bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiologic Characteristics, Prognostic Factors, and Treatment Outcomes in Primary Central Nervous System Lymphoma: A SEER-Based Study
Authors: Tang Dongsheng , Chen Yue , Shi Yuye , Tao Hong , Tao Shandong , Zhang Quan’e , Ding Banghe , He Zhengmei , Yu Liang , Wang Chunling
Published: February 2022

Objective

This study was conducted in order to study the clinical characteristics, prognostic factors, and treatment outcomes in patients with primary central nervous system lymphoma (PCNSL).

Materials and Methods

The data of a total of 5,166 PCNSL patients diagnosed between 2000 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were obtained.

Results

The mean age was 63.1 ± 14.9 years, with a male to female ratio of 1.1:1.0. The most common histologic subtype was diffuse large B-cell lymphoma (DLBCL) (84.6%). The 1-, 3-, and 5-year overall survival (OS) rates were 50.1%, 36.0%, and 27.2%, respectively, and the corresponding disease-specific survival (DSS) rates were 54.4%, 41.3%, and 33.5%, respectively. Multivariate analysis with Cox regression showed that race, sex, age, marital status, surgical resection, and chemotherapy were independent prognostic factors for OS and DSS, but radiotherapy was only for OS. Nomograms specially for DLBCL were established to predict the possibility of OS and DSS. The concordance index (C-index) values of OS and DSS were 0.704 (95% CI 0.687–0.721) and 0.698 (95% CI 0.679–0.717), suggesting the high discrimination ability of the nomograms.

Conclusion

Surgical resection and/or chemotherapy was favorably associated with better OS and DSS. However, radiotherapy was not beneficial for OS and DSS in the long term. A new predictive nomogram and a web-based survival rate calculator we developed showed favorable applicability and accuracy to predict the long-term OS for DLBCL patients specifically.
Complement Factor H in cSCC: Evidence of a Link Between Sun Exposure and Immunosuppression in Skin Cancer Progression
Authors: Johnson Ellise M. , Uppalapati Chandana K. , Pascual Agnes S. , Estrada Sarah I. , Averitte Richard L. , Leyva Kathryn J. , Hull Elizabeth E.
Published: February 2022

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer with an estimated 750,000 cases diagnosed annually in the United States. Most cases are successfully treated with a simple excision procedure, but ~5% of cases metastasize and have a 5-year survival rate of 25-45%. Thus, identification of biomarkers correlated to cSCC progression may be useful in the early identification of high-risk cSCC and in the development of new therapeutic strategies. This work investigates the role of complement factor H (CFH) in the development of cSCC. CFH is a regulatory component of the complement cascade which affects cell mediated immune responses and increases in complement proteins are associated with poor outcomes in multiple cancer types. We provide evidence that sun exposure may increase levels of CFH, suggesting an immunomodulatory role for CFH early in the development of cSCC. We then document increased levels of CFH in cSCC samples, compared to adjacent normal tissue (ANT) routinely excised in a dermatology clinic which, in paired samples, received the same level of sun exposure. We also provide evidence that levels of CFH are even greater in more advanced cases of cSCC. To provide a potential link between CFH and immune modulation, we assessed immune system function by measuring interferon gamma (IFN-γ) and FOXP3 in patient samples. IFN-γ levels were unchanged in cSCC relative to ANT which is consistent with an ineffective cell-mediated immune response. FOXP3 was used to assess prevalence of regulatory T cells within the tissues, indicating either a derailed or inhibitory immune response. Our data suggest that FOXP3 levels are higher in cSCC than in ANT. Our current working model is that increased CFH downstream of sun exposure is an early event in the development of cSCC as it interferes with proper immune surveillance and decreases the effectiveness of the immune response, and creates a more immunosuppressive environment, thus promoting cSCC progression.
A Novel Biopsy Method Based on Bipolar Radiofrequency Biopsy Needles
Authors: Wang Huiyang , Bao Haiwei , Yue Lan , Jiang Tian’an
Published: February 2022

Modern oncology increasingly relies on pathological, molecular, and genomic assessments of biopsied tumor tissue. However, the concern for bleeding complication and malignant seeding severely hinders the application of the biopsy tumor. Here, we developed a 16 G biopsy needle to contain two electrodes insulated from each other and connect to an radiofrequency generator. For evaluating hemostatic efficacy, 50 rabbits were randomly divided into two groups: warfarinization and non-warfarinization group. Two liver biopsies and two splenic biopsies per animal were performed using a 16 G biopsy needle. Each group was further equally divided into five groups according to different hemostatic measures, including non-intervention, embolization using an absorbable gelatin sponge, and ablation by RF with three different needle temperatures (50°C, 70°C, and 90°C). Than, we used VX2 rabbit models (n = 25) and applied the five analogous biopsies to the tumor. The flush fluid from the biopsy needle underwent cytomorphological analysis. Our results that the groups using ablation by RF showed significantly less blood loss than the control group for liver and spleen in both groups (P < 0.001). After RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed on both the macroscopic and histological level. Cytological smears showed that tumor cells were degenerated after RF at 70°C and 90°C. Our findings showed that bipolar RF biopsy needle is a promising tool for reducing hemorrhage after biopsy and avoiding implanting tumor cells in the tract.
Algometer Assessment of Pressure Pain Threshold After Onabotulinumtoxin-A and Physical Therapy Treatments in Patients With Chronic Migraine: An Observational Study
Authors: Deodato Manuela , Granato Antonio , Ceschin Marta , Galmonte Alessandra , Manganotti Paolo
Published: February 2022

The purpose of this study was to evaluate pain hypersensitivity in chronic migraine patients 3 months after undergoing onabotulinumtoxin-A therapy, physical therapy (PT), or the combination of the two. Pressure pain threshold (PPT) was assessed in accordance with Andersen's guidelines, focusing on five muscles in the trigeminocervical area (namely, trapezius, levator scapulae, temporalis, sub-occipitalis, and scalenus medius) and one muscle outside of the area, (i.e., tensor fasciae latae). Moreover, three headache parameters, namely, attack frequency, duration, and pain intensity, were recorded in an ad hoc diary kept by the patients. A total of 30 patients were included in three treatment groups: 1. onabotulinumtoxin-A therapy, 2. PT, and 3. a combination of onabotulinumtoxin-A and PT. The results show that, at the final assessment, the PPT was significantly reduced in the combined treatment group compared to the two single-therapy groups. As regards headache parameters, frequency and duration of the attacks were decreased significantly in all three treatment groups, whereas in pain intensity, the reduction was statistically significant in the combined treatment group and the onabotulinumtoxin-A therapy. Results suggest that a better pain modulation in patients with chronic migraine can be achieved with a combined treatment of onabotulinumtoxin-A and physical therapy. Indeed, the combination of both pharmacological and non-pharmacological treatments results in the reduction of both headache-related parameters and widespread pressure hyperalgesia.
Rapid Maxillary Expansion Has a Beneficial Effect on the Ventilation in Children With Nasal Septal Deviation: A Computational Fluid Dynamics Study
Authors: Chen Shuai , Wang Jingying , Xi Xun , Zhao Yi , Liu Hong , Liu Dongxu
Published: February 2022

Nasal septal deviation (NSD) is one of the most common nasal diseases. Different from common clinical examination methods, computational fluid dynamics (CFD) can provide visual flow information of the nasal cavity. The dimension and volume of the nasal cavity are easily affected by rapid maxillary expansion (RME). The purpose of this study was to use CFD to evaluate the effect of RME on the aerodynamics of the nasal cavity in children with maxillary transverse deficiency and NSD. Computational fluid dynamics was implemented after 3D reconstruction based on the CBCT of 15 children who have completed RME treatment. After treatment, the volume increases in the nasal cavity, nasopharynx, oropharynx, and pharynx were not statistically significant. The wall shear stress of the nasal cavity after RME, 1.749 ± 0.673 Pa, was significantly lower than that before RME, 2.684 ± 0.919 Pa. Meanwhile, the maximal negative pressure in the pharyngeal airway during inspiration was smaller after RME (−31.058 Pa) than before (−48.204 Pa). This study suggests that RME has a beneficial effect on nasal ventilation. The nasal airflow became more symmetrical in the bilateral nasal cavity after RME. Pharyngeal resistance decreased with the reduction in nasal resistance and the increase in the volume of oropharynx after RME.
Association Between Non-invasive Diagnostic Methods of Liver Fibrosis and Type 2 Diabetes in Pediatric Patients With Non-alcoholic Fatty Liver Disease
Authors: Yang Aram , Jung Nayoung , Kim Sinae , Lee Ji-Eun
Published: February 2022

Background and Purpose

The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has been increasing associated with insulin resistance. However, there is a scarcity of related studies in children with NAFLD with type 2 diabetes mellitus (T2DM) compared to adults. We conducted this study to investigate the association between non-invasive diagnostic methods of liver fibrosis and T2DM in pediatric patients with NAFLD.

Methods

We enrolled a total of 152 patients aged <18 years with NAFLD, and compared their data according to the presence of T2DM. We evaluated fibrosis by transient elastography (TE, FibroScan®), and calculated the following fibrosis scores for each patient: NAFLD fibrosis score (NFS), AST: platelet ratio index (APRI), Fibrosis-4 (FIB-4) index, and pediatric NAFLD fibrosis index (PNFI).

Results

In the NAFLD–T2DM group, the NFS and mean controlled attenuation parameter in FibroScan were significantly higher than those in the nondiabetic group. The receiver operating characteristic (ROC) curve values for predicting the presence of T2DM were 0.78 for NFS, 0.64 for FIB-4, 0.62 for PNFI, and 0.61 for APRI. The cutoff HbA1c levels for predicting fibrosis progression in APRI, NFS, and PNFI were 5.7% [area under the curve (AUC) 0.74], 6.4% (AUC 0.71), and 6.4% (AUC 0.55), respectively. In the multivariate analysis, hepatosteatosis on abdomen sonography, NFS, FibroScan F, and APRI were independently associated with T2DM risk.

Conclusions

We significantly characterized non-invasive fibrosis markers and elastography in pediatric NAFLD with T2DM compared with the nondiabetic group. We suggest evaluating the progression of fibrosis in the prediabetic stage in children using a combination of these non-invasive methods.
Traditional Tibetan Medicine Twenty-Five Wei’er Tea Pills Ameliorate Rheumatoid Arthritis Based on Chemical Crosstalk Between Gut Microbiota and the Host
Authors: Li Zixuan , Nie Lijuan , Li Yong , Yang Lu , Jin Lulu , Du Baozhong , Yang Juan , Zhang Xulin , Cui Huantian , Luobu Ouzhu
Published: February 2022

Twenty-Five Wei’er Tea Pills (TFP), a traditional Tibetan medicine, has shown to have a promising therapeutic effect in patients with Rheumatoid arthritis (RA), as well as being safe. Nonetheless, there have been limited pharmacological studies that have explored this therapeutic option. As gut microbiota has been proven to have a critical role in the pathogenesis of RA, this study aims to explore and reveal relevant ways by which TFP interacts with the chemical crosstalk between the gut microbiome and its host. 16S rRNA sequencing, combined with un-targeted metabolomics, were conducted on collagen-induced arthritis (CIA) rats. CIA model rats treated with TFP showed significant improvement in weight gain, pathological phenomena in joints, as well as decreased serum levels of TNF-α, IL-6 and increased level of IL-4 and IL-10. Significant dysfunction in the gut microbiome and alteration in serum metabolites were observed in CIA model rats, which were restored by TFP treatment. Coherence analysis indicated that TFP modulated the pathways of histidine metabolism, phenylalanine metabolism, alanine, aspartate, glutamate metabolism, amino sugar and nucleotide sugar metabolism owing to the abundances of Lactobacillus, Bacteroides, Prevotellaceae_UCG-001 and Christensenellaceae_R-7_group in the gut microflora. The corresponding metabolites involved L-histidine, histamine, phenylethylamine, asparagine, L-aspartic acid, D-fructose 1-phosphate, D-Mannose 6-phosphate, D-Glucose 6-phosphate, and Glucose 1-phosphate. In conclusion, this study reveals the ameliorative effects of TFP on RA through the chemical crosstalk that exists between the gut microbiota and its host, and also further enriches our understandings of the pathogenesis of RA.
Real World Data in Health Technology Assessment of Complex Health Technologies
Authors: Hogervorst Milou A. , Pontén Johan , Vreman Rick A. , Mantel-Teeuwisse Aukje K. , Goettsch Wim G.
Published: February 2022

The available evidence on relative effectiveness and risks of new health technologies is often limited at the time of health technology assessment (HTA). Additionally, a wide variety in real-world data (RWD) policies exist among HTA organizations. This study assessed which challenges, related to the increasingly complex nature of new health technologies, make the acceptance of RWD most likely. A questionnaire was disseminated among 33 EUnetHTA member HTA organizations. The questions focused on accepted data sources, circumstances that allowed for RWD acceptance and barriers to acceptance. The questionnaire was validated and tested for reliability by an expert panel, and pilot-tested before dissemination via LimeSurvey. Twenty-two HTA organizations completed the questionnaire (67%). All reported accepting randomized clinical trials. The most accepted RWD source were patient registries (19/22, 86%), the least accepted were editorials and expert opinions (8/22, 36%). With orphan treatments or companion diagnostics, organizations tended to be most likely to accept RWD sources, 4.3–3.2 on a 5-point Likert scale, respectively. Additional circumstances were reported to accept RWD (e.g., a high disease burden). The two most important barriers to accepting RWD were lacking necessary RWD sources and existing policy structures. European HTA organizations seem positive toward the (wider) use of RWD in HTA of complex therapies. Expanding the use of patient registries could be potentially useful, as a large share of the organizations already accepts this source. However, many barriers still exist to the widespread use of RWD. Our results can be used to prioritize circumstances in which RWD might be accepted.
Hydrogen Sulfide Promotes Thyroid Hormone Synthesis and Secretion by Upregulating Sirtuin-1
Authors: Zhao Xue , Cao Yedi , Jin Hongfang , Wang Xiuli , Zhang Lanbo , Zhang Yang , Yu Yang , Huang Youyuan , Gao Ying , Zhang Junqing
Published: February 2022

Objective: One mechanism of hypothyroidism involves the disruption of thyroid hormone synthesis and secretion by thyrocytes. Hydrogen sulfide (H2S), as a gas signaling molecule, participates in many physiopathologic processes by upregulating sirtuin-1 (SIRT1). The aim of the current study was to explore whether H2S promotes the synthesis and secretion of thyroid hormones by upregulating SIRT1.

Methods: Real-time PCR and immunohistochemistry were used to detect the mRNA and protein expression of H2S-generating enzymes in normal human thyroid tissues. Serum H2S concentrations from hypothyroid patients (n = 32) and euthyroid participants (n = 41) were detected by H2S-selective sensors. Thirty-one Sprague–Dawley rats were divided into control group (n = 10), hypothyroid group (induced by MMI, n = 10) and hypothyroid + NaHS group (n = 11), and the FT4, TT4 and TSH levels were assayed. Human primary thyrocytes were incubated with H2S donor sodium hydrosulfide (NaHS) or NaHS plus SIRT1 inhibitor (EX527) in vitro. Thyroid hormone synthesis- and secretion-related proteins [thyroid peroxidase (TPO), sodium iodide transporter (NIS), Pendrin, monocarboxylic acid transporter 8 (MCT8)] were analyzed by real-time PCR and Western blot.

Results: H2S levels in serum from hypothyroid patients were decreased compared to those from euthyroid participants (p < .05), and serum H2S levels were positively correlated with FT3, FT4, TT3, and TT4 levels in all subjects (all p < .0001). In vivo, NaHS promoted thyroid function in hypothyroid rats (p < .05). In vitro, H2S was detected in supernatant, and CBS mRNA was higher than CSE and 3-MPST in human primary thyrocytes (p < .05). The protein levels of TPO, NIS, Pendrin and MCT8 were upregulated in a concentration-dependent manner for NaHS in thyrocytes. After blocking SIRT1 with EX527, we found that the increasing levels of TPO, NIS, Pendrin, and MCT8 and TPO activity were downregulated in thyrocytes incubated with NaHS, and FT4 levels in the cell supernatant were also decreased significantly (all p < .05).

Conclusion: H2S is mainly generated in thyrocytes by CBS. Serum H2S levels are decreased with hypothyroidism. H2S promotes the synthesis and secretion of thyroid hormones and the expression of related molecules by upregulating SIRT1.
The Magnetic and Thermally-Induced Spin-Related Transport Features Using Germanene Nanoribbons With Zigzag and Klein Edges
Authors: Xu Gang , Tan Xingyi , Ren Dahua
Published: February 2022

The current work employs the first-principles computations and non-equilibrium Greens function to investigate the magnetic and thermally-induced spin-related transport features using germanene nanoribbons with zigzag and Klein edges (ZKGeNRs). It was demonstrated that the ZKGeNRs with various widths (N) are placed in various spin-resolved electronic states. By increasing the width parameter N from 4 to 9, the ZKGeNRs moves from an indirect-gap bipolar magnetic semiconducting state (BMS) to bipolar spin gapless semiconductor (BSGS), and finally to ferromagnetic metal (FM). Moreover, since the right and the left temperatures of the ZKGeNRs device are different, the spin-up and spin-down currents flow in reverse orientations, demonstrating the spin-dependent Seebeck effect (SDSE). Besides, the threshold temperature decreases as N increases and then disappears, while the spin currents increase as N increases. Simulation results indicated that the ZKGeNRs could be an appropriate choice for spin caloritronic devices and could be utilized in future low-power consumption applications.
Juvenile Hormone Studies in Drosophila melanogaster
Authors: Zhang Xiaoshuai , Li Sheng , Liu Suning
Published: February 2022

In the field of insect endocrinology, juvenile hormone (JH) is one of the most wondrous entomological terms. As a unique sesquiterpenoid hormone produced and released by the endocrine gland, corpus allatum (CA), JH is a critical regulator in multiple developmental and physiological processes, such as metamorphosis, reproduction, and behavior. Benefited from the precise genetic interventions and simplicity, the fruit fly, Drosophila melanogaster, is an indispensable model in JH studies. This review is aimed to present the regulatory factors on JH biosynthesis and an overview of the regulatory roles of JH in Drosophila. The future directions of JH studies are also discussed, and a few hot spots are highlighted.
Intrinsically High Capacity of Animal Cells From a Symbiotic Cnidarian to Deal With Pro-Oxidative Conditions
Authors: Cotinat Pauline , Fricano Clara , Toullec Gaëlle , Röttinger Eric , Barnay-Verdier Stéphanie , Furla Paola
Published: February 2022

The cnidarian-dinoflagellate symbiosis is a mutualistic intracellular association based on the photosynthetic activity of the endosymbiont. This relationship involves significant constraints and requires co-evolution processes, such as an extensive capacity of the holobiont to counteract pro-oxidative conditions induced by hyperoxia generated during photosynthesis. In this study, we analyzed the capacity of Anemonia viridis cells to deal with pro-oxidative conditions by in vivo and in vitro approaches. Whole specimens and animal primary cell cultures were submitted to 200 and 500 μM of H2O2 during 7 days. Then, we monitored global health parameters (symbiotic state, viability, and cell growth) and stress biomarkers (global antioxidant capacity, oxidative protein damages, and protein ubiquitination). In animal primary cell cultures, the intracellular reactive oxygen species (ROS) levels were also evaluated under H2O2 treatments. At the whole organism scale, both H2O2 concentrations didn’t affect the survival and animal tissues exhibited a high resistance to H2O2 treatments. Moreover, no bleaching has been observed, even at high H2O2 concentration and after long exposure (7 days). Although, the community has suggested the role of ROS as the cause of bleaching, our results indicating the absence of bleaching under high H2O2 concentration may exculpate this specific ROS from being involved in the molecular processes inducing bleaching. However, counterintuitively, the symbiont compartment appeared sensitive to an H2O2 burst as it displayed oxidative protein damages, despite an enhancement of antioxidant capacity. The in vitro assays allowed highlighting an intrinsic high capacity of isolated animal cells to deal with pro-oxidative conditions, although we observed differences on tolerance between H2O2 treatments. The 200 μM H2O2 concentration appeared to correspond to the tolerance threshold of animal cells. Indeed, no disequilibrium on redox state was observed and only a cell growth decrease was measured. Contrarily, the 500 μM H2O2 concentration induced a stress state, characterized by a cell viability decrease from 1 day and a drastic cell growth arrest after 7 days leading to an uncomplete recovery after treatment. In conclusion, this study highlights the overall high capacity of cnidarian cells to cope with H2O2 and opens new perspective to investigate the molecular mechanisms involved in this peculiar resistance.
Harnessing a Feasible and Versatile ex vivo Calvarial Suture 2-D Culture System to Study Suture Biology
Authors: Quarto Natalina , Menon Siddharth , Griffin Michelle , Huber Julika , Longaker Michael T.
Published: February 2022

As a basic science, craniofacial research embraces multiple facets spanning from molecular regulation of craniofacial development, cell biology/signaling and ultimately translational craniofacial biology. Calvarial sutures coordinate development of the skull, and the premature fusion of one or more, leads to craniosynostosis. Animal models provide significant contributions toward craniofacial biology and clinical/surgical treatments of patients with craniofacial disorders. Studies employing mouse models are costly and time consuming for housing/breeding. Herein, we present the establishment of a calvarial suture explant 2-D culture method that has been proven to be a reliable system showing fidelity with the in vivo harvesting procedure to isolate high yields of skeletal stem/progenitor cells from small number of mice. Moreover, this method allows the opportunity to phenocopying models of craniosynostosis and in vitro tamoxifen-induction of ActincreERT2;R26Rainbow suture explants to trace clonal expansion. This versatile method tackles needs of large number of mice to perform calvarial suture research.
Comparative Physiological and Transcriptomic Analyses Reveal Altered Fe-Deficiency Responses in Tomato Epimutant Colorless Non-ripening
Authors: Chen Wei Wei , Zhu Hui Hui , Wang Jia Yi , Han Guang Hao , Huang Ru Nan , Hong Yi Guo , Yang Jian Li
Published: February 2022

The mechanisms associated with the regulation of iron (Fe) homeostasis have been extensively examined, however, epigenetic regulation of these processes remains largely unknown. Here, we report that a naturally occurring epigenetic mutant, Colorless non-ripening (Cnr), displayed increased Fe-deficiency responses compared to its wild-type Ailsa Craig (AC). RNA-sequencing revealed that a total of 947 and 1,432 genes were up-regulated by Fe deficiency in AC and Cnr roots, respectively, while 923 and 1,432 genes were, respectively, down-regulated. Gene ontology analysis of differentially expressed genes showed that genes encoding enzymes, transporters, and transcription factors were preferentially affected by Fe deficiency. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed differential metabolic responses to Fe deficiency between AC and Cnr. Based on comparative transcriptomic analyses, 24 genes were identified as potential targets of Cnr epimutation, and many of them were found to be implicated in Fe homeostasis. By developing CRISPR/Cas9 genome editing SlSPL-CNR knockout (KO) lines, we found that some Cnr-mediated Fe-deficiency responsive genes showed similar expression patterns between SlSPL-CNR KO plants and the Cnr epimutant. Moreover, both two KO lines displayed Fe-deficiency-induced chlorosis more severe than AC plants. Additionally, the Cnr mutant displayed hypermethylation in the 286-bp epi-mutated region on the SlSPL-CNR promoter, which contributes to repressed expression of SlSPL-CNR when compared with AC plants. However, Fe-deficiency induced no change in DNA methylation both at the 286-bp epi-allele region and the entire region of SlSPL-CNR gene. Taken together, using RNA-sequencing and genetic approaches, we identified Fe-deficiency responsive genes in tomato roots, and demonstrated that SlSPL-CNR is a novel regulator of Fe-deficiency responses in tomato, thereby, paving the way for further functional characterization and regulatory network dissection.
Major Genomic Regions for Wheat Grain Weight as Revealed by QTL Linkage Mapping and Meta-Analysis
Authors: Miao Yongping , Jing Fanli , Ma Jingfu , Liu Yuan , Zhang Peipei , Chen Tao , Che Zhuo , Yang Delong
Published: February 2022

Grain weight is a key determinant for grain yield potential in wheat, which is highly governed by a type of quantitative genetic basis. The identification of major quantitative trait locus (QTL) and functional genes are urgently required for molecular improvements in wheat grain yield. In this study, major genomic regions and putative candidate genes for thousand grain weight (TGW) were revealed by integrative approaches with QTL linkage mapping, meta-analysis and transcriptome evaluation. Forty-five TGW QTLs were detected using a set of recombinant inbred lines, explaining 1.76-12.87% of the phenotypic variation. Of these, ten stable QTLs were identified across more than four environments. Meta-QTL (MQTL) analysis were performed on 394 initial TGW QTLs available from previous studies and the present study, where 274 loci were finally refined into 67 MQTLs. The average confidence interval of these MQTLs was 3.73-fold less than that of initial QTLs. A total of 134 putative candidate genes were mined within MQTL regions by combined analysis of transcriptomic and omics data. Some key putative candidate genes similar to those reported early for grain development and grain weight formation were further discussed. This finding will provide a better understanding of the genetic determinants of TGW and will be useful for marker-assisted selection of high yield in wheat breeding.
SWELLMAP 2, a phyB-Interacting Splicing Factor, Negatively Regulates Seedling Photomorphogenesis in Arabidopsis
Authors: Yan Tingting , Heng Yueqin , Wang Wenwei , Li Jian , Deng Xing Wang
Published: February 2022

Light-triggered transcriptome reprogramming is critical for promoting photomorphogenesis in Arabidopsis seedlings. Nonetheless, recent studies have shed light on the importance of alternative pre-mRNA splicing (AS) in photomorphogenesis. The splicing factors splicing factor for phytochrome signaling (SFPS) and reduced red-light responses in cry1cry2 background1 (RRC1) are involved in the phytochrome B (phyB) signaling pathway and promote photomorphogenesis by controlling pre-mRNA splicing of light- and clock-related genes. However, splicing factors that serve as repressors in phyB signaling pathway remain unreported. Here, we report that the splicing factor SWELLMAP 2 (SMP2) suppresses photomorphogenesis in the light. SMP2 physically interacts with phyB and colocalizes with phyB in photobodies after light exposure. Genetic analyses show that SMP2 antagonizes phyB signaling to promote hypocotyl elongation in the light. The homologs of SMP2 in yeast and human belong to second-step splicing factors required for proper selection of the 3' splice site (3'SS) of an intron. Notably, SMP2 reduces the abundance of the functional REVEILLE 8 a (RVE8a) form, probably by determining the 3'SS, and thereby inhibits RVE8-mediated transcriptional activation of clock genes containing evening elements (EE). Finally, SMP2-mediated reduction of functional RVE8 isoform promotes phytochrome interacting factor 4 (PIF4) expression to fine-tune hypocotyl elongation in the light. Taken together, our data unveil a phyB-interacting splicing factor that negatively regulates photomorphogenesis, providing additional information for further mechanistic investigations regarding phyB-controlled AS of light- and clock-related genes.
Collective Rhythm as an Emergent Property During Human Social Coordination
Authors: Farrera Arodi , Ramos-Fernández Gabriel
Published: February 2022

The literature on social interactions has shown that participants coordinate not only at the behavioral but also at the physiological and neural levels, and that this coordination gives a temporal structure to the individual and social dynamics. However, it has not been fully explored whether such temporal patterns emerge during interpersonal coordination beyond dyads, whether this phenomenon arises from complex cognitive mechanisms or from relatively simple rules of behavior, or which are the sociocultural processes that underlie this phenomenon. We review the evidence for the existence of group-level rhythmic patterns that result from social interactions and argue that the complexity of group dynamics can lead to temporal regularities that cannot be predicted from the individual periodicities: an emergent collective rhythm. Moreover, we use this interpretation of the literature to discuss how taking into account the sociocultural niche in which individuals develop can help explain the seemingly divergent results that have been reported on the social influences and consequences of interpersonal coordination. We make recommendations on further research to test these arguments and their relationship to the feeling of belonging and assimilation experienced during group dynamics.
From Verbal Account to Written Evidence: Do Written Statements Generated by Officers Accurately Represent What Witnesses Say?
Authors: Milne Rebecca , Nunan Jordan , Hope Lorraine , Hodgkins Jemma , Clarke Colin
Published: February 2022

Most countries compile evidence from witnesses and victims manually, whereby the interviewer assimilates what the interviewee says during the course of an interview to produce an evidential statement. This exploratory research examined the quality of evidential statements generated in real world investigations. Transcribed witness/victim interviews (N = 15) were compared to the resultant written statements produced by the interviewing officer and signed as an accurate record by the interviewee. A coding protocol was devised to assess the consistency of information between what was said by the interviewee in the verbal interview and what was reported in the written statement. Statements contained numerous errors including omissions, distortions, and the inclusion of information not mentioned in the verbal interview. This exploratory work highlights an important area for future research focus.
Retrieval Practice Is Effective Regardless of Self-Reported Need for Cognition - Behavioral and Brain Imaging Evidence
Authors: Wiklund-Hörnqvist Carola , Stillesjö Sara , Andersson Micael , Jonsson Bert , Nyberg Lars
Published: February 2022

There is an emerging consensus that retrieval practice is a powerful way to enhance long-term retention and to reduce achievement gaps in school settings. Less is known whether retrieval practice benefits performance in individuals with low intrinsic motivation to spend time and effort on a given task, as measured by self-reported need for cognition (NFC). Here, we examined retrieval practice in relation to individual differences in NFC by combining behavioral and functional magnetic resonance imaging (fMRI) data. Using a within-subject design, upper-secondary school students (N = 274) learned a language-based material (Swahili-Swedish word-pairs), with half of the items by means of retrieval practice with feedback and half by study only. One week later, the students were tested on the word-pairs either in the classroom (n = 204), or in a fMRI scanner (n = 70). In both settings, a retrieval practice effect was observed across different levels of NFC (high or low). Relatedly, comparable fMRI effects were seen in both NFC subgroups. Taken together, our findings provide behavioral and brain-imaging evidence that retrieval practice is effective also for individuals with lower levels of NFC, which is of direct relevance for educational practice.
Playing-Dumb Behavior of Trainers During Online Streaming and Trainee’s Burnout Behavior: Mediating Role of Psychological Disengagement
Authors: Xie Qing , Li Shidong , Malik Haider A. , Chupradit Supat , Chupradit Priyanut W. , Qadus Abdul
Published: February 2022

A trainer’s behavior is a crucial factor, and it can affect the cognitive engagement of trainees in parts of training and development programs; thus, playing-dumb behavior by a trainer can cause lower attachment and less interested trainees during courses. This study was planned to investigate the impact of trainers’ playing-dumb behavior on trainees’ burnout behavior under the mediating role of psychological disengagement in online broadcasting. This study followed a convenience sampling technique under a cross-sectional research design, and data are collected from 371 trainees through a questionnaire. This study follows structural equation modeling to model the path relationship among study constructs. Results of this study indicate the presence of a relationship between trainers’ dumb behavior and its impact on trainee psychological disengagement, which leads to burnout. Findings of this study contribute to the inclusive body of knowledge pertaining to playing-dumb behavior and trainees’ burnout during the course.
Attitudes Toward Signing Avatars Vary Depending on Hearing Status, Age of Signed Language Acquisition, and Avatar Type
Authors: Quandt Lorna C. , Willis Athena , Schwenk Melody , Weeks Kaitlyn , Ferster Ruthie
Published: February 2022

The use of virtual humans (i.e., avatars) holds the potential for interactive, automated interaction in domains such as remote communication, customer service, or public announcements. For signed language users, signing avatars could potentially provide accessible content by sharing information in the signer's preferred or native language. As the development of signing avatars has gained traction in recent years, researchers have come up with many different methods of creating signing avatars. The resulting avatars vary widely in their appearance, the naturalness of their movements, and facial expressions—all of which may potentially impact users' acceptance of the avatars. We designed a study to test the effects of these intrinsic properties of different signing avatars while also examining the extent to which people's own language experiences change their responses to signing avatars. We created video stimuli showing individual signs produced by (1) a live human signer (Human), (2) an avatar made using computer-synthesized animation (CS Avatar), and (3) an avatar made using high-fidelity motion capture (Mocap avatar). We surveyed 191 American Sign Language users, including Deaf (N = 83), Hard-of-Hearing (N = 34), and Hearing (N = 67) groups. Participants rated the three signers on multiple dimensions, which were then combined to form ratings of Attitudes, Impressions, Comprehension, and Naturalness. Analyses demonstrated that the Mocap avatar was rated significantly more positively than the CS avatar on all primary variables. Correlations revealed that signers who acquire sign language later in life are more accepting of and likely to have positive impressions of signing avatars. Finally, those who learned ASL earlier were more likely to give lower, more negative ratings to the CS avatar, but we did not see this association for the Mocap avatar or the Human signer. Together, these findings suggest that movement quality and appearance significantly impact users' ratings of signing avatars and show that signed language users with earlier age of ASL acquisition are the most sensitive to movement quality issues seen in computer-generated avatars. We suggest that future efforts to develop signing avatars consider retaining the fluid movement qualities integral to signed languages.
Second Language Proficiency Modulates the Dependency of Bilingual Language Control on Domain-General Cognitive Control
Authors: Wang Qiping , Wu Xinye , Ji Yannan , Yan Guoli , Wu Junjie
Published: February 2022

The relationship between bilingual language control and domain-general cognitive control has been a hot topic in the research field of bilingualism. Previous studies mostly examined the correlation between performances of bilinguals in language control tasks and that in domain-general cognitive control tasks and came to the conclusions that they overlap, partially overlap, or are qualitatively different. These contradictory conclusions are possibly due to the neglect of the moderating effect of second language (L2) proficiency, that is, the relationship between bilingual language control and domain-general cognitive control might vary with the L2 proficiency of bilinguals. To examine this hypothesis, we recruited 36 unbalanced Chinese-English bilinguals to perform the Simon task (to assess domain-general cognitive control), Oxford Placement Test (to assess L2 proficiency), and picture naming tasks in single-and dual-language contexts (to evoke local and global language control). We find that Simon scores positively predicted switching costs in bilinguals with low L2 proficiency, but not in bilinguals with high L2 proficiency. Furthermore, Simon scores positively predicted mixing costs in bilinguals with high L2 proficiency, but not in bilinguals with low L2 proficiency. These results verify the moderating effect of L2 proficiency on the relationship between bilingual language control and domain-general cognitive control, that is, bilinguals with more proficient L2 rely on domain-general cognitive control less for local language control and more for global language control. This may imply a shift from local to global for the dependency of bilingual language control on domain-general cognitive control during the L2 development of bilinguals.
The Need for Robust Critique of Arts and Health Research: Young People, Art Therapy and Mental Health
Authors: Grebosz-Haring Katarzyna , Thun-Hohenstein Leonhard , Schuchter-Wiegand Anna Katharina , Irons Yoon , Bathke Arne , Phillips Kate , Clift Stephen
Published: February 2022

We describe work in progress to conduct a systematic review of research on effects of arts-based programs for mental health in young people. We are at the stage of searching for relevant studies through major databases and screening extant systematic reviews for additional research which meet our inclusion criteria. At this stage, however, concerns have arisen regarding both the quality of existing primary studies and of recently published systematic reviews in this area of arts and health. As a case in point, in this paper we focus on one research report on art therapy with adolescent girls and its inclusion in three systematic reviews. We demonstrate that the reviews fail to undertake a robust critique of the Bazargan and Pakdaman paper and that the paper and reviews are flawed. Drawing on recent criticisms of systematic reviewing, we consider the value of proceeding with our systematic review as initially planned.
Challenging Empathic Deficit Models of Autism Through Responses to Serious Literature
Authors: Chapple Melissa , Davis Philip , Billington Josie , Williams Sophie , Corcoran Rhiannon
Published: February 2022

Dominant theoretical models of autism and resultant research enquiries have long centered upon an assumed autism-specific empathy deficit. Associated empirical research has largely relied upon cognitive tests that lack ecological validity and associate empathic skill with heuristic-based judgments from limited snapshots of social information. This artificial separation of thought and feeling fails to replicate the complexity of real-world empathy, and places socially tentative individuals at a relative disadvantage. The present study aimed to qualitatively explore how serious literary fiction, through its ability to simulate real-world empathic response, could therefore enable more ecologically valid insights into the comparative empathic experiences of autistic and non-autistic individuals. Eight autistic and seven non-autistic participants read Of Mice and Men for six days while completing a semi-structured reflective diary. On finishing the book, participants were asked to engage in three creative writing tasks that encouraged reflective thinking across the novel. Thematic and literary analysis of the diary reflections and writing tasks revealed three main themes (1) Distance from the Novel; (2) Mobility of Response; (3) Re-Creating Literature. Findings demonstrated the usefulness of serious literature as a research tool for comparing the empathic experiences of autistic and non-autistic individuals. Specifically, autistic individuals often showed enhanced socio-empathic understandings of the literature with no empathy deficits when compared to non-autistic participants.
Temporospatial Alterations in Upper-Limb and Mallet Control Underlie Motor Learning in Marimba Performance
Authors: Loria Tristan , Tan Melissa , de Grosbois John , Huang Aiyun , Thaut Michael H.
Published: February 2022

Sound-producing movements in percussion performance require a high degree of fine motor control. However, there remains a relatively limited empirical understanding of how performance level abilities develop in percussion performance in general, and marimba performance specifically. To address this issue, nine percussionists performed individualised excerpts on marimba within three testing sessions spaced 29 days apart to assess early, intermediate, and late stages of motor learning. Motor learning was quantified via analyses of both the temporal control of mallet movements, and the spatial variability of upper-limb movements. The results showed that temporal control of mallet movements was greater in the intermediate compared to the early learning session, with no significant additional improvements revealed in the late learning session. In addition, spatial variability in the left and right elbows decreased within the intermediate compared to the early learning session. The results suggest that temporal control of mallet movements may be driven by reductions in spatial variability of elbow movements specifically. As a result, this study provides novel evidence for kinematic mechanisms underlying motor learning in percussion which can be applied towards enhancing musical training.
Improving Mood and Cognitive Symptoms in Huntington's Disease With Cariprazine Treatment
Authors: Molnar Maria Judit , Molnar Viktor , Fedor Mariann , Csehi Reka , Acsai Karoly , Borsos Beata , Grosz Zoltan
Published: February 2022

In Huntington's disease (HD), the main clinical symptoms include depression, apathy, cognitive deficits, motor deficiencies and involuntary movements. Cognitive, mood and behavioral changes may precede motor symptoms by up to 15 years. The treatment of these diverse symptoms is challenging. Tetrabenazine and deutetrabenazine are the only medications specifically approved for Huntington's chorea, but they do not affect the non-motor symptoms. For these, antidepressants, antipsychotics, and benzodiazepines have demonstrated benefit in some cases and can be used off-label. These drugs, due to sedative side effects, may negatively influence cognition. Sixteen patients having HD received a 12-week off-label cariprazine (CAR) treatment (1.5–3 mg/day). Cognitive performance and behavioral changes were measured by the Addenbrooke Cognitive Examination (ACE) test, the Cognitive and Behavioral part of the Unified Huntington's Disease Rating Scale (UHDRS), and the Beck Depression Inventory (BDI). Mixed model for repeated measures was fitted to the data, with terms of visit, baseline (BL) and their interaction. Cariprazine treatment resulted in the following changes from BL to week 12, respectively: the mean score of BDI decreased from 17.7 ± 10.7 to 10.0 ± 10.7 (p <0.0097), while the Behavioral Assessment score of the UHDRS decreased from 54.9 ± 11.3 to 32.5 ± 15.4 (p < 0.0001); ACE score increased from 75.1 ± 11.0 to 89.0 ± 9.3 (p < 0.0001); Cognitive Verbal Fluency score from 6.2 ± 2.5 to 7.7 ± 2.7 (p < 0.0103); Symbol Digit Test from 9.2 ± 6.9 to 12.3 ± 8.9 (p < 0.0009). Mild akathisia was the most frequent side effect, presenting in 2 out of 16 patients (12.5%). We conclude that CAR had a positive effect on depressive mood, apathy and cognitive functions in patients with early stage of HD. Based on the neurobiological basis of these symptoms, CAR can improve the dopamine imbalance of the prefrontal cortex. This draws attention to the transdiagnostic approach which supports the further understanding of the similar symptomatology of different neuropsychiatric disorders and helps to identify new indications of pharmaceutical compounds.