bluuebunny/crossref_metadata_2025 huggingface dataset:
Telerehabilitation for Word Retrieval Deficits in Bilinguals With Aphasia: Effectiveness and Reliability as Compared to In-person Language Therapy
Authors: Peñaloza Claudia , Scimeca Michael , Gaona Angelica , Carpenter Erin , Mukadam Nishaat , Gray Teresa , Shamapant Shilpa , Kiran Swathi
Published: May 2021

Background: Bilinguals with post-stroke aphasia (BWA) require treatment options that are sensitive to their particular bilingual background and deficits across languages. However, they may experience limited access to bilingual clinical resources due to reduced availability of bilingual practitioners, geographical constraints, and other difficulties. Telerehabilitation can improve access to bilingual clinical services for BWA and facilitate the delivery of specific language treatments at distance, but more evidence on its effectiveness and reliability is needed. This study aimed to determine the equivalence of effectiveness and reliability of a semantic treatment for word retrieval deficits in BWA delivered via telerehabilitation relative to in-person therapy.

Methods: We examined the retrospective data of 16 BWA who received 20 sessions of therapy based on semantic feature analysis for word retrieval deficits in person (n = 8) or via telerehabilitation (n = 8). The two groups were comparable on age, years of education, time of post-stroke onset, aphasia severity, and naming ability in both languages. Treatment effectiveness (i.e., effect sizes in the treated and the untreated language, and change on secondary outcome measures) and reliability (i.e., clinician adherence to treatment protocol) were computed for each delivery modality and compared across groups.

Results: Significant improvements were observed in most patients, with no significant differences in treatment effect sizes or secondary outcomes in the treated and the untreated language between the teletherapy group and the in-person therapy group. Also, the average percentage of correctly delivered treatment steps by clinicians was high for both therapy delivery methods with no significant differences between the telerehabilitation vs. the in-person modality.

Discussion: This study provides evidence of the equivalence of treatment gains between teletherapy and in-person therapy in BWA and the high reliability with which treatment for word retrieval deficits can be delivered via telerehabilitation, suggesting that the essential treatment components of the intervention can be conducted in a comparable manner in both delivery modalities. We further discuss the benefits and potential challenges of the implementation of telerehabilitation for BWA. In the future, telerehabilitation may increase access to therapy for BWA with varying linguistic and cultural backgrounds, thus, offering a more inclusive treatment approach to this population.
Safety, Tolerability, and Effect of Nusinersen Treatment in Ambulatory Adults With 5q-SMA
Authors: Elsheikh Bakri , Severyn Steven , Zhao Songzhu , Kline David , Linsenmayer Matthew , Kelly Kristina , Tellez Marco , Bartlett Amy , Heintzman Sarah , Reynolds Jerry , Sterling Gary , Weaver Tristan , Rajneesh Kiran , Kolb Stephen J. , Arnold W. David
Published: May 2021

Objective: To determine the safety and tolerability of nusinersen treatment in ambulatory adults with spinal muscular atrophy (SMA) and investigate the treatment effect on muscle strength, physical function, and motor unit physiology.

Methods: Individuals aged 18 years or older with genetically confirmed 5q SMA, three or more copies of the SMN2 gene, and the ability to ambulate 30 feet were enrolled. Safety outcomes included the number of adverse events and serious adverse events, clinically significant vital sign or laboratory parameter abnormalities. Outcome assessments occurred at baseline (prior to the first dose of nusinersen) and then 2, 6, 10, and 14 months post-treatment.

Results: Six women, seven men (mean age: 37 ± 11, range: 18–59 years) were included for analyses. The most common side effects were headache and back pain, but overall procedures and treatments were well-tolerated. No serious adverse events were reported. Maximal Voluntary Isometric Muscle Contraction Testing (MVICT) and 6-min walk test (6MWT) both showed overall stability with significant increases at 2, 6, and 10 months for the 6MWT. More consistent significant treatment effects were noted on the Hammersmith Functional Motor Scale Expanded, SMA-Functional Rating Scale, and forced vital capacity. Treatment resulted in progressively increased ulnar compound muscle action potential and average single motor unit potential amplitudes, but motor unit number estimation remained stable.

Conclusions: Nusinersen treatment is safe and well-tolerated in ambulatory adults with SMA. Treatment resulted in improved motor function and electrophysiological findings suggest that this improvement may be occurring via improved motor unit reinnervation capacity.
Prevalence, Severity, and Clinical Management of Brain Incidental Findings in Healthy Young Adults: MRi-Share Cross-Sectional Study
Authors: Soumaré Aïcha , Beguedou Naka , Laurent Alexandre , Brochet Bruno , Bordes Constance , Mournet Sandy , Mellet Emmanuel , Pereira Edwige , Pollet Clothilde , Lachaize Morgane , Mougin Marie , Tsuchida Ami , Loiseau Hugues , Tourdias Thomas , Tzourio Christophe , Mazoyer Bernard , Debette Stéphanie
Published: May 2021

Background and Objectives: Young adults represent an increasingly large proportion of healthy volunteers in brain imaging research, but descriptions of incidental findings (IFs) in this age group are scarce. We aimed to assess the prevalence and severity of IFs on brain MRIs of healthy young research participants aged 18–35 years, and to describe the protocol implemented to handle them.

Methods: The study population comprised 1,867 participants aged 22.1 ± 2.3 years (72% women) from MRi-Share, the cross-sectional brain MRI substudy of the i-Share student cohort. IFs were flagged during the MRI quality control. We estimated the proportion of participants with IFs [any, requiring medical referral, potentially serious (PSIFs) as defined in the UK biobank]: overall, by type and severity of the final diagnosis, as well as the number of IFs.

Results: 78/1,867 participants had at least one IF [4.2%, 95% Confidence Interval (CI) 3.4–5.2%]. IFs requiring medical referral (n = 38) were observed in 36/1,867 participants (1.9%, 1.4–2.7%), and represented 47.5% of the 80 IFs initially flagged. Referred IFs were retrospectively classified as PSIFs in 25/1,867 participants (1.3%, 0.9–2.0%), accounting for 68.4% of anomalies referred (26/38). The most common final diagnosis was cysts or ventricular abnormalities in all participants (9/1,867; 0.5%, 0.2–0.9%) and in those with referred IFs (9/36; 25.0%, 13.6–41.3%), while it was multiple sclerosis or radiologically isolated syndrome in participants with PSIFs (5/19; 26.3%, 11.5–49.1%) who represented 0.1% (0.0–0.4%) and 0.2% (0.03–0.5%) of all participants, respectively. Final diagnoses were considered serious in 11/1,867 participants (0.6%, 0.3–1.1%). Among participants with referred IFs, 13.9% (5/36) required active intervention, while 50.0% (18/36) were put on clinical surveillance.

Conclusions: In a large brain imaging study of young healthy adults participating in research we observed a non-negligible frequency of IFs. The etiological pattern differed from what has been described in older adults.
Dietary Choline-Enhanced Skin Immune Response of Juvenile Grass Carp Might Be Related to the STAT3 and NF-kB Signaling Pathway (Ctenopharyngodon idella)
Authors: Yuan Ze-Hong , Feng Lin , Jiang Wei-dan , Wu Pei , Liu Yang , Jiang Jun , Kuang Sheng-yao , Tang Ling , Zhou Xiao-qiu
Published: May 2021

To investigate the effects and potential mechanisms of dietary choline on immune function in the skin of juvenile grass carp (Ctenopharyngodon idella), fish were fed different diets containing different levels of choline (142. 2, 407.4, 821.6, 1215.8, 1589.3, and 1996.6 mg/kg) for 70 d and then sampled after a 6-d challenge test. The results exhibited that dietary choline (1) advanced the contents of phosphatidylcholine (PC), betaine, and choline in grass carp skin (P < 0.05) and upregulated the mRNA abundance of choline transporter high-affinity choline transporter 1 (CHT1), choline transporter-like protein 1 (CTL1), and choline transporter-like protein 5 (CTL5), indicating that dietary choline could increase the contents of choline which might be connected with choline transporters in the grass carp skin; (2) receded skin rot symptom after infection with A. hydrophila (Aeromonas hydrophila), increased the levels of IgM, C4, and C3 and the activities of acid phosphatase (ACP) and lysozyme (LZ), raised mucin2, β-defensin, hepcidin, and LEAP-2B mRNA abundance (rather than LEAP-2A), downregulated pro-inflammatory cytokine mRNA abundance (IFN-γ2, IL-15, TNF-α, IL-6, IL-12P40, and IL-1β) in skin of juvenile grass carp (P < 0.05), and upregulated anti-inflammatory cytokine mRNA abundance (IL-10, IL-4/13A, TGF-β1, IL-11, and IL-4/13B) in grass carp skin (P < 0.05), demonstrating that choline enhanced the skin immune function; and (3) downregulated the mRNA abundance of IKKγ, NF-κBp52, IKKβ, c-Rel, NF-κBp65, STAT3b2, STAT3b1, JAK1, and JAK2 as well as protein level of NF-κBp65, p-STAT3 Tyr705, and p-STAT3 Ser727 in nucleus and inhibited the mRNA and protein level of IkBα (P < 0.05), indicating that choline-enhanced immune function might be relevant to the JAK1, 2 /STAT3, and NF-κB signaling pathway in fish skin. In conclusion, choline enhanced the skin immune function which might be related to JAK1, 2/STAT3, and NF-κB signaling molecules in fish. Furthermore, based on immune indices of grass carp (9.28–108.97 g) skin (C3 and IgM contents as well as ACP activities), the choline requirements were estimated to be 1475.81, 1364.24, and 1574.37 mg/kg diet, respectively.
Association of Selenium Intake and Development of Depression in Brazilian Farmers
Authors: Ferreira de Almeida Tatiana Lourençoni , Petarli Glenda Blaser , Cattafesta Monica , Zandonade Eliana , Bezerra Olivia Maria de Paula Alves , Tristão Kelly Guimães , Salaroli Luciane Bresciani
Published: May 2021

Introduction:Depression and deficiency in the consumption of micronutrients are a public health problem, especially in the rural population. The deficiency in selenium consumption affects mental health, contributing to the development of major depressive disorders. Thus, this study aimed to evaluate selenium intake and its association with depressive symptoms in farmers in southeastern Brazil.

Material and Methods:Epidemiological, cross-sectional, and analytical study with 736 farmers aged between 18 and 59. A semistructured questionnaire was used to collect sociodemographic, lifestyle and clinical condition data. For evaluation of food intake, three 24-h recalls were applied, and for identification of depressive episodes, the Mini-International Neuropsychiatric Interview was conducted.

Results:A total of 16.1% (n= 119) of the farmers presented symptoms of major depressive episodes, 5.8% (n= 43) presented symptoms of current depressive episodes, and 10.3% (n= 76) presented symptoms of recurrent major depressive episodes. Sociodemographic factors associated with depression were gender (p< 0.001), marital status (p= 0.004), and socioeconomic class (p= 0.015). The consumption of high doses of selenium was associated with a reduction of ~54% in the chances of occurrence of depression (OR = 0.461; 95% CI = 0.236–0.901).

Conclusion:High selenium intake is associated with a lower prevalence of depression even after adjusting for sociodemographic variables, lifestyle, and pesticide intoxication. The findings of this study contributed to highlighting the high prevalence of depression in rural areas and its relationship with selenium intake.
LncRNA HAS2-AS1 Promotes Glioblastoma Proliferation by Sponging miR-137
Authors: Lu Yalin , Guo Gaochao , Hong Rujun , Chen Xingjie , Sun Yan , Liu Fang , Zhang Zhimeng , Jin Xun , Dong Jun , Yu Kai , Yang Xuejun , Nan Yang , Huang Qiang
Published: May 2021

GBM (Glioblastoma multiform) is the most malignant tumor type of the central nervous system and has poor diagnostic and clinical outcomes. LncRNAs (Long non-coding RNAs) have been reported to participate in multiple biological and pathological processes, but their underlying mechanism remains poorly understood. Here, we aimed to explore the role of the lncRNA HAS2-AS1 (HAS2 antisense RNA 1) in GBM. GSE103227 was analyzed, and qRT-PCR was performed to measure the expression of HAS2-AS1 in GBM. FISH (Fluorescence in situ hybridization) was performed to verify the localization of HAS2-AS1. The interaction between HAS2-AS1 and miR-137 (microRNA-137) was predicted by LncBook and miRcode followed by dual‐luciferase reporter assays, and the relationships among HAS2-AS1, miR-137 and LSD1 (lysine-specific demethylase 1) were assessed by WB (western blot) and qRT-PCR. Colony formation and CCK-8 (cell counting kit-8) assays were performed as functional tests. In vivo, nude mice were used to confirm the function of HAS2-AS1. HAS2-AS1 expression was upregulated in GBM cell lines, and HAS2-AS1 was localized mainly in the cytoplasm. In vitro, high HAS2-AS1 expression promoted proliferation, and knockdown of HAS2-AS1 significantly inhibited proliferation. Furthermore, HAS2-AS1 functioned as a ceRNA (competing endogenous RNA) of miR-137, leading to the disinhibition of its downstream target LSD1. The miR-137 level was downregulated by HAS2-AS1 overexpression and upregulated by HAS2-AS1 knockdown. In a subsequent study, LSD1 expression was negatively regulated by miR-137, while miR-137 reversed the LSD1 expression levels caused by HAS2-AS1. These results were further supported by the nude mouse tumorigenesis experiment; compared with xenografts with high HAS2-AS1 expression, the group with low levels of HAS2-AS1 exhibited suppressed proliferation and better survival. We conclude that lncRNA HAS2-AS1 promotes proliferation by functioning as a miR‐137 decoy to increase LSD1 levels and thus might be a possible biomarker for GBM.
Learning Curve for Lymph Node Dissection Around the Recurrent Laryngeal Nerve in McKeown Minimally Invasive Esophagectomy
Authors: Zhu Zi-Yi , Luo Rao-Jun , He Zheng-Fu , Xu Yong , Xu Shao-Hua , Zhang Qiang
Published: May 2021

Background

Compared to open esophagectomy (OE), minimally invasive esophagectomy (MIE) is associated with lower morbidity and mortality. However, lymph node (LN) dissection around the recurrent laryngeal nerve (RLN) is still an important factor that affects the length of the learning curve of MIE. This study aims to evaluate the surgical outcomes of the first nearly 5-year period and explore the learning curve for LN dissection around the RLN in McKeown MIE by a new single surgical team.

Methods

A total of 285 consecutive patients who underwent McKeown MIE between March 2016 and September 2020 were included at our institution. According to the cumulative sum (CUSUM) analysis of LN dissection around the RLN, the patients were divided into three groups: exploration period, adjustment period, and stable period. We assessed the impact of surgical proficiency on postoperative outcomes and explored the learning curve for LN dissection around the RLN in McKeown MIE.

Results

The CUSUM graph showed that a point of upward inflection for LN dissection around the RLN was observed in 151 cases. After 151 cases, LNs around the right and left RLNs were dissected thoroughly compared to the exploration and adjustment period (P = 0.010 and P = 0.012, respectively), and the postoperative incidence of hoarseness significantly decreased from 11.1 to 1.5% (P<0.001).

Conclusions

Our study results revealed that not only are the LN, around the RLN, sufficiently dissected but also the incidence of hoarseness significantly decreased in the stable phase. Consequently, the learning curve length was approximately 151 cases for LN dissection around the RLN in McKeown MIE.
Salubrinal Exposes Anticancer Properties in Inflammatory Breast Cancer Cells by Manipulating the Endoplasmic Reticulum Stress Pathway
Authors: Alsterda Andrew , Asha Kumari , Powrozek Olivia , Repak Miroslava , Goswami Sudeshna , Dunn Alexandra M. , Memmel Heidi C. , Sharma-Walia Neelam
Published: May 2021

The endoplasmic reticulum (ER) regulates protein folding, post-translational modifications, lipid synthesis, and calcium signaling to attenuate the accumulation of misfolded proteins causing ER stress and maintains cellular homeostasis. The tumor microenvironment is rich in soluble cytokines, chemokines, growth, and angiogenic factors and can drive the ER’s abnormal functioning in healthy cells. Cancer cells adapt well to the tumor microenvironment induced ER stress. We identified that the inflammatory breast cancer (IBC) cells abundantly express osteoprotegerin (OPG) and their tumor microenvironment is rich in OPG protein. OPG also called osteoclast differentiation factor/osteoclastogenesis inhibitory factor (OCIF) is a soluble decoy receptor for receptor activator of nuclear factor-kappa B ligand (RANKL). Employing mass spectrometry analysis, we identified a set of ER chaperones associated with OPG in IBC cell lysates (SUM149PT, SUM1315MO2) compared to healthy human mammary epithelial cells (HMEC). Proximity ligation assay (PLA) and immunoprecipitation assay validated the interaction between OPG and ER chaperone and master regulator of unfolded protein response (UPR) GRP78/BiP (glucose-regulated protein/Binding immunoglobulin protein). We detected remarkably high gene expression of CCAAT enhancer-binding protein homologous protein (CHOP), inositol-requiring enzyme 1 (IRE1α), protein disulfide-isomerase (PDI), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), X-box binding protein 1 (XBP-1) and growth arrest and DNA damage-inducible protein (GADD34) in SUM149PT and SUM190PT cells when compared to HMEC. Similarly, tissue sections of human IBC expressed high levels of ER stress proteins. We evaluated cell death and apoptosis upon Salubrinal and phenylbutyrate treatment in healthy and IBC cells by caspase-3 activity and cleaved poly (ADP-ribose) polymerase (PARP) protein assay. IBC (SUM149PT and SUM190PT) cells were chemosensitive to Salubrinal treatment, possibly via inhibition in OPG secretion, upregulating ATF4, and CHOP, thus ultimately driving caspase-3 mediated IBC cell death. Salubrinal treatment upregulated PDI, which connects ER stress to oxidative stress. We observed increased ROS production and reduced cell proliferation of Salubrinal treated IBC cells. Treatment with antioxidants could rescue IBC cells from ROS and aborted cell proliferation. Our findings implicate that manipulating ER stress with Salubrinal may provide a safer and tailored strategy to target the growth of inflammatory and aggressive forms of breast cancer.
Factors Influencing Mood Disorders and Health Related Quality of Life in Adults With Glioma: A Longitudinal Study
Authors: Leonetti Antonella , Puglisi Guglielmo , Rossi Marco , Viganò Luca , Conti Nibali Marco , Gay Lorenzo , Sciortino Tommaso , Howells Henrietta , Fornia Luca , Riva Marco , Cerri Gabriella , Bello Lorenzo
Published: May 2021

Objective

At present, it is not clear whether Mood Disorders (MD) and poor Health Related Quality of Life (HRQoL) in the glioma population correlate with features of the tumor, or rather with secondary symptoms associated with treatment. The aim of this study was to assess the prevalence of MD and decline in HRQoL in glioma patients, and to determine the main factors associated with these two variables.

Methods

80 patients affected by lower-grade gliomas (LGGs) and 65 affected by high-grade gliomas (HGGs) were evaluated, from admission up to 12 months after surgery, for MD, HRQoL, clinical characteristics, and cognitive functions. Independent factors associated with MD and low HRQoL were identified by using bivariate analysis.

Results

Data showed that prevalence of low HRQoL was comparable in both groups during all the time points assessed (pre, 1, 3, 6 and 12 months after surgery). In contrast at 6 months following surgery, HGGs showed a higher prevalence of MD compared to LGGs;. Bivariate analysis revealed that factors associated with MD and HRQoL in LGGs and HGGs were different over the course of the disease. In LGGs, from the pre-operative period to one year post surgery, MD and low HRQOL were associated with the occurrence of cognitive deficits and, from the third month after surgery onward, they were also associated with the effect exerted by adjuvant treatments. In HGGs, MD were associated with cognitive deficits at 3 and 6 months after surgery, along with older age (65-75 years); HRQoL, in its Physical component in particular, was associated with older age only from 6 months after surgery.

Conclusion

Factors associated with MD and low HRQoL were different in LGGs and HGGs over the course of the disease. In LGGs the effect of adjuvant treatments was prominent in determining the prevalence of both MD and poor HRQoL from the third month after surgery onward. In HGGs, MD and HRQoL were associated with age, at 3 and 6 months after surgery. In both, the occurrence of cognitive deficits was significantly associated with MD.
Melanotic Neuroectodermal Tumor of Infancy: A Clinicopathological and BRAF V600E Mutation Study of 11 Cases
Authors: Xia Rong-Hui , Zhang Chun-Ye , Wang Li-Zhen , Hu Yu-Hua , Sun Jing-Jing , Tian Zhen , Li Jiang
Published: May 2021

Purpose

To investigate the clinicopathological features and BRAF V600E mutation of melanotic neuroectodermal tumor of infancy (MNTI).

Materials and Methods

Eleven cases of MNTI diagnosed at the Department of Oral Pathology were collected. Clinicopathological characteristics were obtained from the medical records. Immunostaining was performed by immunohistochemistry (IHC). Amplification-Refractory Mutation System-qPCR (ARMS-qPCR) and Sanger Sequencing were used to detect BRAF V600E mutation.

Results

Of the 11 cases, 3 cases were female and 8 cases were male. The mean age of the first symptoms was 3.2 months (range: 1 to 6 months). Ten cases (90.9%) located in maxilla but only one (9.1%) in mandible. Most of the cases demonstrated well-defined mass with lytic bone destruction and tooth germ affecting radiologically. Histologically, MNTI was consisted of large polygonal melanin-producing epithelioid cells and small round neuroblast-like cells which arranged in irregular alveolar, tubuloglandular and fissured architecture. The epithelioid cells expressed Vim, Pan-CK, NSE and HMB45, while the smalls cells expressed Syn, NSE and scattered Vim. Most cases showed low Ki-67 index (range: <1% to 50%). None of the MNTI cases showed BRAF V600E mutation. Most cases were treated with enucleation (45.4%) or curettage (36.4%). Among the 11 cases, 6 cases had follow-up information, and 2 cases had recurrence lesions after surgery.

Conclusion

MNTI, an extremely rare tumor, mainly affects male infants with strong preference for maxilla. Distinct histopathological features and immunohistochemical profile are helpful to distinguish from other melanin-containing tumors and small round cell tumors. No BRAF V600E mutation in MNTI is detected in the present study and needs further investigations. The factors that contribute to the local recurrence of MNTI are controversial, but the close follow-up for the patients is recommended.
Frontiers in Bladder Cancer Genomic Research
Authors: Li Yi , Sun Lihui , Guo Xiangyang , Mo Na , Zhang Jinku , Li Chong
Published: May 2021

Most of the etiology studies of bladder cancer focus on genetic changes, mainly including mutation and activation of oncogenes, mutation and inactivation of tumor suppressor genes, and rearrangement or heterozygous deletion of chromosomes. Moreover, bladder cancer is highly heterogeneous mainly due to abnormal changes in the genome and proteome of tumor cells. Surgery is the main treatment for bladder cancer, but because the recurrence rate is high after surgery and most of the muscle-invasive bladder cancer acquires distant metastasis. Therefore, there is a need to combine with chemotherapy to consolidate the treatment effect. However, there are differences in chemosensitivity among patients. In this article, we review the up-to-date genomic researches on bladder cancer occurrence, development, metastasis, and chemosensitivity in patients, in order to provide some theoretical support for the diagnosis and treatment strategy for bladder cancer.
Treatments Outcomes in Histological Variants and Non-Urothelial Bladder Cancer: Results of a Multicenter Retrospective Study
Authors: Epaillard Nicolas , Parent Pauline , Loriot Yohann , Lavaud Pernelle , Vera-Cea E-B. , Martinez-Chanza Nieves , Rodriguez-Vida Alejo , Dumont Clement , Lozano Rebeca , Llácer Casilda , Ratta Raffaele , Oudard Stephane , Thibault Constance , Auclin Edouard
Published: May 2021

Introduction

Less than one-third of bladder cancers are non-pure urothelial carcinoma [with variant histological (VH) or non-urothelial carcinoma (non-UC)] for which no treatment guidelines are available. We aim to evaluate the efficacy of systemic treatments in VH or non-UC bladder cancers.

Materials

Multicenter retrospective analysis of patients treated for advanced or metastatic VH or non-UC bladder cancers. Primary endpoint was overall response rate (ORR) according to treatment line, regimen and histology subtype. Secondary endpoints were progression-free survival (PFS) and overall survival (OS).

Results

Between 2005 and 2020, 46 patients from seven centers were included. The median age was 66 years (58.75; 74.75), 65.2% were male and 67.2% presented VH. At first line, the ORR for the entire population was 54.4% and median OS was 21.6 months (95% confidence interval [CI]: 14.2-38.6). The ORR of the 37 patients treated with chemotherapy at first line was 62.2% with median PFS and OS of 7.3 (95% CI: 4.5-8.6) and 21.6 months (95% CI: 14.2-35.7), respectively. Dose dense MVAC and platinum doublet chemotherapy had the highest ORR (71.4% and 65.2%). The 9 patients treated with immunotherapy at first line had an ORR of 22.2%, a median PFS of 3.3 months (95% CI:2.3-NR) and the median OS was not reached (95% CI:13.8-NR). Response to treatment varied depending on the histological sub-types and on the treatment type.

Conclusion

Chemotherapy and immunotherapy have shown to be effective in VH or non-UC cancers, a rare histological subtype for which we currently have very little data in the literature.
Asphyxia and Neonatal Respiratory Distress Syndrome Are Independent Predictors of the Non-response to Inhaled Nitric Oxide in the Newborns With PPHN
Authors: Zhao Yuwei , Liang Lei , Liu Guanghui , Zheng Hong , Dai Liying , Wang Yan , Wang Lei , Sheng Weiting
Published: May 2021

Aim: Not all the neonates respond with improvement in oxygenation following inhaled nitric oxide treatment (iNO) treatment. The aim of this study was to assess the independent risk factors associated with non-response to iNO during the 2 weeks of postnatal treatment in neonates diagnosed with persistent pulmonary hypertension (PPHN).

Materials and Methods: This retrospective cohort study included all newborns with PPHN who received iNO treatment for more than 24 h. Demographic, obstetric, perinatal data and clinical complications were extracted from the hospitalization records. Subjects were divided into two groups according to their response to iNO inspiration during the first 24 h of iNO treatment. No response was defined as an increase in SpO2 < 5% or the inability to sustain saturation levels in the first 24 h of iNO treatment. For descriptive statistics, χ2 and t-test analysis were used to compare categorical and continuous variables between the two groups. To evaluate independent risk factors of non-responsiveness to iNO treatment, binary logistic regression analysis were performed.

Results: A total of 75 newborns were included in the study. Sixty-two cases were in the responders group, and 13 cases were in the non-responders group. Univariate analysis showed that asphyxia, neonatal respiratory distress syndrome (NRDS), pulmonary surfactant administration, meconium aspiration syndrome (MAS), the severity of pulmonary hypertension (PH), and high-frequency oscillatory ventilation (HFOV) therapy were the high-risk factors affecting the response to iNO treatment in the newborns with PPHN. The binary logistic regression analysis indicated that asphyxia and NRDS incidence were independent predictors of non-responsiveness to iNO treatment [asphyxia: OR 4.193, 95% CI 1.104–15.927, P = 0.035; NRDS: OR 0.154, 95% CI 0.036–0.647, P = 0.011]. The patients in the non-responders group had shorter iNO inspiration followed by MV duration, supplemental oxygen and hospital stay, and higher mortality. There were no significant differences in IVH, PVL, and BPD between two groups.

Conclusion: In the newborns with PPHN, asphyxia and NRDS resulted as the independent risk factors of non-responsiveness to iNO therapy. Asphyxia in the newborns with PPHN is detrimental to the response to iNO treatment, while NRDS is beneficial.
Jiedu Tongluo Granules Ameliorates Post-stroke Depression Rat Model via Regulating NMDAR/BDNF Signaling Pathway
Authors: Zhao Aimei , Ma Bo , Xu Li , Yao Mingjiang , Zhang Yehao , Xue Bingjie , Ren Junguo , Chang Dennis , Liu Jianxun
Published: May 2021

Post-stroke depression (PSD) is one of the most common stroke complications, which seriously affects stroke’s therapeutic effect and brings great pain for patients. The pathological mechanism of PSD has not been revealed. Jiedu Tongluo granules (JDTLG) is an effective traditional Chinese medicine for PSD treatment which is widely used in clinical treatment. JDTLG has a significant therapeutic effect against PSD, but the mechanism is still unclear. The PSD rat model was established by carotid artery embolization combined with chronic sleep deprivation followed by treating with JDTLG. Neurobehavioral and neurofunctional experiments were engaged in studying the neural function of rats. Histomorphology, proteomics, and western blotting researches were performed to investigate the potential molecular mechanisms related to JDTLG therapy. Oral treatment of JDTLG could significantly improve the symptoms of neurological deficit and depression symptoms of PSD rats. Proteomic analysis identified several processes that may involve the regulation of JDTLG on the PSD animal model, including energy metabolism, nervous system, and N-methyl-D-aspartate receptor (NMDAR)/brain-derived neurotrophic factor (BDNF) signal pathway. Our results showed that JDTLG could reduce glutamate (Glu) level and increase gamma-aminobutyric acid (GABA) level via regulating the NMDAR/BDNF pathway, which may play a vital role in the occurrence and development of PSD.
Capsaicin and Proton Differently Modulate Activation Kinetics of Mouse Transient Receptor Potential Vanilloid-1 Channel Induced by Depolarization
Authors: Takahashi Kaori , Araki Kentaro , Miyamoto Hideo , Shirakawa Rikimaru , Yoshida Takashi , Wakamori Minoru
Published: May 2021

The transient receptor potential vanilloid type 1 (TRPV1) channel is a non-selective cation channel expressed with transient receptor potential ankyrin type 1 (TRPA1) in small and medial size neurons of the dorsal root ganglions and trigeminal ganglions. TRPV1 is activated by capsaicin, thermal stimuli higher than 43°C, mechanical stress, and protons (H+). Although the TRPV1 channel does not have positively charged residues at regular intervals on its transmembrane segments, alterations in membrane potential also affect the state of TRPV1 channel. In the presence of capsaicin, voltage-dependent probability of opening of the TRPV1 channel and its kinetics have been examined, but the characteristics in the low pH remain unclear. To understand the voltage-dependency of the TRPV1 channel activation, we recorded capsaicin- and proton-induced mouse TRPV1 channel currents in a heterologous expression system. Outward current evoked by depolarizing square pulses in the presence of capsaicin or protons was fitted to a two-exponential function with a time-independent component. The voltage-dependent changes in amplitude of the three components displayed shallow curves and the changes in their ratio to the total current display similar tendencies in the presence of capsaicin and under the low pH. However, the fast and slow time constants in the presence of capsaicin were respectively 5- and 8-fold lower than those obtained under low pH conditions. These results suggest that the TRPV1 channel slowly drives the feed-forward cycle of pain sensation, and capsaicin and protons differently modulate the voltage-dependent TRPV1 channel gating.
Efficacy of Mudan Granule (Combined With Methylcobalamin) on Type 2 Diabetic Peripheral Neuropathy: Study Protocol for a Double-Blind, Randomized, Placebo-Controlled, Parallel-Arm, Multi-Center Trial
Authors: Zhang Yuehong , Jin De , Duan Yingying , Hao Rui , Chen Keyu , Yu Tongyue , Lian Fengmei , Tong Xiaolin
Published: May 2021

Background: Diabetic peripheral neuropathy (DPN) characterized by nerve damage is a common and disabling chronic microvascular complication in patients with type 2 diabetic mellitus (T2DM), affecting at least half of patients diagnosed with T2DM. Unfortunately, the current treatment for DPN is not ideal. Traditional Chinese medicine (TCM), with a unique theoretical system, has made outstanding contributions in the treatment of T2DM and related complications. Mudan granule, a Chinese patent medicine, has been previously validated that could ameliorate the symptoms, promote nerve tissue repair, increase nerve conduction velocity (NCV) in patients with DPN. However, the previous studies are of variable quality, which limits the clinical application of Mudan granule. Therefore, we designed a double-blind, randomized, placebo-controlled, parallel-arm, multi-center trial to estimate the safety and efficacy of Mudan granule in conjunction with methylcobalamin in individuals suffering from type 2 diabetic peripheral neuropathy.

Methods: This work is conducted as a 14-center, double-blind, randomized, placebo-controlled, parallel-arm trial. In all, 402 subjects (aged 30–70 years) will be recruited and randomized in a 1:1 ratio to an intervention group (n = 201; Mudan granule + methylcobalamin) and a control group (n = 201; placebo + methylcobalamin). Treatment is administered in 24 weeks cycles without any treatment interruption between cycles. Michigan Diabetic Neuropathy Score (MDNS) as the primary outcome will be evaluated at baseline, 12 weeks during the intervention period, and after 24 weeks of the intervention. Adverse events and safety assessments will be also documented. The analysis of all data will be carried out based on a predefined statistical analysis plan.

Discussion: The outcomes from this study will offer important evidence regarding the safety and efficacy that Mudan granule can be used as an alternative and complementary therapeutic intervention in patients with type 2 diabetic peripheral neuropathy.

Clinical trial registration: Registered at https://clinicaltrials.gov/. Trial registration number: NCT04711980. Registered January 2021.
The Role of Embryonic Chick Muscle Cell Culture in the Study of Skeletal Myogenesis
Authors: Costa Manoel L. , Jurberg Arnon D. , Mermelstein Claudia
Published: May 2021

The mechanisms involved in the development of skeletal muscle fibers have been studied in the last 70 years and yet many aspects of this process are still not completely understood. A myriad of in vivo and in vitro invertebrate and vertebrate animal models has been used for dissecting the molecular and cellular events involved in muscle formation. Among the most used animal models for the study of myogenesis are the rodents rat and mouse, the fruit fly Drosophila, and the birds chicken and quail. Here, we describe the robustness and advantages of the chick primary muscle culture model for the study of skeletal myogenesis. In the myoblast culture obtained from embryonic chick pectoralis muscle it is possible to analyze all the steps involved in skeletal myogenesis, such as myoblast proliferation, withdrawal from cell cycle, cell elongation and migration, myoblast alignment and fusion, the assembly of striated myofibrils, and the formation of multinucleated myotubes. The fact that in vitro chick myotubes can harbor hundreds of nuclei, whereas myotubes from cell lines have only a dozen nuclei demonstrates the high level of differentiation of the autonomous chick myogenic program. This striking differentiation is independent of serum withdrawal, which points to the power of the model. We also review the major pro-myogenic and anti-myogenic molecules and signaling pathways involved in chick myogenesis, in addition to providing a detailed protocol for the preparation of embryonic chick myogenic cultures. Moreover, we performed a bibliometric analysis of the articles that used this model to evaluate which were the main explored topics of interest and their contributors. We expect that by describing the major findings, and their advantages, of the studies using the embryonic chick myogenic model we will foster new studies on the molecular and cellular process involved in muscle proliferation and differentiation that are more similar to the actual in vivo condition than the muscle cell lines.
GWAS Mediated Elucidation of Heterosis for Metric Traits in Cotton (Gossypium hirsutum L.) Across Multiple Environments
Authors: Sarfraz Zareen , Iqbal Muhammad Shahid , Geng Xiaoli , Iqbal Muhammad Sajid , Nazir Mian Faisal , Ahmed Haris , He Shoupu , Jia Yinhua , Pan Zhaoe , Sun Gaofei , Ahmad Saghir , Wang Qinglian , Qin Hongde , Liu Jinhai , Liu Hui , Yang Jun , Ma Zhiying , Xu Dongyong , Yang Jinlong , Zhang Jinbiao , Li Zhikun , Cai Zhongmin , Zhang Xuelin , Zhang Xin , Huang Aifen , Yi Xianda , Zhou Guanyin , Li Lin , Zhu Haiyong , Pang Baoyin , Wang Liru , Sun Junling , Du Xiongming
Published: May 2021

For about a century, plant breeding has widely exploited the heterosis phenomenon–often considered as hybrid vigor–to increase agricultural productivity. The ensuing F1 hybrids can substantially outperform their progenitors due to heterozygous combinations that mitigate deleterious mutations occurring in each genome. However, only fragmented knowledge is available concerning the underlying genes and processes that foster heterosis. Although cotton is among the highly valued crops, its improvement programs that involve the exploitation of heterosis are still limited in terms of significant accomplishments to make it broadly applicable in different agro-ecological zones. Here, F1 hybrids were derived from mating a diverse Upland Cotton germplasm with commercially valuable cultivars in the Line × Tester fashion and evaluated across multiple environments for 10 measurable traits. These traits were dissected into five different heterosis types and specific combining ability (SCA). Subsequent genome-wide predictions along-with association analyses uncovered a set of 298 highly significant key single nucleotide polymorphisms (SNPs)/Quantitative Trait Nucleotides (QTNs) and 271 heterotic Quantitative Trait Nucleotides (hQTNs) related to agronomic and fiber quality traits. The integration of a genome wide association study with RNA-sequence analysis yielded 275 candidate genes in the vicinity of key SNPs/QTNs. Fiber micronaire (MIC) and lint percentage (LP) had the maximum number of associated genes, i.e., each with 45 related to QTNs/hQTNs. A total of 54 putative candidate genes were identified in association with HETEROSIS of quoted traits. The novel players in the heterosis mechanism highlighted in this study may prove to be scientifically and biologically important for cotton biologists, and for those breeders engaged in cotton fiber and yield improvement programs.
Can the Non-native Salt Marsh Halophyte Spartina alterniflora Threaten Native Seagrass (Zostera japonica) Habitats? A Case Study in the Yellow River Delta, China
Authors: Yue Shidong , Zhou Yi , Xu Shaochun , Zhang Xiaomei , Liu Mingjie , Qiao Yongliang , Gu Ruiting , Xu Shuai , Zhang Yu
Published: May 2021

Seagrass meadows are critical ecosystems, and they are among the most threatened habitats on the planet. As an anthropogenic biotic invader, Spartina alterniflora Loisel. competes with native plants, threatens native ecosystems and coastal aquaculture, and may cause local biodiversity to decline. The distribution area of the exotic species S. alterniflora in the Yellow River Delta had been expanding to ca.4,000 ha from 1990 to 2018. In this study, we reported, for the first time, the competitive effects of the exotic plant (S. alterniflora) on seagrass (Zostera japonica Asch. & Graebn.) by field investigation and a transplant experiment in the Yellow River Delta. Within the first 3 months of the field experiment, S. alterniflora had pushed forward 14 m into the Z. japonica distribution region. In the study region, the area of S. alterniflora in 2019 increased by 516 times compared with its initial area in 2015. Inhibition of Z. japonica growth increased with the invasion of S. alterniflora. Z. japonica had been degrading significantly under the pressure of S. alterniflora invasion. S. alterniflora propagates sexually via seeds for long distance invasion and asexually by tillers and rhizomes for short distance invasion. Our results describe the invasion pattern of S. alterniflora and can be used to develop strategies for prevention and control of S. alterniflora invasion.
Learning Handwriting: Factors Affecting Pen-Movement Fluency in Beginning Writers
Authors: Fitjar Camilla L. , Rønneberg Vibeke , Nottbusch Guido , Torrance Mark
Published: May 2021

Skilled handwriting of single letters is associated not only with a neat final product but also with fluent pen-movement, characterized by a smooth pen-tip velocity profile. Our study explored fluency when writing single letters in children who were just beginning to learn to handwrite, and the extent to which this was predicted by the children’s pen-control ability and by their letter knowledge. 176 Norwegian children formed letters by copying and from dictation (i.e., in response to hearing letter sounds). Performance on these tasks was assessed in terms of the counts of velocity inversions as the children produced sub-letter features that would be produced by competent handwriters as a single, smooth (ballistic) action. We found that there was considerable variation in these measures across writers, even when producing well-formed letters. Children also copied unfamiliar symbols, completed various pen-control tasks (drawing lines, circles, garlands, and figure eights), and tasks that assessed knowledge of letter sounds and shapes. After controlling for pen-control ability, pen-movement fluency was affected by letter knowledge (specifically children’s performance on a task that required selecting graphemes on the basis of their sound). This was the case when children retrieved letter forms from dictated letter sounds, but also when directly copying letters and, unexpectedly, when copying unfamiliar symbols. These findings suggest that familiarity with a letter affects movement fluency during letter production but may also point towards a more general ability to process new letter-like symbols in children with good letter knowledge.
Perceiving Sound Objects in the Musique Concrète
Authors: Godøy Rolf Inge
Published: May 2021

In the late 1940s and early 1950s, there emerged a radically new kind of music based on recorded environmental sounds instead of sounds of traditional Western musical instruments. Centered in Paris around the composer, music theorist, engineer, and writer Pierre Schaeffer, this became known as musique concrète because of its use of concrete recorded sound fragments, manifesting a departure from the abstract concepts and representations of Western music notation. Furthermore, the term sound object was used to denote our perceptual images of such fragments. Sound objects and their features became the focus of an extensive research effort on the perception and cognition of music in general, remarkably anticipating topics of more recent music psychology research. This sound object theory makes extensive use of metaphors, often related to motion shapes, something that can provide holistic representations of perceptually salient, but temporally distributed, features in different kinds of music.
Development and Internal Validation of a Novel Model to Identify Inflammatory Biomarkers of a Response to Escitalopram in Patients With Major Depressive Disorder
Authors: Zhou Jingjing , Zhou Jia , Sun Zuoli , Feng Lei , Zhu Xuequan , Yang Jian , Wang Gang
Published: May 2021

Objective: The aim of our study was to identify immune- and inflammation-related factors with clinical utility to predict the clinical efficacy of treatment for depression.

Study Design: This was a follow-up study. Participants who met the entry criteria were administered with escitalopram (5–10 mg/day) as an initial treatment. Self-evaluation and observer valuations were arranged at the end of weeks 0, 4, 8, and 12, with blood samples collected at baseline and during weeks 2 and 12. Multivariable logistic regression analysis was then carried out by incorporating three cytokines selected by the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. Internal validation was estimated using the bootstrap method with 1,000 repetitions.

Results: A total of 85 patients with Major Depressive Disorder (MDD), including 62 responders and 23 non-responders, were analyzed. Monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and lipocalin-2 were selected by the LASSO regression model. The area under the curve (AUC) from the logistic model was 0.811 and was confirmed as 0.7887 following bootstrapping validation.

Conclusions: We established and validated a good prediction model to facilitate the individualized prediction of escitalopram treatment for MDD and created a personalized approach to treatment for patients with depression.
Family Dynamics and Grandparents' Anxiety and Depression in Intergenerational Rearing Families: A Correlational Study
Authors: Yang Chun-Yan , Xu Hong-Jiao , Liu Shan-Shan , Wu Yue-Jing , Long Yun , Liu Hong-Sheng , Chen Yao-Pian , Li Xia
Published: May 2021

Background: In China, intergenerational rearing is a ubiquitous phenomenon based on unique national conditions. This study aimed to explore family dynamics in intergenerational rearing families as well as their correlation with older household members' anxiety and depression.

Methods: The elderly from intergenerational (n = 141) and non-intergenerational rearing families (n = 266) were investigated using the following scales: the general information questionnaire, Self-Rating Scale of Systemic Family Dynamics, Geriatric Depression Scale, and Self-Rating Anxiety Scale.

Results: Scores from the four dimensions (family atmosphere, system logic, individuation, and the concept of disease) of the structure of family dynamics were computed. The comparison of these dimensions scores and the total scores of grandparents' anxiety and depression for the two groups were not statistically significant (p > 0.05). In Pearson's correlation analysis, no significant correlation between the family atmosphere dimension and the total score of the grandparents' depression and anxiety scales was observed. The system logic aspect was negatively correlated with depression and anxiety scale scores. The individual dimension was positively correlated with the anxiety scale scores. The disease concept dimension was positively correlated with depression and anxiety scale scores. Hence, the results were statistically significant.

Conclusion: There were no significant differences in terms of family dynamics and risk of anxiety and depression among grandparents between the two family types. The system logic, individuation, and disease concept dimensions were correlated with their anxiety and depression.