Nap Duration During Ramadan Observance Positively Impacts 5-m Shuttle Run Test Performance Performed in the Afternoon
Authors: Boukhris Omar , Hill David W. , Ammar Achraf , Trabelsi Khaled , Hsouna Hsen , Abdessalem Raouf , Mezghanni Nourhen , Souissi Nizar , Bragazzi Nicola Luigi , Chamari Karim , Chtourou Hamdi
Published: February 2022

It is well-documented that changes in the rhythm of life during Ramadan affect sleep schedules (i.e., interruption of night sleep patterns) and are likely to have negative effects on physical and cognitive performances. The aim of the present study was to examine the effect of different naps opportunities’ durations during Ramadan on performance of short-duration repetitive maximal exercise and perception of effort. Fifteen physically active men (age: 21 ± 3 years, height: 177 ± 6 cm, body-mass: 73 ± 10 kg) performed a 6 × 30-s shuttle run test after a 25-min nap (N25), a 45-min nap (N45), and in a no-nap condition (NN) during three experimental periods: ∼2 weeks before Ramadan (BR), the last ten days of Ramadan (ER), and ∼3 weeks after Ramadan (AR). During the shuttle run test performed in the late afternoon, the greatest distance (GD), the total distance (TD) and a fatigue index (FI) were assessed. Rating of perceived exertion (RPE) was determined after each 30-s effort. Dietary intake and sleep quality were assessed in each of the three periods. Compared to BR, GD and TD were lower in the ER testing period (p = 0.005; d = 0.54) but returned to BR levels in the AR period. During ER, carbohydrate intake was lower (p = 0.04; d = 0.2), and sleep duration and sleep quality were reduced (d = 0.27 and 0.54, respectively), although other aspects of dietary intake and sleep pattern were not affected. Compared to NN, GD and TD were higher after N25 (d = 0.57 and 0.34, respectively) and N45 (d = 0.93 and 0.88 respectively). RPE was lower in N45 (p = 0.035, d = 0.84). N45 resulted in higher TD (p = 0.021, d = 0.13) and lower RPE (p = 0.004; d = 0.57) compared to N25 during ER. Taking a daytime nap benefits subsequent performance in a shuttle run test, whether sleep the previous night was normal (as in BR) or compromised (as in ER). The benefits of napping were greater after a 45-min nap opportunity than after a 25-min nap opportunity.
Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases
Authors: Wang Sijian , Wang Biyao , Shang Dehao , Zhang Kaige , Yan Xu , Zhang Xinwen
Published: February 2022

Astrocytes play an important role in the central nervous system (CNS). Ion channels in these cells not only function in ion transport, and maintain water/ion metabolism homeostasis, but also participate in physiological processes of neurons and glial cells by regulating signaling pathways. Increasing evidence indicates the ion channel proteins of astrocytes, such as aquaporins (AQPs), transient receptor potential (TRP) channels, adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels, and P2X7 receptors (P2X7R), are strongly associated with oxidative stress, neuroinflammation and characteristic proteins in neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). Since ion channel protein dysfunction is a significant pathological feature of astrocytes in neurodegenerative diseases, we discuss these critical proteins and their signaling pathways in order to understand the underlying molecular mechanisms, which may yield new therapeutic targets for neurodegenerative disorders.
Flower Mapping in Grasslands With Drones and Deep Learning
Authors: Gallmann Johannes , Schüpbach Beatrice , Jacot Katja , Albrecht Matthias , Winizki Jonas , Kirchgessner Norbert , Aasen Helge
Published: February 2022

Manual assessment of flower abundance of different flowering plant species in grasslands is a time-consuming process. We present an automated approach to determine the flower abundance in grasslands from drone-based aerial images by using deep learning (Faster R-CNN) object detection approach, which was trained and evaluated on data from five flights at two sites. Our deep learning network was able to identify and classify individual flowers. The novel method allowed generating spatially explicit maps of flower abundance that met or exceeded the accuracy of the manual-count-data extrapolation method while being less labor intensive. The results were very good for some types of flowers, with precision and recall being close to or higher than 90%. Other flowers were detected poorly due to reasons such as lack of enough training data, appearance changes due to phenology, or flowers being too small to be reliably distinguishable on the aerial images. The method was able to give precise estimates of the abundance of many flowering plant species. In the future, the collection of more training data will allow better predictions for the flowers that are not well predicted yet. The developed pipeline can be applied to any sort of aerial object detection problem.