bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Gastrointestinal Disorders in Patients With Epilepsy: Reciprocal Influence and Impact on Seizure Occurrence
Authors: Avorio Federica , Cerulli Irelli Emanuele , Morano Alessandra , Fanella Martina , Orlando Biagio , Albini Mariarita , Basili Luca M. , Ruffolo Gabriele , Fattouch Jinane , Manfredi Mario , Russo Emilio , Striano Pasquale , Carabotti Marilia , Giallonardo Anna T. , Severi Carola , Di Bonaventura Carlo
Published: August 2021

Introduction: The complex relationship between the microbiota-gut-brain axis (MGBA) and epilepsy has been increasingly investigated in preclinical studies. Conversely, evidence from clinical studies is still scarce. In recent years, the pivotal role of MGBA dysregulation in the pathophysiology of functional gastrointestinal disorders (FGID) has been recognized. With this background, we aimed to investigate the prevalence of FGID in patients with epilepsy (PWE) and the possible impact of bowel movement abnormalities on seizure recurrence.

Methods: A total of 120 PWE and 113 age-, sex-, and BMI-matched healthy subjects (HS) were consecutively enrolled. A questionnaire to evaluate the presence of FGID (according to Rome III diagnostic criteria) was administrated to all participants. In a subgroup of drug-resistant patients, we administered an ad-hoc questionnaire combining Bristol stool charts and seizure diaries to evaluate seizure trends and bowel movement changes.

Results: A higher prevalence of FGID in PWE (62.5%) than in HS (39.8%) was found (p < 0.001). The most frequently observed disorder was constipation, which was significantly higher in PWE than in HS (43.3 vs. 21.2%, p < 0.001), and was not associated with anti-seizure medication intake according to multivariable analysis. In drug-resistant patients, most seizures occurred during periods of altered bowel movements, especially constipation. A significant weak negative correlation between the number of days with seizures and the number of days with normal bowel movements was observed (p = 0.04). According to multivariable logistic regression analysis, FGID was significantly associated with temporal lobe epilepsy as compared with other lobar localization (p = 0.03).

Conclusions: Our clinical findings shed new light on the complex relationship between epilepsy and the MGBA, suggesting a bidirectional link between bowel movement abnormalities and seizure occurrence. However, larger studies are required to better address this important topic.
The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation
Authors: Chen Liangpei , Yan He , Wang Yufang , He Ziping , Leng Qihao , Huang Shihao , Wu Feilong , Feng Xiangyang , Yan Jie
Published: August 2021

Drug addiction can be seen as a disorder of maladaptive learning characterized by relapse. Therefore, disrupting drug-related memories could be an approach to improving therapies for addiction. Pioneering studies over the last two decades have revealed that consolidated memories are not static, but can be reconsolidated after retrieval, thereby providing candidate pathways for the treatment of addiction. The limbic–corticostriatal system is known to play a vital role in encoding the drug memory engram. Specific structures within this system contribute differently to the process of memory reconsolidation, making it a potential target for preventing relapse. In addition, as molecular processes are also active during memory reconsolidation, amnestic agents can be used to attenuate drug memory. In this review, we focus primarily on the brain structures involved in storing the drug memory engram, as well as the molecular processes involved in drug memory reconsolidation. Notably, we describe reports regarding boundary conditions constraining the therapeutic potential of memory reconsolidation. Furthermore, we discuss the principles that could be employed to modify stored memories. Finally, we emphasize the challenge of reconsolidation-based strategies, but end with an optimistic view on the development of reconsolidation theory for drug relapse prevention.
The Food Bank and Food Pantries Help Food Insecure Participants Maintain Fruit and Vegetable Intake During COVID-19
Authors: Bertmann Farryl , Rogomentich Katherine , Belarmino Emily H. , Niles Meredith T.
Published: August 2021

Charitable food services, including food banks and pantries, support individual and households' food access, potentially maintaining food security and diet quality during emergencies. During the COVID-19 pandemic, the use of food banks and pantries has increased in the US. Here we examine perceptions of food banks and food pantries and their relationship to food security and fruit and vegetable (FV) intake during the first 6 months of the COVID-19 pandemic, using a statewide representative survey (n = 600) of residents of Vermont. The utilization of food pantries was more common among food insecure households and households with children. Among food insecure respondents, those who did not use a food pantry were significantly more likely to report consuming less FV during the pandemic. Further, we find respondents who are food insecure and using a food pantry report consuming more FV since the onset of the COVID-19 pandemic. We found that respondents who were both food insecure and reported not using a food pantry were significantly more likely to report both a reduction in fruit consumption (b = −0.58; p = 0.001) and a reduction in vegetable consumption (b = −0.415; p = 0.012). These results indicate that these services may support food access and one important dimension of diet quality (FV intake) for at-risk populations during emergencies.
Profiling Analysis of Volatile and Non-volatile Compounds in Vitis Vinifera Berries (cv. Chardonnay) and Spontaneous Bud Mutation
Authors: Zheng Ting , Zhang Saihang , Leng Xiangpeng , Sadeghnezhad Ehsan , Li Teng , Pervaiz Tariq , Liu Fanqi , Jia Haifeng , Fang Jinggui
Published: August 2021

A novel clonal variety ofVitis viniferawas identified from “Chardonnay” using inter-simple sequence repeat (ISSR) markers and called “bud mutation. ” The metabolomic profiles in Chardonnay and bud mutation berries indicated essential differences in the expression of key genes in the pathways of 2-C-methyl-D-erythritol-4-phosphate (MEP) and lipoxygenase-hydroperoxide lyase (LOX-HPL). Bud mutation fruits also matured 10 days earlier than Chardonnay and have higher carotenoid, sugar, and acidic compound contents. Furthermore, the gene expression was examined in the biosynthetic pathways of two ripening-associated hormones, abscisic acid (ABA) and jasmonic acid (JA), which significantly increased in bud mutation compared with the Chardonnay fruit. The synthesis and metabolism of amino acids, terpenes, fatty acids, volatile components, and specialized metabolites significantly increased in bud mutation. Therefore, in comparison with Chardonnay, bud mutation is considered a highly aroma-producing grape variety for an improvement in the beverage industry.
Safety and Effectiveness of High-Precision Hyperthermic Intraperitoneal Perfusion Chemotherapy in Peritoneal Carcinomatosis: A Real-World Study
Authors: Ba Mingchen , Cui Shuzhong , Long Hui , Gong Yuanfeng , Wu Yinbing , Lin Kunpeng , Tu Yinuo , Zhang Bohuo , Wu Wanbo
Published: August 2021

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been reported to effectively control peritoneal carcinomatosis (PC) in various patient populations, but there is a lack of real-world data. This study aimed to examine the safety and effectiveness of HIPEC in patients with PC in a real-world setting.

Methods

This was a retrospective study of patients with PC treated with the high-precision BR-TRG-I type HIPEC device between December 2006 and December 2016. Vital signs during HIPEC and adverse events were recorded. Effectiveness was evaluated by total objective remission rate (ORR), which was based on ascites’ remission 4 weeks after HIPEC.

Results

A total of 1,200 patients were included. There were 518 males and 682 females, with a mean age of 58.6 ± 6.5 years (range, 32–76 years). Among the patients, 93.6% of the patients (1123/1200) successfully received the three sessions of HIPEC, 158 had massive ascites. The changes of vital signs during HIPEC were within acceptable ranges, and patients only had a transient fever and abdominal distension. Regarding the HIPEC-related complications, hemorrhage was observed in seven (0.6%) patients, anastomotic leakage in four (0.5%), and intestinal obstruction in eight (0.7%). Nine (0.8%, 9/1200) patients had CTCAE grade IV bone marrow suppression, and three (0.3%, 3/1200) patients had severe renal failure (SRF), which were considered to be drug-related. The ORR of malignant ascites was 95.6% (151/158).

Conclusion

This real-world study strongly suggests that HIPEC was safe in treating PC patients with a low rate of adverse events and leads to benefits in PC patients with massive malignant ascites.
CD86 Molecule Might Be a Novel Immune-Related Prognostic Biomarker for Patients With Bladder Cancer by Bioinformatics and Experimental Assays
Authors: Yan Xin , Du Guo-Wei , Chen Zhao , Liu Tong-Zu , Li Sheng
Published: August 2021

As one of the most common malignancies in the urinary system, bladder cancer (BC) occupies a high mortality and recurrence rate. BC carries an ominous prognosis. Thus, we aimed to identify a novel immune-related prognostic biomarker and therapeutic target for immunotherapy in the present study. We first constructed a co-expression network based on immune-related genes (IRGs). Two key modules showed high association with the clinical feature interested us most were further identified. Forty-five IRGs were screened out and regarded as hub genes in the co-expression network. We further constructed a protein-protein interaction (PPI) network, and five independent methods were used for hub gene identification. Three hub genes were identified in the present study. CD86 molecule (CD86) was screened out by performing overall survival (OS) analysis. Subsequent analyses by using some bioinformatics and experimental assays confirmed that CD86 was an immune-related prognostic biomarker, which might be a novel target for immunotherapy in BC. A small molecule drug named suloctidil was also identified, which showed potential for BC treatment.
Case Report: Dual Checkpoint Inhibition in Advanced Metastatic Osteosarcoma Results in Remission of All Tumor Manifestations—A Report of a Stunning Success in a 37-Year-Old Patient
Authors: Sterz Ulrich , Grube Matthias , Herr Wolfgang , Menhart Karin , Wendl Christina , Vogelhuber Martin
Published: August 2021

Background

Patients with unresectable metastasized osteosarcoma have a poor prognosis. Current treatment options do not offer a chance to cure the disease in this situation. Despite the fact that immunotherapy has expanded its indications continuously over previous years, its use is not yet established in osteosarcoma. There is a lack of randomized controlled studies that could show a significant benefit in this rare tumor entity. So far, efficacy of immunotherapy is only reported in individual cases as well as in mouse models. To predict a response to immunotherapy, testing for programmed death-ligand 1 (PD-L1) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) can be useful, but status is not yet clear for most cancer entities.

Methods

Single case study and review of the literature.

Case Presentation

This report presents the case of a 37-year-old patient with metastatic advanced osteosarcoma, who had no more established options for tumor treatment left. PD-L1 expression in the most recent tumor sample was high (tumor proportion score (TPS) 90%, combined positive score (CPS) 92%) but no MSI could be detected. In an individual therapy attempt, an ongoing and profound remission of all tumor manifestations due to four cycles of immunotherapy with ipilimumab and nivolumab was reached. Despite discontinuation of immunotherapy for 3 months due to therapy-related pneumonitis, remission of all tumor manifestations was ongoing, and no detectable relapse in restaging before onset of Nivolumab-maintenance could be observed.

Conclusion

The present case constitutes the first report of an adult patient with metastasized advanced osteosarcoma who reached a deep remission of disease by immunotherapy with ipilimumab and nivolumab, which continued even though immunotherapy had to be interrupted. To verify whether the high expression of PD-L1, as seen in this patient, is a predictive marker for response to immunotherapy in osteosarcoma, requires further investigation.
A Novel Prognostic Model Based on Ferroptosis-Related Gene Signature for Bladder Cancer
Authors: Yang Libo , Li Chunyan , Qin Yang , Zhang Guoying , Zhao Bin , Wang Ziyuan , Huang Youguang , Yang Yong
Published: August 2021

Background

Bladder cancer (BC) is a molecular heterogeneous malignant tumor; the treatment strategies for advanced-stage patients were limited. Therefore, it is vital for improving the clinical outcome of BC patients to identify key biomarkers affecting prognosis. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. Ferroptosis-related genes (FRGs) can be promising candidate biomarkers in BC. The objective of our study was to construct a prognostic model to improve the prognosis prediction of BC.

Methods

The mRNA expression profiles and corresponding clinical data of bladder urothelial carcinoma (BLCA) patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. FRGs were identified by downloading data from FerrDb. Differential analysis was performed to identify differentially expressed genes (DEGs) related to ferroptosis. Univariate and multivariate Cox regression analyses were conducted to establish a prognostic model in the TCGA cohort. BLCA patients from the GEO cohort were used for validation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were used to explore underlying mechanisms.

Results

Nine genes (ALB, BID, FADS2, FANCD2, IFNG, MIOX, PLIN4, SCD, and SLC2A3) were identified to construct a prognostic model. Patients were classified into high-risk and low-risk groups according to the signature-based risk score. Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) survival analysis confirmed the superior predictive performance of the novel survival model based on the nine-FRG signature. Multivariate Cox regression analyses showed that risk score was an independent risk factor associated with overall survival (OS). GO and KEGG enrichment analysis indicated that apart from ferroptosis-related pathways, immune-related pathways were significantly enriched. ssGSEA analysis indicated that the immune status was different between the two risk groups.

Conclusion

The results of our study indicated that a novel prognostic model based on the nine-FRG signature can be used for prognostic prediction in BC patients. FRGs are potential prognostic biomarkers and therapeutic targets.
Long Non-Coding RNA LINC01569 Promotes Proliferation and Metastasis in Colorectal Cancer by miR-381-3p/RAP2A Axis
Authors: Ye Guang-yao , Zhang Zi-zhen , Zhu Chun-chao , Cong Zhi-jie , Cui Zhe , Chen Lu , Zhao Gang
Published: August 2021

Background

Long non-coding RNAs (lncRNAs) display regulatory function flexibly in tumor onset and developments. Our study aimed to delve into the roles of lncRNA LINC01569 (LINC01569) in colorectal cancer (CRC) progression to study the potential mechanisms.

Methods

The genetic expression profiles of miR-381-3p and LINC01569 were measured by RT-PCR. The subcellular localization of LINC01569 in CRC cells was identified using subcellular fractionation location. Loss-of-function assays were performed to explore the potential effects of LINC01569 on CRC progression. Dual-luciferase reporter analysis was employed to verify the binding connections among LINC01569, miR-381-3p, and RAP2A.

Results

LINC01569 expression was distinctly increased in CRC. Curiously, if LINC01569 is removed, CRC cells will not migrate, proliferate, and invade remarkably. Molecular mechanism exploration uncovered that LINC01569 acted as a ceRNA competing with RAP2A to bind with miR-381-3p. Furthermore, rescue experiments corroborated the fact that miR-381-3p suppression reversed the inhibitory actions of LINC01569 knockdown on the expression of RAP2A and CRC progression.

Conclusion

Overall, our findings indicate that LINC01569 plays a key role in CRC development by means of aiming at the miR-381-3p/RAP2A axis and can be equivalent to an underlying medicinal target to save CRC patients.
Esophageal Perforation and EVAC in Pediatric Patients: A Case Series of Four Children
Authors: Ritz Laura Antonia , Hajji Mohammad Samer , Schwerd Tobias , Koletzko Sibylle , von Schweinitz Dietrich , Lurz Eberhard , Hubertus Jochen
Published: August 2021

Introduction: In pediatric patients, esophageal perforation (EP) is rare but associated with significant morbidity and mortality rates of up to 20–30%. In addition to standard treatment options, endoscopic esophageal vacuum-assisted closure (EVAC) therapy has shown promising results, especially in adult patients. Thus far, the only data on technical success and effectiveness of EVAC in pediatric patients were published in 2018 by Manfredi et al. at Boston Children's Hospital. The sparse data on EVAC in children indicates that this promising technique has been barely utilized in pediatric patients. More data are needed to evaluate efficacy and outcomes of this technique in pediatric patients.

Method: We reviewed five cases of therapy using EVAC, ArgyleTM Replogle Suction Catheter (RSC), or both on pediatric patients with EP in our institution between October 2018 and April 2020.

Results: Five patients with EP (median 3.4 years; 2 males) were treated with EVAC, RSC, or a combination. Complete closure of EP was not achieved after EVAC alone, though patients' health stabilized and inflammation and size of EP decreased after EVAC. Four patients then were treated with RSC until the EP healed. One patient needed surgery as the recurrent fistula did not heal sufficiently after 3 weeks of EVAC therapy. Two patients developed stenosis and were successfully treated with dilatations. One patient treated with RSC alone showed persistent EP after 5 weeks.

Conclusion: EVAC in pediatric patients is technically feasible and a promising method to treat EP, regardless of the underlying cause. EVAC therapy can be terminated as soon as local inflammation and C-reactive protein levels decrease, even if the mucosa is not healed completely at that time. A promising subsequent treatment is RSC. An earlier switch to RSC can substantially reduce the need of anesthesia during subsequent treatments. Our findings indicate that EVAC is more effective than RSC alone. In some cases, EVAC can be used to improve the tissues condition in preparation for a re-do surgery. At 1 year after therapy, all but one patient demonstrated sufficient weight gain. Further prospective studies with a larger cohort are required to confirm our observations from this small case series.
Orally Administered Probiotics Decrease Aggregatibacter actinomycetemcomitans but Not Other Periodontal Pathogenic Bacteria Counts in the Oral Cavity: A Systematic Review and Meta-Analysis
Authors: Sang-Ngoen Thanyaporn , Czumbel László Márk , Sadaeng Wuttapon , Mikó Alexandra , Németh Dávid István , Mátrai Péter , Hegyi Péter , Tóth Barbara , Csupor Dezső , Kiss István , Szabó Andrea , Gerber Gábor , Varga Gábor , Kerémi Beáta
Published: August 2021

Introduction: At the initial part of the gastrointestinal tract, multiple tissues serve the normal function of food delivery. Periodontal structures are integral elements of these. When they deteriorate, it is extremely challenging to regenerate and reconstruct them. The conventional intervention for periodontal disease is scaling and root planning with the aim of reducing pathogenic bacteria. However, periodontal pathogens can rapidly recolonize treated areas. Probiotics have been proposed as novel tools for managing oral health by suppressing pathogenic bacteria through their anti-inflammatory effect, but the available data are controversial.

Aim: Therefore, we performed a meta-analysis to study the effect of probiotics on periodontal pathogenic bacteria.

Methods: The study was registered in PROSPERO under registration number CRD42018094903. A comprehensive literature search from four electronic databases (PubMed, Cochrane CENTRAL, Embase, and Web of Science) yielded nine eligible records for statistical analysis. Studies measuring bacterial counts in saliva and supra- and subgingival plaque were included. Bacterial counts were analyzed using standard mean difference (SMD) and by a random effects model with the DerSimonian–Laird estimation.

Results: The results showed a significant decrease in the overall count of Aggregatibacter actinomycetemcomitans in the probiotic-treated group compared to the control at 4 weeks (SMD: −0.28; 95% CI: −0.56–−0.01; p = 0.045) but not later. Analyzing the bacterial counts in subgroups, namely, in saliva and supra- and subgingival plaque, separately, yielded no significant difference. Probiotics had no significant effect on the overall count of Porphyromonas gingivalis at 4 weeks (SMD: −0.02; 95% CI: −0.35−0.31; p = 0.914) or later. Subgroup analysis also revealed no significant difference between treatment and control groups nor did probiotics significantly decrease the overall and subgroup bacterial counts of Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum.

Conclusion: Our data support the beneficial effect of probiotics in reducing A. actinomycetemcomitans counts, but not of other key periodontal pathogenic bacteria in periodontal disease patients. However, due to the complex mechanism associated with periodontal disease and the limitations of the available studies, there is a further need for well-designed randomized clinical trials to assess the efficacy of probiotics.
Prostaglandin Reductase 1 as a Potential Therapeutic Target for Cancer Therapy
Authors: Wang Xing , Yin Guobing , Zhang Wei , Song Kunling , Zhang Longbin , Guo Zufeng
Published: August 2021

Altered tumor metabolism is a hallmark of cancer and targeting tumor metabolism has been considered as an attractive strategy for cancer therapy. Prostaglandin Reductase 1 (PTGR1) is a rate-limiting enzyme involved in the arachidonic acid metabolism pathway and mainly responsible for the deactivation of some eicosanoids, including prostaglandins and leukotriene B4. A growing evidence suggested that PTGR1 plays a significant role in cancer and has emerged as a novel target for cancer therapeutics. In this review, we summarize the progress made in recent years toward the understanding of PTGR1 function and structure, highlight the roles of PTGR1 in cancer, and describe potential inhibitors of PTGR1. Finally, we provide some thoughts on future directions that might facilitate the PTGR1 research and therapeutics development.
The Role of HSP70 in the Protective Effects of NVP-AUY922 on Multiple Organ Dysfunction Syndrome in Endotoxemic Rats
Authors: Liu Pang-Yen , Shen Hsin-Hsueh , Kung Ching-Wen , Chen Shu-Ying , Lu Chia-Hsien , Lee Yen-Mei
Published: August 2021

Sepsis is defined as a life-threatening organ dysfunction syndrome with high morbidity and mortality caused by bacterial infection. The major characteristics of sepsis are systemic inflammatory responses accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation (DIC). As a molecular chaperon to repair unfolded proteins, heat shock protein 70 (HSP70) maintains cellular homeostasis and shows protective effects on inflammatory damage. HSP 90 inhibitors were reported to exert anti-inflammatory effects via activation of the heat shock factor-1 (HSF-1), leading to induction of HSP70. We evaluated the beneficial effect of HSP 90 inhibitor NVP-AUY 922 (NVP) on multiple organ dysfunction syndrome induced by lipopolysaccharide (LPS) and further explored the underlying mechanism. NVP (5 mg/kg, i.p.) was administered 20 h prior to LPS initiation (LPS 30 mg/kg, i.v. infusion for 4 h) in male Wistar rats. Results demonstrated that pretreatment with NVP significantly increased survival rate and prevented hypotension at 6 h after LPS injection. Plasma levels of ALT, CRE and LDH as well as IL-1β and TNF-α were significantly reduced by NVP at 6 h after LPS challenge. The induction of inducible NO synthase in the liver, lung and heart and NF-κB p-p65 and caspase 3 protein expression in the heart were also attenuated by NVP. In addition, NVP markedly induced HSP70 and HO-1 proteins in the liver, lung and heart after LPS injection. These results indicated that NVP possessed the anti-inflammatory and antioxidant effects on LPS-induced acute inflammation, which might be associated with HSP70 and HO-1, leading to prevent MODS in sepsis. NVP might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS.
Impact of Climate Change on Health and Well-Being of People in Hindu Kush Himalayan Region: A Narrative Review
Authors: Dhimal Meghnath , Bhandari Dinesh , Dhimal Mandira Lamichhane , Kafle Naviya , Pyakurel Prajjwal , Mahotra Narayan , Akhtar Saeed , Ismail Tariq , Dhiman Ramesh C. , Groneberg David A. , Shrestha Uttam Babu , Müller Ruth
Published: August 2021

Climate change and variability affect virtually everyone and every region of the world but the effects are nowhere more prominent than in mountain regions and people living therein. The Hindu Kush Himalayan (HKH) region is a vast expanse encompassing 18% of the world’s mountainous area. Sprawling over 4.3 million km2, the HKH region occupies areas of eight countries namely Nepal, Bhutan, Afghanistan, Bangladesh, China, India, Myanmar, and Pakistan. The HKH region is warming at a rate higher than the global average and precipitation has also increased significantly over the last 6 decades along with increased frequency and intensity of some extreme events. Changes in temperature and precipitation have affected and will like to affect the climate-dependent sectors such as hydrology, agriculture, biodiversity, and human health. This paper aims to document how climate change has impacted and will impact, health and well-being of the people in the HKH region and offers adaptation and mitigation measures to reduce the impacts of climate change on health and well-being of the people. In the HKH region, climate change boosts infectious diseases, non-communicable diseases (NCDs), malnutrition, and injuries. Hence, climate change adaptation and mitigation measures are needed urgently to safeguard vulnerable populations residing in the HKH region.
Albumin Oxidation Status in Sepsis Patients Treated With Albumin or Crystalloids
Authors: Bonifazi Matteo , Meessen Jennifer , Pérez Alba , Vasques Francesco , Busana Mattia , Vassalli Francesco , Novelli Deborah , Bernasconi Roberto , Signori Chiara , Masson Serge , Romitti Federica , Giosa Lorenzo , Macrì Matteo , Pasticci Iacopo , Palumbo Maria Michela , Mota Francisco , Costa Montserrat , Caironi Pietro , Latini Roberto , Quintel Michael , Gattinoni Luciano
Published: August 2021

Inflammation and oxidative stress characterize sepsis and determine its severity. In this study, we investigated the relationship between albumin oxidation and sepsis severity in a selected cohort of patients from the Albumin Italian Outcome Study (ALBIOS). A retrospective analysis was conducted on the oxidation forms of human albumin [human mercapto-albumin (HMA), human non-mercapto-albumin form 1 (HNA1) and human non-mercapto-albumin form 2 (HNA2)] in 60 patients with severe sepsis or septic shock and 21 healthy controls. The sepsis patients were randomized (1:1) to treatment with 20% albumin and crystalloid solution or crystalloid solution alone. The albumin oxidation forms were measured at day 1 and day 7. To assess the albumin oxidation forms as a function of oxidative stress, the 60 sepsis patients, regardless of the treatment, were grouped based on baseline sequential organ failure assessment (SOFA) score as surrogate marker of oxidative stress. At day 1, septic patients had significantly lower levels of HMA and higher levels of HNA1 and HNA2 than healthy controls. HMA and HNA1 concentrations were similar in patients treated with albumin or crystalloids at day 1, while HNA2 concentration was significantly greater in albumin-treated patients (p < 0.001). On day 7, HMA was significantly higher in albumin-treated patients, while HNA2 significantly increased only in the crystalloids-treated group, reaching values comparable with the albumin group. When pooling the septic patients regardless of treatment, albumin oxidation was similar across all SOFA groups at day 1, but at day 7 HMA was lower at higher SOFA scores. Mortality rate was independently associated with albumin oxidation levels measured at day 7 (HMA log-rank = 0.027 and HNA2 log-rank = 0.002), irrespective of treatment group. In adjusted regression analyses for 90-day mortality, this effect remained significant for HMA and HNA2. Our data suggest that the oxidation status of albumin is modified according to the time of exposure to oxidative stress (differences between day 1 and day 7). After 7 days of treatment, lower SOFA scores correlate with higher albumin antioxidant capacity. The trend toward a positive effect of albumin treatment, while not statistically significant, warrants further investigation.
Upregulation of miR181a/miR212 Improves Myogenic Commitment in Murine Fusion-Negative Rhabdomyosarcoma
Authors: Pozzo Enrico , Giarratana Nefele , Sassi Gabriele , Elmastas Merve , Killian Theo , Wang Chao-chi , Marini Vittoria , Ronzoni Flavio , Yustein Jason , Uyttebroeck Anne , Sampaolesi Maurilio
Published: August 2021

Fusion-negative rhabdomyosarcoma (FN-RMS) is the most common soft tissue sarcoma of childhood arising from undifferentiated skeletal muscle cells from uncertain origin. Currently used therapies are poorly tumor-specific and fail to tackle the molecular machinery underlying the tumorigenicity and uncontrolled proliferation of FN-RMS. We and other groups recently found that microRNAs (miRNA) network contributes to myogenic epigenetic memory and can influence pluripotent stem cell commitments. Here, we used the previously identified promyogenic miRNAs and tailored it to the murine FN-RMS. Subsequently, we addressed the effects of miRNAs in vivo by performing syngeneic transplant of pre-treated FN-RMS cell line in C57Bl/6 mice. miRNA pre-treatment affects murine FN-RMS cell proliferation in vivo as showed by bioluminescence imaging analysis, resulting in better muscle performances as highlighted by treadmill exhaustion tests. In conclusion, in our study we identified a novel miRNA combination tackling the anti-myogenic features of FN-RMS by reducing proliferation and described novel antitumorigenic therapeutic targets that can be further explored for future pre-clinical applications.
Nitrogen Fertilisation Increases Specific Root Respiration in Ectomycorrhizal but Not in Arbuscular Mycorrhizal Plants: A Meta-Analysis
Authors: Bicharanloo Bahareh , Cavagnaro Timothy R. , Keitel Claudia , Dijkstra Feike A.
Published: August 2021

Plants spend a high proportion of their photosynthetically fixed carbon (C) belowground to support mycorrhizal associations in return for nutrients, but this C expenditure may decrease with increased soil nutrient availability. In this study, we assessed how the effects of nitrogen (N) fertiliser on specific root respiration (SRR) varied among mycorrhizal type (Myco type). We conducted a multi-level meta-analysis across 1,600 observations from 32 publications. SRR increased in ectomycorrhizal (ECM) plants with more than 100 kg N ha−1 applied, did not change in arbuscular mycorrhizal (AM) and non-mycorrhizal (NM) plants, but increased in plants with a dual mycorrhizal association in response to N fertilisation. Our results suggest that high N availability (>100 kg N ha−1) could disadvantage the growth of ECM plants because of increased C costs associated with maintaining higher root N concentrations, while the insensitivity in SRR by AM plants to N fertilisation may be because AM fungi are more important for phosphorus (P) uptake.
Breeding With Major and Minor Genes: Genomic Selection for Quantitative Disease Resistance
Authors: Merrick Lance F. , Burke Adrienne B. , Chen Xianming , Carter Arron H.
Published: August 2021

Disease resistance in plants is mostly quantitative, with both major and minor genes controlling resistance. This research aimed to optimize genomic selection (GS) models for use in breeding programs that are needed to select both major and minor genes for resistance. In this study, stripe rust (Puccinia striiformis Westend. f. sp. tritici Erikss.) of wheat (Triticum aestivum L.) was used as a model for quantitative disease resistance. The quantitative nature of stripe rust is usually phenotyped with two disease traits, infection type (IT) and disease severity (SEV). We compared two types of training populations composed of 2,630 breeding lines (BLs) phenotyped in single-plot trials from 4 years (2016–2020) and 475 diversity panel (DP) lines from 4 years (2013–2016), both across two locations. We also compared the accuracy of models using four different major gene markers and genome-wide association study (GWAS) markers as fixed effects. The prediction models used 31,975 markers that are replicated 50 times using a 5-fold cross-validation. We then compared GS models using a marker-assisted selection (MAS) to compare the prediction accuracy of the markers alone and in combination. GS models had higher accuracies than MAS and reached an accuracy of 0.72 for disease SEV. The major gene and GWAS markers had only a small to nil increase in the prediction accuracy more than the base GS model, with the highest accuracy increase of 0.03 for the major markers and 0.06 for the GWAS markers. There was a statistical increase in the accuracy using the disease SEV trait, BLs, population type, and combining years. There was also a statistical increase in the accuracy using the major markers in the validation sets as the mean accuracy decreased. The inclusion of fixed effects in low prediction scenarios increased the accuracy up to 0.06 for GS models using significant GWAS markers. Our results indicate that GS can accurately predict quantitative disease resistance in the presence of major and minor genes.
Religious Affiliation, Daily Spirituals, and Private Religious Factors Promote Marital Commitment Among Married Couples: Does Religiosity Help People Amid the COVID-19 Crisis?
Authors: Aman Jaffar , Abbas Jaffar , Lela Umi , Shi Guoqing
Published: August 2021

Religious studies are a vital branch of social science that seeks to explain the beliefs of human society and deals with the practices and beliefs of individuals. This distinctive study focuses on such influential aspects of a healthy life, which could play a vital role in the marital quality and matrimonial commitment of individuals. The study principally focused on inspecting the role of religiosity in healthy marital commitment among individuals. It is a distinctive and central value in regulating a healthy social life. This research designed a conceptual model for assessing marital commitment, and the study model comprised two primary variables. The study received datasets through a survey questionnaire based on participants from five private and public sectors. The research study conducted an empirical analysis to test the proposed conceptual framework. The findings exhibited that the value of the R2 model was 0.484, meaning the level of religiosity had a substantial impression on healthy and lasting marital commitment. According to the final outline of the model factors associated with building religious support factors (β = 0.491), the marital commitment had a better and healthier impact. The goodness-of-fit of the measurement of the conceptual model showed a value of 0.51, which indicated that the theoretical model had sufficient consistency and rationality, and accurately fitted the data. Such an advanced statistical model is missing from the previous literature. The study results provide helpful insight to elucidate the social dynamics of marital commitment. The findings designate that religious practices strengthen and promote nuptial commitment. The study is novel in the context of religiosity impact on martial commitment with a cultural background of Pakistan. The generalizability of the study does not apply to the entire population or other regions. Future studies can investigate other religious variables to explore further research findings. The findings are helpful for decision-makers and policymakers to concentrate on marital issues and challenges confronted by couples worldwide.
Work–Life Balance of the Employed Population During the Emergency Situation of COVID-19 in Latvia
Authors: Lonska Jelena , Mietule Iveta , Litavniece Lienite , Arbidane Iluta , Vanadzins Ivars , Matisane Linda , Paegle Linda
Published: August 2021

All the employees face the challenge of finding the right work–life balance. The ability of employees to deal with the successful combining of work, family responsibilities, and personal life is crucial for both employers and family members of employees. During the COVID-19 emergency situation, many people around the world were forced to work remotely. Initially, there were observed some certain expectations about the possibility of working from home as a positive factor that will promote work–life balance. However, over time, negative tendencies were also revealed, as employees were only one call or message away from the employer, and uncertainty and leisure time with family often created more stress. As many organizations and individuals were not ready for this sudden change, many mistakes were made, which further raised the issue of work–life balance. The aim of the research was to evaluate the flexibility of reconciling work and private life of Latvian employees in various socio-demographic groups during the COVID-19 emergency situation in spring 2020, to investigate how family life influenced employees’ ability to perform work duties, to find out if employees had any additional housework responsibilities and how their workload changed concerning housework amount during the COVID-19 emergency situation. The research is based on the data obtained in the survey of the Latvian employed population, which was conducted within the framework of the Latvian National Research Programme Project “CoLife” in the second half of 2020. As a result, the hypothesis of the research that all groups of employees experienced work–life balance difficulties during the COVID-19 emergency situation has been partially confirmed, i.e., women in the 18–44 age group and respondents with minor children in the household more likely faced difficulties of work–life balance. The scientific research methods that were used in the research are the monographic method, content analysis, survey, data processing with SPSS to determine the mutual independence of the data from the questionnaires.
Knowing Groundlessness: An Enactive Approach to a Shift From Cognition to Non-Dual Awareness
Authors: Meling Daniel
Published: August 2021

The enactive approach has become an influential paradigm in cognitive science. One of its most important claims is that cognition is sense-making: to cognize is to enact a world of meaning. Thus, a world is not pregiven but enacted through sense-making. Most importantly, sense-making is not a fixed process or thing. It does not have substantial existence. Instead, it isgroundless: it springs from a dynamic of relations, without substantial ground. Thereby, as all cognition is groundless, this groundlessness is considered the central underlying principle of cognition. This article takes that key concept of the enactive approach and argues that it is not only a theoretical statement. Rather, groundlessness is directly accessible inlived experience. The two guiding questions of this article concern that lived experience of groundlessness: (1)Whatis it toknowgroundlessness? (2)Howcan oneknowgroundlessness? Accordingly, it elaborates (1) how this knowing of groundlessness fits into the theoretical framework of the enactive approach. Also, it describes (2) how it can be directly experienced when certain requirements are met. In an additional reflexive analysis, the context-dependency and observer-relativity of those statements themselves is highlighted. Through those steps, this article exhibits the importance of knowing groundlessness for a cognitive science discourse: this underlying groundlessness is not only the “ground” of cognition, but it also can be investigatedempiricallythrough lived experience. However, it requires a methodology that is radically different from classical cognitive science. This article ends with envisioning a future praxis of cognitive science which enables researchers to investigate not only theoretically but empirically the “foundationless foundation” of cognition: groundlessness.
Cognition-Mortality Associations Are More Pronounced When Estimated Jointly in Longitudinal and Time-to-Event Models
Authors: Aichele Stephen , Cekic Sezen , Rabbitt Patrick , Ghisletta Paolo
Published: August 2021

With aging populations worldwide, there is growing interest in links between cognitive decline and elevated mortality risk—and, by extension, analytic approaches to further clarify these associations. Toward this end, some researchers have compared cognitive trajectories of survivors vs. decedents while others have examined longitudinal changes in cognition as predictive of mortality risk. A two-stage modeling framework is typically used in this latter approach; however, several recent studies have used joint longitudinal-survival modeling (i.e., estimating longitudinal change in cognition conditionally on mortality risk, and vice versa). Methodological differences inherent to these approaches may influence estimates of cognitive decline and cognition-mortality associations. These effects may vary across cognitive domains insofar as changes in broad fluid and crystallized abilities are differentially sensitive to aging and mortality risk. We compared these analytic approaches as applied to data from a large-sample, repeated-measures study of older adults (N = 5,954; ages 50–87 years at assessment; 4,453 deceased at last census). Cognitive trajectories indicated worse performance in decedents and when estimated jointly with mortality risk, but this was attenuated after adjustment for health-related covariates. Better cognitive performance predicted lower mortality risk, and, importantly, cognition-mortality associations were more pronounced when estimated in joint models. Associations between mortality risk and crystallized abilities only emerged under joint estimation. This may have important implications for cognitive reserve, which posits that knowledge and skills considered well-preserved in later life (i.e., crystallized abilities) may compensate for declines in abilities more prone to neurodegeneration, such as recall memory and problem solving. Joint longitudinal-survival models thus appear to be important (and currently underutilized) for research in cognitive epidemiology.
Born to Code: Does the Portrayal of Computer Scientists as Geniuses Undermine Adolescent Youths' Motivational Beliefs?
Authors: Starr Christine R.
Published: August 2021

Introduction: Computer scientists are often stereotyped as geniuses who are naturally gifted in pSTEM (physical Sciences, Technology, Engineering, and Math). Prior correlational research found that this genius stereotype is negatively related to students' pSTEM motivation. However, the effect has not been explored experimentally to evaluate possible casual influences. Using situated expectancy-value theory as a framework, the present experiment tested whether media invoking the genius stereotype negatively impacts high school students' expectancy and value beliefs regarding pSTEM.

Methods: The sample comprised of 213 U.S. high school students (53% boys, 46% Asian). Participants read one of two versions of an article profiling a student majoring in computer science. The genius condition emphasized the student's natural talent and the importance of being gifted for success in computer science, whereas the control condition did not mention these attributes. Pre- and post-test measures of pSTEM expectancy and value beliefs were assessed.

Results and Conclusions: Students in the genius condition, but not the control condition, demonstrated a significant decline in pSTEM value beliefs. There was no effect on expectancy beliefs. Thus, popular stereotypes of persons in pSTEM as geniuses may contribute to students devaluing of pSTEM subjects. These stereotypes may be especially threatening to girls and students from minoritized backgrounds. Implications are discussed, including the need to address genius stereotypes in pSTEM classrooms.
Effects of Coronavirus Fears on Anxiety and Depressive Disorder Symptoms in Clinical and Subclinical Adolescents: The Role of Negative Affect, Intolerance of Uncertainty, and Emotion Regulation Strategies
Authors: Sandín Bonifacio , Espinosa Victoria , Valiente Rosa M. , García-Escalera Julia , Schmitt Julia C. , Arnáez Sandra , Chorot Paloma
Published: August 2021

Fears related to COVID-19 (“coronavirus fears”) have emerged as a new psychological effect of the current COVID-19 pandemic and have been associated with psychological distress and impairment. Other adverse effects include an increase in anxiety and depression symptoms and the respective disorders. The purpose of the current study was to examine the incremental validity of coronavirus fears and transdiagnostic factors in the prediction of the severity of anxiety and depressive disorder symptoms. A sample of 144 adolescents [aged 12–18 years, 55 boys (38.2%) and 89 girls (61.8%)] most of whom showed elevated levels of anxiety and depressive disorder symptoms completed several self-report measures online assessing coronavirus fears, transdiagnostic vulnerability and protective factors, and emotion regulation strategies. Results based on a series of hierarchical multiple regression analyses revealed that coronavirus fears, negative affect, intolerance of uncertainty, acceptance/tolerance, rumination and suppression explained unique variance in the severity of anxiety and depressive disorder symptoms. Path analysis demonstrated that acceptance/tolerance, rumination and suppression mediated the association between higher level transdiagnostic factors and the severity of major depressive disorder symptoms. Findings provide support for the hierarchical transdiagnostic model of emotional disorders and suggest that clinicians should be aware of coronavirus fears. Also, the results warrant the need to consider transdiagnostic vulnerability and protective processes in the new protocols for the treatment of emotional disorders.