bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
Authors: Willits Adam B. , Grossi Victoria , Glidden Nicole C. , Hyams Jeffrey S. , Young Erin E.
Published: November 2021

Objectives: Functional Abdominal Pain (FAP) and Irritable Bowel Syndrome (IBS) are common recurrent abdominal pain diagnoses with the hallmark, lack of inflammation. To identify a biological signature for IBS/FAP in the colon, this study used genetic profiling to uncover gene expression changes associated with IBS/FAP and abdominal pain.

Methods: Patients (8 to 17 years) newly diagnosed with IBS or FAP were enrolled in the study. At diagnostic colonoscopy, three rectal biopsies were collected, and gene expression analysis was performed using a Qiagen PCR Array. Relative fold difference in gene expression for 84 pain-associated genes was calculated using the 2-ΔΔ Cq method compared with pain-free controls. Factors affecting pain burden (Pain Burden Interview; PBI) were analyzed, including age, sex, rectal inflammation, and gene expression. Data were analyzed using multiple stepwise linear regression and 2-tailed t tests (P ≤ 0.05).

Results: Of the 22 total patients in the study, 19 were diagnosed with either IBS-Constipation (frequency of 5.26%), IBS-Diarrhea (47.37%), IBS-Mixed (10.53%), or FAP (36.84%). IBS/FAP patients reported significantly higher pain burden at the time of diagnosis compared to pain-free controls (p < 0.001), as well as significantly higher abdominal pain (p = 0.01). Of the 84 genes, expression of GRIN1 (p = 0.02), MAPK3 (p = 0.04), P2X4 (p = 0.04), and PTGES3 (p = 0.02) were all significantly associated with PBI score.

Discussion: Abdominal pain associated with IBS/FAP in pediatric patients may be linked to the expression of GRIN1, MAPK3, P2X4, and PTGES3, pointing to potential novel therapeutic targets for management of recurring abdominal pain.
Association Between Platelet-to-Lymphocyte Ratio and Preterm Necrotizing Enterocolitis
Authors: Zheng Juan , Wang Hua
Published: November 2021

Introduction: Necrotizing enterocolitis (NEC) is a fatal condition for very-low-birth-weight infants. Necrotizing enterocolitis is a multi-factor phenomenon that results in intestinal mucosal damage and leads to intestinal necrosis. However, sensitive laboratory indicators for NEC are lacking, making early diagnosis difficult. This study aimed to explore the relationship between the platelet-to-lymphocyte ratio (PLR) and NEC in preterm neonates to enable an earlier diagnosis of the condition.

Methods: This was a retrospective case–control study of preterm neonates diagnosed with NEC between January 2018 and December 2019 in the West China Second University Hospital. Controls were selected from preterm neonatal intensive care unit (NICU) graduates, and they were matched for gestation and year of birth to the preterms diagnosed without NEC. In total, 93 and 107 infants were included in the NEC and control groups, respectively. Empowerstats analysis was used to identify the association between PLR and preterm NEC.

Results: The NEC group had significantly higher PLR levels than the control group. PLR > 100 within 1 week before NEC diagnosis was a risk factor for NEC. There was a positive connection between PLR and preterm NEC. A PLR of >100 was determined as the optimal cutoff for predicting preterm NEC, with patients with PLR >100 having a higher risk of NEC [odds ratio (OR): 18.82 (95% confidence interval (CI): 2.93–120.98), p = 0.002].

Conclusions: A PLR of >100 within 1 week after clinical abnormalities is associated with a high risk of NEC in preterm neonates.
Outcomes of High-Flow Nasal Cannula Vs. Nasal Continuous Positive Airway Pressure in Young Children With Respiratory Distress: A Systematic Review and Meta-Analysis
Authors: Zhao Xueqin , Qin Qiaozhi , Zhang Xian
Published: November 2021

Background: Continuous positive airway pressure (CPAP) has been associated with a lower risk of treatment failure than high-flow nasal cannula (HFNC) in pediatric patients with respiratory distress and severe hypoxemia. However, the publication of new trials on children younger than 2 years warrants a review and updated meta-analysis of the evidence.

Methods: We conducted a systematic search in the PubMed, Scopus, and Google scholar databases for randomized controlled trials (RCTs) in pediatric patients with acute respiratory distress that examined outcomes of interest by the two usual management modalities (CPAP and HFNC). We used pooled adjusted relative risks (RRs) to present the strength of association for categorical outcomes and weighted mean differences (WMDs) for continuous outcomes.

Results: We included data from six articles in the meta-analysis. The quality of the studies was deemed good. Included studies had infants with either acute viral bronchiolitis or pneumonia. Compared to CPAP, HFNC treatment carried a significantly higher risk of treatment failure [RR, 1.45; 95% CI, 1.06 to 1.99; I2 = 0.0%, n = 6]. Patients receiving HFNC had a lower risk of adverse events, mainly nasal trauma [RR, 0.30; 95% CI, 0.14 to 0.62; I2 = 0.0%, n = 2] than the others. The risk of mortality [RR, 3.33; 95% CI, 0.95, 11.67; n = 1] and need for intubation [RR, 1.69; 95% CI, 0.97, 2.94; I2 = 0.0%, n = 5] were statistically similar between the two management strategies; however, the direction of the pooled effect sizes is indicative of a nearly three times higher mortality and two times higher risk of intubation in those receiving HFNC. We found no statistically significant differences between the two management modalities in terms of modified woods clinical asthma score (M-WCAS; denoting severity of respiratory distress) and hospitalization length (days). Patients receiving HFNC had the time to treatment failure reduced by approximately 3 h [WMD, −3.35; 95% CI, −4.93 to −1.76; I2 = 0.0%, n = 2] compared to those on CPAP.

Conclusions: Among children with respiratory distress younger than 2 years, HFNC appears to be associated with higher risk of treatment failure and possibly, an increased risk of need for intubation and mortality. Adequately powered trials are needed to confirm which management strategy is better.
Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?
Authors: Merli Pietro , Ifversen Marianne , Truong Tony H. , Marquart Hanne V. , Buechner Jochen , Wölfl Matthias , Bader Peter
Published: November 2021

Minimal residual disease (MRD) assessment plays a central role in risk stratification and treatment guidance in paediatric patients with acute lymphoblastic leukaemia (ALL). As such, MRD prior to haematopoietic stem cell transplantation (HSCT) is a major factor that is independently correlated with outcome. High burden of MRD is negatively correlated with post-transplant survival, as both the risk of leukaemia recurrence and non-relapse mortality increase with greater levels of MRD. Despite growing evidence supporting these findings, controversies still exist. In particular, it is still not clear whether multiparameter flow cytometry and real-time quantitative polymerase chain reaction, which is used to recognise immunoglobulin and T-cell receptor gene rearrangements, can be employed interchangeably. Moreover, the higher sensitivity in MRD quantification offered by next-generation sequencing techniques may further refine the ability to stratify transplant-associated risks. While MRD quantification from bone marrow prior to HSCT remains the state of the art, heavily pre-treated patients may benefit from additional staging, such as using 18F-fluorodeoxyglucose positron emission tomography/computed tomography to detect focal residues of disease. Additionally, the timing of MRD detection (i.e., immediately before administration of the conditioning regimen or weeks before) is a matter of debate. Pre-transplant MRD negativity has previously been associated with superior outcomes; however, in the recent For Omitting Radiation Under Majority age (FORUM) study, pre-HSCT MRD positivity was associated with neither relapse risk nor survival. In this review, we discuss the level of MRD that may require pre-transplant therapy intensification, risking time delay and complications (as well as losing the window for HSCT if disease progression occurs), as opposed to an adapted post-transplant strategy to achieve long-term remission. Indeed, MRD monitoring may be a valuable tool to guide individualised treatment decisions, including tapering of immunosuppression, cellular therapies (such as donor lymphocyte infusions) or additional immunotherapy (such as bispecific T-cell engagers or chimeric antigen receptor T-cell therapy).
Somatostatin and Its Receptors in Myocardial Ischemia/Reperfusion Injury and Cardioprotection
Authors: Vörös Imre , Sághy Éva , Pohóczky Krisztina , Makkos András , Onódi Zsófia , Brenner Gábor B. , Baranyai Tamás , Ágg Bence , Váradi Barnabás , Kemény Ágnes , Leszek Przemyslaw , Görbe Anikó , Varga Zoltán V. , Giricz Zoltán , Schulz Rainer , Helyes Zsuzsanna , Ferdinandy Péter
Published: November 2021

Little is known about the role of the neuropeptide somatostatin (SST) in myocardial ischemia/reperfusion injury and cardioprotection. Here, we investigated the direct cardiocytoprotective effect of SST on ischemia/reperfusion injury in cardiomyocyte cultures, as well as the expression of SST and its receptors in pig and human heart tissues. SST induced a bell-shaped, concentration-dependent cardiocytoprotection in both adult rat primary cardiomyocytes and H9C2 cells subjected to simulated ischemia/reperfusion injury. Furthermore, in a translational porcine closed-chest acute myocardial infarction model, ischemic preconditioning increased plasma SST-like immunoreactivity. Interestingly, SST expression was detectable at the protein, but not at the mRNA level in the pig left ventricles. SSTR1 and SSTR2, but not the other SST receptors, were detectable at the mRNA level by PCR and sequencing in the pig left ventricle. Moreover, remote ischemic conditioning upregulated SSTR1 mRNA. Similarly, SST expression was also detectable in healthy human interventricular septum samples at the protein level. Furthermore, SST-like immunoreactivity decreased in interventricular septum samples of patients with ischemic cardiomyopathy. SSTR1, SSTR2, and SSTR5 but not SST and the other SST receptors were detectable at the mRNA level by sequencing in healthy human left ventricles. In addition, in healthy human left ventricle samples, SSTR1 and SSTR2 mRNAs were expressed especially in vascular endothelial and some other cell types as detected by RNA Scope®in situ hybridization. This is the first demonstration that SST exerts a direct cardiocytoprotective effect against simulated ischemia/reperfusion injury. Moreover, SST is expressed in the heart tissue at the peptide level; however, it is likely to be of sensory neural origin since its mRNA is not detectable. SSTR1 and SSTR2 might be involved in the cardioprotective action of SST, but other mechanisms cannot be excluded.
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33
Authors: Jovicic Nemanja , Petrovic Ivica , Pejnovic Nada , Ljujic Biljana , Miletic Kovacevic Marina , Pavlovic Sladjana , Jeftic Ilija , Djukic Aleksandar , Srejovic Ivan , Jakovljevic Vladimir , Lukic Miodrag L
Published: November 2021

Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD–STZ)–induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD–STZ–induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD–STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ST2+cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12–18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes.
Near Infrared Spectroscopy for High-Temporal Resolution Cerebral Physiome Characterization in TBI: A Narrative Review of Techniques, Applications, and Future Directions
Authors: Gomez Alwyn , Sainbhi Amanjyot Singh , Froese Logan , Batson Carleen , Alizadeh Arsalan , Mendelson Asher A. , Zeiler Frederick A.
Published: November 2021

Multimodal monitoring has been gaining traction in the critical care of patients following traumatic brain injury (TBI). Through providing a deeper understanding of the individual patient’s comprehensive physiologic state, or “physiome,” following injury, these methods hold the promise of improving personalized care and advancing precision medicine. One of the modalities being explored in TBI care is near-infrared spectroscopy (NIRS), given it’s non-invasive nature and ability to interrogate microvascular and tissue oxygen metabolism. In this narrative review, we begin by discussing the principles of NIRS technology, including spatially, frequency, and time-resolved variants. Subsequently, the applications of NIRS in various phases of clinical care following TBI are explored. These applications include the pre-hospital, intraoperative, neurocritical care, and outpatient/rehabilitation setting. The utility of NIRS to predict functional outcomes and evaluate dysfunctional cerebrovascular reactivity is also discussed. Finally, future applications and potential advancements in NIRS-based physiologic monitoring of TBI patients are presented, with a description of the potential integration with other omics biomarkers.
Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
Authors: He Yang-Yang , Xie Xin-Mei , Zhang Hong-Da , Ye Jue , Gencer Selin , van der Vorst Emiel P. C. , Döring Yvonne , Weber Christian , Pang Xiao-Bin , Jing Zhi-Cheng , Yan Yi , Han Zhi-Yan
Published: November 2021

Objective: Pulmonary hypertension (PH) associated with hypoxia and lung disease (Group 3) is the second most common form of PH and associated with increased morbidity and mortality. This study was aimed to identify hypoxia induced metabolism associated genes (MAGs) for better understanding of hypoxic PH.

Methods: Rat pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured in normoxic or hypoxic condition for 24 h. Cells were harvested for liquid chromatography-mass spectrometry analysis. Functional annotation of distinguishing metabolites was performed using Metaboanalyst. Top 10 enriched metabolite sets were selected for the identification of metabolism associated genes (MAGs) with a relevance score >8 in Genecards. Transcriptomic data from lungs of hypoxic PH in mice/rats or of PH patients were accessed from Gene Expression Omnibus (GEO) database or open-access online platform. Connectivity Map analysis was performed to identify potential compounds to reverse the metabolism associated gene profile under hypoxia stress. The construction and module analysis of the protein-protein interaction (PPI) network was performed. Hub genes were then identified and used to generate LASSO model to determine its accuracy to predict occurrence of PH.

Results: A total of 36 altered metabolites and 1,259 unique MAGs were identified in rat PASMCs under hypoxia. 38 differentially expressed MAGs in mouse lungs of hypoxic PH were revealed, with enrichment in multi-pathways including regulation of glucose metabolic process, which might be reversed by drugs such as blebbistatin. 5 differentially expressed MAGs were displayed in SMCs of Sugen 5416/hypoxia induced PH rats at the single cell resolution. Furthermore, 6 hub genes (Cat, Ephx1, Gpx3, Gstm4, Gstm5, and Gsto1) out of 42 unique hypoxia induced MAGs were identified. Higher Cat, Ephx1 and lower Gsto1 were displayed in mouse lungs under hypoxia (all p < 0.05), in consistent with the alteration in lungs of PH patients. The hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.90).

Conclusion: Our findings revealed six hypoxia-induced metabolism associated hub genes, and shed some light on the molecular mechanism and therapeutic targets in hypoxic PH.
Effects of Vitamin D3 and Meso-Zeaxanthin on Human Retinal Pigmented Epithelial Cells in Three Integrated in vitro Paradigms of Age-Related Macular Degeneration
Authors: Lazzara Francesca , Conti Federica , Platania Chiara Bianca Maria , Eandi Chiara M. , Drago Filippo , Bucolo Claudio
Published: November 2021

Age-related macular degeneration (AMD) is a degenerative retinal disease and one of major causes of irreversible vision loss. AMD has been linked to several pathological factors, such as oxidative stress and inflammation. Moreover, Aβ (1–42) oligomers have been found in drusen, the extracellular deposits that accumulate beneath the retinal pigmented epithelium in AMD patients. Hereby, we investigated the hypothesis that treatment with 1,25(OH) 2D3 (vitamin D3) and meso-zeaxathin, physiologically present in the eye, would counteract the toxic effects of three different insults on immortalized human retinal pigmented epithelial cells (ARPE-19). Specifically, ARPE-19 cells have been challenged with Aβ (1–42) oligomers, H2O2, LPS, and TNF-α, respectively. In the present study, we demonstrated that the combination of 1,25(OH)2D3 and meso-zeaxanthin significantly counteracted the cell damage induced by the three insults, at least in these in vitro integrated paradigms of AMD. These results suggest that combination of 1,25(OH)2D3 and meso-zeaxathin could be a useful approach to contrast pathological features of AMD, such as retinal inflammation and oxidative stress.
Mechanical Response of Listric Faults in the Three Gorges Reservoir Area Based on Three-Dimensional Morphological Characteristics
Authors: Duan Guoyong , Wang Lehua , Deng Huafeng , Zhang Jingyu , Luo Zuosen , Jiang Qiao
Published: November 2021

Faults or joints widely exist in rock masses, which deeply affect the mechanical properties of rock. The seismic frequency of the Gaoqiao fault and its surrounding areas in the Three Gorges Reservoir area before and after water storage is significantly higher than that in other areas. In this study, a curved joint is used to simulate the occurrence characteristics of the Gaoqiao fault, and the influence of reservoir water is simulated by adjusting the fracture water pressure. Compared with the changes of joint surface morphology parameters before and after the test, it is found that the macro failure characteristics of rock samples are in good agreement with the micromorphology changes of the joint surface. Among them, the parameters such as root-mean-square height (Sq), arithmetic mean height (Sa), reverse load area ratio (Smc), and minimum autocorrelation length (Sal) can better characterize the joint surface deterioration of rock samples under the action of fracture water pressure. The test results have a certain reference value for studying the fault response under the action of reservoir water.
Microbial Consortia for Effective Biocontrol of Root and Foliar Diseases in Tomato
Authors: Minchev Zhivko , Kostenko Olga , Soler Roxina , Pozo María J.
Published: November 2021

The use of beneficial microorganisms for the biological control of plant diseases and pests has emerged as a viable alternative to chemical pesticides in agriculture. Traditionally, microbe-based biocontrol strategies for crop protection relied on the application of single microorganisms. However, the design of microbial consortia for improving the reliability of current biological control practices is now a major trend in biotechnology, and it is already being exploited commercially in the context of sustainable agriculture. In the present study, exploiting the microbial library of the biocontrol company Koppert Biological Systems, we designed microbial consortia composed of carefully selected, well-characterized beneficial bacteria and fungi displaying diverse biocontrol modes of action. We compared their ability to control shoot and root pathogens when applied separately or in combination as microbial consortia, and across different application strategies that imply direct microbial antagonism or induced systemic plant resistance. We hypothesized that consortia will be more versatile than the single strains, displaying an extended functionality, as they will be able to control a wider range of plant diseases through diverse mechanisms and application methods. Our results confirmed our hypothesis, revealing that while different individual microorganisms were the most effective in controlling the root pathogen Fusarium oxysporum or the foliar pathogen Botrytis cinerea in tomato, the consortia showed an extended functionality, effectively controlling both pathogens under any of the application schemes, always reaching the same protection levels as the best performing single strains. Our findings illustrate the potential of microbial consortia, composed of carefully selected and compatible beneficial microorganisms, including bacteria and fungi, for the development of stable and versatile biological control products for plant protection against a wider range of diseases.
Genetic Transformation of Apomictic Grasses: Progress and Constraints
Authors: Bellido Andrés M. , Souza Canadá Eduado D. , Permingeat Hugo R. , Echenique Viviana
Published: November 2021

The available methods for plant transformation and expansion beyond its limits remain especially critical for crop improvement. For grass species, this is even more critical, mainly due to drawbacks in in vitro regeneration. Despite the existence of many protocols in grasses to achieve genetic transformation through Agrobacterium or biolistic gene delivery, their efficiencies are genotype-dependent and still very low due to the recalcitrance of these species to in vitro regeneration. Many plant transformation facilities for cereals and other important crops may be found around the world in universities and enterprises, but this is not the case for apomictic species, many of which are C4 grasses. Moreover, apomixis (asexual reproduction by seeds) represents an additional constraint for breeding. However, the transformation of an apomictic clone is an attractive strategy, as the transgene is immediately fixed in a highly adapted genetic background, capable of large-scale clonal propagation. With the exception of some species like Brachiaria brizantha which is planted in approximately 100 M ha in Brazil, apomixis is almost non-present in economically important crops. However, as it is sometimes present in their wild relatives, the main goal is to transfer this trait to crops to fix heterosis. Until now this has been a difficult task, mainly because many aspects of apomixis are unknown. Over the last few years, many candidate genes have been identified and attempts have been made to characterize them functionally in Arabidopsis and rice. However, functional analysis in true apomictic species lags far behind, mainly due to the complexity of its genomes, of the trait itself, and the lack of efficient genetic transformation protocols. In this study, we review the current status of the in vitro culture and genetic transformation methods focusing on apomictic grasses, and the prospects for the application of new tools assayed in other related species, with two aims: to pave the way for discovering the molecular pathways involved in apomixis and to develop new capacities for breeding purposes because many of these grasses are important forage or biofuel resources.
Using Rational Models to Interpret the Results of Experiments on Accent Adaptation
Authors: Tan Maryann , Xie Xin , Jaeger T. Florian
Published: November 2021

Exposure to unfamiliar non-native speech tends to improve comprehension. One hypothesis holds that listeners adapt to non-native-accented speech through distributional learning—by inferring the statistics of the talker's phonetic cues. Models based on this hypothesis provide a good fit to incremental changes after exposure to atypical native speech. These models have, however, not previously been applied to non-native accents, which typically differ from native speech in many dimensions. Motivated by a seeming failure to replicate a well-replicated finding from accent adaptation, we use ideal observers to test whether our results can be understood solely based on the statistics of the relevant cue distributions in the native- and non-native-accented speech. The simple computational model we use for this purpose can be used predictively by other researchers working on similar questions. All code and data are shared.
Emotional Distress in Cancer Patients During the First Wave of the COVID-19 Pandemic
Authors: Toquero Patricia , Blanco Fernández Carmen , López Martí María Pilar , Hernández Marín Berta , Vera Cea E. Beatriz , Garrido García Ana , Méndez Carrascosa Elena , Bañón Torres Dulce , Donnay Candil Olga , Ballesteros García Ana Isabel , Sánchez-Torres José Miguel , Costas Rojo Pablo , Mondéjar Rebeca , Colomer Ramon , Romero-Laorden Nuria
Published: November 2021

Background: The COVID-19 pandemic has caused mental health problems worldwide. The psychopathological implications of COVID-19 in cancer patients have rarely been addressed. Considering the increased vulnerability of oncology patients, this issue needs to be addressed to improve the long-term mental health status of these patients.

Methods: We conducted a prospective study in outpatients under active cancer treatment during the first wave of the COVID-19 pandemic. A semi-structured 24-question survey was designed to measure baseline sociodemographic, psychosocial and COVID-19 exposure characteristics. The Hospital Anxiety and Depression Scale was used to measure psychological symptoms. A descriptive and analytical univariate analysis of the variables studied was performed. We used the Z-score to compare different populations (experimental and historical control cohort).

Results: 104 patients were included, the majority of which were women (64.4%), were above 65 years of age (57.7%), had either lung and breast cancer (56.7%), had advanced disease (64%) and were undergoing chemotherapy (63.5%). 51% of them expressed greater fear of cancer than of COVID-19 infection or both.

In relation to HADS, 52.8% of emotional distress, 42.3% of anxiety and 58.6% of depression rates were detected. The main factors related with higher rates of psychological symptomatology were history of previous psychotropic drug consumption and the adoption of additional infection prevention measures because they considered themselves at risk of severe COVID-19 infection (p = 0.008; p = 0.003 for emotional distress, p = 0.026; p = 0.004 for anxiety, and p = 0.013; p = 0.008 for depression). Tumor type, stage, oncologic treatment or rescheduling of cancer treatments were not related to higher levels of psychological symptomatology.

Comparison of our results with another population of similar characteristics was not significant (Z score = −1.88; p = 0.060).

Conclusions: We detected high rates of emotional distress during the first wave of the COVID-19 pandemic among cancer patients in active treatment (52.8%). This was higher and clinically relevant than observed in a comparable population (42.5%), although not significant. Cancer itself is the main factor of concern for cancer patients, above and beyond the emotional distress generated by COVID-19 pandemic.
Baseline Power of Theta Oscillations Predicts Mystical-Type Experiences Induced by DMT in a Natural Setting
Authors: Tagliazucchi Enzo , Zamberlan Federico , Cavanna Federico , de la Fuente Laura , Romero Celeste , Sanz Perl Yonatan , Pallavicini Carla
Published: November 2021

N,N-Dimethyltryptamine (DMT) is a classic psychedelic capable of inducing short-lasting but profound changes in consciousness. As with other psychedelics, the experience induced by DMT strongly depends upon contextual factors, yet the neurobiological determinants of this variability remain unknown. The present study investigated changes in neural oscillations elicited by inhaled DMT, and whether baseline electroencephalography (EEG) recordings could predict the subjective effects reported by the participants. Healthy volunteers (N = 35) were measured with EEG before and during the acute effects of DMT consumed in a natural setting. Source-localized neural oscillations were correlated with the results of multiple questionnaires employed to assess the subjective effects of the drug. DMT resulted in a marked reduction of alpha and beta oscillations, and increased posterior spectral power in the delta, theta and gamma bands. The power of fronto-temporal theta oscillations was inversely correlated with scales indexing feelings of unity and transcendence, which are an integral part of the phenomenology of mystical-type experiences. The robustness of these results was supported using a machine learning model for regression trained and tested following a cross-validation procedure. These results are consistent with the observation that the state of mind prior to consuming a psychedelic drug influences the ensuing subjective experience of the user. They also suggest that baseline EEG screenings before administration of a serotonergic psychedelic could be useful to estimate the likelihood of inducing mystical-type experiences, previously linked to sustained positive effects in well-being and improved outcome of therapeutic interventions.
Cannabidiol Cigarettes as Adjunctive Treatment for Psychotic Disorders – A Randomized, Open-Label Pilot-Study
Authors: Köck Patrick , Lang Elisabeth , Trulley Valerie-Noelle , Dechent Frieder , Mercer-Chalmers-Bender Katja , Frei Priska , Huber Christian , Borgwardt Stefan
Published: November 2021

Background: Psychotic disorders are associated with high rates of comorbid substance use disorders. Use of cannabis rich in tetrahydrocannabinol (THC) is linked to an increased risk of psychosis, worsening of psychotic symptoms, and an adverse course of psychotic disorders. Previous studies suggest oral cannabidiol (CBD) as possible novel antipsychotic agent; however, no studies evaluated the effects of smoked CBD.

Objective: The main aim of the study was to clarify the antipsychotic potential of CBD used as adjunctive therapy simulating a naturalistic setting. Our trial is the first study evaluating the effects of smoked CBD-cigarettes as adjunctive therapy for psychotic symptoms.

Methods: A randomized, placebo-controlled open-label trial of cigarettes containing CBD-rich cannabis (THC < 1%) as adjunctive therapy to standard psychiatric treatment was conducted (ClinicalTrials.gov identifier NCT04700930). Primary outcomes were mean scores of Positive and Negative Syndrome Scale (PANSS), Brøset Violence Checklist, the Beck's Depression Inventory (BDI), the Subjective Well-Being Under Neuroleptics Scale short form (SWN-K), and antipsychotic medication equivalent doses. Outcomes were assessed after 4 weeks of acute treatment and long-term follow-up after discontinuation of CBD-cigarettes after 25 weeks. Participants were 31 acutely psychotic patients with tobacco use disorder and a mean age of 35.1 ± 10.58 years (71% male). Comorbid cannabis use was diagnosed in 51.6%.

Results: A discontinuous multilevel model revealed no significant group differences for primary outcomes. After 4 weeks of acute treatment, mean PANSS and BDI decreased in both groups, while an increase of antipsychotic medication equivalent was observed in the placebo group.

Conclusions: The presented findings might suggest an antipsychotic medication sparing effect of CBD-cigarettes as adjunctive treatment of acute psychosis. However, the low number of participants did not allow for further statistical analysis. Hence, a larger study sample and a more rigorous study design (blinding of the interventional product, fixed dosing regimen) may reveal different results.

Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04700930
Do Women in Nepal Like Playing a Mobile Game? MANTRA: A Mobile Gamified App for Improving Healthcare Seeking Behavior in Rural Nepal
Authors: Kayastha Rachya , Mueller Sonja , Yadav Punam , Kelman Ilan , Boscor Andrei , Saville Naomi , Arjyal Abriti , Baral Sushil , Fordham Maureen , Hearn Gareth , Kostkova Patty
Published: November 2021

In Low and Middle Income Countries (LMIC), one of the causes of maternal and child mortality is a lack of medical knowledge and consequently the inability to seek timely healthcare. Mobile health (mHealth) technology is gradually becoming a universal intervention platform across the globe due to ubiquity of mobile phones and network coverage. MANTRA is a novel mHealth intervention developed to tackle maternal and child health issues through a serious mobile game app in rural Nepal, which demonstrated a statistically significant knowledge improvement in rural women. This paper explores the perceptions and usability of the MANTRA app amongst rural women and Female Community Health Volunteers (FCHVs) in Nepal. Despite the challenges of a target user group with limited educational levels and low smartphone experience, all participants viewed the MANTRA app with approval and enthusiasm. They were willing to engage further with the mHealth intervention and to share their experience and knowledge with fellow community members. Participants also showed an increase in awareness of danger signs enabling them to make better informed health decisions in the future. FCHVs viewed the app as a validation tool providing and support for greater impact of their efforts in rural Nepal. Growing mobile ownership, network coverage and availability of smartphones along with acceptance of the prototype MANTRA app in rural communities suggest encouraging prospects for mHealth interventions to be incorporated in the national health infrastructure in Nepal and other LMICs.
Impact of Adverse Childhood Experiences on Older Adult Poverty: Mediating Role of Depression
Authors: Liao Hui , Yan Chaoyang , Ma Ying , Wang Jing
Published: November 2021

Background: Adverse childhood experiences (ACEs) refer to traumatic events experienced by children in early life, including abuse, neglect, and family dysfunction, which are common worldwide. ACEs are harmful to mental health, and psychological problems can influence personal economic poverty in adulthood. We focused on family dysfunction and discussed the effect of different types of ACEs on poverty and the corresponding mediating effect of depression.

Materials and Methods: A total of 9,910 individuals who were 60 years or older from the China Health and Retirement Longitudinal Study in 2014 and 2015 were analysed. The chi-square test was used to compare poverty incidence among subgroups of independent or control variables. Binary logistic regression analysis was used to test the effect of different types of ACEs on depression, and four logistic regression models were established to observe the association between ACEs on older adult poverty and the mediating effect of depression. The path diagram of the direct effect and indirect effect was drawn to test the mediating effect of depression.

Results: Early death of father, the male guardian getting upset and witnessing violence of father to mother are the risk factors for older adult poverty, whereas female guardian getting upset, relationship with female guardians and parental quarrel are protective factors for older adult poverty. Furthermore, depression has a partial mediating effect on some factors including early death of father, male guardian getting upset, relationship with female guardian, parental quarrel, and witnessing violence of father to mother.

Conclusions: Paternal ACE factors can directly make children more likely to fall into poverty as older adults and can indirectly influence older adult poverty through the partial mediating effect of depression. Assisting poor families, providing psychological counselling, formulating family visit plans, nurturing orphan children under state supervision, and other policies that focus on groups that have experienced paternal ACE events are essential to eliminating the risk factors that influence older adult poverty.
Feasibility and Enjoyment of Exercise Video Games in Older Adults
Authors: Freed Sara A. , Sprague Briana N. , Stephan Abigail T. , Doyle Cassidy E. , Tian Junyan , Phillips Christine B. , Ross Lesley A.
Published: November 2021

Introduction: Several interventions have been developed to enhance social connectedness among older adults. However, little research has demonstrated their performance in a social distancing environment. Exergames are not only beneficial to older adults' physical and cognitive health, but they also allow players to interact with each other at a distance, which can reduce loneliness and increase social connection. The aim of this pilot study was to investigate older adults' perceptions of two commercially available exergames.

Methods: Twenty healthy community-dwelling older adults (M age = 73.30, SD = 5.95, range = 65–84 years, 80% women) were recruited in this pilot study between July 2019 and February 2020. They were asked to play two exergames for 10 min each on the Xbox One with Kinect console: Just Dance and Kinect Sports Rivals. After gameplay, they provided both quantitative and qualitative feedback on these games.

Results: Participants reported an average rating for exergame enjoyment. Greater enjoyment was significantly related with younger age and greater extraversion but not gender. Participants were highly motivated to do well on the games but reported lower scores for likelihood of playing these games in the future. Greater likelihood of future play was associated with younger age but not gender or extraversion. “Not aerobic or strengthen enough; not enough exertion,” and “slower movements, repetition, clear purpose of doing the exercise” were some factors that would influence their decision to buy and play these games.

Discussion: The preliminary results of this pilot study suggest that exergames may help address social isolation and loneliness—particularly during times of social distancing. Before applying exergames as a social isolation or loneliness intervention for older adults, study replication in larger representative studies and future work that examines important design issues related to older adults' experiences with these games is needed.
A Cross-Sectional Survey on COVID-19 Vaccine Hesitancy Among Parents From Shandong vs. Zhejiang
Authors: Xu Yunyun , Xu Dongjuan , Luo Liyan , Ma Fengqiao , Wang Ping , Li Hongfei , Li Qing , Wei Lianyan , Diao Jiuzhou , Liu Yuanyuan , Zhang Weiqiang , Zheng Xiaolei
Published: November 2021

Introduction:With the approval of COVID-19 vaccinations for children and adolescents in China, parental vaccine hesitancy will emerge as a new challenge with regard to the administration of these vaccines. However, little is known regarding this hesitancy as well as regional differences that may exist between parents from Shandong vs. Zhejiang.

Methods:To assess these issues, an online survey was conducted via a Wenjuanxing platform over the period from July 22 to August 14, 2021. Parents from Shandong and Zhejiang were recruited from Wechat groups and results from a total of 917 subjects were analyzed. Factors evaluated in this survey included socio-demographic variables, parental vaccine hesitancy, Parental Attitudes toward Childhood Vaccines (PACV) domains (behavior, safety and efficacy, general attitudes) and social support.

Results:Compared with those from Shandong (N= 443), parents from Zhejiang (N= 474) showed significantly higher prevalence rates of COVID-19 vaccine hesitancy (19.4 vs. 11.7%,p= 0.001). Multivariate logistic regression showed that yearly household incomes of ≥120,000 RMB (p= 0.041), medical workers (p= 0.022) and general attitudes of PACV (p= 0.004) were risk factors for vaccine hesitancy among parents from Shandong, while behavior (p= 0.004), safety and efficacy (p< 0.001) and general attitudes of PACV (p= 0.002) were risk factors for parents from Zhejiang. Among parents with vaccine hesitancy (N= 144), concerns over side effects (91.0%) and unknown effects (84.0%) of the COVID-19 vaccine were the most prevalent reasons for hesitancy. Evidence providing proof of vaccine safety (67.4%) and assurance of a low risk of being infected by COVID-19 (60.4%) were the two most effective persuasive factors.

Conclusion:Parents from Zhejiang showed a higher prevalence of COVID-19 vaccine hesitancy as compared with those from Shandong. Behavior, safety and efficacy, and general attitudes of PACV were the risk factors associated with this hesitancy in these parents from Zhejiang. Given the identification of the various reasons for parental vaccine hesitancy, different strategies as well as regional adjustments in these strategies will be required for an effective and convincing protocol for childhood vaccinations.
Linking Free Text Documentation of Functioning and Disability to the ICF With Natural Language Processing
Authors: Newman-Griffis Denis , Camacho Maldonado Jonathan , Ho Pei-Shu , Sacco Maryanne , Jimenez Silva Rafael , Porcino Julia , Chan Leighton
Published: November 2021

Background: Invaluable information on patient functioning and the complex interactions that define it is recorded in free text portions of the Electronic Health Record (EHR). Leveraging this information to improve clinical decision-making and conduct research requires natural language processing (NLP) technologies to identify and organize the information recorded in clinical documentation.

Methods: We used natural language processing methods to analyze information about patient functioning recorded in two collections of clinical documents pertaining to claims for federal disability benefits from the U.S. Social Security Administration (SSA). We grounded our analysis in the International Classification of Functioning, Disability, and Health (ICF), and used the Activities and Participation domain of the ICF to classify information about functioning in three key areas: mobility, self-care, and domestic life. After annotating functional status information in our datasets through expert clinical review, we trained machine learning-based NLP models to automatically assign ICF categories to mentions of functional activity.

Results: We found that rich and diverse information on patient functioning was documented in the free text records. Annotation of 289 documents for Mobility information yielded 2,455 mentions of Mobility activities and 3,176 specific actions corresponding to 13 ICF-based categories. Annotation of 329 documents for Self-Care and Domestic Life information yielded 3,990 activity mentions and 4,665 specific actions corresponding to 16 ICF-based categories. NLP systems for automated ICF coding achieved over 80% macro-averaged F-measure on both datasets, indicating strong performance across all ICF categories used.

Conclusions: Natural language processing can help to navigate the tradeoff between flexible and expressive clinical documentation of functioning and standardizable data for comparability and learning. The ICF has practical limitations for classifying functional status information in clinical documentation but presents a valuable framework for organizing the information recorded in health records about patient functioning. This study advances the development of robust, ICF-based NLP technologies to analyze information on patient functioning and has significant implications for NLP-powered analysis of functional status information in disability benefits management, clinical care, and research.
Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy
Authors: Gui Qin , Lyons Denver J. , Deeb Janina Golob , Belvin B. Ross , Hoffman Paul S. , Lewis Janina P.
Published: November 2021

Periodontitis is an inflammatory condition triggered by selected oral microbiota; thus treatment strategies should be aimed at reducing the abundance of the pathogenic bacteria. An obstacle to preclinical testing of such strategies is the availability of reliable animal models. Here, a non-human primate (NHP), Macaca mulatta, was used to examine the effectiveness of a novel antimicrobial, amixicile, which inhibits pyruvate–ferredoxin oxidoreductase (PFOR) present in anaerobic bacteria. Animals were assessed for their periodontal health, including radiography, clinical attachment loss (CAL), presence of plaque (PI), bleeding on probing (BOP) and pocket depth (PD), and sampled for saliva, gingival crevicular fluid (GCF), and subgingival plaque to determine their baseline clinical status. Amixicile was then administered for 2 weeks (40 mg/kg/day) and the animals were monitored for periodontal health immediately after the antibiotic treatment, then at 1 month-, 3 months-, and 6-months posttreatment. Microbial species present in plaque and saliva were determined through 16S rDNA sequencing. Baseline assessment of the microbiome has shown a significant proportion of bacteria belonging to the Streptococcus, Haemophilus, Porphyromonas, Gemella, and Fusobacterium genera. The abundance of Porphyromonas and Fusobacterium was reduced following treatment with amixicile, whereas that of Escherichia, Haemophilus, and Gemella were elevated. CAL, PD, and BOP were also significantly reduced following the treatment. In conclusion, the NHP model proves useful for preclinical studies of strategies targeting selected members of the oral microbiome. We show that amixicile reduces the levels of anaerobic bacteria under in vivo conditions, correlating with a reduction in CAL, PD, and BOP, thus validating its usefulness as an antimicrobial strategy.