bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of pipeline embolization device vs. traditional coils in embolization of intracranial aneurysms: A systematic review and meta-analysis
Authors: Li Wei , Xiao Zaixing , Zhao Kaixuan , Yang Shijie , Zhang Yichuan , Li Bin , Zhou Yu , Ma Yong , Chai Erqing
Published: September 2022

Introduction

In recent years, the Pipeline embolization device (PED) has been widely used in the embolization of intracranial aneurysms, but there are some inconsistent findings on whether its efficacy and safety are superior to those of traditional coils embolization (coils alone, stent-assisted coils and balloon-assisted coils). The purpose of this meta-analysis was to evaluate the safety and efficacy of PED in intracranial aneurysm embolization by comparing with traditional coils.

Methods

We systematically searched PubMed, Embase, Web of Science, and The Cochrane Library databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the efficacy of PED with traditional coils in intracranial aneurysm embolization published before April 1, 2022. The endpoints observed in this meta-analysis were procedure-related intracranial hemorrhage, procedure-related intracranial ischemia, other procedure-related complications (e.g., aneurysm rupture, neurological impairment, etc.), retreatment rate, complete occlusion (100%) of the aneurysm at the last follow-up, and favorable functional outcome (MRS ≤ 2).

Results

A total of 10 studies with a total of 1,400 patients (PED group: 576 and Traditional coils: 824) were included in this meta-analysis. A comprehensive analysis of the included literature showed that the PED group had a higher rate of complete aneurysm occlusion [OR = 2.62, 95% Cl (1.94, 3.55), p < 0.00001] and Lower re-treatment rate [OR = 0.20, 95% Cl (0.12, 0.34 p < 0.00001)] compared with the traditional coil embolization group at the last follow-up. In terms of procedure-related intracranial hemorrhage [OR = 3.04, 95% Cl (1.08, 8.57), p = 0.04] and other procedure-related complications [OR = 2.91, 95% Cl (1.48, 5.57), p = 0.002], the incidence of PED was higher than that of the traditional coil embolization group. Moreover, in terms of favorable functional outcome [OR = 0.4, 95% Cl (0.22, 0.71), p = 0.002] of patients at the last follow-up, the PED group was lower than the traditional coil embolization group. There was no statistically significant between the two groups in terms of surgery-related intracranial ischemia complications [OR = 0.88, 95% Cl (0.47, 1.64), p = 0.68].

Conclusion

PED had higher rates of complete aneurysm occlusion and lower rates of aneurysm retreatment compared with traditional coils, but traditional coils was superior to the PED group in terms of procedure-related intracranial hemorrhage complication and other procedure-related complications (aneurysm rupture, neurological impairment), and favorable functional outcome (mRS ≤ 2). This result still needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022325673.
HD-tDCS of primary and higher-order motor cortex affects action word processing
Authors: Johari Karim , Riccardi Nicholas , Malyutina Svetlana , Modi Mirage , Desai Rutvik H.
Published: September 2022

The contribution of action-perception systems of the brain to lexical semantics remains controversial. Here, we used high-definition transcranial direct current stimulation (HD-tDCS) in healthy adults to examine the role of primary (left hand motor area; HMA) and higher-order (left anterior inferior parietal lobe; aIPL) action areas in action-related word processing (action verbs and manipulable nouns) compared to non-action-related control words (non-action verbs and non-manipulable nouns). We investigated stimulation-related effects at three levels of semantic processing: subliminal, implicit, and explicit. Broadly, we found that stimulation of HMA and aIPL resulted in relative facilitation of action-related language processing compared to non-action. HMA stimulation facilitated action verb processing in subliminal and implicit task contexts, suggesting that HMA helps represent action verbs even in semantically shallow tasks. HMA stimulation also facilitated manipulable noun comprehension in an explicit semantic task, suggesting that HMA contributes to manipulable noun comprehension when semantic demands are high. aIPL stimulation facilitated both manipulable noun and action verb processing during an implicit task. We suggest that both HMA and aIPL play a functional role in action semantics. HMA plays a general role in the semantics of actions and manipulable objects, while aIPL is important only when visuo-motor coordination is required for the action.
Natural killer cells-related immune traits and amyotrophic lateral sclerosis: A Mendelian randomization study
Authors: Gong Zhenxiang , Liu Yang , Ding Fengfei , Ba Li , Zhang Min
Published: September 2022

Background

Observational studies have suggested that peripheral immune disorders are associated with amyotrophic lateral sclerosis (ALS). Previous studies predominantly focused on changes in adaptive immunity. However, emerging evidence showed natural killer (NK) cells, an essential component of innate immunity, were involved in the degeneration of motor neurons. However, the causal relationship between dysregulated NK cells-related immune traits and ALS remains unclear.

Objective

This study aimed to explore the causal relationship between NK cells-related immune traits and the risk of ALS.

Materials and methods

Single nucleotide polymorphisms (SNPs) significantly associated with NK cells-related immune traits were selected as instrumental variables to estimate their causal effects on ALS. SNPs from a genome-wide association study (GWAS) on NK cells-related immune traits were used as exposure instruments, including an absolute NK-cells count, absolute HLA-DR+ NK-cells count, NK cells/lymphocytes, NK cells/CD3– lymphocytes, HLA DR+ NK cells/NK cells, HLA DR+ NK cells/CD3– lymphocytes, and the median fluorescence intensities of CD16–CD56+ on NK cells and HLA-DR+ NK cells. Summary-level GWAS statistics of ALS were used as the outcome data. Exposure and outcome data were analyzed using the two-sample Mendelian randomization (MR) method.

Results

Each one standard deviation increase in the expression levels of CD16–CD56+ on NK cells and HLA-DR+ NK cells were associated with a lower risk of ALS in both the MR-Egger and inverse variance weighted methods (P < 0.05). The results proved robust under all sensitivity analyses. Neither instrumental outliers nor heterogeneity were detected.

Conclusion

Our results suggest that higher expression levels of CD16–CD56+ on NK cells and HLA-DR+ NK cells are associated with a lower risk of ALS.
Regulation of nuclear factor erythroid-2-related factor 2 as a potential therapeutic target in intracerebral hemorrhage
Authors: Zhang Yuan , Yu Wanpeng , Liu Yingying , Chang Wenguang , Wang Man , Zhang Lei
Published: September 2022

Hemorrhagic stroke can be categorized into several subtypes. The most common is intracerebral hemorrhage (ICH), which exhibits significant morbidity and mortality, affecting the lives of millions of people worldwide every year. Brain injury after ICH includes the primary injury that results from direct compression as well as stimulation by the hematoma and secondary brain injury (SBI) that is due to ischemia and hypoxia in the penumbra around the hematoma. A number of recent studies have analyzed the mechanisms producing the oxidative stress and inflammation that develop following hematoma formation and are associated with the ICH induced by the SBI as well as the resulting neurological dysfunction. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical component in mediating oxidative stress and anti-inflammatory response. We summarize the pathological mechanisms of ICH focusing on oxidative stress and the regulatory role of Nrf2, and review the mechanisms regulating Nrf2 at the transcriptional and post-transcriptional levels by influencing gene expression levels, protein stability, subcellular localization, and synergistic effects with other transcription factors. We further reviewing the efficacy of several Nrf2 activators in the treatment of ICH in experimental ICH models. Activation of Nrf2 might produce antioxidant, anti-inflammatory, and neuron-protection effects, which could potentially be a focus for developing future treatments and prevention of ICH.
Effects of molecular weight on intestinal anti-inflammatory activities of β-D-glucan from Ganoderma lucidum
Authors: Liu Yanfang , Tang Qingjiu , Feng Jie , Liu Jing , Tang Chuanhong , Yan Mengqiu , Zhou Shuai , Liu Liping , Zhou Jing , Zhang Jingsong
Published: September 2022

To investigate the influence of molecular weight (Mw) on the anti-inflammatory activity of β-D-glucan from Ganoderma lucidum, ultrasonic irradiation was applied to treat the β-D-glucan (GLP, 2.42 × 106 g/mol) solution to obtain two degraded fractions with molecular weight of 6.53 × 105 g/mol (GLPC) and 3.49 × 104 g/mol (GLPN). Structural analysis proved that the degraded fractions possessed similar repeated units with the original β-D-glucan. The in vitro anti-inflammatory activity studies showed that all fractions could significantly inhibit LPS-induced expression of cytokines including TNF-α, IL-8, MIF and MCP-1 in Caco-2 cells at certain concentrations. Moreover, GLPC and GLPN exhibited better anti-inflammatory activity than GLPC. The intestinal anti-inflammatory activity evaluated by dextran sulfate sodium (DSS)—induced colitis mice model showed that intragastric administration of GLPN (lower Mw fraction) could significantly recover inflamed tissues of mice. Compared with GLP and GLPC, GLPN exhibited stronger ability to inhibit the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). The results revealed that Mw of β-D-glucan influenced its anti-inflammatory activity and decreasing of Mw would improve the activity, which provided evidence for the potential use of β-D-glucan from G. lucidum as anti-colitis ingredients.
Beyond bariatric surgery and weight loss medicaments. A systematic review of the current practice in obesity rehabilitative inpatient programs in adults and pediatrics
Authors: Spadaccini Daniele , Guazzotti Silvia , Goncalves Correia Filipa Patricia , Daffara Tommaso , Tini Sabrina , Antonioli Alessandro , Aimaretti Gianluca , Marzullo Paolo , Caputo Marina , Antoniotti Valentina , Prodam Flavia
Published: September 2022

Background

Obesity treatment strategies mainly include outpatient lifestyle modification, drugs and bariatric surgery. Voluntary rehabilitative inpatient programs are gaining relevance as potential alternative settings of care that focus on weight loss and prevention of weight regain through a multidisciplinary approach, but their prevalence is still limited due to the high costs.

Aim

Considering the lack of evidence in this area, the objective of this study is to systematically review the currently available literature on non-pharmacological and non-surgical inpatient programs aimed at weight loss, to clarify the efficacy and the characteristics of these interventions.

Methods

Proper English language articles from 2000 to 2022 were searched on relevant databases. Quality assessment was performed by two different authors using ROB2 and robvis tools. Adult and pediatric studies were reviewed separately and their characteristics were systematically displayed.

Results

36 articles were included (20 on adults, 16 on children, and adolescents) for a total of 5,510 individuals. The multidisciplinary approach was mainly comprehensive of a low-calorie diet, scheduled physical activity, and psychological support based on behavioral treatment. Educational and cooking sessions were present at a lower rate. Globally, inpatient weight loss programs showed a consistent efficacy in reducing body weight and inducing beneficial effects on quality of life, psychological well-being, eating behavior, physical performance, and fatigue. Follow-up data were scarce, but with a high percentage of patients regaining weight after a short period.

Conclusion

Weight loss inpatient rehabilitation is a promising area that has evidence of all-rounded success in the amelioration of several aspects related to obesity. Nevertheless, it appears to be quite inconsistent in preserving these benefits after the intervention. This might slow the innovation process in this area and preclude further investments from national healthcare. Personalized and enriched programs could show greater impact when focusing on the behavioral and educational aspects, which are crucial points, in particular in pediatrics, for setting up a long-lasting lifestyle modification. More studies are therefore necessary to evaluate long-term efficacy based on the different work-up models.
Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk
Authors: Marhuenda-Muñoz María , Domínguez-López Inés , Langohr Klaus , Tresserra-Rimbau Anna , Martínez González Miguel Ángel , Salas-Salvadó Jordi , Corella Dolores , Zomeño María Dolores , Martínez J. Alfredo , Alonso-Gómez Angel M. , Wärnberg Julia , Vioque Jesús , Romaguera Dora , López-Miranda José , Estruch Ramón , Tinahones Francisco J. , Lapetra José , Serra-Majem Ll. , Bueno-Cavanillas Aurora , Tur Josep A. , Martín-Sánchez Vicente , Pintó Xavier , Delgado-Rodríguez Miguel , Matía-Martín Pilar , Vidal Josep , Vázquez Clotilde , Daimiel Lidia , Ros Emilio , Toledo Estefanía , Fernández de la Puente Cervera María , Barragán Rocío , Fitó Montse , Tojal-Sierra Lucas , Gómez-Gracia Enrique , Zazo Juan Manuel , Morey Marga , García-Ríos Antonio , Casas Rosa , Gómez-Pérez Ana M. , Santos-Lozano José Manuel , Vázquez-Ruiz Zenaida , Atzeni Alessandro , Asensio Eva M. , Gili-Riu M. Mar , Bullon Vanessa , Moreno-Rodriguez Anai , Lecea Oscar , Babio Nancy , Peñas Lopez Francesca , Gómez Melis Guadalupe , Lamuela-Raventós Rosa M.
Published: September 2022

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [−2.79 mg/dl (95% CI: −4.25, −1.34) and −5.15 mg/dl (95% CI: −7.38, −2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [−0.09% (95% CI: −0.14, −0.03) and −0.15 % (95% CI: −0.23, −0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: −0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [−1.35 mg/dl (95% CI: −2.12, −0.59), p-value: 0.001].
Anti-inflammatory Streptococcus thermophilus CNRZ160 limits sarcopenia induced by low-grade inflammation in older adult rats
Authors: Savary-Auzeloux Isabelle , Jarzaguet Marianne , Migné Carole , Kemeny Jean-Louis , Novais-Gameiro Lorraine , de Azevedo Marcela , Mathé Véronique , Mariotti François , Langella Philippe , Chatel Jean-Marc , Dardevet Dominique
Published: September 2022

Background and aims

Aging is characterized, at the systemic level, by the development of low-grade inflammation, which has been identified as determining sarcopenia by blunting postprandial muscle anabolism. The causes of this “inflammageing” is still not clearly defined. An increased intestinal permeability, a microbiota dysbiosis and subsequent generation of intestinal then generalized inflammation have been hypothesized. The objective of this study was to test in vivo during aging if (1) a chronic low-grade intestinal inflammation can lead to anabolic resistance and muscle loss and (2) if a bacterial strain presenting anti-inflammatory properties could prevent these adverse effects.

Methods

Young adult (6 m) and elderly rats (18 m) received Dextran Sodium Sulfate (DSS) for 28 days to generate low-grade intestinal inflammation, and received (PB1 or PB2 groups) or not (DSS group) one of the two S. Thermophilus strains (5 × 109 CFU/day) previously shown to present an anti-inflammatory potential in vitro. They were compared to pair fed control (PF). Muscle and colon weights and protein synthesis (using 13C Valine) were measured at slaughter. Muscle proteolysis, gut permeability and inflammatory markers were assessed only in old animals by RT-PCR or proteins quantifications (ELISA).

Results

In both adult and old rats, DSS reduced absolute protein synthesis (ASR) in gastrocnemius muscle [−12.4% (PB1) and −9.5% (PB2) vs. PF, P < 0.05] and increased ASR in colon (+86% and +30.5%, respectively vs. PF, P < 0.05). PB1 (CNRZ160 strain) but not PB2 resulted in a higher muscle ASR as compared to DSS in adults (+18%, P < 0.05), a trend also observed for PB1 in old animals (+12%, P = 0.10). This was associated with a blunted increase in colon ASR. In old rats, PB1 also significantly decreased expression of markers of autophagy and ubiquitin-proteasome pathways vs. DSS groups and improved gut permeability (assessed by Occludin, Zonula Occludens 1 and Claudin 1 expression, P < 0.05) and alleviated systemic inflammation (A2M: −48% vs. DSS, P < 0.05).

Conclusion

The loss of muscle anabolism associated with low-grade intestinal inflammation can be prevented by supplementation with anti-inflammatory CNRZ160 strain. We propose that the moderated gut inflammation by CNRZ160 may result in curtailed amino acids (AA) utilization by the gut, and subsequent restored AA systemic availability to support muscle protein accretion. Therefore, CNRZ160 could be considered as an efficient probiotic to modulate muscle mass loss and limit sarcopenia during aging.
Mapping underweight in children using data from the five Ethiopia Demographic and Health Survey data conducted between 2000 and 2019: A geospatial analysis using the Bayesian framework
Authors: Atalell Kendalem Asmare , Alemu Tewodros Getaneh , Wubneh Chalachew Adugna
Published: September 2022

Background and aims

The Sustainable Development Goal is targeted to end all types of malnutrition including underweight by 2030. However, the reduction rate is not as expected to meet the target. Thus, we aimed to investigate the spatiotemporal distributions and drivers of underweight among children aged below 5 years in Ethiopia.

Methods

Geostatistical analysis using the Bayesian framework was conducted to map the spatial and Spatiotemporal distributions of underweight. Data for the primary outcome was obtained from the Ethiopian Demographic and Health Survey 2000–2019. Covariate data were accessed from different credible online sources at high resolutions. Spatial binomial regression was fitted to identify drivers of underweight using the Bayesian approach.

Results

The overall national prevalence of underweight was 44.7, 37.7, 35.4, 25.5, and 23.8% in 2000, 2005, 2011, 2016, and 2019, respectively, with a total reduction rate of 46.8%. Significant spatial clustering of underweight was observed in Northern, Northwestern, Southeastern, Eastern borders, and the border between Oromia and SNNPR regions. Mean annual temperature (mean regression coefficient (β): −0.39; 95% credible interval (95% CrI): −0.63, −0.14), altitude (β:−0.30; 95% CrI: 0.57, −0.05), population density (β:−0.03; 95% CrI: −0.03, −0.02), and distance to water bodies (β:−0.03; 95% CrI: −0.05, −0.004) were negatively associated with being underweight. However, travel time to the nearest cities in minutes (β: 0.09; 95% CrI: 0.03, 0.14) was positively associated with being underweight.

Conclusion

The national prevalence of underweight is reduced slower than expected in Ethiopia, with significant spatial variations across subnational and local levels. Temperature, altitude, population density, and distance to water bodies were negatively associated with underweight, whereas travel time to the nearest cities was positively associated with underweight in Ethiopia. Improving child nutrition through creating awareness and providing clean water should be strengthened.
Radioresistance in rhabdomyosarcomas: Much more than a question of dose
Authors: Camero Simona , Cassandri Matteo , Pomella Silvia , Milazzo Luisa , Vulcano Francesca , Porrazzo Antonella , Barillari Giovanni , Marchese Cinzia , Codenotti Silvia , Tomaciello Miriam , Rota Rossella , Fanzani Alessandro , Megiorni Francesca , Marampon Francesco
Published: September 2022

Management of rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, frequently accounting the genitourinary tract is complex and requires a multimodal therapy. In particular, as a consequence of the advancement in dose conformity technology, radiation therapy (RT) has now become the standard therapeutic option for patients with RMS. In the clinical practice, dose and timing of RT are adjusted on the basis of patients’ risk stratification to reduce late toxicity and side effects on normal tissues. However, despite the substantial improvement in cure rates, local failure and recurrence frequently occur. In this review, we summarize the general principles of the treatment of RMS, focusing on RT, and the main molecular pathways and specific proteins involved into radioresistance in RMS tumors. Specifically, we focused on DNA damage/repair, reactive oxygen species, cancer stem cells, and epigenetic modifications that have been reported in the context of RMS neoplasia in both in vitro and in vivo studies. The precise elucidation of the radioresistance-related molecular mechanisms is of pivotal importance to set up new more effective and tolerable combined therapeutic approaches that can radiosensitize cancer cells to finally ameliorate the overall survival of patients with RMS, especially for the most aggressive subtypes.
LASTR is a novel prognostic biomarker and predicts response to cancer immunotherapy in gastric cancer
Authors: Liu Jun-Yan , Yao Jing , Liu Jia-Jia , He Tao , Wang Fang-Jie , Xie Tian-Yu , Cui Jian-Xin , Yang Xiao-Dong
Published: September 2022

Gastric cancer (GC), a malignant tumor of digestive tract, is characterized by a high death rate. Thus, it is of particular importance to clarify the mechanisms of GC and gain new molecular targets for the sake of preventing and treating GC. It was reported that long non-coding RNAs (IncRNAs) are prognostic factors to cancer. Ferroptosis refers to a process of programmed cell death dependent on iron. This study sets out to investigate the expression and function of ferroptosis-related lncRNA (FRlncRNA) in GC. TCGA datasets offered RNA-seq data for 375 GC patients and clinical data for 443 GC patients. Based on Pearson’s correlation analysis, we studied their expression and identified the FRlncRNAs. Differentially expressed prognosis related to FRlncRNA were determined with the help of the Wilcoxon test and univariate Cox regression analysis. To evaluate the accuracy of the prognostic capacity, researchers used the Kaplan-Meier technique, as well as univariate and multivariate Cox regression and receiver operating characteristic (ROC) curve studies. We also carried out the real-time PCR and CCK8 assays to examine the expression and function of FRlncRNA. In this study, we identified 50 ferroptosis-related DEGs which were involved in tumor progression. In addition, we identified 33 survival-related FRlncRNAs. Among them, lncRNA associated with SART3 regulation of splicing(LASTR) was confirmed to be highly expressed in GC specimens compared to non-tumor specimens in this cohort. Survival assays illuminated that the high LASTR expression predicted a shorter overall survival and progression-free survival of GC patients. Based on multivariate Cox regression analyses, it was confirmed that the GC had a worse chance of surviving the disease overall if their tumors expressed LASTR, which was an independent prognostic indication. Then, Loss-of-function tests showed that knocking down LASTR had a significant effect on reducing the proliferation of GC cells. Finally, we found that the expression of LASTR was negatively associated with CD8 T cells, T cells, Th17 cells, and T helper cells. Overall, our findings identified a novel survival-related FRlncRNA, LASTR which possibly can serve as a novel prognostic biomarker predicting response to cancer immunotherapy and therapeutic target for GC patients.
Upregulation of TIMM8A is correlated with prognosis and immune regulation in BC
Authors: Zhang Yu , Lin Lin , Wu Yunfei , Bing Pingping , Zhou Jun , Yu Wei
Published: September 2022

Backgrounds

Breast cancer is a common malignant tumors in women. TIMM8A was up-regulated in different cancers. The aim of this work was to clarify the value of TIMM8A in the diagnosis, prognosis of Breast Cancer (BC), and its association with immune cells and immune detection points. Gene mutations.

Methods

The transcription and expression profile of TIMM8A between BC and normal tissues was downloaded from The Cancer Genome atlas (TCGA). The expression of TIMM8A protein was evaluated by human protein map. The correlation between TIMM8A and clinical features was analyzed using the R package to establish a ROC diagnostic curve. cBioPortal and MethSurv were used to identify gene alterations and DNA methylation and their effects on prognosis. The tumor immune estimation resource (TIMER) database and tumor immune system interaction database (TISIDB) database were used to determine the relationship between TIMM8A gene expression levels and immune infiltration. The CTD database was used to predict related drugs that inhibit TIMM8A, and the PubChem database was used to determine the molecular structure of potentially effective drug small molecules.

Results

The expression of TIMM8A in breast cancer tissues was significantly higher than that in normally adjacent tissues to cancer. ROC curve analysis showed that the AUC value of TIMM8A was 0.679. Kaplan-Meier method showed that patients with high TIMM8A had a lower prognosis (Overall Survival HR = 1.83 (1.31 − 2.54), P < 0.001) than patients with low TIMM8A expression of breast cancer (148.5 months vs. 115.4 months, P < 0.001). Methylation levels at seven CpG were associated with prognosis. Correlation analysis showed that TIMM8A expression was associated with tumor immune cell infiltration. There was a significant positive correlation of TIMM8A with PDL-1, and CTLA-4 in BC. In addition, CTD database analysis identified 15 small molecular drugs that target TIMM8A, such as Cyclosporine, Leflunomide, and Tretinoin, which might be effective therapies for targeted inhibition of TIMM8A.

Conclusion

In breast cancer, up-regulated TIMM 8A was significantly related to lower survival rate and higher immune invasiveness. Our research showed that TIMM 8A could be used as a biomarker for poor prognosis of breast cancer and a potential target of immunotherapy.
Risk and prognosis of second corpus uteri cancer after radiation therapy for pelvic cancer: A population-based analysis
Authors: Yu Guanhua , Wei Ran , Li Shuofeng , Wang Yongjiao , Liu Hengchang , Chen Tianli , Guan Xu , Wang Xishan , Jiang Zheng
Published: September 2022

Background

Radiation therapy (RT) is a standard treatment for the local control of primary pelvic cancers (PPC), yet the risk of second corpus uteri cancer (SCUC) in PPC patients undergoing RT is still controversial. This study investigated the impact of RT on the risk of SCUC and assessed the survival outcome.

Methods

We queried nine cancer registries for PPC cases in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of SCUC was analyzed using Cox regression and Fine–Gray competing risk regression analysis. The Poisson regression analysis was employed to assess the standardized incidence ratios (SIRs) and radiation-attributed risk (RR) for SCUC. We evaluated the overall survival of patients with SCUC using the Kaplan–Meier method.

Results

Receiving radiotherapy was strongly associated with a higher risk of developing SCUC for PPC patients in Fine–Gray competing risk regression (No-RT vs. RT: adjusted HR = 1.77; 95% CI, 1.40–2.28; p < 0.001). The incidence of SCUC in PPC patients who received RT was higher than in the US general population (SIR, 1.66; 95% CI, 1.41–1.93; p < 0.05), but the incidence of SCUC in patients who did not receive RT was lower than with the US general population (SIR, 0.68; 95% CI, 0.61–0.75; p < 0.05). The dynamic SIR and RR for SCUC decreased with decreasing age at PPC diagnosis and decreased with time progress. In terms of overall survival, 10-year survival rates with SCUC after No-RT (NRT) and SCUC after RT were 45.9% and 25.9% (HR = 1.82; 95% CI, 1.46–2.29; p < 0.001), respectively.

Conclusion

Radiotherapy for primary pelvic cancers is associated with a higher risk of developing SCUC than patients unexposed to radiotherapy. We suggest that patients with pelvic RT, especially young patients, should receive long-term monitoring for the risk of developing SCUC.
An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer
Authors: Xue Zhengfa , Yang Shuxin , Luo Yun , He Ming , Qiao Huimin , Peng Wei , Tong Suxin , Hong Guini , Guo You
Published: September 2022

Background and purpose

Accumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored in LARC in this study.

Material and methods

A novel analytic framework was developed based on within-sample relative expression orderings for identifying tumor immune-associated gene pairs and identified an immuno-score signature from bulk transcriptome profiling analysis of 200 LARC patients. And sequencing and microarray analysis of gene expression was conducted to investigate the association between the signature and response to nCRT, immunotherapy, and cell function of CD4 and CD8. The results were validated using 111 pretreated samples from publicly available datasets in multiple aspects and survival analyses.

Results

The immuno-score signature of 18 immune-related gene pairs (referred to as IPS) was validated on bulk microarray and RNA-Seq data. According to the model’s immune score, LARC patients were divided into high- and low-score groups. The patients with high-score were greater sensitivity to nCRT and immunotherapy, gaining a significantly improved prognosis. In addition, the immune-score gene pair signature was associated with type I anti-tumor T cell responses, positive regulators of T cell functions, and chromosomal instability while reflecting differences between CD8+ T cell subtypes.

Conclusion

The immuno-score signature underlines a key role of tumor immune components in nCRT response, and predicts the prognosis of LARC patients as well.
Novel treatments in optic pathway gliomas
Authors: Maheshwari Akash , Pakravan Mohammad , Charoenkijkajorn Chaow , Beres Shannon J. , Lee Andrew G.
Published: September 2022

Optic pathway gliomas (OPG) are primary tumors of the optic nerve, chiasm, and/or tract that can be associated with neurofibromatosis type 1 (NF1). OPG generally have a benign histopathology, but a variable clinical course. Observation is generally recommended at initial diagnosis if vision is stable or normal for age, however, treatment may include chemotherapy, radiotherapy, or surgery in select cases. This manuscript reviews the literature on OPG with an emphasis on recent developments in treatment.
Remote ischemic postconditioning increased cerebral blood flow and oxygenation assessed by magnetic resonance imaging in newborn piglets after hypoxia-ischemia
Authors: Kerrn-Jespersen Sigrid , Andersen Mads , Bennedsgaard Kristine , Andelius Ted Carl Kejlberg , Pedersen Michael , Kyng Kasper Jacobsen , Henriksen Tine Brink
Published: September 2022

Background

We have previously investigated neurological outcomes following remote ischemic postconditioning (RIPC) in a newborn piglet model of hypoxic-ischemic encephalopathy. The aim of this study was to further investigate potential mechanisms of neuroprotection by comparing newborn piglets subjected to global hypoxia-ischemia (HI) treated with and without RIPC with regards to measures of cerebral blood flow and oxygenation assessed by functional magnetic resonance imaging.

Materials and methods

A total of 50 piglets were subjected to 45 min global HI and randomized to either no treatment or RIPC treatment. Magnetic resonance imaging was performed 72 h after the HI insult with perfusion-weighted (arterial spin labeling, ASL) and oxygenation-weighted (blood-oxygen-level-dependent, BOLD) sequences in the whole brain, basal ganglia, thalamus, and cortex. Four sham animals received anesthesia and mechanical ventilation only.

Results

Piglets treated with RIPC had higher measures of cerebral blood flow in all regions of interest and the whole brain (mean difference: 2.6 ml/100 g/min, 95% CI: 0.1; 5.2) compared with the untreated controls. They also had higher BOLD values in the basal ganglia and the whole brain (mean difference: 4.2 T2*, 95% CI: 0.4; 7.9). Measures were similar between piglets treated with RIPC and sham animals.

Conclusion

Piglets treated with RIPC had higher measures of cerebral blood flow and oxygenation assessed by magnetic resonance imaging in the whole brain and several regions of interest compared with untreated controls 72 h after the HI insult. Whether this reflects a potential neuroprotective mechanism of RIPC requires further study.
Ophthalmomyiasis in a preterm neonate resulting in blindness: A case report from Botswana
Authors: Nakstad Britt , Zandile Yeni , Gaebolae Kesiilwe , Banda Francis Msume , Dinotshe Tebo , Imran Fizzah , Gezmu Alemayehu Mekonnen
Published: September 2022

Myiasis is an infestation of human tissue by insect larvae. While rare, healthcare-associated myiasis has been reported from immobilized patients in resource-limited healthcare facilities in warm climates without adequate vector control measures. We describe a case of Ophthalmomyiasis in a hospitalized neonate in Botswana that resulted in vision loss. The neonate, who was initially hospitalized due to the complications of prematurity, received phototherapy for jaundice, and to avoid phototherapy-related retinopathy, the neonate’s eyes were covered using cotton gauze and adhesive tapes that potentially damaged the skin as commercially available eye covering was not in stock. Therefore, eye covering was not changed and when the eye covering was removed almost 3 days after placement, insect larvae were noted in the patient’s eyes and nose. Ophthalmologic evaluation revealed perforated corneal ulcer and uveal prolapse in the right eye resulting in complete blindness and corneal scarring of the left eye. The patient’s clinical course was further complicated by an Enterobacter species bloodstream infection. This case highlights the importance of vector control as a major patient safety measure for neonatal units in warm climates. Flies had been observed in the room and mitigation measures included reducing fly populations through traps, screens, and removal of standing water and leftover food. Every mother and staff were sanitizing hands when entering the room and gowns were used. This case also reinforces the importance to conduct vigilant monitoring of patients, especially neonates with eyes covered during phototherapy.
Identifying optimal PD-1/PD-L1 inhibitors in first-line treatment of patients with advanced squamous non-small cell lung cancer in China: Updated systematic review and network meta-analysis
Authors: Zhao Mingye , Shao Taihang , Ren Yinan , Zhou Caicun , Tang Wenxi
Published: September 2022

Objective:After Gemstone-302 was published in Lancet in January 2022, seven PD-(L)1 inhibitors launched or about to be launched in China, but there are no head-to-head RCTs reporting the comparative efficacy for squamous non-small cell lung cancer (sq-NSCLC). Therefore, we aimed to indirectly compare the efficacy of these treatments to provide evidence for clinical decision and Chinese national reimbursement drug listing.

Methods:We collected phase III clinical trials targeted on stage IIIB–IV patients for first-line immunotherapy of sq-NSCLC by systematically searching databases. Relative effects of competing treatments were assessed by Bayesian network meta-analysis and non-parametric restricted mean survival time (RMST) model. Hazard ratio (HR), severe adverse events (SAEs, grade 3–5), progression-free survival (PFS) and overall survival (OS) years were the outcomes. Subgroup analysis was done according to PD-(L)1 expression, smoking, gender, Eastern Cooperative Oncology Group performance status, age and disease stage. Sensitivity analysis using the range of parameters distribution as well as different comparison methods was performed to test the robustness of the results.

Results:A total of 7 clinical trials with 2,640 patients were included. For OS, the efficiency (HR, 95%CI) ranks from high to low were sugemalimab (0.48, 0.32–0.73), camrelizumab (0.55, 0.40–0.76), sintilimab (0.56, 0.35–0.90), pembrolizumab (0.71, 0.58–0.87) and atezolizumab (0.88, 0.73–1.05). For PFS, the efficiency ranks from high to low were sugemalimab (0.33, 0.24–0.45), camrelizumab (0.37, 0.30–0.46), tislelizumab (0.53, 0.36–0.79), sintilimab (0.54, 0.42–0.69), toripalimab (0.56, 0.38–0.83), pembrolizumab (0.57, 0.47–0.70) and atezolizumab (0.71, 0.59–0.85). Proportional hazard models and non-proportional hazard models showed consistent efficiency ranks. When extrapolated to long-term survival benefit, under non-proportional hazard ratio, sugemalimab achieved the highest PFS benefit (lifeyears, LYs) in 2 years (1.323), with camrelizumab (1.320), sintilimab (1.243), tislelizumab (1.189), pembrolizumab (0.990) and atezolizumab (0.947) ranking in order; Camrelizumab achieved the highest OS benefit (LYs) in 10 years (2.723), with atezolizumab (2.445) and pembrolizumab (2.397) ranking in order. RMST model showed similar results. In terms of safety, PD-(L)1 inhibitors increased the incidence of SAEs when combined with chemotherapy, sugemalimab and camrelizumab was the safest drugs.

Conclusion:Sugemalimab is superior both in HR and long-term survival benefit for Chinese patients with advanced sq-NSCLC.
Study and exploration of the pharmacokinetics of traditional Tibetan medicine Ruyi Zhenbao tablets after single and long-term administration
Authors: Hou Hongping , Chen Tengfei , Xu Ziying , Yu Zihui , Wang Caixia , Liu Rongxia , Peng Bo , Yang Wei , Li Feng , Che Xiangyi , Li Bing , Wang Yu , Song Ling , Gao Yunhang , Ye Zuguang , Zhang Guangping
Published: September 2022

Tibetan medicine is one of the oldest traditional medicine systems in the world. Taking the Ruyi Zhenbao tablet (RYZB) as an example, which is a widely used classic oral Tibetan medicine, this article discusses the pharmacokinetics of single administration and long-term treatment and analyzed its metabolic properties and tissue distribution in vivo. After single administration, blood samples were collected before administration and at different time points after administration in different groups of rats. In the study of long-term treatment effects, blood samples were collected from the animals in each group on days 1, 15, and 30 and on day 15 after withdrawal. The results showed that after a single administration, the dose change had no significant effect on the T1/2 and Tmax of agarotetrol, isoliquiritigenin, and piperine (p > 0.05). There was a certain correlation between the increase in AUC0-t and the Cmax of agarotetrol, isoliquiritigenin, piperine, and the increase in dosage, with a dose range of 0.225–0.900 g/kg. There were no significant differences in Cmax and AUC0-t of ferulic acid at different doses (p > 0.05). Meanwhile, there was no significant sex-based difference in the pharmacokinetic parameters of these four components in rats. After long-term administration, the distribution agarotetrol in various tissues of rats was kidney > liver > heart > brain; the tissue distribution in low- and medium-dose groups of isoliquiritigenin was liver > kidney > heart > brain, and in the high-dose group, kidney > liver > heart > brain. The tissue distribution of piperine in each dose group was liver > kidney > heart > brain, and that of ferulic acid in each dose group was kidney > liver > heart > brain. Through the establishment of the previously developed methodology, the pharmacokinetic properties of RYZB were analyzed after a single administration and long-term administration. Our findings confirmed this approach for the exploration and establishment of a pharmacokinetic evaluation of Tibetan medicine, to support its guiding role in clinical application, but also to accelerate research into Tibetan medicine theory and medicine and to provide a solid foundation for the translation of Tibetan medicine throughout the world.
Inherited and acquired vitamin B12 deficiencies: Which administration route to choose for supplementation?
Authors: Elangovan Ramyia , Baruteau Julien
Published: September 2022

Vitamin B12 or cobalamin deficiency is a commonly encountered clinical scenario and most clinicians will have familiarity prescribing Vitamin B12 to treat their patients. Despite the high prevalence of this condition, there is widespread heterogeneity regarding routes, schedules and dosages of vitamin B12 administration. In this review, we summarise the complex metabolic pathway of Vitamin B12, the inherited and acquired causes of Vitamin B12 deficiency and subsequently highlight the disparate international practice of prescribing Vitamin B12 replacement therapy. We describe the evidence base underpinning the novel sublingual, intranasal and subcutaneous modes of B12 replacement in comparison to intramuscular and oral routes, with their respective benefits for patient compliance and cost-saving.
Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis
Authors: Xiang Shate , Zhang Jingjing , Zhang Mengge , Qian Suhai , Wang Rongyun , Wang Yao , Xiang Yingshi , Ding Xinghong
Published: September 2022

Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE.

Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16.

Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs.

Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].
Spatio-temporal dynamics in the mixed fractional nonlinear Schrödinger equation
Authors: Aceves Alejandro , Copeland Austin
Published: September 2022

The effective engineering of linear and nonlinear optical properties in photonic media has led to new advances in the theory and applications of spatio-temporal light–matter interactions. In some instances, research has been motivated by phenomena in a quantum mechanical framework; two notable examples being Anderson localization and parity–time symmetry. Herein, we present theoretical and numerical results on light propagation in the presence of fractional diffraction and classical dispersion, highlighting the role mixed functionality has on stability, spatio-temporal localization, and possible collapse events.
Temporal dusty plasma afterglow: A review
Authors: Couëdel Lénaïc
Published: September 2022

In complex plasmas, dust particles are charged through their interactions with the electrons and ions of the surrounding plasma. In low-temperature laboratory plasmas, dust particles most commonly acquire a negative charge. In particular, in a laboratory glow-discharge plasma, the typical charge for a micrometer-size grain generally attains a few thousands of electronic charges. Under stable discharge conditions, this large negative charge is relatively well-characterized. However, for unsteady discharge conditions, the charge can differ and even fluctuate. In particular, when the power source of the discharge is turned off, the charged species of the plasma diffuse away and recombine into neutral species: this is a temporal afterglow. When dust particles are present inside a temporal plasma afterglow, the diffusion of charged species and the plasma decay dynamics are affected. Moreover, the dust particle charges also evolve during the afterglow period. In the late afterglow, dust particles are known to keep residual charges. The value of these residual charges strongly depends on the ambipolar-to-free diffusion transition. In addition, the presence of a constant electric field, causing ions to drift through the neutral gas, has a strong influence on the final dust particle residual charges, eventually leading to large positive residual charges. In this review article, the dynamics of temporal complex plasma afterglow are discussed. Experimental and theoretical results are presented. The basics of temporal afterglow modeling are also given.
Topological defects of dipolar bose-einstein condensates with dresselhaus spin-orbit coupling in an anharmonic trap
Authors: Yang Hui , Gao Yan , Yu Bo , Zhang Jinhua
Published: September 2022

We consider the topological defects and spin structures of binary Bose-Einstein condensates (BECs) with Dresselhaus spin-orbit coupling (D-SOC) and dipole-dipole interaction (DDI) in an anharmonic trap. The combined effects of D-SOC, DDI and anharmonic trap on the ground-state phases of the system are analyzed. Our results show various structural phase transitions can be achieved by adjusting the magnitudes of the D-SOC and DDI. Meantime, a ground-state phase diagram is given as a function of the D-SOC and DDI strengths. In addition, we find that tuning the D-SOC and the DDI can derive novel rich topological configurations, including ghost vortex, half-quantum vortex, skyrmion pair, vertical skyrmion string and horizontal skyrmion string.