bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients
Authors: Zhaoyun Liu , Rong Fu
Published: July 2021

Despite new efficacy drugs and cell therapy have been used for multiple myeloma (MM) patients, some patients will relapse over time. We wonder the immune system play a vital role as well as MM cell during the development of disease. It is clear that the characteristic of myeloma cell is associated with the survival of MM patients. However, the link between the immune profiling and the prognosis of the disease is still not entirely clear. As more study focus on the role of immunity on multiple myeloma pathogenesis. There are plenty of study about the predictive role of immunity on the survival of multiple myeloma patients. Up to mow, the majority reviews published have focused on the immunotherapy and immune pathogenesis. It is indispensable to overlook the predictive role of immunity on multiple myeloma patients. Here, we give a review of vital previous works and recent progress related to the predictive role of immune profiling on multiple myeloma, such as absolute lymphocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocytes and cytokines.
Assessing the Functional Heterogeneity of Monocytes in Human Septic Shock: a Proof-of-Concept Microfluidic Assay of TNFα Secretion
Authors: Llitjos Jean-François , Bounab Yacine , Rousseau Christophe , Dixneuf Sophie , Rimbault Blandine , Chiche Jean-Daniel , Textoris Julien , Pène Frédéric , Védrine Christophe
Published: July 2021

Objective

The development of advanced single-cell technologies to decipher inter-cellular heterogeneity has enabled the dynamic assessment of individual cells behavior over time, overcoming the limitation of traditional assays. Here, we evaluated the feasibility of an advanced microfluidic assay combined to fluorescence microscopy to address the behavior of circulating monocytes from septic shock patients.

Methods

Seven septic shock patients and ten healthy volunteers were enrolled in the study. Using the proposed microfluidic assay we investigated the production over time of LPS-elicited TNFα by single monocytes encapsulated within droplets. Cellular endocytic activity was assessed by internalization of magnetic nanoparticles. Besides, we assessed HLA-DR membrane expression and LPS-induced TNFα production in monocytes through classical flow cytometry assays.

Results

Consistent with the flow cytometry results, the total number of TNFα molecules secreted by encapsulated single monocytes was significantly decreased in septic shock patients compared to healthy donors. TNFα production was dampened as soon as 30 and 60 minutes after LPS stimulation in monocytes from septic patients. Furthermore, the microfluidic assay revealed heterogeneous individual behavior of monocytes from septic shock patients. Of note, monocytes from both healthy donors and patients exhibited similar phagocytic activities over time.

Conclusion

The microfluidic assay highlights the functional heterogeneity of monocytes, and provides in-depth resolution in assessing the hallmark monocyte deactivation encountered in post-septic immunosuppression.
Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection
Authors: Falconi-Agapito Francesca , Kerkhof Karen , Merino Xiomara , Michiels Johan , Van Esbroeck Marjan , Bartholomeeusen Koen , Talledo Michael , Ariën Kevin K.
Published: July 2021

Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.
Integrative Transcriptomic Analysis Reveals the Immune Mechanism for a CyHV-3-Resistant Common Carp Strain
Authors: Jia Zhiying , Wu Nan , Jiang Xiaona , Li Heng , Sun Jiaxin , Shi Mijuan , Li Chitao , Ge Yanlong , Hu Xuesong , Ye Weidong , Tang Ying , Shan Junwei , Cheng Yingyin , Xia Xiao-Qin , Shi Lianyu
Published: July 2021

Anti-disease breeding is becoming the most promising solution to cyprinid herpesvirus-3 (CyHV-3) infection, the major threat to common carp aquaculture. Virus challenging studies suggested that a breeding strain of common carp developed resistance to CyHV-3 infection. This study illustrates the immune mechanisms involved in both sensitivity and anti-virus ability for CyHV3 infection in fish. An integrative analysis of the protein-coding genes and long non-coding RNAs (lncRNAs) using transcriptomic data was performed. Tissues from the head kidney of common carp were extracted at days 0 (the healthy control) and 7 after CyHV-3 infection (the survivors) and used to analyze the transcriptome through both Illumina and PacBio sequencing. Following analysis of the GO terms and KEGG pathways involved, the immune-related terms and pathways were merged. To dig out details on the immune aspect, the DEGs were filtered using the current common carp immune gene library. Immune gene categories and their corresponding genes in different comparison groups were revealed. Also, the immunological Gene Ontology terms for lncRNA modulation were retained. The weighted gene co-expression network analysis was used to reveal the regulation of immune genes by lncRNA. The results demonstrated that the breeding carp strain develops a marked resistance to CyHV-3 infection through a specific innate immune mechanism. The featured biological processes were autophagy, phagocytosis, cytotoxicity, and virus blockage by lectins and MUC3. Moreover, the immune-suppressive signals, such as suppression of IL21R on STAT3, PI3K mediated inhibition of inflammation by dopamine upon infection, as well as the inhibition of NLRC3 on STING during a steady state. Possible susceptible factors for CyHV-3, such as ITGB1, TLR18, and CCL4, were also revealed from the non-breeding strain. The results of this study also suggested that Nramp and PAI regulated by LncRNA could facilitate virus infection and proliferation for infected cells respectively, while T cell leukemia homeobox 3 (TLX3), as well as galectin 3 function by lncRNA, may play a role in the resistance mechanism. Therefore, immune factors that are immunogenetically insensitive or susceptible to CyHV-3 infection have been revealed.
Not All Those Who Wander Are Lost – Responses of Fishers’ Communities to Shifts in the Distribution and Abundance of Fish
Authors: Papaioannou Eva A. , Selden Rebecca L. , Olson Julia , McCay Bonnie J. , Pinsky Malin L. , St. Martin Kevin
Published: July 2021

As species respond to warming water temperatures, fishers dependent upon such species are being compelled to make choices concerning harvest strategies. Should they “follow fish” to new fishing grounds? Should they change their mix of target species? Should they relocate their operations to new ports? We examined how fishing communities in the Northeast United States —a hotspot of recent warming—have already responded to documented shifts in the distribution and abundance of fluke, red and silver hake. We focused on groundfish trawl communities that historically targeted these species and examined their “at-sea” responses by combining qualitative interviews with quantitative analysis of fishing records and ecological surveys. Three distinct responses emerged: shifting fishing grounds, shifting target species, and shifting port of landing. Our research finds that following the fish is rare and only occurred in one of the assessed communities, the large trawler community of Beaufort, North Carolina. The more common response was a shift in target species and a change in catch composition. However, regulations and markets often constrained the ability to take advantage of a changing mix of species within fishing grounds. Indeed, the overall species diversity in catch has declined among all of our focal communities suggesting that communities have lost the ability to be flexible when it may be most needed as a response to climate change. Additionally, the high value of fluke and the need to land in southern states with higher quota allocations is likely a driver of the changing nature of “community” with increasing vessels landing outside their home port, especially when landing fluke. Our findings suggest that fidelity to historical fishing grounds combined with perceiving environmental change as non-permanent, predispose many fishers to trust in “cyclicality” and return of species over time. However, this strategy may make those communities unable or unwilling to “follow fish” more vulnerable to changes in distribution and abundance due to climate change. Our findings have the potential to directly inform resource management policies as well as more deliberate adaptations by communities themselves as they strive to address the imminent risks of climate change.
Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration
Authors: Horn Miranda D. , MacLean Andrew G.
Published: July 2021

Extracellular vesicles (EVs) are small, membrane-bound vesicles released by cells as a means of intercellular communication. EVs transfer proteins, nucleic acids, and other biologically relevant molecules from one cell to another. In the context of viral infections, EVs can also contain viruses, viral proteins, and viral nucleic acids. While there is some evidence that the inclusion of viral components within EVs may be part of the host defense, much of the research in this field supports a pro-viral role for EVs. Packaging of viruses within EVs has repeatedly been shown to protect viruses from antibody neutralization while also allowing for their integration into cells otherwise impervious to the virus. EVs also bidirectionally cross the blood-brain barrier (BBB), providing a potential route for peripheral viruses to enter the brain while exiting EVs may serve as valuable biomarkers of neurological disease burden. Within the brain, EVs can alter glial activity, increase neuroinflammation, and induce neurotoxicity. The purpose of this mini-review is to summarize research related to viral manipulation of EV-mediated intercellular communication and how such manipulation may lead to infection of the central nervous system, chronic neuroinflammation, and neurodegeneration.
Sensory Stimulation of the Foot and Ankle Early Post-stroke: A Pilot and Feasibility Study
Authors: Aries Alison M. , Pomeroy Valerie M. , Sim Julius , Read Susan , Hunter Susan M.
Published: July 2021

Background: Somatosensory stimulation of the lower extremity could improve motor recovery and walking post-stroke. This pilot study investigated the feasibility of a subsequent randomized controlled trial (RCT) to determine whether task-specific gait training is more effective following either (a) intensive hands-on somatosensory stimulation or (b) wearing textured insoles.

Objectives: Determine recruitment and attrition rates, adherence to intervention, acceptability and viability of interventions and outcome measures, and estimate variance of outcome data to inform sample size for a subsequent RCT.

Methods: Design: randomized, single-blinded, mixed-methods pilot study.

Setting: In-patient rehabilitation ward and community.

Participants:n = 34, 18+years, 42–112 days following anterior or posterior circulation stroke, able to follow simple commands, able to walk independently pre-stroke, and providing informed consent.

Intervention: Twenty 30-min sessions of task-specific gait training (TSGT) (delivered over 6 weeks) in addition to either: (a) 30–60 min mobilization and tactile stimulation (MTS); or (b) unlimited textured insole (TI) wearing.

Outcomes: Ankle range of movement (electrogoniometer), touch-pressure sensory thresholds (Semmes Weinstein Monofilaments), motor impairment (Lower Extremity Motricity Index), walking ability and speed (Functional Ambulation Category, 5-m walk test, pressure insoles) and function (modified Rivermead Mobility Index), measured before randomization, post-intervention, and 1-month thereafter (follow-up). Adherence to allocated intervention and actual dose delivered (fidelity) were documented in case report forms and daily diaries. Focus groups further explored acceptability of interventions and study experience.

Analysis: Recruitment, attrition, and dose adherence rates were calculated as percentages of possible totals. Thematic analysis of daily diaries and focus group data was undertaken. Standard deviations of outcome measures were calculated and used to inform a sample size calculation.

Results: Recruitment, attrition, and adherence rates were 48.57, 5.88, and 96.88%, respectively. Focus groups, daily-diaries and case report forms indicated acceptability of interventions and outcome measures to participants. The 5-m walk was selected as primary outcome measure for a future trial [mean (SD) at end of intervention: 16.86 (11.24) MTS group and 21.56 (13.57) TI group]; sample size calculation indicated 60 participants are required per group.

Conclusion: Recruitment, attrition and adherence rates and acceptability of interventions and outcomes justify a subsequent powered RCT of MTS+TSGT compared with TI+TSGT.
Motor Imagery: A Resource in the Fatigue Rehabilitation for Return-to-Work in Multiple Sclerosis Patients—A Mini Systematic Review
Authors: Agostini Francesco , Pezzi Letizia , Paoloni Marco , Insabella Roberta , Attanasi Carmine , Bernetti Andrea , Saggini Raoul , Mangone Massimiliano , Paolucci Teresa
Published: July 2021

Fatigue is a multidimensional symptom with both physical and cognitive aspects, which can affect the quality of daily and working life activities. Motor Imagery (MI) represents an important resource for use during the rehabilitation processes, useful, among others, for job integration/reintegration, of neurological pathologies, such as Multiple Sclerosis (MS). To define the effective rehabilitation protocols that integrate MI for the reduction of fatigue in patients with MS (PwMS), a literary review was performed through August 2020. Five articles were included in the qualitative synthesis, including two feasibility pilot randomized control trials (RCTs) and 3 RCTs with good quality according to the PEDro score and a low risk of bias according to the Cochrane Collaboration tool. The literature suggested that MI, in association with rhythmic-auditory cues, may be an effective rehabilitation resource for reducing fatigue. Positive effects were observed on perceived cognitive and psychological fatigue. PwMS require greater compensatory strategies than healthy individuals, and the use of rhythmic-auditory cues may be useful for optimizing the cognitive processing of MI, which acts as an internal stimulus that is enhanced and made more vivid by outside cues. These findings provide evidence that MI is a promising rehabilitation tool for reducing fatigue in PwMS and return to work strategies.
Simulating Visibility and Reading Performance in Low Vision
Authors: Xiong Ying-Zi , Lei Quan , Calabrèse Aurélie , Legge Gordon E.
Published: July 2021

Purpose

Low vision reduces text visibility and causes difficulties in reading. A valid low-vision simulation could be used to evaluate the accessibility of digital text for readers with low vision. We examined the validity of a digital simulation for replicating the text visibility and reading performance of low-vision individuals.

Methods

Low-vision visibility was modeled with contrast sensitivity functions (CSFs) with parameters to represent reduced acuity and contrast sensitivity. Digital filtering incorporating these CSFs were applied to digital versions of the Lighthouse Letter Acuity Chart and the Pelli-Robson Contrast Sensitivity Chart. Reading performance (reading acuity, critical print size, and maximum reading speed) was assessed with filtered versions of the MNREAD reading acuity Chart. Thirty-six normally sighted young adults completed chart testing under normal and simulated low-vision conditions. Fifty-eight low-vision subjects (thirty with macular pathology and twenty-eight with non-macular pathology) and fifteen normally sighted older subjects completed chart testing with their habitual viewing. We hypothesized that the performance of the normally sighted young adults under simulated low-vision conditions would match the corresponding performance of actual low-vision subjects.

Results

When simulating low-vision conditions with visual acuity better than 1.50 logMAR (Snellen 20/630) and contrast sensitivity better than 0.15 log unit, the simulation adequately reduced the acuity and contrast sensitivity in normally sighted young subjects to the desired low-vision levels. When performing the MNREAD test with simulated low vision, the normally sighted young adults had faster maximum reading speed than both the Non-macular and Macular groups, by an average of 0.07 and 0.12 log word per minute, respectively. However, they adequately replicated the reading acuity as well as the critical print size, up to 2.00 logMAR of both low-vision groups.

Conclusion

A low-vision simulation based on clinical measures of visual acuity and contrast sensitivity can provide good estimates of reading performance and the accessibility of digital text for a broad range of low-vision conditions.
Nutritional Impact and Its Potential Consequences on COVID-19 Severity
Authors: Mortaz Esmaeil , Bezemer Gillina , Alipoor Shamila D. , Varahram Mohammad , Mumby Sharon , Folkerts Gert , Garssen Johan , Adcock Ian M.
Published: July 2021

Background:During late 2019 a viral disease due to a novel coronavirus was reported in Wuhan, China, which rapidly developed into an exploding pandemic and poses a severe threat to human health all over the world. Until now (May 2021), there are insufficient treatment options for the management of this global disease and shortage of vaccines. Important aspects that help to defeat coronavirus infection seems to be having a healthy, strong, and resilient immune system. Nutrition and metabolic disorders, such as obesity and diabetes play a crucial role on the community health situation in general and especially during this new pandemic. There seems to be an enormous impact of lifestyle, metabolic disorders, and immune status on coronavirus disease 2019 (COVID-19) severity and recovery. For this reason, it is important to consider the impact of lifestyle and the consumption of well-defined healthy diets during the pandemic.

Aims:In this review, we summarise recent findings on the effect of nutrition on COVID-19 susceptibility and disease severity and treatment. Understanding how specific dietary features might help to improve the public health strategies to reduce the rate and severity of COVID-19.
The Treatment Outcomes of Olfactory Neuroblastoma Patients With Frontal Lobe Invasion
Authors: Wang Jie , Wang Li , He Huanyu , Li Yi , Song Xinmao
Published: July 2021

Background

To investigate whether frontal lobe invasion (FLI) was an unfavorable prognostic factor in patients with olfactory neuroblastoma (ONB), and to explore the optimal treatment strategy for ONB patients with FLI.

Methods

Some 37 patients with FLI were retrospectively studied, and 74 well-matched patients without FLI were enrolled as the control group. The long-term survivals were compared between the two groups.

Results

No significant differences were found between the two groups in overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS) (all p >0.05). Multivariate analyses showed that FLI wasn’t an independent predictor for OS (HR = 1.100, 95% CI = 0.437–2.772, p = 0.840). Among the 37 patients with FLI, patients who received surgery combined with chemo-/radiotherapy showed better OS (89.4% vs. 53.6%, p = 0.001) and PFS (87.8% vs. 53.6%, p = 0.001) compared with those who didn’t undergo surgery.

Conclusions

FLI wasn’t a poor prognostic factor for ONB patients. Endoscopic resection combined with radiotherapy was an effective therapeutic method for ONB patients with FLI.
Modifying Effects of Glucose and Insulin/Insulin-Like Growth Factors on Colon Cancer Cells
Authors: Berk Şeyda , Janssen Joseph A. M. J. L. , van Koetsveld Peter M. , Dogan Fadime , Değerli Naci , Özcan Servet , Kelestimur Fahrettin , Hofland Leo J.
Published: July 2021

There are only a few experimental studies which have investigated effects of glucose alone, and glucose in combination with insulin/insulin-like growth factors (IGF) on the growth of colon cancer. In the present study, we studied in vitro in human colorectal cancer cells originating from four Dukes’ stages of colorectal cancer the effects of glucose, insulin and IGFs on proliferation, migration, cell cycle progression and gene expression of the IGF system. Growth of colon cancer cells originating from a Dukes’ stage A was glucose-dependent, whereas growth of cancer cells from Dukes’ stage B, C and D was glucose-independent. Stimulatory effects of insulin and IGFs on cell growth were observed only in colon cancer cells originating from Dukes’ stage C and D. IGF-II stimulated migration in Dukes’ stage B cells only. The growth stimulatory effects in Dukes’ stage C and D colorectal cancer cells were accompanied by G2/M arrest and associated with an increased IGF-IR/IGF-II receptor ratio. In conclusion, our in vitro data suggest that the stimulating effects of glucose, IGFs and insulin on proliferation differ between colorectal cancer cells from early and late Dukes’ stages. Stimulatory effects of glucose on proliferation appear predominantly present in stage Dukes’ stage A colorectal cancer cells, while in contrast growth factor-mediated stimulation of cell proliferation is more pronounced in Dukes’ late stage (metastasized) colorectal cancer cells. Moreover, our study suggests that a stringent glucose control may be important to control tumor growth in early stages of colorectal cancer, while inhibition of the endocrine actions of the IGFs and insulin become more important in the late (metastasized) stages of colorectal cancer to restrain growth of colon cancer cells.
DeepCUBIT: Predicting Lymphovascular Invasion or Pathological Lymph Node Involvement of Clinical T1 Stage Non-Small Cell Lung Cancer on Chest CT Scan Using Deep Cubical Nodule Transfer Learning Algorithm
Authors: Beck Kyongmin Sarah , Gil Bomi , Na Sae Jung , Hong Ji Hyung , Chun Sang Hoon , An Ho Jung , Kim Jae Jun , Hong Soon Auck , Lee Bora , Shim Won Sang , Park Sungsoo , Ko Yoon Ho
Published: July 2021

The prediction of lymphovascular invasion (LVI) or pathological nodal involvement of tumor cells is critical for successful treatment in early stage non-small cell lung cancer (NSCLC). We developed and validated a Deep Cubical Nodule Transfer Learning Algorithm (DeepCUBIT) using transfer learning and 3D Convolutional Neural Network (CNN) to predict LVI or pathological nodal involvement on chest CT images. A total of 695 preoperative CT images of resected NSCLC with tumor size of less than or equal to 3 cm from 2008 to 2015 were used to train and validate the DeepCUBIT model using five-fold cross-validation method. We also used tumor size and consolidation to tumor ratio (C/T ratio) to build a support vector machine (SVM) classifier. Two-hundred and fifty-four out of 695 samples (36.5%) had LVI or nodal involvement. An integrated model (3D CNN + Tumor size + C/T ratio) showed sensitivity of 31.8%, specificity of 89.8%, accuracy of 76.4%, and AUC of 0.759 on external validation cohort. Three single SVM models, using 3D CNN (DeepCUBIT), tumor size or C/T ratio, showed AUCs of 0.717, 0.630 and 0.683, respectively on external validation cohort. DeepCUBIT showed the best single model compared to the models using only C/T ratio or tumor size. In addition, the DeepCUBIT model could significantly identify the prognosis of resected NSCLC patients even in stage I. DeepCUBIT using transfer learning and 3D CNN can accurately predict LVI or nodal involvement in cT1 size NSCLC on CT images. Thus, it can provide a more accurate selection of candidates who will benefit from limited surgery without increasing the risk of recurrence.
Cardiovascular Outcomes in the Patients With Primary Central Nervous System Lymphoma: A Multi-Registry Based Cohort Study of 4,038 Cases
Authors: Qiu Zicong , Tang Yongshi , Jiang Yanting , Su Miao , Wang Xuemin , Xu Xiuhong , Chen Yuerong
Published: July 2021

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive non-Hodgkin lymphoma. Treatment-related cardiovascular lesion has become one of the most common complications in patients with tumor. However, very little is known about the cardiovascular death (CVD) of the patients with PCNSL. This study aims at identifying the cardiovascular outcomes of PCNSL patients and making comparison on CVD with extra central nervous system lymphoma (ECNSL). Clinical information of PCNSL and ECNSL was retrieved from the Surveillance, Epidemiology and End Results database. The risk factors of CVD in PCNSL patients and the comparison on the CVD hazard between PCNSL and ECNSL were assessed with the competing risks regression. A 1:2 propensity score matching was used to reduce the imbalanced baseline characteristics between PCNSL and ECNSL. Four thousand thirty-eight PCNSL subjects and 246,760 ECNSL subjects were enrolled in this retrospective study. CVD was the leading cause (41.2%) of non-cancer death in PCNSL patients and mostly occurred within the first year of diagnosis. Age over 60s and diagnosis in 2000–2008 were significantly associated with the elevated risk of CVD in PCNSL patients, while chemotherapy and radiotherapy play no role on the cardiovascular outcomes. Compared with ECNSL patients, the risk of CVD in PCNSL patients were 40% approximately lower. The risk of CVD in the patients with PCNSL still remains unclear currently. Clinicians ought to pay more attention on the risk of CVD in PCNSL patients, especially the elder patients within the first year of diagnosis.
Extracurricular Physical Activities and the Condition of Being an Only Child as a Conditioning Factor in the Psychomotor Development of 5-Year-Old Children
Authors: Gil-Madrona Pedro , Romero-Martínez Sonia J. , Roz-Faraco Carmen C.
Published: July 2021

In early childhood education, there is a great interdependence among motor, affective, and cognitive development. A better understanding of psychomotor development and its variables by pediatricians and those who oversee educational tasks at this stage of development, such as teachers, psychologists, counselors, and parents themselves, can influence the design of educational intervention proposals. To that effect, the present study aims to analyze the influence of some family characteristics such as the condition of being an only child or having siblings and whether the child carries out extracurricular activities linked to physical activities and sports. To achieve this objective, a Checklist of Psychomotor Activities (CPA) assessment instrument was used based on the observation of a sample of 694 children aged 5 years who were enrolled in the second cycle of child education in the province of Albacete. The results show that those children who performed extracurricular activities related to physical activities and sports had a greater development of laterality and postural tonic control than those who did not attend this type of activities. At the same time, differences were found in the affective and relational levels and in the perceptual-motor aspects in favor of children who have siblings compared with children who are only children. There is no other research that addresses both issues in the same study, and this is a strength of the present study.
Synergistic Activity of the HSP90 Inhibitor Ganetespib With Lapatinib Reverses Acquired Lapatinib Resistance in HER2-Positive Breast Cancer Cells
Authors: Ye Min , Huang Wei , Liu Rui , Kong Yingli , Liu Yang , Chen Xiaole , Xu Jianhua
Published: July 2021

Lapatinib is an FDA-approved EGFR and HER2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer patients. However, its therapeutic efficacy is limited by primary or acquired resistance. In the present study, we established breast cancers cells with acquired lapatinib resistance and investigated the antitumor activity of the second-generation HSP90 inhibitor ganetespib in association with lapatinib in lapatinib-sensitive and -resistant cells. The combination treatment showed synergistic inhibition of HER and the downstream PI3K/Akt and Ras/MEK/ERK pathways, in addition to enhancing induction of early apoptotic cell death and G1 arrest in both parent and lapatinib-resistant cells in vitro. The joint administration of ganetespib and lapatinib depleted the aberrant nuclear transcription factor STAT3, a mediator of the cell cycle and apoptosis-related pathways that is probably involved in the lapatinib resistance of HER2-positive breast cancer cells. In conjunctive with the augmented inhibition of tumor growth observed in both SKBR3 and SKBR3-L xenografts compared to monotherapy, our data provide a sound preclinical basis for combination treatment with lapatinib and ganetespib for refractory HER2-positive breast cancer.
Hepatoprotective Effects of Different Extracts From Triphala Against CCl4-Induced Acute Liver Injury in Mice
Authors: Wei Xichuan , Luo Chuanhong , He Yanan , Huang Haozhou , Ran Fei , Liao Wei , Tan Peng , Fan Sanhu , Cheng Yuan , Zhang Dingkun , Lin Junzhi , Han Li
Published: July 2021

Background:Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined.

Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury.

Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting.

Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1.

Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.
Genetic Variants in PTGS1 and NOS3 Genes Increase the Risk of Upper Gastrointestinal Bleeding: A Case–Control Study
Authors: Forgerini Marcela , Urbano Gustavo , Nadai Tales Rubens de , Batah Sabrina Setembre , Fabro Alexandre Todorovic , Mastroianni Patrícia de Carvalho
Published: July 2021

Objective: To assess the association between PTGS1 and NOS3 variant alleles and the risk to develop upper gastrointestinal bleeding (UGIB) secondary to complicated peptic disease.

Methods: A case–control study was conducted in a Brazilian complex hospital from July 2016 to March 2020. Case: Patients with UGIB diagnosis. Control: Patients admitted for surgery not related to gastrointestinal disorders. Variables: UGIB (outcome), genetic variants in PTGS1 and NOS3 genes (independent), and sex, age, schooling, ethnicity, previous history of gastrointestinal disorders, Helicobacter pylori serology, comorbidity, drug therapy, and lifestyle (confounding). The single-nucleotide polymorphisms (SNPs) of the PTSG1 gene (rs1330344, rs3842787, rs10306114, and rs5788) and NOS3 gene (rs2070744 and rs1799983) were determined using the real-time polymerase chain reaction. Helicobacter pylori serology was determined through the chemiluminescence technique. Logistic regression models were built and deviations of allelic frequencies from Hardy–Weinberg equilibrium were verified.

Results: 200 cases and 706 controls were recruited. Carriers of the AG genotype of rs10306114 (OR: 2.55, CI 95%: 1.13–5.76) and CA + AA genotypes of rs5788 (OR: 2.53, CI 95%: 1.14–5.59) were associated with an increased risk for the UGIB development. In nonsteroidal anti-inflammatory drugs (NSAIDs) users, the six variants evaluated modified the magnitude of the risk of UGIB, whereas in low-dose aspirin (LDA) users, an increased risk of UGIB was observed for four of them (rs1330344, rs10306114, rs2070744, and rs1799983). Personal ulcer history (p-value: < 0.001); Helicobacter pylori infection (p-value: < 0.011); NSAIDs, LDA, and oral anticoagulant use (p-value: < 0.001); and alcohol intake (p-value: < 0.001) were also identified as independent risk factors for UGIB.

Conclusion: This study presents two unprecedented analyses within the scope of the UGIB (rs10306114 and rs2070744), and our findings showing an increased risk of UGIB in the presence of the genetic variants rs10306114 and rs5788, regardless of the drug exposure. Besides, the presence of the evaluated variants might modify the magnitude of the risk of UGIB in LDA/NSAIDs users. Therefore, our data suggest the need for a personalized therapy and drug use monitoring in order to promote patient safety.
Hyperprogressive Disease in Cancers Treated With Immune Checkpoint Inhibitors
Authors: Shen Pan , Han Liang , Ba Xin , Qin Kai , Tu Shenghao
Published: July 2021

Immunotherapy, which takes advantage of the immune system to eliminate cancer cells, has been widely studied and applied in oncology. Immune checkpoint inhibitors (ICIs) prevent the immune system from being turned off before cancer cells are eliminated. They have proven to be among the most promising and effective immunotherapies, with significant survival benefits and durable responses in diverse tumor types. However, an increasing number of retrospective studies have found that some patients treated with ICIs experience unusual responses, including accelerated proliferation of tumor cells and rapid progression of the disease, with poor outcomes. Such unexpected adverse events are termed hyperprogressive disease (HPD), and their occurrence suggests that ICIs are detrimental to a subset of cancer patients. HPD is common, with an incidence ranging between 4 and 29% in several cancer types. However, the mechanisms of HPD remain poorly understood, and no clinical predictive factors of HPD have been identified. In this review, we summarize current findings, including retrospective studies and case reports, and focus on several key issues including the defining characteristics, predictive biomarkers, potential mechanisms of HPD, and strategies for avoiding HPD after ICI treatment.
Dissecting the Role of Mesenchymal Stem Cells in Idiopathic Pulmonary Fibrosis: Cause or Solution
Authors: Samarelli Anna Valeria , Tonelli Roberto , Heijink Irene , Martin Medina Aina , Marchioni Alessandro , Bruzzi Giulia , Castaniere Ivana , Andrisani Dario , Gozzi Filippo , Manicardi Linda , Moretti Antonio , Cerri Stefania , Fantini Riccardo , Tabbì Luca , Nani Chiara , Mastrolia Ilenia , Weiss Daniel J. , Dominici Massimo , Clini Enrico
Published: July 2021

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of idiopathic interstitial pneumonias, characterized by chronic and progressive fibrosis subverting the lung’s architecture, pulmonary functional decline, progressive respiratory failure, and high mortality (median survival 3 years after diagnosis). Among the mechanisms associated with disease onset and progression, it has been hypothesized that IPF lungs might be affected either by a regenerative deficit of the alveolar epithelium or by a dysregulation of repair mechanisms in response to alveolar and vascular damage. This latter might be related to the progressive dysfunction and exhaustion of the resident stem cells together with a process of cellular and tissue senescence. The role of endogenous mesenchymal stromal/stem cells (MSCs) resident in the lung in the homeostasis of these mechanisms is still a matter of debate. Although endogenous MSCs may play a critical role in lung repair, they are also involved in cellular senescence and tissue ageing processes with loss of lung regenerative potential. In addition, MSCs have immunomodulatory properties and can secrete anti-fibrotic factors. Thus, MSCs obtained from other sources administered systemically or directly into the lung have been investigated for lung epithelial repair and have been explored as a potential therapy for the treatment of lung diseases including IPF. Given these multiple potential roles of MSCs, this review aims both at elucidating the role of resident lung MSCs in IPF pathogenesis and the role of administered MSCs from other sources for potential IPF therapies.
Psychological Capital Differs Among Rural Left-Behind Children and Is Associated With Emotional and Behavioral Problems
Authors: Zhu Cuiying , Yin Xiaolan , Li Zhihua , Zhou Lujun
Published: July 2021

This study aims to explore, through latent profile analysis (LPA), rural left-behind children’s psychological capital and its relationship with emotional and behavioral indicators. In this study, 677 rural-based left-behind children (average age 11.7 ± 1.58 years) in Hunan Province, China, were recruited and assessed using the Rural Left-behind Children’s Psychological Capital Questionnaire and the Children’s Strengths and Difficulties Questionnaire. We found that psychological capital was divided into three latent profiles: high (43.3% of the sample), medium (46.1%), and low (10.6%). Compared to the other two types, the children with low psychological capital returned higher scores for emotional symptoms, conduct disorder, hyperactivity and impulsivity, and peer-interaction problems, but lower prosocial behavior scores. Meanwhile, examination of the effects of gender and grade found that most of the elementary school students had high psychological capital, and that there was no significant difference among the groups in regard to gender. In summary, distinct differences in psychological capital were found among left-behind children, and the latent profiles were determined to be related to grade, emotional symptoms, hyperactivity and impulsivity, and prosocial behavior. There was also a significant difference in emotional and behavioral indicators across the different latent profiles.
No Effects of Mental Fatigue and Cerebral Stimulation on Physical Performance of Master Swimmers
Authors: Penna Eduardo Macedo , Filho Edson , Campos Bruno Teobaldo , Ferreira Renato Melo , Parma Juliana Otoni , Lage Guilherme Menezes , Coswig Victor Silveira , Wanner Samuel Penna , Prado Luciano Sales
Published: July 2021

Background: Mental fatigue is a psychobiological state caused by extended periods of cognitive effort, and evidence suggests that mentally fatigued athletes present impaired physical performance. Different ergogenic aids have been proposed to counteract the deleterious effects of mental fatigue, but whether brain stimulation can counteract mental fatigue is still unknown. This scenario is even more obscure considering the effects of these interventions (mental fatigue induction and brain stimulation) in a very experienced population consisting of master athletes.

Method: Ten master swimmers (30 ± 6 years old and 14 ± 8 years of experience) participated in the study. They underwent four experimental conditions before an 800-m freestyle test: mental fatigue with brain stimulation; mental fatigue without brain stimulation; absence of mental fatigue with brain stimulation; and absence of mental fatigue and no brain stimulation. Mental fatigue was induced by a cognitively demanding Stroop Color Test, whereas stimulation was applied on the temporal cortex. After that, the athletes swan 800 m as fast as possible and provided their ratings of perceived exertion (RPE) every 200 m.

Results: Mental fatigue was effectively induced, as evidenced by a greater fatigue perception and more errors in the last blocks of the cognitive task. Mental fatigue induction did not influence performance (time to complete the swimming trial) and RPE. Similarly, brain stimulation failed to change these two parameters, regardless of mental fatigue induction.

Conclusion: The prolonged physical performance of experienced master athletes is not influenced, under the present conditions, by mental fatigue induction, cerebral stimulation, and their association.
Adverse Childhood Experiences and Neurocognition in Schizophrenia Spectrum Disorders: Age at First Exposure and Multiplicity Matter
Authors: Kasznia Justyna , Pytel Aleksandra , Stańczykiewicz Bartłomiej , Samochowiec Jerzy , Preś Joanna , Rachubińska Karolina , Misiak Błażej
Published: July 2021

Adverse childhood experiences (ACEs) might be related to cognitive impairments observed in schizophrenia spectrum disorders (SSD). However, it remains unknown what aspects of ACEs are associated with cognitive impairments in SSD. Therefore, we aimed to investigate the association between various characteristics of ACEs (age at first exposure, severity, and multiplicity) and cognition in SSD and healthy controls (HCs). We enrolled 127 individuals with SSD and 56 HCs. Cognitive performance was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Childhood Experience of Care and Abuse Questionnaire was administered to record a history of ACEs. The following characteristics of ACEs were analyzed: multiplicity, severity, and age at first exposure. Individuals with SSD had significantly lower scores on all RBANS domains. Multiplicity and severity of ACEs were significantly higher in patients with SSD compared to HCs. In both groups, greater multiplicity of ACEs was associated with lower scores of global cognition and delayed memory. Additionally, in subjects with SSD, greater multiplicity and younger age at first exposure were associated with lower scores of attention. The present findings indicate that greater multiplicity and younger age at first exposure are the most important aspects of ACEs contributing to cognitive impairments observed in SSD. Moreover, ACEs might exert differential impact on cognition in SSD and HCs.
Role of Threat and Coping Appraisal in Protection Motivation for Adoption of Preventive Behavior During COVID-19 Pandemic
Authors: Lahiri Arista , Jha Sweety Suman , Chakraborty Arup , Dobe Madhumita , Dey Abhijit
Published: July 2021

With more than 100 million cases and over 2 million deaths globally, the COVID-19 pandemic continues to remain a major threat. Identifying the behavioral factors influencing preventive behaviors for COVID-19 are crucial in devising public health policies to promote essential strategies to combat the pandemic in an efficient manner. The current study was therefore conducted to estimate the prevalence of COVID-19 preventive behaviors and measure their association with behavioral constructs like threat perception, response efficacy, and self-efficacy, as per socio-demographic background. A region-stratified online survey focusing on the constructs of protection motivation theory, for example, threat and coping appraisal for preventive health practices against COVID-19, was carried out among adult users of social media in India. Generalized linear models with cluster-adjusted-robust standard errors were used to analyze the responses and model the preventive practices among the study population. Analysis of a total 2,646 responses revealed that proper perceptions regarding cause, symptoms, and transmission of COVID-19 were prevalent in the majority of the respondents. The majority of the participants reported frequent use of face masks (93.20%), followed by frequent washing of hands with soap and water (84.90%). The majority of the respondents affirmed that, though not frequently but sometimes, they avoid touching the face with unclean hands. Frequently covering mouth with the crook of the elbow while sneezing and coughing, and maintaining physical distance when outside was noted among 74.14 and 83.84%, respectively. The proportion of participants frequently using sanitizers to clean hands and those infrequently practicing the same were comparable. Self-efficacy for preventive practices and threat-appraisal of COVID-19 illness were identified as important determinants of the selected COVID-19 preventive behaviors, independently. The analysis confirmed that practices of the behaviors were mostly synergistic to each other. Current findings highlight that formulation of precise risk communication strategies to improve perceptions regarding threat appraisal and self-efficacy could facilitate desirable practices, which are also effective in the prevention of airborne infections and, hence, may contribute toward broader policy directions. The evidence urges the implementation of precision-driven risk communication and diffusion of these practices to attain behavioral herd immunity.