bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor angiogenesis at baseline identified by 18F-Alfatide II PET/CT may predict survival among patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy
Authors: Wei Yuchun , Qin Xueting , Liu Xiaoli , Zheng Jinsong , Luan Xiaohui , Zhou Yue , Yu Jinming , Yuan Shuanghu
Published: February 2022

Background

The study investigated the predictive value of tumor angiogenesis observed by 18F-ALF-NOTA-PRGD2 II (denoted as 18F-Alfatide II) positron emission tomography (PET)/computed tomography (CT) before concurrent chemoradiotherapy (CCRT) for treatment response and survival among patients with locally advanced non-small cell lung cancer (LA-NSCLC).

Methods

Patients with unresectable stage IIIA or IIIB NSCLC (AJCC Cancer Staging 7th Edition) who received CCRT were included in this prospective study. All patients had undergone 18F-Alfatide PET/CT scanning before CCRT, and analyzed parameters included maximum uptake values (SUVmax) of primary tumor (SUVP) and metastatic lymph nodes (SUVLN) and mean uptake value of blood pool (SUVblood). Tumor-to-background ratios (TBRs) and changes in tumor diameter before and after CCRT (ΔD) were calculated. The ratios of SUVP to SUVblood, SUVLN to SUVblood, and SUVP to SUVLN were denoted as TBRP, TBRLN, and T/LN. Short-term treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.

Results

Of 38 enrolled patients, 28 completed CCRT. SUVP, SUVLN, TBRP, TBRLN and T/LN showed significant correlation with PFS (all P < 0.05). SUVP was negatively correlated with OS (P = 0.005). SUVP and TBRP were higher in non-responders than in responders (6.55 ± 2.74 vs. 4.61 ± 1.94, P = 0.039; 10.49 ± 7.58 vs. 7.73 ± 6.09, P = 0.023). ΔD was significantly greater in responders (2.78 ± 1.37) than in non-responders (-0.16 ± 1.33, P < 0.001). Exploratory receiver operating characteristic curve analysis identified TBRP (area under the curve [AUC] = 0.764, P = 0.018), with a cutoff value of 6.52, as the only parameter significantly predictive of the response to CCRT, with sensitivity, specificity, and accuracy values of 71.43%, 78.57%, and 75.00%, respectively. ROC curve analysis also identified SUVP (AUC = 0.942, P < 0.001, cutoff value 4.64) and TBRP (AUC = 0.895, P = 0.001, cutoff value 4.95) as predictive of OS with high sensitivity (84.21%, 93.75%), specificity (100.00%, 66.67%), and accuracy (89.29%, 82.14%).

Conclusions

Evaluation of tumor angiogenesis by 18F-Alfatide II at baseline may be useful in predicting the short-term response to CCRT as well as PFS and OS in patients with LA-NSCLC.
High frequency of PDGFRA and MUC family gene mutations in diffuse hemispheric glioma, H3 G34-mutant: a glimmer of hope?
Authors: Hu Wanming , Duan Hao , Zhong Sheng , Zeng Jing , Mou Yonggao
Published: February 2022

Background

Diffuse hemispheric glioma H3 G34-mutant (G34-DHG) is a new type of pediatric-type diffuse high-grade glioma in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The current treatment for G34-DHG involves a combination of surgery and conventional radiotherapy or chemotherapy; however, the therapeutic efficacy of this approach is not satisfactory. In recent years, molecular targeted therapy and immunotherapy have achieved significant benefits in a variety of tumors. In-depth understanding of molecular changes and immune infiltration in G34-DHGs will help to establish personalized tumor treatment strategies. Here, we report the clinicopathological, molecular and immune infiltration characteristics of G34-DHG cases from our center along with cases from the HERBY Trial and the Chinese Glioma Genome Atlas database (CGGA).

Methods

Hematoxylin–eosin (HE) and immunohistochemistry (IHC) staining were used to present the clinicopathological characteristics of 10 Chinese G34-DHG patients treated at our institution. To address the molecular characteristics of G34-DHG, we performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) analyses of 5 patients from our center and 3 Chinese patients from the Chinese Glioma Genome Atlas (CGGA) database. Additionally, 7 European G34-DHG patients from the HERBY Trail were also subjected to analyses, with 7 cases of WES data and 2 cases of RNA-seq data. Six G34-DHG patients from another organization were used as external validation.

Results

WES showed a high frequency of PDGFRA mutation in G34-DHGs (12/15). We further identified frequent mutations in MUC family genes in G34-DHGs, including MUC16 (8/15) and MUC17 (8/15). Although no statistical difference was found, PDGFRA mutation tended to be an indicator for worse prognosis whereas MUC16/MUC17 mutation indicated a favorable prognosis in G34-DHGs. RNA sequencing results revealed that most G34-DHG are considered to be immune cold tumors. However, one patient in our cohort with MUC16 mutation showed significant immune infiltration, and the total overall survival of this patient reached 75 months.

Conclusions

Our results demonstrate that G34-DHG is a new high-grade glioma with high frequency of PDGFRA and MUC gene family mutations. PDGFRA may serve as an indicator of poor prognosis and an effective therapeutic target. Moreover, MUC16 tends to be a favorable prognostic factor and indicates high immune infiltration in certain patients, and these findings may provide a new direction for targeted therapy and immunotherapy of patients with G34-DHGs.
Mutational signatures reveal ternary relationships between homologous recombination repair, APOBEC, and mismatch repair in gynecological cancers
Authors: Farmanbar Amir , Firouzi Sanaz , Kneller Robert , Khiabanian Hossein
Published: February 2022

Background

Revealing the impacts of endogenous and exogenous mutagenesis processes is essential for understanding the etiology of somatic genomic alterations and designing precise prognostication and treatment strategies for cancer. DNA repair deficiency is one of the main sources of endogenous mutagenesis and is increasingly recognized as a target for cancer therapeutics. The role and prevalence of mechanisms that underly different forms of DNA repair deficiencies and their interactions remain to be elucidated in gynecological malignancies.

Methods

We analyzed 1231 exomes and 268 whole-genomes from three major gynecological malignancies including uterine corpus endometrial carcinoma (UCEC) as well as ovarian and cervical cancers. We also analyzed data from 134 related cell lines. We extracted and compared de novo and refitted mutational signature profiles using complementary and confirmatory approaches and performed interaction analysis to detect co-occurring and mutually exclusive signatures.

Results

We found an inverse relationship between homologous recombination deficiency (HRd) and mismatch repair deficiency (MMRd). Moreover, APOBEC co-occurred with HRd but was mutually exclusive with MMRd. UCEC tumors were dominated by MMRd, yet a subset of them manifested the HRd and APOBEC signatures. Conversely, ovarian tumors were dominated by HRd, while a subset represented MMRd and APOBEC. In contrast to both, cervical tumors were dominated by APOBEC with a small subsets showing the POLE, HRd, and MMRd signatures. Although the type, prevalence, and heterogeneity of mutational signatures varied across the tumor types, the patterns of co-occurrence and exclusivity were consistently observed in all. Notably, mutational signatures in gynecological tumor cell lines reflected those detected in primary tumors.

Conclusions

Taken together, these analyses indicate that application of mutation signature analysis not only advances our understanding of mutational processes and their interactions, but also it has the potential to stratify patients that could benefit from treatments available for tumors harboring distinct mutational signatures and to improve clinical decision-making for gynecological malignancies.
Radiomic analysis for predicting prognosis of colorectal cancer from preoperative 18F-FDG PET/CT
Authors: Lv Lilang , Xin Bowen , Hao Yichao , Yang Ziyi , Xu Junyan , Wang Lisheng , Wang Xiuying , Song Shaoli , Guo Xiaomao
Published: February 2022

Background

To develop and validate a survival model with clinico-biological features and18F- FDG PET/CT radiomic features via machine learning, and for predicting the prognosis from the primary tumor of colorectal cancer.

Methods

A total of 196 pathologically confirmed patients with colorectal cancer (stage I to stage IV) were included. Preoperative clinical factors, serum tumor markers, and PET/CT radiomic features were included for the recurrence-free survival analysis. For the modeling and validation, patients were randomly divided into the training (n = 137) and validation (n = 59) set, while the 78 stage III patients [training (n = 55), and validation (n = 23)] was divided for the further experiment. After selecting features by the log-rank test and variable-hunting methods, random survival forest (RSF) models were built on the training set to analyze the prognostic value of selected features. The performance of models was measured by C-index and was tested on the validation set with bootstrapping. Feature importance and the Pearson correlation were also analyzed.

Results

Radiomics signature (containing four PET/CT features and four clinical factors) achieved the best result for prognostic prediction of 196 patients (C-index 0.780, 95% CI 0.634–0.877). Moreover, four features (including two clinical features and two radiomics features) were selected for prognostic prediction of the 78 stage III patients (C-index was 0.820, 95% CI 0.676–0.900). K–M curves of both models significantly stratified low-risk and high-risk groups (P < 0.0001). Pearson correlation analysis demonstrated that selected radiomics features were correlated with tumor metabolic factors, such as SUVmean, SUVmax.

Conclusion

This study presents integrated clinico-biological-radiological models that can accurately predict the prognosis in colorectal cancer using the preoperative18F-FDG PET/CT radiomics in colorectal cancer. It is of potential value in assisting the management and decision making for precision treatment in colorectal cancer.

Trial registrationThe retrospectively registered study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (No. 1909207-14-1910) and the data were analyzed anonymously.
Vagus nerve stimulation modulates hippocampal inflammation caused by continuous stress in rats
Authors: Namgung Uk , Kim Ki-Joong , Jo Byung-Gon , Park Jong-Min
Published: February 2022

Background

Previous studies have shown that vagus nerve stimulation (VNS) can attenuate inflammatory responses in peripheral tissues and also improve some neurological disorders and cognitive function in the brain. However, it is not clear how VNS is involved in neuropathological processes in brain tissues. Here, we investigated the regulatory effects of VNS on the production of proinflammatory cytokines in the hippocampus of an animal model of continuous stress (CS).

Methods

CS was induced by placing rats in cages immersed with water, and acute or chronic electrical stimulation was applied to the cervical vagus nerve of CS animals. Protein levels in the gastric and hippocampal tissues were measured by western blotting and protein signals analyzed by immunofluorescence staining. von Frey test and forced swimming test were performed to assess pain sensitivity and depressive-like behavior in rats, respectively.

Results

Levels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues were significantly increased in CS animals compared to the untreated control and downregulated by acute VNS (aVNS). Iba-1-labeled microglial cells in the hippocampus of CS animals revealed morphological features of activated inflammatory cells and then changed to a normal shape by VNS. VNS elevated hippocampal expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in CS animals, and pharmacological blockade of α7 nAChR increased the production of TNF-α, IL-1β, and IL-6, thus suppressing cholinergic anti-inflammatory activity that was mediated by VNS. Chronic VNS (cVNS) down-regulated the hippocampal production of active form of caspase 3 and 5-HT1A receptors and also decreased levels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues of CS animals. Pain sensitivity and depressive-like behavior, which were increased by CS, were improved by cVNS.

Conclusions

Our data suggest that VNS may be involved in modulating pathophysiological processes caused by CS in the brain.
Maresin 1 promotes nerve regeneration and alleviates neuropathic pain after nerve injury
Authors: Wei Jinhuan , Su Wenfeng , Zhao Yayu , Wei Zhongya , Hua Yuchen , Xue Peng , Zhu Xiang , Chen Ying , Chen Gang
Published: February 2022

Background

Peripheral nerve injury (PNI) is a public health concern that results in sensory and motor disorders as well as neuropathic pain and secondary lesions. Currently, effective treatments for PNI are still limited. For example, while nerve growth factor (NGF) is widely used in the treatment of PNI to promote nerve regeneration, it also induces pain. Maresin 1 (MaR1) is an anti-inflammatory and proresolving mediator that has the potential to regenerate tissue. We determined whether MaR1 is able to promote nerve regeneration as well as alleviating neuropathic pain, and to be considered as a putative therapeutic agent for treating PNI.

Methods

PNI models were constructed with 8-week-old adult male ICR mice and treated with NGF, MaR1 or saline by local application, intrathecal injection or intraplantar injection. Behavioral analysis and muscle atrophy test were assessed after treatment. Immunofluorescence assay was performed to examine the expression of ATF-3, GFAP, IBA1, and NF200. The expression transcript levels of inflammatory factors IL1β, IL-6, and TNF-α were detected by quantitative real-time RT-PCR. AKT, ERK, mTOR, PI3K, phosphorylated AKT, phosphorylated ERK, phosphorylated mTOR, and phosphorylated PI3K levels were examined by western blot analysis. Whole-cell patch-clamp recordings were executed to detect transient receptor potential vanilloid 1 (TRPV1) currents.

Results

MaR1 demonstrated a more robust ability to promote sensory and motor function recovery in mice after sciatic nerve crush injury than NGF. Immunohistochemistry analyses showed that the administration of MaR1 to mice with nerve crush injury reduced the number of damaged DRG neurons, promoted injured nerve regeneration and inhibited gastrocnemius muscle atrophy. Western blot analysis of ND7/23 cells cultured with MaR1 or DRG neurons collected from MaR1 treated mice revealed that MaR1 regulated neurite outgrowth through the PI3K–AKT–mTOR signaling pathway. Moreover, MaR1 dose-dependently attenuated the mechanical allodynia and thermal hyperalgesia induced by nerve injury. Consistent with the analgesic effect, MaR1 inhibited capsaicin-elicited TRPV1 currents, repressed the nerve injury-induced activation of spinal microglia and astrocytes and reduced the production of proinflammatory cytokines in the spinal cord dorsal horn in PNI mice.

Conclusions

Application of MaR1 to PNI mice significantly promoted nerve regeneration and alleviated neuropathic pain, suggesting that MaR1 is a promising therapeutic agent for PNI.
TNFα-mediated necroptosis in brain endothelial cells as a potential mechanism of increased seizure susceptibility in mice following systemic inflammation
Authors: Huang Wan-Yu , Lai Yen-Ling , Liu Ko-Hung , Lin Shankung , Chen Hsuan-Ying , Liang Chih-Hung , Wu Hung-Ming , Hsu Kuei-Sen
Published: February 2022

Background

Systemic inflammation is a potent contributor to increased seizure susceptibility. However, information regarding the effects of systemic inflammation on cerebral vascular integrity that influence neuron excitability is scarce. Necroptosis is closely associated with inflammation in various neurological diseases. In this study, necroptosis was hypothesized to be involved in the mechanism underlying sepsis-associated neuronal excitability in the cerebrovascular components (e.g., endothelia cells).

Methods

Lipopolysaccharide (LPS) was used to induce systemic inflammation. Kainic acid intraperitoneal injection was used to measure the susceptibility of the mice to seizure. The pharmacological inhibitors C87 and GSK872 were used to block the signaling of TNFα receptors and necroptosis. In order to determine the features of the sepsis-associated response in the cerebral vasculature and CNS, brain tissues of mice were obtained for assays of the necroptosis-related protein expression, and for immunofluorescence staining to identify morphological changes in the endothelia and glia. In addition, microdialysis assay was used to assess the changes in extracellular potassium and glutamate levels in the brain.

Results

Some noteworthy findings, such as increased seizure susceptibility and brain endothelial necroptosis, Kir4.1 dysfunction, and microglia activation were observed in mice following LPS injection. C87 treatment, a TNFα receptor inhibitor, showed considerable attenuation of increased kainic acid-induced seizure susceptibility, endothelial cell necroptosis, microglia activation and restoration of Kir4.1 protein expression in LPS-treated mice. Treatment with GSK872, a RIP3 inhibitor, such as C87, showed similar effects on these changes following LPS injection.

Conclusions

The findings of this study showed that TNFα-mediated necroptosis induced cerebrovascular endothelial damage, neuroinflammation and astrocyte Kir4.1 dysregulation, which may coalesce to contribute to the increased seizure susceptibility in LPS-treated mice. Pharmacologic inhibition targeting this necroptosis pathway may provide a promising therapeutic approach to the reduction of sepsis-associated brain endothelia cell injury, astrocyte ion channel dysfunction, and subsequent neuronal excitability.
Universal Thermal Climate Index (UTCI) and adverse pregnancy outcomes in Ahvaz, Iran
Authors: Khodadadi Narges , Dastoorpoor Maryam , Khanjani Narges , Ghasemi Afsaneh
Published: February 2022

Background

Climate change may jeopardize the health of mothers and their offspring. There are few studies on the association between increasing temperature and pregnancy outcomes. The aim of this study was to investigate the relation between Universal Thermal Climate Index (UTCI) and adverse pregnancy outcomes including stillbirth, low birth weight (LBW), preterm labor (PTL), spontaneous abortion (SA), preeclampsia and hypertension in Ahvaz, Iran.

Methods

Distributed Lag Non-linear Models (DLNM) combined with quasi-Poisson regression were used to research the effect of UTCI on adverse pregnancy outcomes. The effect of time trend, air pollutants (NO2, SO2and PM10), and weekdays were adjusted.

Results

The results showed that the low values of UTCI index (11.6 °C, in lags 0–6, 0–13) caused significant increase in the risk of preterm labor. However, hot thermal stress (high UTCI) significantly increased the risk of stillbirth in lag 0–13. We did not observe any significant relation between UTCI and other pregnancy outcomes in this study.

Conclusions

It seems like both hot and cold weathers can be associated with adverse pregnancy outcomes.
Factors associated with the uptake of long-acting reversible contraception among female sex workers in post-conflict Northern Uganda: a cross-sectional study
Authors: Ouma Simple , Tumwesigye Nazarius Mbona , Abbo Catherine , Ndejjo Rawlance
Published: February 2022

Background

Long-acting reversible contraception (LARC) is the most effective and reliable contraception option for female sex workers (FSWs) who desire future fertility. Unlike the other reversible contraceptive methods, LARC use requires only periodic users’ involvement at the time of application and re-application. However, only a few studies on LARC uptake among FSWs are available in Uganda. To fill this knowledge gap, we examined factors associated with the uptake of LARC among FSWs in post-conflict Northern Uganda.

Methods

We conducted a cross-sectional study among adult FSWs operating in the post-conflict Gulu district in Northern Uganda. We collected quantitative data among 280 FSWs of reproductive ages (18–49 years) who were neither pregnant nor using permanent contraception. We utilized a pretested semi-structured questionnaire to gather information from each participant through face-to-face interviews. We collected data on socio-demographic characteristics, sex work-related characteristics, obstetric history, HIV status, and LARC uptake. Data were then entered into EPI INFO 7, cleaned, and analyzed using multivariable Poisson regression in STATA 14.0 to obtained adjusted prevalence ratios (PR).

Results

Among the study participants: the mean age (SD, range) was 26.5 (5.9, 18–45) years, 48.6% reported at least one unintended pregnancy during sex work, and 37.4% had at least one induced abortion. Meanwhile, only less than two in three (58.6%) participants were using LARC. At multivariable level, factors that remained independently associated with LARC uptake included: longer duration of sex work (adjusted PR = 1.44, 95% CI: 1.03–2.02), higher parity (adjusted PR = 1.13, 95% CI: 1.02–1.26), history of unintended pregnancies during sex work (adjusted PR = 1.24 CI: 1.01–1.51), and being a brothel/lodge-based FSWs (adjusted PR = 1.28, 95% CI: 1.01–1.63).

Conclusions

The above findings revealed a gap in the uptake of LARC among FSWs in post-conflict Northern Uganda influenced by duration of sex work, parity, unintended pregnancies during sex work, and place of sex work. Interventions to improve LARC uptake should target the newly recruited FSWs with low parity and the non-brothel/lodge-based FSWs.
Surgical treatment of chronic Achilles tendon rupture results in improved gait biomechanics
Authors: Nordenholm Anna , Senorski Eric Hamrin , Westin Olof , Nilsson Helander Katarina , Möller Michael , Karlsson Jón , Zügner Roland
Published: February 2022

Background

Chronic Achilles tendon rupture is associated with persistent weakness at push-off with the affected foot and poor balance, resulting in significant alterations to normal gait. Surgical repair is the most common treatment for improving gait in patients with a Chronic Achilles tendon rupture, but, to date, the outcomes have not been quantified in the literature.

Methods

A total of 23 patients with a Chronic Achilles tendon rupture (mean age 61 ± 15 years) underwent three-dimensional gait analysis according to a standardized protocol using an optical tracking system. Data of spatiotemporal, kinematic and kinetic variables were collected preoperatively and one year postoperatively. In addition, the postoperative gait biomechanics were compared with the gait biomechanics of a control group consisting of 70 healthy individuals (mean age 49 ± 20 years). The prospectively collected data were analyzed by an independent t test.

Results

Postoperatively, increments were found in gait speed (mean difference − 0.12 m/s), stride length (− 0.12 m), peak ankle moment (− 0.64 Nm/kg), peak ankle power (− 1.38 W/kg), peak knee power (− 0.36 m) and reduced step width (0.01 m), compared with preoperative gait biomechanics (p < 0.014). Compared with the control group, patients with a Chronic Achilles tendon rupture exhibited slower postoperative gait speed (mean difference 0.24 m/s), wider step width (− 0.02 m), shorter stride length (0.16 m), longer relative stance phase (− 2.15%), lower peak knee flexion (17.03 degrees), greater peak knee extension (2.58 degrees), lower peak ankle moment (0.35 Nm/kg), peak ankle power (1.22 W/kg) and peak knee power (1.62 W/kg), (p < 0.010).

Conclusion

Surgical intervention and postoperative rehabilitation can be an effective treatment for alterations in gait after a Chronic rupture of the Achilles tendon. However, at one year postoperatively, patients still exhibit impairments in spatiotemporal variables and knee and ankle power compared with healthy controls.
The dual roles of autophagy and the GPCRs-mediating autophagy signaling pathway after cerebral ischemic stroke
Authors: Hou Weichen , Hao Yulei , Sun Li , Zhao Yang , Zheng Xiangyu , Song Lei
Published: February 2022

Ischemic stroke, caused by a lack of blood supply in brain tissues, is the third leading cause of human death and disability worldwide, and usually results in sensory and motor dysfunction, cognitive impairment, and in severe cases, even death. Autophagy is a highly conserved lysosome-dependent process in which eukaryotic cells removal misfolded proteins and damaged organelles in cytoplasm, which is critical for energy metabolism, organelle renewal, and maintenance of intracellular homeostasis. Increasing evidence suggests that autophagy plays important roles in pathophysiological mechanisms under ischemic conditions. However, there are still controversies about whether autophagy plays a neuroprotective or damaging role after ischemia. G-protein-coupled receptors (GPCRs), one of the largest protein receptor superfamilies in mammals, play crucial roles in various physiological and pathological processes. Statistics show that GPCRs are the targets of about one-fifth of drugs known in the world, predicting potential values as targets for drug research. Studies have demonstrated that nutritional deprivation can directly or indirectly activate GPCRs, mediating a series of downstream biological processes, including autophagy. It can be concluded that there are interactions between autophagy and GPCRs signaling pathway, which provides research evidence for regulating GPCRs-mediated autophagy. This review aims to systematically discuss the underlying mechanism and dual roles of autophagy in cerebral ischemia, and describe the GPCRs-mediated autophagy, hoping to probe promising therapeutic targets for ischemic stroke through in-depth exploration of the GPCRs-mediated autophagy signaling pathway.
Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID): statistical analysis plan for a randomized controlled trial
Authors: Arabi Yaseen , Aldekhyl Sara , Al Qahtani Saad , Al-Dorzi Hasan M. , Abdukahil Sheryl Ann , Jose Jesna , Al Harbi Mohammad Khulaif , Al Haji Husain , Al Mutairi Mohammed , Al Zumai Omar , Al Qasim Eman , Al Wehaibi Wedyan , Alshahrani Mohammed , Albrahim Talal , Mady Ahmed , Al Bshabshe Ali , Al Aseri Zohair , Al Duhailib Zainab , Kharaba Ayman , Alqahtani Rakan , Algethamy Haifa , Alfaris Omar , Alnafel Omar , Al-Fares Abdulrahman A. , Tlayjeh Haytham
Published: February 2022

Background

Noninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation has multiple advantages over other oxygen support modalities but data about effectiveness are limited.

Methods

In this multicenter randomized trial of helmet noninvasive ventilation for COVID-19 patients, 320 adult ICU patients (aged ≥14 years or as per local standards) with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (ratio of arterial oxygen partial pressure to fraction of inspired oxygen < 200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate of 10 L/min or higher) will be randomized to helmet noninvasive ventilation with usual care or usual care alone, which may include mask noninvasive ventilation, high-flow nasal oxygen, or standard oxygen therapy. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction in 28-day mortality from 40 to 25%. The primary outcome will be compared between the helmet and usual care group in the intention-to-treat using the chi-square test. Results will be reported as relative risk  and 95% confidence interval. The first patient was enrolled on February 8, 2021. As of August 1, 2021, 252 patients have been enrolled from 7 centers in Saudi Arabia and Kuwait.

Discussion

We developed a detailed statistical analysis plan to guide the analysis of the Helmet-COVID trial, which is expected to conclude enrollment in November 2021.

Trial registration

ClinicalTrials.govNCT04477668. Registered on July 20, 2020
Generation of individualized immunocompatible endothelial cells from HLA-I-matched human pluripotent stem cells
Authors: Song Chanchan , Wang Linli , Li Qingyang , Liao Baoyi , Qiao Weihua , Li Qiang , Dong Nianguo , Li Liangping
Published: February 2022

Background

Endothelial cells (ECs) derived from human-induced pluripotent stem cell (iPSC) are a valuable cell resource for cardiovascular regeneration. To avoid time-consuming preparation from primary autologous cells, the allogeneic iPSC-ECs are being expected to become “off-the-shelf” cell products. However, allorejection caused by HLA mismatching is a major barrier for this strategy. Although the “hypoimmunogenic” iPSCs could be simply generated by inhibition of HLA-I expression via β-2 microglobulin knockout (B2M KO), the deletion of HLA-I expression will activate natural killer (NK) cells, which kill the HLA-I negative cells. To inhibit NK activation, we proposed to generate HLA-matched iPSCs based on patient’s HLA genotyping by HLA exchanging approach to express the required HLA allele.

Methods

To establish a prototype of HLA exchanging system, the expression of HLA-I molecules of iPSCs was inhibited by CRISPR/Cas9-mediated B2M KO, and then HLA-A*11:01 allele, as a model molecule, was introduced into B2M KO iPSCs by lentiviral gene transfer. HLA-I-modified iPSCs were tested for their pluripotency and ability to differentiate into ECs. The stimulation of iPSC-EC to allogeneic T and NK cells was detected by respective co-culture of PBMC-EC and NK-EC. Finally, the iPSC-ECs were used as the seeding cells to re-endothelialize the decellularized valves.

Results

We generated the iPSCs only expressed one HLA-A allele (HLA-A *11:01) by B2M KO plus HLA gene transfer. These HLA-I-modified iPSCs maintained pluripotency and furthermore were successfully differentiated into functional ECs assessed by tube formation assay. Single HLA-A*11:01-matched iPSC-ECs significantly less induced the allogeneic response of CD8+ T cell and NK cells expressing matched HLA-A*11:01 and other HLA-A,-B and -C alleles. These cells were successfully used to re-endothelialize the decellularized valves.

Conclusions

In summary, a simple HLA-I exchanging system has been created by efficient HLA engineering of iPSCs to evade both of the alloresponse of CD8+ T cells and the activation of NK cells. This technology has been applied to generate iPSC-ECs for the engineering of cellular heart valves. Our strategy should be extremely useful if the “off-the-shelf” and “non-immunogenic” allogeneic iPSCs were created for the common HLA alleles.
Unlicensed assisted transmission in vehicular edge computing networks
Authors: Ji Zhongbao , Lu Xiao , Yin Rui , Wu Celimuge
Published: February 2022

Recently, the emerging computation-intensive in-vehicle applications and the exponentially growing data have posed a serious challenge to resource-limited in-vehicle devices. By integrating the mobile edge computing (MEC) into the vehicle networks, vehicular edge computing (VEC) is envisioned as a promising solution. In this paper, we divide the VEC system into small time slots, which effectively simulates dense small-scale computing scenarios in the rapidly varying channel environment over time. Furthermore, to alleviate the shortage of spectrum resources, vehicles can offload part of computing tasks to the edge server not only through licensed channels but also through unlicensed channels. However, dynamic topology changes and complex communication characteristics of the vehicle networks lead to the strategies of task offloading and resource allocation being difficult to obtain. By decoupling the non-convex optimizing problem and splitting it into multiple sub-problems, we design a joint power, spectrum and computing resource allocation strategy with low complexity, in order to minimize the total energy consumption of all vehicles for processing tasks. Theoretical analysis and simulation results validate the effectiveness of the proposed scheme that employing licensed and unlicensed access in VEC networks can reduce the energy consumption of vehicles for processing tasks in comparison with baseline schemes.
Analytical analysis of fractional-order sequential hybrid system with numerical application
Authors: Khan Aziz , Khan Zareen A. , Abdeljawad Thabet , Khan Hasib
Published: February 2022

We investigate a general sequential hybrid class of fractional differential equations in the Caputo and Atangana–Baleanu fractional senses of derivatives. We consider the existence and uniqueness of solutions and the Hyers–Ulam (H-U) stability for a general class. We use the Banach and Leray–Schauder alternative theorems for the existence criteria. With the help of nonnegative Green’s functions, the fractional-order class is turned into m-equivalent integral forms. As an application of our problem, a fractional-order smoking model in terms of the Atangana–Baleanu derivative is presented as a particular case.
Confirmation value of Western blotting in detecting anti-treponema pallidum specific antibodies with suspicious results
Authors: Xu Siqi , Li Hongsheng , Wu Xiaoyan , Guo Jianwei , Zhang Jiaoli , Hu Xuqi
Published: February 2022

Background

Due to the inconsistent results of anti-treponema pallidum (TP) specific antibodies by enzyme-linked immunosorbent assay (ELISA) and Treponema pallidum granule agglutination assay (TPPA) in clinical work, there will be a certain proportion of false-positives and false-negatives depending on TPPA as confirmation results. This study aimed to evaluate the necessity of Western blotting (WB) in samples with inconsistent results in detecting anti-TP antibodies by ELISA and TPPA.

Methods

Specific anti-TP test results in our clinical laboratory were retrospectively analyzed. The specimens with a positive or a negative result, but with colored ELISA plates, were retested by TPPA. WB was used to confirm the suspicious results between ELISA and TPPA. The Chi-square test was used to analyze whether the difference was statistically significant.

Results

A total of 106,757 anti-TP specimens were screened by ELISA from August 2018 to December 2019; 3972 were retested by TPPA, and 3809 were positive by TPPA. ELISA and TPPA showed different results in 163 specimens. Among them, 29 specimens were negative and 134 were positive by ELISA; 76 were negative, 23 were positive, and 64 were “reserve” by TPPA; 93 were negative, 31 were positive, and 39 were suspicious by the WB confirmation test. Compared with WB, the difference in the results of ELISA and TPPA was statistically significant.

Conclusions

TPPA is an effective retest method for anti-TP antibody detection. If the results of anti-TP antibodies by ELISA and TPPA are inconsistent, it is necessary to use WB for confirmation.

Trial registration This retrospective analysis is in accordance with the ethical guidelines of China and approved by the second hospital of Jiaxing (jxey-2018048).
Active IgG4-related disease with bone marrow involvement: a report of 2 cases and case-based review
Authors: Liu Shiyi , Wang Hui , Su Tao
Published: February 2022

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease, histopathologically characterized by dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in affected organs. Classic hematologic presentations including lymphadenopathy, eosinophilia and polyclonal hypergammaglobulinemia are common, whereas bone marrow involvement of IgG4-RD is rarely reported. Here we present two patients of multi-organ IgG4-RD with bone marrow involvement, one on bone marrow biopsy, and the other on PET/CT. Presentations of other organ involvement included biopsy-proven IgG4-related tubulointerstitial nephritis, lymphadenopathies, submaxillary glands, arteritis, asthma, dysosmia, and constitutional symptoms. Bone marrow involvement was initially suspected due to leukopenia, anemia and thrombocytopenia in case#1, and was finally confirmed by histological evidence of significant IgG4-positive plasma cells infiltration in bone marrow. In case#2, we incidentally observed high uptakes of multi-bone marrow on 18F-FDG-PET/CT, with the maximum SUV value similar to that of the kidneys, submaxillary glands and hilar, mediastinal lymph nodes by 18F-FDG-PET/CT. Symptoms and all the hematologic presentation improved rapidly in both patients after steroids initiation. These two cases illustrate the rare bone marrow involvement in active IgG4-RD accompanied by other hematologic syndromes. The significance of disease pathogenesis is worthy of further study.
Efficacy of combination triple therapy with vasopressin, steroid, and epinephrine in cardiac arrest: a systematic review and meta-analysis of randomized-controlled trials
Authors: Saghafi Fatemeh , Bagheri Negar , Salehi-Abargouei Amin , Sahebnasagh Adeleh
Published: February 2022

Background

This study investigated whether combination therapy with vasopressin, steroid, and epinephrine (VSE) improves in-hospital survival and return of spontaneous circulation (ROSC) during and after resuscitation in-hospital cardiac arrest (CA).

Materials and methods

Various databases were explored from inception until October 2021 for relevant published clinical trials and cohort studies.

Results

Three clinical trials were included. Pooled analysis suggested that VSE was significantly associated with increased ROSC in patients with in-hospital CA (IHCA) (odds ratio (OR): 2.281, 95% confidence interval (CI): 1.304–3.989, P value = 0.004). Meta-analysis of two studies (368 patients) demonstrated a significant difference in the reduction of mean arterial pressure (MAP) during and 15–20 min after cardiopulmonary resuscitation (standardized mean difference (SMD): 1.069, 95% CI: 0.851–1.288, P value < 0.001), renal failure free days (SMD = 0.590; 95% CI: 0.312–0.869 days; P value < 0.001), and coagulation failure free days (SMD = 0.403; 95% CI: 0.128–0.679, P value = 0.004). However, no significant difference was observed for survival-to-discharge ratio (OR: 2.082, 95% CI: 0.638–6.796, P value = 0.225) and ventilator free days (SMD = 0.201, 95% CI: − 0.677, 1.079 days; P value = 0.838).

Conclusions

VSE combination therapy during and after IHCA may have beneficial effects in terms of the ROSC, renal and circulatory failure free days, and MAP.

Prospero registration: CRD42020178297 (05/07/2020).
River Styles and stream power analysis reveal the diversity of fluvial morphology in a Philippine tropical catchment
Authors: Tolentino Pamela Louise M. , Perez John Edward G. , Guardian Esmael L. , Boothroyd Richard J. , Hoey Trevor B. , Williams Richard D. , Fryirs Kirstie A. , Brierley Gary J. , David Carlos Primo C.
Published: February 2022

Characterisation of hydromorphological attributes is crucial for effective river management. Such information is often overlooked in tropical regions such as the Philippines where river management strategies mainly focus on issues around water quality and quantity. We address this knowledge gap using the River Styles Framework as a template to identify the diversity of river morphodynamics. We identify eight distinct River Styles (river types) in the Bislak catchment (586 km2) in the Philippines, showing considerable geomorphic diversity within a relatively small catchment area. Three River Styles in a Confined valley setting occupy 57% of the catchment area, another three in a partly confined valley setting occupy 37%, and two in the remaining 6% are found in a laterally unconfined valley setting. Five characteristic downstream patterns of River Styles were identified across the catchment. We observe that variation in channel slope for a given catchment area (i.e., total stream power) is insufficient to differentiate between river types. Hence, topographic analyses should be complemented with broader framed, catchment-specific approaches to river characterisation. The outputs and understandings from the geomorphic analysis of rivers undertaken in this study can support river management applications by explicitly incorporating understandings of river diversity and dynamics. This has the potential to reshape how river management is undertaken, to shift from reactive, engineering-based approaches that dominate in the Philippines, to more sustainable, ecosystem-based approaches to management.
Application of generative adversarial networks (GAN) for ophthalmology image domains: a survey
Authors: You Aram , Kim Jin Kuk , Ryu Ik Hee , Yoo Tae Keun
Published: February 2022

Background

Recent advances in deep learning techniques have led to improved diagnostic abilities in ophthalmology. A generative adversarial network (GAN), which consists of two competing types of deep neural networks, including a generator and a discriminator, has demonstrated remarkable performance in image synthesis and image-to-image translation. The adoption of GAN for medical imaging is increasing for image generation and translation, but it is not familiar to researchers in the field of ophthalmology. In this work, we present a literature review on the application of GAN in ophthalmology image domains to discuss important contributions and to identify potential future research directions.

Methods

We performed a survey on studies using GAN published before June 2021 only, and we introduced various applications of GAN in ophthalmology image domains. The search identified 48 peer-reviewed papers in the final review. The type of GAN used in the analysis, task, imaging domain, and the outcome were collected to verify the usefulness of the GAN.

Results

In ophthalmology image domains, GAN can perform segmentation, data augmentation, denoising, domain transfer, super-resolution, post-intervention prediction, and feature extraction. GAN techniques have established an extension of datasets and modalities in ophthalmology. GAN has several limitations, such as mode collapse, spatial deformities, unintended changes, and the generation of high-frequency noises and artifacts of checkerboard patterns.

Conclusions

The use of GAN has benefited the various tasks in ophthalmology image domains. Based on our observations, the adoption of GAN in ophthalmology is still in a very early stage of clinical validation compared with deep learning classification techniques because several problems need to be overcome for practical use. However, the proper selection of the GAN technique and statistical modeling of ocular imaging will greatly improve the performance of each image analysis. Finally, this survey would enable researchers to access the appropriate GAN technique to maximize the potential of ophthalmology datasets for deep learning research.
Coarse-graining and the Haar wavelet transform for multiscale analysis
Authors: Bosl William J. , Loddenkemper Tobias , Vieluf Solveig
Published: February 2022

Background

Multiscale entropy (MSE) has become increasingly common as a quantitative tool for analysis of physiological signals. The MSE computation involves first decomposing a signal into multiple sub-signal ‘scales’ using a coarse-graining algorithm.

Methods

The coarse-graining algorithm averages adjacent values in a time series to produce a coarser scale time series. The Haar wavelet transform convolutes a time series with a scaled square wave function to produce an approximation which is equivalent to averaging points.

Results

Coarse-graining is mathematically identical to the Haar wavelet transform approximations. Thus, multiscale entropy is entropy computed on sub-signals derived from approximations of the Haar wavelet transform. By describing coarse-graining algorithms properly as Haar wavelet transforms, the meaning of ‘scales’ as wavelet approximations becomes transparent. The computed value of entropy is different with different wavelet basis functions, suggesting further research is needed to determine optimal methods for computing multiscale entropy.

Conclusion

Coarse-graining is mathematically identical to Haar wavelet approximations at power-of-two scales. Referring to coarse-graining as a Haar wavelet transform motivates research into the optimal approach to signal decomposition for entropy analysis.
Threats, attacks and defenses to federated learning: issues, taxonomy and perspectives
Authors: Liu Pengrui , Xu Xiangrui , Wang Wei
Published: February 2022

Empirical attacks on Federated Learning (FL) systems indicate that FL is fraught with numerous attack surfaces throughout the FL execution. These attacks can not only cause models to fail in specific tasks, but also infer private information. While previous surveys have identified the risks, listed the attack methods available in the literature or provided a basic taxonomy to classify them, they mainly focused on the risks in the training phase of FL. In this work, we survey the threats, attacks and defenses to FL throughout the whole process of FL in three phases, including Data and Behavior Auditing Phase, Training Phase and Predicting Phase. We further provide a comprehensive analysis of these threats, attacks and defenses, and summarize their issues and taxonomy. Our work considers security and privacy of FL based on the viewpoint of the execution process of FL. We highlight that establishing a trusted FL requires adequate measures to mitigate security and privacy threats at each phase. Finally, we discuss the limitations of current attacks and defense approaches and provide an outlook on promising future research directions in FL.
Comparative study between conventional ultrasound strain elastography and an AI-enabled elastography software in differentiating breast masses
Authors: Kamal Eman Faker , Kamal Rasha Mohamed , Mahmoud Ahmed M. , Mekhaimar Mahmoud Ibrahim , Hanafy Mennatallah Mohamed
Published: February 2022

Background

Conventional ultrasound elastography is a relatively novel noninvasive imaging study that assesses tissue stiffness and helps in the characterization of breast lesions. However, strain elastography is not available in some ultrasound machines especially those before 2003 and is susceptible by motion artifacts. Our aim was to compare the results of conventional ultrasound elastography and the results of an advanced intelligence-enabled elastography software. Also, we aimed to assess the feasibility of the AI-enabled elastography software to overcome the unavailability of the conventional elastography software in some new ultrasound machines.

Results

The study included 53 patients, who had breast lesions either clinically felt or detected during screening. All patients were subjected to both grayscale US imaging and conventional ultrasound elastography; quasi-static compression was applied during acquiring one of the cine-loops of the grayscale US imaging. Also, the cine-loops of the grayscale US imaging while quasi-static compression were processed by an AI-enabled elastography software. Then, the results of the strain ratio (SR) calculated by conventional elastography software and those by AI-enabled elastography software were compared. The strain ratio calculated using the AI-enabled elastography software showed better results than conventional ultrasound elastography strain ratio. The AI-enabled software shows better specificity, sensitivity, positive predictive values, and negative predictive values than the conventional ultrasound elastography.

Conclusion

The AI-enabled elastography software shows promising results compared to the conventional US elastography. Elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer but may complement the conventional US to improve diagnostic performance.