bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal Dynamics and Geodetic Mass Changes of Glaciers With Varying Debris Cover in the Pangong Region of Trans-Himalayan Ladakh, India Between 1990 and 2019
Authors: Majeed Ulfat , Rashid Irfan , Najar Nadeem Ahmad , Gul Nafeeza
Published: December 2021

Glaciers across the Himalayan arc are showing varying signs of recession. Glaciers in the eastern and western parts of the Himalayan arc are retreating more rapidly as compared to other regions. This differential retreat is often attributed to climatic, topographic, and geologic influences. The glaciers in the Trans-Himalayan region of Ladakh are believed to be relatively stable as compared to other parts of the western Himalaya. The present study ascertained the area changes and frontal retreat of 87 glaciers in the Pangong Region between 1990 and 2019 using satellite data. The geodetic mass changes were also assessed using SRTM and TanDEM-X digital elevation models of 2000 and 2012 respectively. Besides, the glacier outlines were delineated manually and compared with existing regional and global glacier inventories that are available over the region. The GlabTop model was used to simulate the glacier-bed overdeepenings of four glaciers that are associated with a proglacial lake. The study also analyzed the impact of topographic influences and varying debris cover on glacier recession. This analysis indicated deglaciation of 6.7 ± 0.1% (0.23% a−1) from 1990 to 2019 over the Pangong Region with clean-ice glaciers showing a higher retreat (8.4 ± 0.28%) compared to the debris-covered glaciers (5.7 ± 0.14%). However, the overall recession is lower compared to other parts of northwestern Himalayas. The glacier recession showed a positive correlation with mean glacier slope (r = 0.3) and debris cover (r = 0.1) with bigger size glaciers having retreated at a lesser pace compared to smaller ones. This underpins the need for in-situ data about debris thickness to precisely ascertain the role of debris on glacier recession in the Trans-Himalayan Ladakh where debris thickness data is absent. The mean glacier elevation did not indicate any influence on glacier recession. From 2000 to 12, the glaciers lost an ice mass amounting to 0.33 ± 0.05 m we. per year. The formation of four new proglacial lakes, although small (<6 ha), need to be monitored using remote sensing data while the infrastructure development activities should not be permitted given glacial lake outburst flood risk.
Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates
Authors: Herring Brendon , Jang Samuel , Whitt Jason , Goliwas Kayla , Aburjania Zviadi , Dudeja Vikas , Ren Bin , Berry Joel , Bibb James , Frost Andra , Chen Herbert , Rose John Bart , Jaskula-Sztul Renata
Published: December 2021

Few models exist for studying neuroendocrine tumors (NETs), and there are mounting concerns that the currently available array of cell lines is not representative of NET biology. The lack of stable patient-derived NET xenograft models further limits the scientific community’s ability to make conclusions about NETs and their response to therapy in patients. To address these limitations, we propose the use of an ex vivo 3D flow-perfusion bioreactor system for culturing and studying patient-derived NET surrogates. Herein, we demonstrate the utility of the bioreactor system for culturing NET surrogates and provide methods for evaluating the efficacy of therapeutic agents on human NET cell line xenograft constructs and patient-derived NET surrogates. We also demonstrate that patient-derived NET tissues can be propagated using the bioreactor system and investigate the near-infrared (NIR) dye IR-783 for its use in monitoring their status within the bioreactor. The results indicate that the bioreactor system and similar 3D culture models may be valuable tools for culturing patient-derived NETs and monitoring their response to therapy ex vivo.
Case Report: A Novel ABCC8 Variant in a Chinese Pedigree of Maturity-Onset Diabetes of the Young
Authors: Tang Chaoyan , Meng Liheng , Zhang Ping , Liang Xinghuan , Dang Chaozhi , Liang Hui , Wu Junfeng , Lan Haiyun , Qin Yingfen
Published: December 2021

Background

We aimed to analyze a novel ABCC8 variant of a Chinese patient with suspected maturity-onset diabetes of the young (MODY) and to provide evidence for precise diagnosis and appropriate treatment.

Method

A Chinese family with suspected MODY was recruited in this study, which included a 15-year-old female patient with diabetes. Clinical data and blood samples were collected from the proband and other family members. All of the living relatives were given an oral glucose tolerance test. Next-generation sequencing was performed to identify the mutated genes in the proband. Sanger sequencing was utilized to confirm the location of the pathogenic variant in all subjects. Further treatment was referred to targeted family members according to genetic testing.

Results

The proband was found to have a random blood glucose level of 244.8 mg/dl and an HbA1c level of 9.2%. Before this investigation, her grandparents had been diagnosed with diabetes. The second uncle, two aunts, mother, and cousin of the proband were diagnosed with diabetes by abnormal HbA1C (6.5–12.1%) and fasting blood glucose (FBG, 91.4–189.7 mg/dl). The second aunt of the proband had impaired glucose homeostasis (HbA1C = 6.4% and FBG = 88.0 mg/dl). One novel missense variant c.1432G>A (p.A478T) in exon 9 of the ABCC8 gene was detected in the proband with suspected MODY. The variant was also found in six family members with diabetes or impaired glucose homeostasis, including her second uncle, two aunts, mother, and cousin. After the treatment was switched to glimepiride, the fasting blood glucose was adjusted to 99.54 mg/dl, the 2-h postprandial blood glucose was 153.54 mg/dl, serum fructosamine was 259 μmol/l, and HbA1c was 5.8%. The glycemic control remained optimal, and no hypoglycemic episodes were observed in the living relatives.

Conclusion

This study revealed one novel missense variant of the ABCC8 gene in Chinese families. The present findings indicated that the members of this family responded to treatment with sulfonylureas as previously seen in ABCC8 MODY.
The Association Between Diabetes Mellitus and Risk of Sarcopenia: Accumulated Evidences From Observational Studies
Authors: Qiao Yu-Shun , Chai Yin-He , Gong Hong-Jian , Zhuldyz Zhiyessova , Stehouwer Coen D. A. , Zhou Jian-Bo , Simó Rafael
Published: December 2021

Aim

We performed a meta-analysis of observational studies to evaluate the association between the presence of sarcopenia and HbA1c, prediabetes, diabetes and diabetic complications.

Method

The PubMed, Embase, Cochrane and Web of Science databases were searched from inception to May 2021. We included full-text English language articles that reported the prevalence of sarcopenia in patients with and without diabetes. Quality assessment was performed according to the Newcastle- Ottawa scale for observational studies.

Results

Sixteen studies were included in the meta-analysis. Three studies showed that high HbA1c levels lead to loss of muscle mass, and one study involving prediabetes showed that people with prediabetes had lower muscle mass, strength, and performance than non-diabetic population. Seven studies showed that people with diabetes had a higher risk of sarcopenia than those without diabetes (combined OR: 2.09, 95% CI:1.62-2.70). The remaining five studies suggested that diabetic complications increased the risk of sarcopenia (combined OR: 2.09,95% CI:1.62-2.70).

Conclusion

High HbA1c levels, prediabetes, diabetes and diabetes complications were associated with an increased risk of sarcopenia. Therapeutic strategies addressed to avoid the conversion of IGT to diabetes and to optimize glycemic control are warranted to prevent or arrest sarcopenia in the diabetic population
Association of Preadmission Metformin Use and Prognosis in Patients With Sepsis and Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Li Yuanzhe , Zhao Huayan , Guo Yalin , Duan Yongtao , Guo Yanjun , Ding Xianfei
Published: December 2021

Background and Aim

A growing body of evidence suggests that preadmission metformin use could decrease the mortality of septic patients with diabetes mellitus (DM); however, the findings remain controversial. Therefore, this meta-analysis was conducted on available studies to confirm the relationship between preadmission metformin use and mortality in patients with sepsis and DM.

Methods

A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed for studies published before August 8, 2021. Observational studies assessing the correlation between metformin use and mortality in patients with sepsis and DM were considered eligible studies. We used the Newcastle–Ottawa Scale (NOS) to assess the outcome quality of each included article. Furthermore, the odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using the inverse variance method with random effects modeling.

Results

Eleven articles including 8195 patients were analyzed in this meta-analysis. All the included articles were scored as low risk of bias. Our results showed that preadmission metformin use had a lower mortality rate (OR, 0.74; 95% CIs, 0.62–0.88, P < 0.01) in patients with sepsis and DM. Surprisingly, there was no statistically significant difference in the levels of serum creatinine (weighted mean difference (WMD), 0.36; 95% CIs, −0.03–0.75; P = 0.84) and lactic acid (WMD, −0.16; 95% CIs, −0.49–0.18; P = 0.07) between preadmission metformin use and non-metformin use.

Conclusions

This study is the most comprehensive meta-analysis at present, which shows that preadmission metformin use may reduce mortality and not increase the levels of serum creatinine and lactic acid in adult patients with sepsis and DM. Therefore, these data suggest that the potential efficacy of metformin could be assessed in future clinical studies.

Systematic Review Registration

https://inplasy.com/?s=INPLASY2021100113, identifier INPLASY2021100113.
Modelling Wind Damage to Southeastern U.S. Trees: Effects of Wind Profile, Gaps, Neighborhood Interactions, and Wind Direction
Authors: Peterson Chris J. , Cannon Jeffery B.
Published: December 2021

Tree damage from a variety of types of wind events is widespread and of great ecological and economic importance. In terms of areas impacted, tropical storms have the most widespread effects on tropical and temperate forests, with southeastern U.S. forests particularly prone to tropical storm damage. This impact motivates attempts to understand the tree and forest characteristics that influence levels of damage. This study presents initial findings from a spatially explicit, individual-based mechanistic wind severity model, ForSTORM, parameterized from winching research on trees in southeastern U.S. This model allows independent control of six wind and neighborhood parameters likely to influence the patterns of wind damage, such as gap formation, the shape of the vertical wind profile, indirect damage, and support from neighbors. We arranged the subject trees in two virtual stands orientations with identical positions relative to each other, but with one virtual stand rotated 90 degrees from the other virtual stand – to explore the effect of wind coming from two alternative directions. The model reproduces several trends observed in field damage surveys, as well as analogous CWS models developed for other forests, and reveals unexpected insights. Wind profiles with higher extinction coefficients, or steeper decrease in wind speed from canopy top to lower levels, resulted in significantly higher critical wind speeds, thus reducing level of damage for a given wind speed. Three alternative formulations of wind profiles also led to significant differences in critical wind speed (CWS), although the effect of profile was less than effect of different extinction coefficients. The CWS differed little between the two alternative stand orientations. Support from neighboring trees resulted in significantly higher critical wind speeds, regardless of type of wind profile or spatial arrangement of trees. The presence or absence of gaps caused marginally significant different in CWS, while inclusion of indirect damage along with direct damage did not significantly change CWS from those caused by direct damage alone. Empirical research that could most benefit this modelling approach includes improving crown area measurement, refining drag coefficients, and development of a biomechanical framework for neighbor support.
Noninvasive Prenatal Screening Based on Second-Trimester Ultrasonographic Soft Markers in Low-Risk Pregnant Women
Authors: Liu Yunyun , Jing Xiaosha , Xing Lingling , Liu Sha , Liu Jianlong , Cheng Jing , Deng Cechuan , Bai Ting , Xia Tianyu , Wei Xiang , Luo Yuan , Zhou Quanfang , Zhu Qian , Liu Hongqian
Published: December 2021

Background: We aimed to assess the clinical application of noninvasive prenatal screening (NIPS) based on second-trimester ultrasonographic soft markers (USMs) in low-risk pregnant women.

Methods: Data of pregnant women between April 2015 and December 2019 were retrospectively analyzed. Pregnant women [age at expected date of confinement (EDC) of <35 years; low risks for trisomy 21 (T21) and trisomy 18 (T18) based on maternal serum screening; presenting second-trimester USMs (7 types)] who successfully underwent NIPS and had available follow-up information were included in our study. Cases with positive NIPS results were prenatally diagnosed. All patients were followed up for 6 months to 2 years after NIPS, and their clinical outcomes were obtained. Subgroup analyses were performed according to the different USMs.

Results: NIPS suggested that among a total of 10,023 cases, 37 (0.37%) were at high risk of aneuploidy, including 4 T21, 6 trisomy 13 (T13), and 27 sex chromosome abnormalities (SCA). Ten cases with aneuploidy (0.10%) were confirmed by prenatal diagnosis, consisting of two T21 and eight SCA. The eight fetuses with SCA consisted of one monosomy X, two XXY, one XXXY, one XXX, one XYY, and two mosaicisms. T21 was detected in one fetus with absent or hypoplastic nasal bone and one fetus with echogenic intracardiac focus (EICF). SCA was detected in five fetuses with EICF, two fetuses with multiple soft markers, and one fetus with echogenic bowel. The positive rate of chromosomal aneuploidy was significantly higher in fetuses with absent or hypoplastic nasal bone (6.25 vs. 0.10%, p = 0.017), echogenic bowel (3.7 vs. 0.10%, p = 0.029), and multiple soft markers (0.678 vs. 0.10%, p = 0.045) than in the total fetuses. The positive predictive values (PPVs) of NIPS in these three groups were 100%, 50%, and 100%, respectively. EICF accounted for 93.25% (9,346/10,023) of the study population, whereas the PPV of NIPS was only 20%.

Conclusion: NIPS is an advanced screening test for low-risk pregnant women. In the 10,023 pregnant women sampled, SCA were more common than autosomal trisomy, and EICF was the most frequent USM but the least predictive aneuploidy. Further aneuploidy evaluation is suggested for low-risk pregnant women whose ultrasound indicates absent or hypoplastic nasal bone, echogenic bowel, or multiple soft markers. NIPS can serve as a second-line complementary screening for these women.
Decreased Absolute Number of Circulating Regulatory T Cells in Patients With Takayasu’s Arteritis
Authors: Jia Wen , Fu Zi-Li , Wang Xia , Luo Jing , Yan Cheng-Lan , Cao Jian-Ping , Yan-Liu   , Xie Jian-Fang , Liu Guang-Ying , Gao Chong , Li Xiao-Feng
Published: December 2021

Background

Takayasu’s arteritis (TA) is a type of primary large vessel vasculitis. Th1, Th17, and Tfh cells have been reported to be associated with TA relapse. However, the relationship between regulatory T cells (Tregs) and TA remains unclear.

Objective

To analyze the levels of circulating lymphocytes, especially Treg cells (CD4+CD25+FOXP3+ T cells) and serum cytokines in TA patients and explore their relationship with their changes and TA disease activity.

Methods

A total of 57 TA patients and 43 sex- and age-matched healthy controls (HCs) were enrolled. According to NIH standards, 36 patients had active disease status. Flow cytometry combined with counting was used to detect the absolute numbers and ratios of Th1, Th2, Th17, and Treg cells in the peripheral blood of all the subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines.

Results

Compared to HCs, the absolute number and proportion of peripheral Treg cells in TA patients was significantly decreased, while Th17 cells were significantly increased. Furthermore, compared to the inactive group, the TA active group had significantly increased levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, but lower IL-10 levels. The absolute number of Th2 cells was negatively associated with platelet (PLT) and NIS scores in TA patients. The proportion of Th2 cells was negatively associated with the erythrocyte sedimentation rate in TA patients. After treatment, Treg cells were markedly increased.

Conclusion

There was a Th17-Treg cell imbalance with a significant reduction in peripheral Treg cells and an increase in Th17 cells in TA patients compared to the HCs. The levels of IL-6, IL-10, IL-17, and TNF-α appeared to be related to disease activity.
Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status
Authors: Gong Shaomin , Jin Shi , Li Yang , Jiang Wuhua , Zhang Zhen , Shen Ziyan , Wang Jialin , Zhou Huili , Liu Xiao , Xu Xialian , Ding Xiaoqiang , Shi Yiqin , Liu Hong
Published: December 2021

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.
pH Low Insertion Peptide-Modified Programmed Cell Death-Ligand 1 Potently Suppresses T-Cell Activation Under Acidic Condition
Authors: Sun Ying , Hu Linhan , Yang Peng , Zhang Min , Wang Xinwei , Xiao He , Qiao Chunxia , Wang Jing , Luo Longlong , Feng Jiannan , Zheng Yuanqiang , Wang Yi , Shi Yanchun , Chen Guojiang
Published: December 2021

Programmed cell death-ligand 1 (PD-L1)/PD-1 axis is critical for maintenance of immune homeostasis by limiting overactivation of effector T-cell responses. The impairment of PD-L1/PD-1 signals play an important role in the pathogenesis of inflammatory diseases, making this pathway an ideal target for novel therapeutics to induce immune tolerance. Given weakly acidic environment as a putative hallmark of inflammation, in this study we designed a new cargo by linking the ectodomain of murine PD-L1 to the N terminus of pHLIPs, a low pH-responding and membrane-insertion peptide, and demonstrated its potent immune-suppressive activity. Specifically, PD-L1-pHLIP spanned the cellular membrane and perfectly recognized its ligand PD-1 in acidic buffer. Immobile PD-L1-pHLIP actively inhibited T-cell proliferation and IFN-γ production. Importantly, soluble PD-L1-pHLIP retained its function to dampen T-cell responses under acidic condition instead of neutral aqueous solution. Overall, these data suggest that PD-L1-pHLIP has potentials to be a novel therapeutic avenue for T-cell-mediated inflammatory diseases.
S-540956, a CpG Oligonucleotide Annealed to a Complementary Strand With an Amphiphilic Chain Unit, Acts as a Potent Cancer Vaccine Adjuvant by Targeting Draining Lymph Nodes
Authors: Nakagawa Takayuki , Tanino Tetsuya , Onishi Motoyasu , Tofukuji Soichi , Kanazawa Takayuki , Ishioka Yukichi , Itoh Takeshi , Kugimiya Akira , Katayama Kazufumi , Yamamoto Takuya , Nagira Morio , Ishii Ken J.
Published: December 2021

Robust induction of cancer-antigen-specific CD8+T cells is essential for the success of cancer peptide vaccines, which are composed of a peptide derived from a cancer-specific antigen and an immune-potentiating adjuvant, such as a Toll-like receptor (TLR) agonist. Efficient delivery of a vaccine antigen and an adjuvant to antigen-presenting cells in the draining lymph nodes (LNs) holds key to maximize vaccine efficacy. Here, we developed S-540956, a novel TLR9-agonistic adjuvant consisting of B-type CpG ODN2006 (also known as CpG7909), annealed to its complementary sequence oligodeoxynucleotide (ODN) conjugated to a lipid; it could target both a cancer peptide antigen and a CpG-adjuvant in the draining LNs. S-540956 accumulation in the draining LNs and activation of plasmacytoid dendritic cells (pDCs) were significantly higher than that of ODN2006. Mechanistic analysis revealed that S-540956 enhanced the induction of MHC class I peptide-specific CD8+T cell responsesviaTLR9 in a CD4+T cell-independent manner. In mice, the therapeutic effect of S-540956-adjuvanted with a human papillomavirus (HPV)-E7 peptide vaccine against HPV-E7-expressing TC-1 tumors was significantly better than that of an ODN2006-adjuvanted vaccine. Our findings demonstrate a novel adjuvant discovery with the complementary strand conjugated to a lipid, which enabled draining LN targeting and increased ODN2006 accumulation in draining LNs, thereby enhancing the adjuvant effect. Our findings imply that S-540956 is a promising adjuvant for cancer peptide vaccines and has a high potential for applications in various vaccines, including recombinant protein vaccines.
Case Report: Clinical and Imaging Characteristics of a Patient with Anti-flotillin Autoantibodies: Neuromyelitis Optica or Multiple Sclerosis?
Authors: Shang Ke , Cheng Chang , Qin Chuan , Xiao Jun , Deng Gang , Bu Bi-Tao , Xu Sha-Bei , Tian Dai-Shi
Published: December 2021

Background

Demyelination diseases are complex puzzles that are not always straightforward to diagnose. Multiple sclerosis and neuromyelitis optica are two that are frequently encountered. Numerous autoantibodies newly discovered in recent years have significantly aided clinical reasoning and diagnosis in differentiating demyelination disorders. Here we report a case of demyelination disease with anti-flotillin autoantibodies positive, which is not common in past references.

Case summary

The patient presented with characteristic neuromyelitis optica symptoms and had remission and relapse. But his images exhibited characteristics of both neuromyelitis optica spectrum illness and multiple sclerosis.

Conclusion

This is the first case report describing the clinical course and imaging characteristics of demyelination illness associated with anti-flotillin autoantibodies. Although so far it appears to be a subtype of multiple sclerosis, there is still a potential that it is separate from MS and NMOSD.
Facile Fabrication and Properties of Super-hydrophobic MgAl-LDH Films With Excellent Corrosion Resistance on AZ31 Magnesium Alloy
Authors: Han Xing , Hu Jia , Wang Yong-Qin , Xiao Tian-Bing , Xia Wei , Chen Yan-Ning , Wu Liang
Published: December 2021

A super-hydrophobic anti-corrosion film was facilely prepared via in situ growth of layered double hydroxides (LDHs) on the etched AZ31 magnesium alloy and then modification by 1H, 1H, 2H, 2H-perfluorooctyltrimethoxysilane (PFOTMS) in this work. The morphology, structure, composition, surface roughness and water contact angles (WCA), and the anti-corrosion performance of the samples were investigated. The results revealed that the micro/nano hierarchical surface morphology of the films was composed of island structures obtained after chemical etching and MgAl-LDH nanowalls grown in situ. The best hydrophobicity (CA = 163°) was obtained on the MgAl-LDHs with the maximum surface roughness. Additionally, the potentiodynamic polarization, electrochemical impedance spectroscopy, and immersion test indicated that the super-hydrophobic LDH films provided better corrosion resistance to AZ31 magnesium alloy due to the double-protection derived from the LDHs and super-hydrophobic properties. Furthermore, the contact angle could be kept at above 140° after dipped in 3.5 wt% NaCl solution for 6 days.
Application of Hyaluronic Acid as a Biopolymer Material in Reconstruction of Interdental Papilla in Rats
Authors: Zhang Yiding , Zhang Yifan , Wu Hongkun , Hong Guang
Published: December 2021

Applying hyaluronic acid, a biopolymer material, in the treatment of interdental papilla reconstruction has become a trend. The main objective of this research is to investigate the histologic effect of hyaluronic acid on interdental papilla over time. Deficient interdental papilla models were surgically created in sixty-two Sprague-Dawley (SD) rats and were randomly treated with the injection of hyaluronic acid (HA group) or phosphate-buffered saline (sham control group) or left untreated (control group). After 2, 4, and 8 weeks, the rats were sacrificed in batches to observe the histological changes. A fluorochrome label was used to monitor bone formation in 8 weeks. Immunohistochemical analyses were performed to evaluate the expression of potentially relevant cytokines, vascular endothelial growth factor (VEGF), bone morphogenetic protein-2 (BMP-2), and Wnt-induced secreted protein 1 (WISP1) in the gingival tissue in 8 weeks. A preliminary study of HA degradation after 24 weeks was performed in two rats. Following the HA injection, no inflammation or granulomatous foreign body reaction was observed. HA was able to promote collagen fiber and alveolar bone regular formation in the reconstruction site. HA also enhanced VEGF, BMP-2, and WISP-1 expression in gingival tissue (p＜0.05). After 24 weeks, there was no HA filler observed in the interdental papilla. In conclusion, our study suggested that HA is an effective way to reconstruct deficient interdental papilla.
Vitrectomy vs. Spontaneous Closure for Traumatic Macular Hole: A Systematic Review and Meta-Analysis
Authors: Zhou Qi , Feng Haoyue , Lv Hongbin , Fu Zhongmei , Xue Yuyu , Ye Hejiang
Published: December 2021

Objective: This systematic review and meta-analysis aimed to determine the traumatic macular hole (TMH) closure rate and visual acuity (VA) improvement rate by comparing two treatment methods for TMH: vitrectomy and observation for spontaneous closure.

Methods: PubMed, Cochrane, Web of Science Library, Embase, CNKI, Wanfang, VIP, and Sino Med were systematically searched from their inception to June 10, 2021. Studies in the surgery group (n = 32) and studies in the observation group (n = 12) were meta-analyzed. The primary outcomes were the TMH closure and VA improvement rates in the surgery and observation groups. The secondary outcomes were best-corrected visual acuity (BCVA) improvement in the surgery group. Stata software (version 15.1) was used for the analyses.

Results: Thirty-six studies that included 1,009 eyes were selected for this meta-analysis, among which 33 were retrospective studies and 3 were prospective studies. The meta-analysis showed that the random-model pooled event rate for TMH closure was 0.37 (95% confidence interval [CI], 0.26–0.48) in the observation group, while it was 0.9 (95% CI, 0.85–0.94) in the surgery group. The fixed-model pooled event rate for VA improvement was 0.39 (95% CI, 0.33–0.45) in the observation group, while the random-model pooled event rate of VA improvement for the surgery group was 0.72 (95% CI, 0.63–0.80). The pooled event rate for BCVA improvement in the surgery group was 0.39 (95% CI, 0.33–0.46).

Conclusions: This meta-analysis suggests that TMH hole closure and VA improvement rates in the surgery group were significantly higher than those in the observation group. Vitrectomy is an effective method for treating TMH. However, further randomized controlled trials (RCTs) are required to evaluate the efficacy and safety of surgery and observation for TMH treatment.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42021276684.
Higher Lymph Node Metastasis Rate and Poorer Prognosis of Intestinal-Type Gastric Cancer Compared to Diffuse-Type Gastric Cancer in Early-Onset Early-Stage Gastric Cancer: A Retrospective Study
Authors: Tang Chao-Tao , Chen Si-Hai
Published: December 2021

Background: The incidence of early-onset gastric cancer (GC) that was diagnosed at <50 years is increasing, but there is a knowledge gap on early-onset early-stage GC (EEGC) that was defined as early-onset GC limited to the mucosa or submucosa. Therefore, we comprehensively analysed the clinical features based on Lauren type.

Methods: Logistic and Cox analyses were used to investigate risk factors for lymph node metastasis (LNM) and prognosis, respectively. Propensity score matching (PSM) was used to adjust confounding factors. Protein mass spectrometry analysis was used to explore the molecular mechanism of LNM.

Result: Our study included 581 patients with EEGC from the Surveillance, Epidemiology, and End Results (SEER) database and 226 patients with EEGC from our own centre. We identified intestinal type, T1b stage, and tumour size (>3 cm) as risk factors for LNM using SEER and our own data. We also found that the prognosis of patients with intestinal-type EEGC was poorer than patients with diffuse-type EEGC, and T1b stage and positive LNM were hazard factors for survival. After analysing the expression of proteins between positive and negative LNM in the intestinal or diffuse type, we found no similar proteins between these groups. The differentially expressed genes (DEGs) in the intestinal type functioned as epithelial cell signalling in Helicobacter pylori. The DEGs in the diffuse type functioned in the tricarboxylic acid cycle (TCA cycle) and oxidative phosphorylation.

Conclusion: For EEGC, our study was the first report to demonstrate that the intestinal type was a risk factor for LNM and survival compared to the diffuse type, and the oncogenic expression promoting the occurrence of LNM was different. These findings suggest that clinicians should pay more attention to intestinal-type EEGC than diffuse-type EEGC.
The Impact of Trace Elements on Osteoarthritis
Authors: Li Guoyong , Cheng Tao , Yu Xuefeng
Published: December 2021

Osteoarthritis (OA) is a progressive degenerative disease characterized by cartilage degradation, synovial inflammation, subchondral sclerosis and osteophyte formation. It has a multifactorial etiology with potential contributions from heredity, endocrine function, abnormal mechanical load and nutrition. Of particular considerations are trace element status. Several trace elements, such as boron and magnesium are essential for normal development of the bone and joint in human. While cadmium correlates with the severity of OA. The present review focuses on the roles of trace elements (boron, cadmium, copper, iron, magnesium, manganese, selenium, zinc) in OA and explores the mechanisms by which they act.
Physical Activity and the Risk of Hemorrhagic Stroke: A Population-Based Longitudinal Follow-Up Study in Taiwan
Authors: Feng Shih-Hao , Chen Li-Sheng , Yeh Kuo-Cheng , Pan Shin-Liang
Published: December 2021

Background:Data on the relationship between physical activity (PA) and hemorrhagic stroke (HS) are limited in Asian populations. This population-based longitudinal follow-up study therefore investigates whether PA is associated with a reduced risk of HS in Taiwan.

Methods:A total of 58,857 subjects who had participated in the Keelung Community-based Integrated Screening Program between 2005 and 2012 were enrolled. Information about their PA, obtained using questionnaires, was used to categorize them into three groups according to their average weekly time engaged in it: (1) no PA, (2) low PA (<90 min weekly), and (3) high PA (90 min per week or more). Cox proportional hazard regression was used to evaluate the effect of PA on HS. Stratified analysis by sex and comorbidities (diabetes mellitus, hypertension, and hyperlipidemia) were conducted to evaluate their impact on the relationship between PA and HS.

Results:Compared to the no-PA group, the adjusted hazard ratio of HS for the low-PA group was 0.74 (95% CI, 0.57–0.96,p= 0.0219), and for the high-PA group, 0.72 (95% CI, 0.58–0.90,p= 0.004). The stratified analyses showed that, for the non-comorbidity strata, the beneficial effect of PA on reducing HS risk became stronger as PA increased. However, in the diabetes and hypertension strata, high PA did not appear to have any greater protective effect than low PA.

Conclusions:Our findings suggested that even <90 min of PA per week might be beneficial to reduce HS risk. Such a low level of PA is likely to be more achievable and easier to maintain for the general population. Additionally, personalized recommendations based on pre-existing comorbidities may help optimize the beneficial effects of PA on HS prevention.
The Effects of Delivery Mode on the Gut Microbiota and Health: State of Art
Authors: Zhang Chenchen , Li Lixiang , Jin Biying , Xu Xinyan , Zuo Xiuli , Li Yanqing , Li Zhen
Published: December 2021

The delivery mode is an important factor driving alteration in the gut microbiota during the neonatal period. Several studies prove that the alteration of gut microbiota induced by cesarean section could influence the activation of intestinal epithelial cells and the development of immune system. Further, some autoimmune and metabolic disorders may be related to the microbiota dysbiosis in infants caused by cesarean section. It is noteworthy that probiotics could promote the intestinal microecology, which may further prevent and treat cesarean section related diseases. This review summarized the great significance of delivery mode on microbiota and health, as well as provided clinically feasible methods for the prevention and treatment of cesarean section related gut diseases.
Gut Microbiome Regulation of Autophagic Flux and Neurodegenerative Disease Risks
Authors: Shoubridge Andrew P. , Fourrier Célia , Choo Jocelyn M. , Proud Christopher G. , Sargeant Timothy J. , Rogers Geraint B.
Published: December 2021

The gut microbiome-brain axis exerts considerable influence on the development and regulation of the central nervous system. Numerous pathways have been identified by which the gut microbiome communicates with the brain, falling largely into the two broad categories of neuronal innervation and immune-mediated mechanisms. We describe an additional route by which intestinal microbiology could mediate modifiable risk for neuropathology and neurodegeneration in particular. Autophagy, a ubiquitous cellular process involved in the prevention of cell damage and maintenance of effective cellular function, acts to clear and recycle cellular debris. In doing so, autophagy prevents the accumulation of toxic proteins and the development of neuroinflammation, both common features of dementia. Levels of autophagy are influenced by a range of extrinsic exposures, including nutrient deprivation, infection, and hypoxia. These relationships between exposures and rates of autophagy are likely to be mediated, as least in part, by the gut microbiome. For example, the suppression of histone acetylation by microbiome-derived short-chain fatty acids appears to be a major contributor to upregulation of autophagic function. We discuss the potential contribution of the microbiome-autophagy axis to neurological health and examine the potential of exploiting this link to predict and prevent neurodegenerative diseases.
Enhanced Contractive Tension and Upregulated Muscarinic Receptor 2/3 in Colorectum Contribute to Constipation in 6-Hydroxydopamine-Induced Parkinson’s Disease Rats
Authors: Zhang Xiao-Li , Zhang Xiao-Hui , Yu Xiao , Zheng Li-Fei , Feng Xiao-Yan , Liu Chen-Zhe , Quan Zhu-Sheng , Zhang Yue , Zhu Jin-Xia
Published: December 2021

Constipation and defecatory dysfunctions are frequent symptoms in patients with Parkinson’s disease (PD). The pathology of Lewy bodies in colonic and rectal cholinergic neurons suggests that cholinergic pathways are involved in colorectal dysmotility in PD. However, the underlying mechanism is unclear. The aim of the present study is to examine the effect of central dopaminergic denervation in rats, induced by injection 6-hydroxydopamine into the bilateral substania nigra (6-OHDA rats), on colorectal contractive activity, content of acetylcholine (ACh), vasoactive intestinal peptide (VIP) and expression of neural nitric oxide synthase (nNOS) and muscarinic receptor (MR). Strain gauge force transducers combined with electrical field stimulation (EFS), gut transit time, immunohistochemistry, ELISA, western blot and ultraperformance liquid chromatography tandem mass spectrometry were used in this study. The 6-OHDA rats exhibited outlet obstruction constipation characterized by prolonged transit time, enhanced contractive tension and fecal retention in colorectum. Pretreatment with tetrodotoxin significantly increased the colorectal motility. EFS-induced cholinergic contractions were diminished in the colorectum. Bethanechol chloride promoted colorectal motility in a dose-dependent manner, and much stronger reactivity of bethanechol chloride was observed in 6-OHDA rats. The ACh, VIP and protein expression of nNOS was decreased, but M2R and M3R were notably upregulated in colorectal muscularis externa. Moreover, the number of cholinergic neurons was reduced in sacral parasympathetic nucleus (SPN) of 6-OHDA rats. In conclusion, central nigrostriatal dopaminergic denervation is associated with decreased cholinergic neurons in SPN, decreased ACh, VIP content, and nNOS expression and upregulated M2R and M3R in colorectum, resulting in colorectal dysmotility, which contributes to outlet obstruction constipation. The study provides new insights into the mechanism of constipation and potential therapeutic targets for constipation in PD patients.
Effects of Aging on the Structure and Expression of NMDA Receptors of Somatostatin Expressing Neurons in the Mouse Hippocampus
Authors: Gramuntell Yaiza , Klimczak Patrycja , Coviello Simona , Perez-Rando Marta , Nacher Juan
Published: December 2021

Changes in the physiology, neurochemistry and structure of neurons, particularly of their dendritic spines, are thought to be crucial players in age-related cognitive decline. One of the most studied brain structures affected by aging is the hippocampus, known to be involved in different essential cognitive processes. While the aging-associated quantitative changes in dendritic spines of hippocampal pyramidal cells have already been studied, the relationship between aging and the structural dynamics of hippocampal interneurons remains relatively unknown. Spines are not a frequent feature in cortical inhibitory neurons, but these postsynaptic structures are abundant in a subpopulation of somatostatin expressing interneurons, particularly in oriens-lacunosum moleculare (O-LM) cells in the hippocampal CA1. Previous studies from our laboratory have shown that the spines of these interneurons are highly plastic and influenced by NMDA receptor manipulation. Thus, in the present study, we have investigated the impact of aging on this interneuronal subpopulation. The analyses were performed in 3−, 9−, and 16-month-old GIN mice, a strain in which somatostatin positive interneurons express GFP. We studied the changes in the density of dendritic spines, en passant boutons, and the expression of NMDA receptors (GluN1 and GluN2B) using confocal microscopy and image analysis. We observed a significant decrease in dendritic spine density in 9-month-old animals when compared with 3-month-old animals. We also observed a decrease in the expression of the GluN2B subunit in O-LM cells, but not of that of GluN1, during aging. These results will constitute the basis for more advanced studies of the structure and connectivity of interneurons during aging and their contribution to cognitive decline.
A Correlation Analysis of Geomagnetic Field Characteristics in Geomagnetic Perceiving Navigation
Authors: Li Hong , Qu Junsuo , Jiang Xiangkui , Niu Yun
Published: December 2021

It is well-known that geomagnetic fields have multiple components or parameters, and that these geomagnetic parameters are related to each other. In this paper, a parameter selection method is proposed, and this paper mainly discusses the correlation of geomagnetic field parameters for geomagnetic navigation technology. For the correlation analysis between geomagnetic parameters, the similarity calculation of the correlation coefficient is firstly introduced for geomagnetic navigation technology, and the grouped results are obtained by data analysis. At the same time, the search algorithm (Hex-path algorithm) is used to verify the correlation analysis results. The results show the same convergent state for the approximate correlation coefficient. In other words, the simulation results are in agreement with the similarity calculation results.
Interaction of α9α10 Nicotinic Receptors With Peptides and Proteins From Animal Venoms
Authors: Tsetlin Victor , Haufe Yves , Safronova Valentina , Serov Dmitriy , Shadamarshan PranavKumar , Son Lina , Shelukhina Irina , Kudryavtsev Denis , Kryukova Elena , Kasheverov Igor , Nicke Annette , Utkin Yuri
Published: December 2021

Unlike most neuronal nicotinic acetylcholine receptor (nAChR) subunits, α7, α9, and α10 subunits are able to form functional homo- or heteromeric receptors without any β subunits. While the α7 subtype is widely distributed in the mammalian brain and several peripheral tissues, α9 and α9α10 nAChRs are mainly found in the cochlea and immune cells. α-Conotoxins that specifically block the α9α10 receptor showed anti-nociceptive and anti-hyperalgesic effects in animal models. Hence, this subtype is considered a drug target for analgesics. In contrast to the α9α10-selective α-conotoxins, the three-finger toxin α-bungarotoxin inhibits muscle-type and α7 nAChRs in addition to α9α10 nAChRs. However, the selectivity of α-neurotoxins at the α9α10 subtype was less intensively investigated. Here, we compared the potencies of α-conotoxins and α-neurotoxins at the human α9α10 nAChR by two-electrode voltage clamp analysis upon expression in Xenopus oocytes. In addition, we analyzed effects of several α9α10-selective α-conotoxins on mouse granulocytes from bone marrow to identify possible physiological functions of the α9α10 nAChR subtype in these cells. The α-conotoxin-induced IL-10 release was measured upon LPS-stimulation. We found that α-conotoxins RgIA, PeIA, and Vc1.1 enhance the IL-10 expression in granulocytes which might explain the known anti-inflammatory and associated analgesic activities of α9α10-selective α-conotoxins. Furthermore, we show that two long-chain α-neurotoxins from the cobra Naja melanoleuca venom that were earlier shown to bind to muscle-type and α7 nAChRs, also inhibit the α9α10 subtype at nanomolar concentrations with one of them showing a significantly slower dissociation from this receptor than α-bungarotoxin.
Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain
Authors: Iglesias González Ana Belén , Jakobsson Jon E. T. , Vieillard Jennifer , Lagerström Malin C. , Kullander Klas , Boije Henrik
Published: December 2021

The spinal locomotor network is frequently used for studies into how neuronal circuits are formed and how cellular activity shape behavioral patterns. A population of dI6 interneurons, marked by the Doublesex and mab-3 related transcription factor 3 (Dmrt3), has been shown to participate in the coordination of locomotion and gaits in horses, mice and zebrafish. Analyses of Dmrt3 neurons based on morphology, functionality and the expression of transcription factors have identified different subtypes. Here we analyzed the transcriptomes of individual cells belonging to the Dmrt3 lineage from zebrafish and mice to unravel the molecular code that underlies their subfunctionalization. Indeed, clustering of Dmrt3 neurons based on their gene expression verified known subtypes and revealed novel populations expressing unique markers. Differences in birth order, differential expression of axon guidance genes, neurotransmitters, and their receptors, as well as genes affecting electrophysiological properties, were identified as factors likely underlying diversity. In addition, the comparison between fish and mice populations offers insights into the evolutionary driven subspecialization concomitant with the emergence of limbed locomotion.
Recombinant COL6 α2 as a Self-Organization Factor That Triggers Orderly Nerve Regeneration Without Guidance Cues
Authors: Fang Zhou , Zou Jian-Long
Published: December 2021

Collagen VI (COL6) in the microenvironment was recently identified as an extracellular signal that bears the function of promoting orderly axon bundle formation. However, the large molecular weight of COL6 (≈2,000 kDa) limits its production and clinical application. It remains unclear whether the smaller subunit α chains of COL6 can exert axon bundling and ordering effects independently. Herein, based on a dorsal root ganglion (DRG) ex vivo model, the contributions of three main COL6 α chains on orderly nerve bundle formation were analyzed, and COL6 α2 showed the largest contribution weight. A recombinant COL6 α2 chain was produced and demonstrated to promote the formation of orderly axon bundles through the NCAM1-mediated pathway. The addition of COL6 α2 in conventional hydrogel triggered orderly nerve regeneration in a rat sciatic nerve defect model. Immunogenicity assessment showed weaker immunogenicity of COL6 α2 compared to that of the COL6 complex. These findings suggest that recombinant COL6 α2 is a promising material for orderly nerve regeneration.
InverseMuscleNET: Alternative Machine Learning Solution to Static Optimization and Inverse Muscle Modeling
Authors: Nasr Ali , Inkol Keaton A. , Bell Sydney , McPhee John
Published: December 2021

InverseMuscleNET, a machine learning model, is proposed as an alternative to static optimization for resolving the redundancy issue in inverse muscle models. A recurrent neural network (RNN) was optimally configured, trained, and tested to estimate the pattern of muscle activation signals. Five biomechanical variables (joint angle, joint velocity, joint acceleration, joint torque, and activation torque) were used as inputs to the RNN. A set of surface electromyography (EMG) signals, experimentally measured around the shoulder joint for flexion/extension, were used to train and validate the RNN model. The obtained machine learning model yields a normalized regression in the range of 88–91% between experimental data and estimated muscle activation. A sequential backward selection algorithm was used as a sensitivity analysis to discover the less dominant inputs. The order of most essential signals to least dominant ones was as follows: joint angle, activation torque, joint torque, joint velocity, and joint acceleration. The RNN model required 0.06 s of the previous biomechanical input signals and 0.01 s of the predicted feedback EMG signals, demonstrating the dynamic temporal relationships of the muscle activation profiles. The proposed approach permits a fast and direct estimation ability instead of iterative solutions for the inverse muscle model. It raises the possibility of integrating such a model in a real-time device for functional rehabilitation and sports evaluation devices with real-time estimation and tracking. This method provides clinicians with a means of estimating EMG activity without an invasive electrode setup.