bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Rbfox1 Does Not Affect Survival of Retinal Ganglion Cells Injured by Optic Nerve Crush
Authors: Gu Lei , Kwong Jacky M. , Caprioli Joseph , Piri Natik
Published: May 2021

Rbfox1 is a multifunctional RNA binding protein that regulates alternative splicing, transcription, mRNA stability and translation. Its roles in neurogenesis and neuronal functions are well established. Recent studies also implicate Rbfox1 in the regulation of gene networks that support cell survival during stress. We have earlier characterized the expression of Rbfox1 in amacrine and retinal ganglion cells (RGCs) and showed that deletion of Rbfox1 in adult animals results in depth perception deficiency. The current study investigates the effect of Rbfox1 downregulation on survival of RGCs injured by optic nerve crush (ONC). Seven days after ONC, animals sustained severe degeneration of RGC axons in the optic nerve and significant loss of RGC somas. Semi-quantitative grading of optic nerve damage in control + ONC, control + tamoxifen + ONC, and Rbfox1–/– + ONC groups ranged from 4.6 to 4.8 on a scale of 1 (normal; no degenerated axons were noted) to 5 (total degeneration; all axons showed degenerated organelles, axonal content, and myelin sheath), indicating a severe degeneration. Among these three ONC groups, no statistical significance was observed when any two groups were compared. The number of RGC somas were quantitatively analyzed in superior, inferior, nasal and temporal retinal quadrants at 0.5, 1, and 1.5 mm from the center of the optic disc. The average RGC densities (cells/mm2) were: control 6,438 ± 1,203; control + ONC 2,779 ± 573; control + tamoxifen 6,163 ± 861; control + tamoxifen + ONC 2,573 ± 555; Rbfox1–/– 6,437 ± 893; and Rbfox1–/– + ONC 2,537 ± 526. The RGC loss in control + ONC, control + tamoxifen + ONC and Rbfox1–/– + ONC was 57% (P = 1.44954E-42), 58% (P = 1.37543E-57) and 61% (P = 5.552E-59) compared to RGC numbers in the relevant uninjured groups, respectively. No statistically significant difference was observed between any two groups of uninjured animals or between any two ONC groups. Our data indicate that Rbfox1-mediated pathways have no effect on survival of RGCs injured by ONC.
Network Path Convergence Shapes Low-Level Processing in the Visual Cortex
Authors: Varga Bálint , Soós Bettina , Jákli Balázs , Bálint Eszter , Somogyvári Zoltán , Négyessy László
Published: May 2021

Hierarchical counterstream via feedforward and feedback interactions is a major organizing principle of the cerebral cortex. The counterstream, as a topological feature of the network of cortical areas, is captured by the convergence and divergence of paths through directed links. So defined, the convergence degree (CD) reveals the reciprocal nature of forward and backward connections, and also hierarchically relevant integrative properties of areas through their inward and outward connections. We asked if topology shapes large-scale cortical functioning by studying the role of CD in network resilience and Granger causal coupling in a model of hierarchical network dynamics. Our results indicate that topological synchronizability is highly vulnerable to attacking edges based on CD, while global network efficiency depends mostly on edge betweenness, a measure of the connectedness of a link. Furthermore, similar to anatomical hierarchy determined by the laminar distribution of connections, CD highly correlated with causal coupling in feedforward gamma, and feedback alpha-beta band synchronizations in a well-studied subnetwork, including low-level visual cortical areas. In contrast, causal coupling did not correlate with edge betweenness. Considering the entire network, the CD-based hierarchy correlated well with both the anatomical and functional hierarchy for low-level areas that are far apart in the hierarchy. Conversely, in a large part of the anatomical network where hierarchical distances are small between the areas, the correlations were not significant. These findings suggest that CD-based and functional hierarchies are interrelated in low-level processing in the visual cortex. Our results are consistent with the idea that the interplay of multiple hierarchical features forms the basis of flexible functional cortical interactions.
Evolving Interplay Between Dietary Polyphenols and Gut Microbiota—An Emerging Importance in Healthcare
Authors: Ray Suman Kumar , Mukherjee Sukhes
Published: May 2021

Polyphenols are natural plant compounds and are the most abundant antioxidants in the human diet. As the gastrointestinal tract is the primary organ provided to diet sections, the diet may be regarded as one of the essential factors in the functionality, integrity, and composition of intestinal microbiota. In the gastrointestinal tract, many polyphenols remain unabsorbed and may accumulate in the large intestine, where the intestinal microbiota are most widely metabolized. When assuming primary roles for promoting host well-being, this intestinal health environment is presented to the effect of external influences, including dietary patterns. A few different methodologies have been developed to increase solvency and transport across the gastrointestinal tract and move it to targeted intestinal regions to resolve dietary polyphenols at the low bioavailability. Polyphenols form a fascinating community among the different nutritional substances, as some of them have been found to have critical biological activities that include antioxidant, antimicrobial, or anticarcinogenic activities. Besides, it affects metabolism and immunity of the intestines and has anti-inflammatory properties. The well-being status of subjects can also benefit from the development of bioactive polyphenol-determined metabolites, although the mechanisms have not been identified. Even though the incredible variety of health-advancing activities of dietary polyphenols has been widely studied, their effect on intestinal biology adaptation, and two-way relationship between polyphenols and microbiota is still poorly understood. We focused on results of polyphenols in diet with biological activities, gut ecology, and the influence of their proportional links on human well-being and disease in this study.
The Relevance of Diet, Physical Activity, Exercise, and Persuasive Technology in the Prevention and Treatment of Sarcopenic Obesity in Older Adults
Authors: Schoufour Josje D. , Tieland Michael , Barazzoni Rocco , Ben Allouch Somaya , Bie Joey van der , Boirie Yves , Cruz-Jentoft Alfonso J. , Eglseer Doris , Topinková Eva , Visser Bart , Voortman Trudy , Tsagari Amalia , Weijs Peter J. M.
Published: May 2021

The aging population faces two conditions that threaten healthy aging: high fat mass (obesity) and low muscle mass and function (sarcopenia). The combination of both—referred to as sarcopenic obesity—synergistically increases the risk of adverse health outcomes. The two conditions often co-occur because they reinforce each other and share common etiologies, including poor nutrition and inactivity. All aging people are at risk of gaining weight and losing muscle mass and could benefit from improvements in physical activity, exercise and dietary intake. one specific window of opportunity is during the transient time of retirement, as older adults already need to restructure their daily activities. It is key to change lifestyle behavior in a sustainable manner, providing scientifically proven, personalized, and acceptable principles that can be integrated in daily life. Health technologies (e.g., applications) can provide promising tools to deliver personalized and appealing lifestyle interventions to a large group of people while keeping health care costs low. Several studies show that health technologies have a strong positive effect on physical activity, exercise and dietary intake. Specifically, health technology is increasingly applied to older people, although strong evidence for long term effects in changing lifestyle behavior is generally lacking. Concluding, technology could play an important role in the highly warranted prevention of sarcopenic obesity in older adults. Although health technology seems to be a promising tool to stimulate changes in physical activity, exercise and dietary intake, studies on long lasting effects and specifically targeted on older people around the time of retirement are warranted.
Antihypertensive and Immunomodulatory Effects of Defatted Corn Germ Hydrolysates: An in vivo Study
Authors: Zhu Jiaqi , Li Jing , Guo Yiting , Quaisie Janet , Hong Chen , Ma Haile
Published: May 2021

This study investigated the antihypertensive and immunomodulatory effects of defatted corn germ hydrolysates (DCGHs) in vivo and their potential regulatory mechanisms. The systolic blood pressure (SBP) of spontaneously hypertensive rats (SHRs) was significantly reduced (10.30%) by the long-term intragastric administration of DCGHs (high doses). Also, there was drastic inhibition of angiotensin-I-converting enzyme (ACE) activity in the lung, kidney, and heart tissues by 24.53, 22.28, and 12.93%, respectively. It could regulate the blood pressure by adjusting the balance between endothelium-derived vasoconstrictor factors and endothelium-derived relaxing factors. Meanwhile, DCGHs enhanced the phagocytosis of mononuclear macrophages, cellular immunity, and humoral immunity of ICR mice by increasing the phagocytic index of mononuclear macrophages (23.71%), ear swelling degree (44.82%), and antibody levels (52.32%). Moreover, it stimulated the release of immunoactive substances (e.g., lysozyme, interferon-γ, immunoglobulin G, and complement 3). Consequently, DCGHs could suitably be used in the formulation of novel functional foods with antihypertensive and immunomodulatory properties.
Current Evidence of the Efficacy and Safety of Neoadjuvant EGFR-TKIs for Patients With Non-small Cell Lung Cancer
Authors: Shi Xiaoshun , Dong Xiaoying , Zhai Jianxue , Liu Xiguang , Lu Di , Ni Zhen , Wu Hua , Cai Kaican
Published: May 2021

Purpose

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been indicated to be an effective treatment for advanced EGFR-mutant NSCLC. However, the neoadjuvant application of EGFR-TKIs in resectable NSCLC needs further investigation. Here, we aimed to evaluate the efficacy and safety of neoadjuvant EGFR-TKIs for lung cancer.

Methods

Published studies on neoadjuvant EGFR-TKIs in NSCLC were identified in PubMed, Web of Science, and EMBASE until June 1, 2020. Data on surgical rates, objective response rates (ORRs), pathologic responses, and adverse event (AE) rates were retrieved for proportional meta-analysis.

Results

In total, 7 enrolled studies involving 129 EGFR-TKI-sensitive NSCLC patients were included in this analysis. The overall surgical rate in these studies was 95% (95% CI: 83% to 100%), with an ORR of 48% (95% CI: 39% to 57%) in the population with EGFR-TKI-sensitive mutations, whereas the ORR including wild-type EGFR patients was 28% (95% CI: 14% to 44%). The rate of grade 1-2 AEs was 69% (95% CI: 41% to 91%) but with an acceptable rate of grade 3-4 AEs of 0% (95% CI: 0% to 5%). The pooled rates of rash and diarrhea were 56% (95% CI: 31% to 79%) and 25% (95% CI: 6% to 51%), respectively. The impact of neoadjuvant EGFR-TKIs on survival remains inconclusive.

Conclusions

Neoadjuvant EGFR-TKIs showed objective responses in approximately half of EGFR-sensitive NSCLC patients with a tolerable adverse effect profile. The favorable impact of neoadjuvant EGFR-TKIs on NSCLC needs more evidence for validation, such as the comparison of survival improvement between EGFR-TKIs and chemotherapy. The efficacy of neoadjuvant next-generation EGFR-TKIs in clinical trials remains unclear.
Intramuscular Expression of Plasmid-Encoded FVII-Fc Immunoconjugate for Tumor Immunotherapy by Targeting Tumoral Blood Vessels and Cells
Authors: Ma Liping , Wang Guanru , Liu Sijia , Bi Feng , Liu Ming , Wang Gang
Published: May 2021

Tissue factor (TF) has been confirmed to be specifically expressed by vascular endothelial cells (VECs) in solid tumors and certain types of malignant tumor cells. Coagulation factor VII (FVII) can specifically bind to TF with high affinity, so the FVII-TF interaction provides an ideal target for tumor therapy. Expression of proteins in skeletal muscles is a simple and economical avenue for continuous production of therapeutic molecules. However, it is difficult to treat solid tumors till now due to the limited number of therapeutic proteins produced by the intramuscular gene expression system. Herein, we strived to explore whether anti-tumor effects can be achieved via intramuscular delivery of a plasmid encoding a FVII-guided immunoconjugate (Icon) molecule by a previously established Pluronic L64/electropulse (L/E) technique. Our study exhibited several interesting outcomes. 1) The mouse light chain of FVII (mLFVII) molecule could guide red fluorescent protein (RFP) to accumulate predominantly at tumor sites in a TF-dependent manner. 2) Intramuscular expression of mLFVII-hFc (human IgG1 Fc) Icon could significantly inhibit the growth of both liver and lung cancers in nude mice, and the inhibition extent was proportional to the level of tumor-expressed TF. 3) The number of blood vessels and the amount of blood flow in tumors were significantly decreased in mLFVII-hFc Icon-treated mice. 4) This immunotherapy system did not display obvious side effects. Our study provided an efficient and economical system for tumor immunotherapy by targeting both blood vessels and tumor cells. It is also an open system for synergistic therapy by conveniently integrating other anticancer regimens.
Molecular Identification and Genetic Characterization of Early-Stage Multiple Primary Lung Cancer by Large-Panel Next-Generation Sequencing Analysis
Authors: Pei Guotian , Li Mingwei , Min Xianjun , Liu Qiang , Li Dasheng , Yang Yingshun , Wang Shuai , Wang Xiaoyu , Wang Huina , Cheng Huanqing , Cao Shanbo , Huang Yuqing
Published: May 2021

Objective

The incidence of early stage multiple primary lung cancer (MPLC) has been increasing in recent years, while the ideal strategy for its diagnosis and treatment remains controversial. The present study conducted genomic analysis to identify a new molecular classification method for accurately predicting the diagnosis and therapy for patients with early stage MPLC.

Methods

A total of 240 tissue samples from 203 patients with multiple-non-small-cell lung cancers (NSCLCs) (n = 30), early stage single-NSCLC (Group A, n = 94), and advanced-stage NSCLC (Group B, n = 79) were subjected to targeted multigene panel sequencing.

Results

Thirty patients for whom next-generation sequencing was performed on >1 tumor were identified, yielding 45 tumor pairs. The frequencies of EGFR, TP53, RBM10, ERBB2, and CDKN2A mutations exhibited significant differences between early and advanced-stage NSCLCs. The prevalence of the EGFR L858R mutation in early stage NSCLC was remarkably higher than that in advanced-stage NSCLC (P = 0.047). The molecular method classified tumor pairs into 26 definite MPLC tumors and four intrapulmonary metastasis (IM) tumors. A high rate of discordance in driver genetic alterations was found in the different tumor lesions of MPLC patients. The prospective Martini histologic prediction of MPLC was discordant with the molecular method for three patients (16.7%), particularly in the prediction of IM (91.7% discordant).

Conclusions

Comprehensive molecular evaluation allows the unambiguous delineation of clonal relationships among tumors. In comparison, the Martini and Melamed criteria have notable limitations in the recognition of IM. Our results support the adoption of a large panel to supplement histology for strongly discriminating NSCLC clonal relationships in clinical practice.
Increased CDC6 Expression Associates With Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma
Authors: Yicong Yao , Wang Yi , Denglong Wu , Baoying Hu
Published: May 2021

Background

CDC6 (Cell division control protein 6), located at chromosome 17q21.3, plays an important role in the early stage of DNA replication and has unique functions in various malignant tumors. Here, we evaluate the relationship between CDC6 expression and oncology outcomes in patients with clear cell renal cell carcinoma (ccRCC).

Methods

A retrospective analysis of 118 ccRCC patients in Affiliated Hospital of Nantong University from 2015 to 2017 was performed. Triplicate tissue microarrays (TMA) were prepared from formalin-fixed and paraffin-embedded specimens. Immunohistochemistry (IHC) was conducted to evaluate the relationship between CDC6 expression and standard pathological features and prognosis. The RNA sequencing data and corresponding clinical information were acquired from the TCGA database. GSEA was used to identify signal pathways related to CDC6. Cox regression analysis was used to assess independent prognostic factors. In addition, the relationship between CDC6 and immunity was also investigated.

Results

The results of Kaplan–Meier curve indicated that the OS of the patients with high expression of CDC6 was shorter than that of the patients with low CDC6 expression. Integrating the TCGA database and IHC staining, the results showed that CDC6 in ccRCC tissue was obviously up-regulated compared with adjacent normal kidney tissue. The results of Logistic regression analysis demonstrated that ccRCC patients with high expression of CDC6 are more likely to develop advanced disease than ccRCC patients with low CDC6 expression. The results of GSEA showed that the high expression of CDC6 was related to multiple signaling pathways. As for immunity, it was also related to TMB, immune checkpoint molecules, tumor microenvironment and immune infiltration. There were significantly correlations with CDC6 and immune cell infiltration levels and tumor microenvironment. The results of further results of the TCGA database showed that CDC6 was obviously related to immune checkpoint molecules and immune cells.

Conclusions

Increased expression of CDC6 is a potentially prognostic factor of poor prognosis in ccRCC patients.
The Cost-Effectiveness of Congenital Adrenal Hyperplasia Newborn Screening in Brazil: A Comparison Between Screened and Unscreened Cohorts
Authors: Miranda Mirela Costa de , Haddad Luciana Bertocco de Paiva , Trindade Evelinda , Cassenote Alex , Hayashi Giselle Y. , Damiani Durval , Costa Fernanda Cavalieri , Madureira Guiomar , Mendonca Berenice Bilharinho de , Bachega Tania A. S. S.
Published: May 2021

Background: Newborn screening for congenital adrenal hyperplasia (CAH-NBS) is not yet a worldwide consensus, in part due to inconclusive evidence regarding cost-effectiveness because the analysis requires an understanding of the short- and long-term costs of care associated with delayed diagnosis.

Objective: The present study aimed to conduct a cost-effectiveness analysis (CEA) to compare the costs associated with CAH-NBS and clinical diagnosis.

Methods: A decision model comparing the two strategies was tested by sensitivity analysis. The cost analysis perspective was the public health system. Unscreened patients' data were extracted from medical records of Hospital das Clinicas, Saõ Paulo, and screened data were extracted from the NBS Referral Center of São Paulo. The population comprised 195 classical patients with CAH, clinically diagnosed and confirmed by hormonal/CYP21A2 analysis, and 378,790 newborns screened during 2017. Adverse outcomes related to late diagnosis were measured in both cohorts, and the incremental cost-effectiveness ratio (ICER) was calculated. We hypothesized that CAH-NBS would be cost-effective.

Results: Twenty-five screened infants were confirmed with CAH (incidence: 1:15,135). The mortality rate was estimated to be 11% in unscreened infants, and no deaths were reported in the screened cohort. Comparing the unscreened and screened cohorts, mean serum sodium levels were 121.2 mEq/L (118.3–124.1) and 131.8 mEq/L (129.3–134.5), mean ages at diagnosis were 38.8 and 17 days, and hospitalization occurred in 76% and 58% of the salt-wasting patients with the in the two cohorts, respectively. The NBS incremental cost was US$ 771,185.82 per death averted, which yielded an ICER of US$ 25,535.95 per discounted life-year saved.

Conclusions: CAH-NBS is important in preventing CAH mortality/morbidity, can reduce costs associated with adverse outcomes, and appears cost-effective.
Dexmedetomidine Inhibits ASIC Activity via Activation of α2A Adrenergic Receptors in Rat Dorsal Root Ganglion Neurons
Authors: Wei Shuang , Qiu Chun-Yu , Jin Ying , Liu Ting-Ting , Hu Wang-Ping
Published: May 2021

Dexmedetomidine (DEX), a selective α2 adrenergic receptor (α2-AR) agonist, has been shown to have peripheral analgesic effects in a variety of pain conditions. However, the precise molecular mechanisms have not yet been fully elucidated. Acid sensing ion channels (ASICs) are the major player in pain associated with tissue acidosis. Given that both α2-ARs and ASICs exist in dorsal root ganglia (DRG) neurons, we therefore investigated the effects of DEX on the functional activity of ASICs. Herein, whole-cell patch-clamp recordings demonstrated that DEX suppressed ASIC-mediated and acid-evoked currents and action potentials in dissociated rat DRG neurons. DEX shifted downwards concentration-response curve to protons, with a decrease of 35.83 ± 3.91% in the maximal current response to pH 4.5. DEX-induced inhibition of ASIC currents was blocked by the α2A-AR antagonist BRL44408 in DRG neurons. DEX also inhibited ASIC3 currents in CHO cells co-expressing ASIC3 and α2A-ARs, but not in ASIC3 transfected CHO cells without α2A-ARs expression. DEX-induced inhibition of ASIC currents was mimicked by the protein kinase A inhibitor H-89, and blocked by intracellular application of the Gi/o protein inhibitor pertussis toxin and the cAMP analog 8-Br-cAMP. In addition, peripherally administration of DEX dose-dependently relieved nociceptive responses to intraplantar injection of acetic acid in rats through local α2A-ARs. Our results indicated that DEX inhibited the functional activity of ASICs via α2A-ARs and intracellular Gi/o proteins and cAMP/protein kinase A signaling pathway in rat DRG neurons, which was a novel potential mechanism that probably mediated peripheral analgesia of DEX.
Sensing Enhancement of Electromagnetically Induced Transparency Effect in Terahertz Metamaterial by Substrate Etching
Authors: Lin Tingling , Huang Yi , Zhong Shuncong , Luo Manting , Zhong Yujie , Yu Yingjie , Ding Jian
Published: May 2021

A broad range of terahertz (THz) metamaterials have been developed for refractive index sensing. However, most of these metamaterials barely make sufficient use of the excited electric field which is crucial to achieve high sensitivity. Here, we proposed a metamaterial sensor possessing electromagnetically induced transparency (EIT) resonance that is formed by the interference of dipole and quadrupole resonance. In particular, the strengthening of light-matter interaction is realized through substrate etching, leading to a remarkable improvement in sensitivity. Hence, three kinds of etching mode were presented to maximize the utilization of the electric field, and the corresponding highest sensitivity is enhanced by up to ~2.2-fold, from 0.260 to 0.826 THz/RIU. The proposed idea to etch substrate with a strong light-matter interaction can be extended to other metamaterial sensors and possesses potential applications in integrating metamaterial and microfluid for biosensing.
Effect of Mesh Wettability Modification on Atmospheric and Industrial Fog Harvesting
Authors: Kang Jong Hoon , Lee Jeong-Won , Kim Ji Yeon , Moon Jong Woon , Jang Hyeon Seo , Jung Sung Yong
Published: May 2021

Freshwater shortage has been receiving considerable attention, and water harvesting is one of the potential solutions to this water crisis. Several researchers have tried to improve the harvesting capabilities by changing mesh wettability for atmospheric fog harvesting. However, the wettability effect on water harvesting from white plumes has not yet been investigated thoroughly, despite industrial cooling towers being considered as alternative water resources, because of the large amounts of fog plumes generated. In this study, surface wettability was modified with a robust and simple method for practical scaled-up applications, and we explored the influence of mesh wettability on atmospheric and industrial fog harvesting. In atmospheric fog harvesting, both superhydrophilic meshes (SHPMs), and superhydrophobic meshes (SHBMs) were found to improve the harvesting performance, with superhydrophobic treatments providing the best collection efficiency. In contrast, only superhydrophilicity improves the performance in industrial fog harvesting with flat mesh screens. We hypothesize that this research will be useful for mesh design, as it analyzes the influence of mesh wettability on the performance of water collection in both atmospheric and industrial water harvesting.
Generation and Detection of Structured Light: A Review
Authors: Wang Jian , Liang Yize
Published: May 2021

Structured light beams have rapidly advanced over the past few years, from specific spatial-transverse/longitudinal structure to tailored spatiotemporal structure. Such beams with diverse spatial structures or spatiotemporal structures have brought various breakthroughs to many fields, including optical communications, optical sensing, micromanipulation, quantum information processing, and super-resolution imaging. Thus, plenty of methods have been proposed, and lots of devices have been manufactured to generate structured light beams by tailoring the structures of beams in the space domain and the space–time domain. In this paper, we firstly give a brief introduction of different types of structured light. Then, we review the recent research progress in the generation and detection of structured light on different platforms, such as free space, optical fiber, and integrated devices. Finally, challenges and perspectives are also discussed.
The Effect of Free Androgen Index on the Quality of Life of Women With Polycystic Ovary Syndrome: A Cross-Sectional Study
Authors: Abdalla Mohammed Altigani , Deshmukh Harshal , Mohammed Irfaan , Atkin Stephen , Reid Marie , Sathyapalan Thozhukat
Published: May 2021

Purpose: Free androgen index (FAI) and anti-Mullerian hormone (AMH) are independently associated with polycystic ovary syndrome (PCOS). This study aimed to describe the relationship between these two markers and health-related quality of life (HR-QoL) in women with PCOS.

Methods: This cross-sectional study consisted of 81 women in the Hull PCOS biobank, who fulfilled the Rotterdam consensus criteria for the diagnosis of PCOS. The primary outcome was to measure the various domains of the QoL in the modified polycystic ovary syndrome questionnaire (MPCOSQ).

Results: Mean age of the study participants was 28 ± 6.0 years, mean body mass index (BMI) 33.5 ± 7.8 kg/m2, mean FAI (6 ± 5.5), free testosterone (2.99 ± 0.75) and mean AMH (3.5 ± 0.8 units). In linear regression analysis, the FAI was associated with overall mean MPCOSQ score (Beta = 0.53, P-value = 0.0002), and with depression (Beta = 0.45, P-value = 0.01), hirsutism (Beta = 0.99, P-value = 0.0002) and menstrual irregularity (Beta = 0.31, P-value = 0.04). However, with adjustment for age and BMI, FAI was only associated with the hirsutism domain (Beta = 0.94, P-value = 0.001) of the MPCOSQ. FAI was also associated with the weight domain (Beta = 0.63 P-value = 0.005) of MPCOSQ. However, AMH was not associated with the overall mean MPCOSQ score or with any of its domains.

Conclusion: FAI but not AMH was associated with QoL in women with PCOS, and this effect was mediated by BMI.
Cardiorespiratory Coordination in Hypercapnic Test Before and After High-Altitude Expedition
Authors: Gultyaeva Valentina V. , Uryumtsev Dmitriy Y. , Zinchenko Margarita I. , Melnikov Vladimir N. , Balioz Natalia V. , Krivoschekov Sergey G.
Published: May 2021

Coordination of cardiovascular and respiratory systems enables a wide range of human adaptation and depends upon the functional state of an individual organism. Hypoxia is known to elicit changes in oxygen and carbon dioxide sensitivity, while training alters cardiorespiratory coordination (CRC). The delayed effect of high altitude (HA) acclimatization on CRC in mountaineers remains unknown. The objective of this study was to compare CRC in acute hypercapnia in mountaineers before and after a HA expedition. Nine trained male mountaineers were investigated at sea level before (Pre-HA) and after a 20-day sojourn at altitudes of 4,000–7,000 m (Post-HA) in three states (Baseline, Hypercapnic Rebreathing, and Recovery). A principal component (PC) analysis was performed to evaluate the CRC. The number of mountaineers with one PC increased Post-HA (nine out of nine), compared to Pre-HA (five out of nine) [Chi-square (df = 1) = 5.14, P = 0.023]; the percentage of total variance explained by PC1 increased [Pre-HA median 65.6 (Q1 64.9/Q3 74.9), Post-HA 75.6 (73.3/77.9), P = 0.028]. Post-HA, the loadings of the expired fraction of O2, CO2, and ventilation onto PC1 did not change, and the loading of heart rate increased [Pre-HA 0.64 (0.45/0.68) and Post-HA 0.76 (0.65/0.82), P = 0.038]. During the Recovery, the percentage of total variance explained by PC1 was higher than during the Baseline. Post-HA, there was a high correlation between the Exercise addiction scores and the eigenvalues of PC1 (r = 0.9, P = 0.001). Thus, acute hypercapnic exposure reveals the Post-HA increase in cardiorespiratory coordination, which is highly related to the level of exercise addiction.
Myogenetic Oligodeoxynucleotide (myoDN) Recovers the Differentiation of Skeletal Muscle Myoblasts Deteriorated by Diabetes Mellitus
Authors: Nakamura Shunichi , Yonekura Shinichi , Shimosato Takeshi , Takaya Tomohide
Published: May 2021

Skeletal muscle wasting in patients with diabetes mellitus (DM) is a complication of decreased muscle mass and strength, and is a serious risk factor that may result in mortality. Deteriorated differentiation of muscle precursor cells, called myoblasts, in DM patients is considered to be one of the causes of muscle wasting. We recently developed myogenetic oligodeoxynucleotides (myoDNs), which are 18-base single-strand DNAs that promote myoblast differentiation by targeting nucleolin. Herein, we report the applicability of a myoDN, iSN04, to myoblasts isolated from patients with type 1 and type 2 DM. Myogenesis of DM myoblasts was exacerbated concordantly with a delayed shift of myogenic transcription and induction of interleukins. Analogous phenotypes were reproduced in healthy myoblasts cultured with excessive glucose or palmitic acid, mimicking hyperglycemia or hyperlipidemia. iSN04 treatment recovered the deteriorated differentiation of plural DM myoblasts by downregulating myostatin and interleukin-8 (IL-8). iSN04 also ameliorated the impaired myogenic differentiation induced by glucose or palmitic acid. These results demonstrate that myoDNs can directly facilitate myoblast differentiation in DM patients, making them novel candidates for nucleic acid drugs to treat muscle wasting in patients with DM.
Livestream Experiments: The Role of COVID-19, Agency, Presence, and Social Context in Facilitating Social Connectedness
Authors: Onderdijk Kelsey E. , Swarbrick Dana , Van Kerrebroeck Bavo , Mantei Maximillian , Vuoskoski Jonna K. , Maes Pieter-Jan , Leman Marc
Published: May 2021

Musical life became disrupted in 2020 due to the COVID-19 pandemic. Many musicians and venues turned to online alternatives, such as livestreaming. In this study, three livestreamed concerts were organized to examine separate, yet interconnected concepts—agency, presence, and social context—to ascertain which components of livestreamed concerts facilitate social connectedness. Hierarchical Bayesian modeling was conducted on 83 complete responses to examine the effects of the manipulations on feelings of social connectedness with the artist and the audience. Results showed that in concert 1, where half of the participants were allowed to vote for the final song to be played, this option did not result in the experience of more agency. Instead, if their preferred song was played (regardless of voting ability) participants experienced greater connectedness to the artist. In concert 2, participants who attended the concert with virtual reality headsets experienced greater feelings of physical presence, as well as greater feelings of connectedness with the artist, than those that viewed a normal YouTube livestream. In concert 3, attendance through Zoom led to greater experience of social presence, but predicted less connectedness with the artist, compared to a normal YouTube livestream. Crucially, a greater negative impact of COVID-19 (e.g., loneliness) predicted feelings of connectedness with the artist, possibly because participants fulfilled their social needs with this parasocial interaction. Examining data from all concerts suggested that physical presence was a predictor of connectedness with both the artist and the audience, while social presence only predicted connectedness with the audience. Correlational analyses revealed that reductions in loneliness and isolation were associated with feelings of shared agency, physical and social presence, and connectedness to the audience. Overall, the findings suggest that in order to reduce feelings of loneliness and increase connectedness, concert organizers and musicians could tune elements of their livestreams to facilitate feelings of physical and social presence.
Age at Nomination Among Soccer Players Nominated for Major International Individual Awards: A Better Proxy for the Age of Peak Individual Soccer Performance?
Authors: Oterhals Geir , Lorås Håvard , Pedersen Arve Vorland
Published: May 2021

Individual soccer performance is notoriously difficult to measure due to the many contributing sub-variables and the variety of contexts within which skills must be utilised. Furthermore, performance differs across rather specialised playing positions. In research, soccer performance is often measured using combinations of, or even single, sub-variables. All too often these variables have not been validated against actual performance. Another approach is the use of proxies. In sports research, the age of athletes when winning championship medals has been used as a proxy for determining their age of peak performance. In soccer, studies have used the average age of players in top European leagues or in the Champions League to determine the age of individual peak performance. Such approaches have methodological shortcomings and may underestimate the peak. We explore the use of a new proxy, the age at nomination for major individual awards, to determine the average age at peak individual soccer performance. A total of 1,981 players nominated for major awards from 1956 to 2019 were included, and a subset of 653 retired players was extracted, thus including players’ complete careers. Players’ average ages at nomination, at their first nomination, and at their last ever nomination were calculated, and differences across playing positions were calculated together with changes over time in the average age at peak. Based on our proxy, the age of individual peak soccer performance occurs around 27–28 years, varying across playing positions from 26 to 31 years. A player’s first peak, on average, seems to coincide with known peaks of physiological variables; their last-ever peak occurs long after physiological performance has started to decline, indicating that the decline can be compensated for by other variables. The peak age is higher than previously reported for soccer; however, it is similar to those in other team ball sports. The average age at peak performance has increased over time, especially in the last decade. Our approach of using proxies for unearthing information about hidden features of otherwise immeasurable complex performance appears to be viable, and such proxies may be used to validate sub-variables that measure complex behaviour.
Bibliometrics and Visual Analysis of the Research Status and Trends of Postpartum Depression From 2000 to 2020
Authors: Bai Xue , Song Zixuan , Zhou Yangzi , Wang Xiaoxue , Wang Yuting , Zhang Dandan
Published: May 2021

The purpose of this study was to evaluate the international scientific output on postpartum depression (PPD) research during 2000–2020 through a bibliometric analysis and to explore research hotspots, frontiers, and trends in the field of postpartum depression. We searched the Web of Science Core Collection for publications on postpartum depression published between 2000 and 2020. CiteSpace, gCluto, and other software applications were used to analyze the data by year, journal, and country. A total of 2,963 publications were retrieved and 96 countries or regions published related papers. The United States had the largest number of published papers and the highest betweenness centrality, which is the dominant position in the field of postpartum depression. A total of 717 journals published papers, with the Archives of Womens Mental Health ranked first in terms of volume and betweenness centrality. In this study, 31 high-frequency main MeSH terms/subheadings were selected. The high-frequency MeSH terms were clustered into six categories: an overview of depression-related research, diagnostic and screening scales for postpartum depression, epidemiological investigation into postpartum depression, treatment and drug selection for postpartum depression, psychological research on postpartum depression, and etiology, physiopathology, complications, genetics of postpartum depression. Finally, we used strategic diagram to analyze research trends in postpartum depression. This study has identified a continuous significant increase in the publication of PPD articles. Currently, the etiology, physiological pathology, intervention and treatment of complications on PPD are immature, which provides reference for the trend of obstetric psychology.
The Association Between Social Support, COVID-19 Exposure, and Medical Students' Mental Health
Authors: Yin Yi , Yang Xingjie , Gao Lan , Zhang Suoyuan , Qi Meng , Zhang Ligang , Tan Yunlong , Chen Jingxu
Published: May 2021

Background: The coronavirus disease−2019 (COVID-19) pandemic has halted in-person medical education worldwide. Limited studies have reported on the mental health status of medical students during this public health emergency. This study aimed to explore the association of personal virus exposure, regional epidemic condition, and social support with medical students' depressive and anxiety symptoms during the COVID-19 outbreak in China.

Methods: In February 2020, 5,982 medical students (60.0% females, Meanage = 21.7 years, Medianage = 22 years) completed an online survey consisting of demographics, personal virus exposure, the Patient Health Questionnaire, the Generalized Anxiety Disorder Scale, and the Social Support Rating Scale.

Results: The prevalence rates of mild to severe depressive symptoms and anxiety symptoms were 35.2 and 22.8%, respectively. Multivariate linear regression showed that students with low- or medium-level social support had a higher risk of experiencing depressive or anxiety symptoms than those with high-level social support. COVID-19 exposure was positively associated with mild to severe depressive or anxiety symptoms. Respondents living in provinces with 500–1,000 confirmed COVID-19 cases had an increased risk of experiencing mild to severe depressive symptoms compared with those living in provinces with <100 cases. Other related factors were gender and years of training.

Conclusions: Some medical students suffered from a poor psychological status during the COVID-19 outbreak. Low social support was a stronger factor related to poor mental status compared with COVID-19 exposure or the provincial epidemic condition. Thus, we suggest that colleges or universities provide social support and mental health screening.
Problematic Use of Internet-Related Activities and Perceived Weight Stigma in Schoolchildren: A Longitudinal Study Across Different Epidemic Periods of COVID-19 in China
Authors: Fung Xavier C. C. , Siu Andrew M. H. , Potenza Marc N. , O'Brien Kerry S. , Latner Janet D. , Chen Chao-Ying , Chen I-Hua , Lin Chung-Ying
Published: May 2021

Background:Social distancing and school suspension due to the coronavirus pandemic (COVID-19) may have a negative impact on children's behavior and well-being. Problematic smartphone use (PSU), problematic social media use (PSMU) and perceived weight stigma (PWS) are particularly important issues for children, yet we have a poor understanding of how these may have been affected by lockdowns and physical isolation resulting from COVID-19. This research aimed to understand how these psychosocial and behavioral variables may be associated with psychological distress, and how these associations may have changed during the COVID-19 pandemic.

Methods:A total of 489 children completed a three-wave longitudinal study from January 2020 to June 2020. The first wave was conducted before the COVID-19 outbreak. The second wave was conducted during the outbreak. The third wave was conducted during post-COVID-19 lockdown. Questionnaires measured psychological distress, PSU, PSMU, and PWS.

Results:PSU, PSMU, PWS and psychological distress were all significantly associated with each other. PSU was significantly higher during outbreak. PWS was significantly higher before outbreak. We found an increased association between PSMU and PWS across three waves in all three models. The association between PSU and depression/anxiety decreased across three waves; however, association between PSMU and depression/anxiety increased across three waves.

Conclusions:COVID-19 initiated school suspension and associated lockdowns appear to have exacerbated PSU and depression among children. However, PWS was reduced during this period. Children should use smartphones and social media safely and cautiously, and be aware of the potential exposure to weight stigmatization.
Costs and Scale-Up Costs of Integrating HIV Self-Testing Into Civil Society Organisation-Led Programmes for Key Populations in Côte d'Ivoire, Senegal, and Mali
Authors: d'Elbée Marc , Traore Métogara Mohamed , Badiane Kéba , Vautier Anthony , Simo Fotso Arlette , Kabemba Odé Kanku , Rouveau Nicolas , Godfrey-Faussett Peter , Maheu-Giroux Mathieu , Boily Marie-Claude , Medley Graham Francis , Larmarange Joseph , Terris-Prestholt Fern
Published: May 2021

Despite significant progress on the proportion of individuals who know their HIV status in 2020, Côte d'Ivoire (76%), Senegal (78%), and Mali (48%) remain far below, and key populations (KP) including female sex workers (FSW), men who have sex with men (MSM), and people who use drugs (PWUD) are the most vulnerable groups with a HIV prevalence at 5–30%. HIV self-testing (HIVST), a process where a person collects his/her own specimen, performs a test, and interprets the result, was introduced in 2019 as a new testing modality through the ATLAS project coordinated by the international partner organisation Solthis (IPO). We estimate the costs of implementing HIVST through 23 civil society organisations (CSO)-led models for KP in Côte d'Ivoire (N= 7), Senegal (N= 11), and Mali (N= 5). We modelled costs for programme transition (2021) and early scale-up (2022–2023). Between July 2019 and September 2020, a total of 51,028, 14,472, and 34,353 HIVST kits were distributed in Côte d'Ivoire, Senegal, and Mali, respectively. Across countries, 64–80% of HIVST kits were distributed to FSW, 20–31% to MSM, and 5–8% to PWUD. Average costs per HIVST kit distributed were $15 for FSW (Côte d'Ivoire: $13, Senegal: $17, Mali: $16), $23 for MSM (Côte d'Ivoire: $15, Senegal: $27, Mali: $28), and $80 for PWUD (Côte d'Ivoire: $16, Senegal: $144), driven by personnel costs (47–78% of total costs), and HIVST kits costs (2–20%). Average costs at scale-up were $11 for FSW (Côte d'Ivoire: $9, Senegal: $13, Mali: $10), $16 for MSM (Côte d'Ivoire: $9, Senegal: $23, Mali: $17), and $32 for PWUD (Côte d'Ivoire: $14, Senegal: $50). Cost reductions were mainly explained by the spreading of IPO costs over higher HIVST distribution volumes and progressive IPO withdrawal at scale-up. In all countries, CSO-led HIVST kit provision to KP showed relatively high costs during the study period related to the progressive integration of the programme to CSO activities and contextual challenges (COVID-19 pandemic, country safety concerns). In transition to scale-up and integration of the HIVST programme into CSO activities, this model shows large potential for substantial economies of scale. Further research will assess the overall cost-effectiveness of this model.
Comparison of Microscopic Interacting Boson Model and Quasiparticle Random Phase Approximation 0νββ Decay Nuclear Matrix Elements
Authors: Kotila Jenni
Published: May 2021

The fundamental nature of the neutrino is presently a subject of great interest. A way to access the absolute mass scale and the fundamental nature of the neutrino is to utilize the atomic nuclei through their rare decays, the neutrinoless double beta (0νββ) decay in particular. The experimentally measurable observable is the half-life of the decay, which can be factorized to consist of phase space factor, axial vector coupling constant, nuclear matrix element, and function containing physics beyond the standard model. Thus reliable description of nuclear matrix element is of crucial importance in order to extract information governed by the function containing physics beyond the standard model, neutrino mass parameter in particular. Comparison of double beta decay nuclear matrix elements obtained using microscopic interacting boson model (IBM-2) and quasiparticle random phase approximation (QRPA) has revealed close correspondence, even though the assumptions in these two models are rather different. The origin of this compatibility is not yet clear, and thorough investigation of decomposed matrix elements in terms of different contributions arising from induced currents and the finite nucleon size is expected to contribute to more accurate values for the double beta decay nuclear matrix elements. Such comparison is performed using detailed calculations on both models and obtained results are then discussed together with recent experimental results.
A New Hyper-Parameter Optimization Method for Power Load Forecast Based on Recurrent Neural Networks
Authors: Li Yaru , Zhang Yulai , Cai Yongping
Published: May 2021

The selection of the hyper-parameters plays a critical role in the task of prediction based on the recurrent neural networks (RNN). Traditionally, the hyper-parameters of the machine learning models are selected by simulations as well as human experiences. In recent years, multiple algorithms based on Bayesian optimization (BO) are developed to determine the optimal values of the hyper-parameters. In most of these methods, gradients are required to be calculated. In this work, the particle swarm optimization (PSO) is used under the BO framework to develop a new method for hyper-parameter optimization. The proposed algorithm (BO-PSO) is free of gradient calculation and the particles can be optimized in parallel naturally. So the computational complexity can be effectively reduced which means better hyper-parameters can be obtained under the same amount of calculation. Experiments are done on real world power load data, where the proposed method outperforms the existing state-of-the-art algorithms, BO with limit-BFGS-bound (BO-L-BFGS-B) and BO with truncated-newton (BO-TNC), in terms of the prediction accuracy. The errors of the prediction result in different models show that BO-PSO is an effective hyper-parameter optimization method.