bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive effect of combined exercise on adipokines levels and pubertal signs in overweight and obese girls with central precocious puberty
Authors: Shokri Elnaz , Heidarianpour Ali , Razavi Zahra 
Published: November 2021

Abstract
Background
The prevalence of precocious puberty is increasing. Obesity has been demonstrated to be associated with changes in the adipokine profile and incidence of early puberty in girls. This study assessed the pubertal signs, the levels of adiponectin, resistin, and tumor necrosis factor-alpha (TNF-α) after 12 weeks of combined exercise and 4 weeks of detraining in overweight and obese girls with precocious puberty.

Methods
Thirty overweight and obese girls (aged 7–9) with precocious puberty, who had received Triptorelin, were randomly divided into two groups (15 exercise and 15 control). Initially, serum levels of adiponectin, resistin, TNF-α, luteinising hormone (LH), and follicle-stimulating hormone (FSH) and the signs of puberty progression (bone age, uterine length, and ovarian volume) were measured. The exercise group performed 60 min of combined (aerobic and resistance) exercise three times/week for 12 weeks. The control group did not receive any exercise. 48 h after the last training session and after 4 weeks of detraining, all research variables were measured (also in the control group). The statistical method used for data analysis was repeated measures ANOVA.

Results
In the exercise group, adiponectin significantly increased and resistin significantly decreased after 12 weeks. After 4 weeks of detraining, adiponectin significantly decreased, but resistin significantly increased. TNF-α levels did not change significantly during the study. There was no significant difference in all of the factors in the control group. Throughout the 16-week study period, the rate of puberty and LH significantly decreased in both exercise and control groups, but FSH, LH/FSH and ovarian volume significantly decreased in the exercise group alone (P<0.05).

Conclusions
Combined exercise increased adiponectin and decreased resistin and the rate of puberty. However, after 4 weeks of detraining, these effects diminished but did not disappear.

Trial registration
IRCT, IRCT56471. Registered 25 may 2021 - Retrospectively registered, https://fa.irct.ir/user/profile
Relationship of symptom stress, care needs, social support, and meaning in life to quality of life in patients with heart failure from the acute to chronic stages: a longitudinal study
Authors: Liu Min-Hui , Chiou Ai-Fu , Wang Chao-Hung , Yu Wen-Pin , Lin Mei-Hui 
Published: November 2021

AbstractBackgroundPatients with heart failure (HF) experience continuous changes in symptom distress, care needs, social support, and meaning in life from acute decompensation to chronic phases. The longitudinal relationship between these four factors and quality of life (QOL) was not fully explored.AimsTo simultaneously investigate the relationship between all factors and QOL from hospitalization to 6 months after discharge, and the impact of the changes in these factors on QOL at different time points.MethodsA longitudinal design with panel research (4 time points) was used. From January 2017 to December 2019, patients hospitalized due to acute decompensated HF were consecutively enrolled and followed up for 6 months. Patients were interviewed with questionnaires assessing symptom distress, care needs, social support, meaning in life and QOL at hospitalization and 1, 3 and 6 months after discharge.ResultsA total of 184 patients completed 6 months of follow-up. From baseline to 6 months, QOL continuously improved along with decreases in symptoms and care needs, but increases in social support and meaning in life. Better QOL was associated with younger age, higher education level, economic independence, less symptom distress and care needs, and stronger meaning in life (p < 0.05). Compared with hospitalization, decreases in care needs and increases in meaning in life at 1, 3 and 6 months were associated with an increase in physical QOL (p < 0.01). The decrease in care needs and increase in meaning in life at 3 months were associated with an increase in mental QOL (p < 0.05). The increase in social support at 6 months was associated with increases in both physical and mental QOL (p < 0.01). Changes in symptom distress were not correlated with changes in QOL from baseline to all time points. In the multivariable analysis, these findings were independent of age, educational level and economic status.ConclusionsAlthough symptom distress is associated with QOL after acute decompensated HF, QOL cannot be improved only by improvement in symptoms. With differential duration of improvement in each factor, the integration of alleviation in care needs and strengthening in social support and meaning in life might provide additional benefits in QOL.
Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
Authors: Bernegger Sabine , Vidmar Robert , Fonovic Marko , Posselt Gernot , Turk Boris , Wessler Silja 
Published: November 2021

Abstract
Background
High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesions are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism of H. pylori interference with the epithelial barrier integrity.

Results
Using a proteomic approach we identified human desmoglein-2 (hDsg2), neuropilin-1, ephrin-B2, and semaphorin-4D as novel extracellular HpHtrA substrates and confirmed the well characterized target hCdh1. HpHtrA-mediated hDsg2 cleavage was further analyzed by in vitro cleavage assays using recombinant proteins. In infection experiments, we demonstrated hDsg2 shedding from H. pylori-colonized MKN28 and NCI-N87 cells independently of pathogen-induced matrix-metalloproteases or ADAM10 and ADAM17.

Conclusions
Characterizing the substrate specificity of HpHtrA revealed efficient hDsg2 cleavage underlining the importance of HpHtrA in opening intercellular junctions.
Mechanistically informed non-invasive peripheral nerve stimulation for peripheral neuropathic pain: a randomised double-blind sham-controlled trial
Authors: Johnson Selina , Marshall Anne , Hughes Dyfrig , Holmes Emily , Henrich Florian , Nurmikko Turo , Sharma Manohar , Frank Bernhard , Bassett Paul , Marshall Andrew , Magerl Walter , Goebel Andreas 
Published: November 2021

Abstract
Background
Induction of long-term synaptic depression (LTD) is proposed as a treatment mechanism for chronic pain but remains untested in clinical populations. Two interlinked studies; (1) A patient-assessor blinded, randomised, sham-controlled clinical trial and (2) an open-label mechanistic study, sought to examine therapeutic LTD for persons with chronic peripheral nerve injury pain.

Methods
(1) Patients were randomised using a concealed, computer-generated schedule to either active or sham non-invasive low-frequency nerve stimulation (LFS), for 3 months (minimum 10 min/day). The primary outcome was average pain intensity (0–10 Likert scale) recorded over 1 week, at 3 months, compared between study groups. (2) On trial completion, consenting subjects entered a mechanistic study assessing somatosensory changes in response to LFS.

Results
(1) 76 patients were randomised (38 per group), with 65 (31 active, 34 sham) included in the intention to treat analysis. The primary outcome was not significant, pain scores were 0.3 units lower in active group (95% CI − 1.0, 0.3; p = 0.30) giving an effect size of 0.19 (Cohen’s D). Two non-device related serious adverse events were reported. (2) In the mechanistic study (n = 19) primary outcomes of mechanical pain sensitivity (p = 0.006) and dynamic mechanical allodynia (p = 0.043) significantly improved indicating reduced mechanical hyperalgesia.

Conclusions
Results from the RCT failed to reach significance. Results from the mechanistic study provide new evidence for effective induction of LTD in a clinical population. Taken together results add to mechanistic understanding of LTD and help inform future study design and approaches to treatment.
Trial registration ISRCTN53432663.
Improving postural stability among people with lower-limb amputations by tactile sensory substitution
Authors: Chen Lijun , Feng Yanggang , Chen Baojun , Wang Qining , Wei Kunlin 
Published: November 2021

Abstract
Background
For people with lower-limb amputations, wearing a prosthetic limb helps restore their motor abilities for daily activities. However, the prosthesis's potential benefits are hindered by limited somatosensory feedback from the affected limb and its prosthesis. Previous studies have examined various sensory substitution systems to alleviate this problem; the prominent approach is to convert foot–ground interaction to tactile stimulations. However, positive outcomes for improving their postural stability are still rare. We hypothesized that the sensory substiution system based on surrogated tactile stimulus is capable of improving the standing stability among people with lower-limb amputations.

Methods
We designed a wearable device consisting of four pressure sensors and two vibrators and tested it among people with unilateral transtibial amputations (n = 7) and non-disabled participants (n = 8). The real-time measurements of foot pressure were fused into a single representation of foot–ground interaction force, which was encoded by varying vibration intensity of the two vibrators attached to the participants’ forearm. The vibration intensity followed a logarithmic function of the force representation, in keeping with principles of tactile psychophysics. The participants were tested with a classical postural stability task in which visual disturbances perturbed their quiet standing.

Results
With a brief familiarization of the system, the participants exhibited better postural stability against visual disturbances when switching on sensory substitution than without. The body sway was substantially reduced, as shown in head movements and excursions of the center of pressure. The improvement was present for both groups of participants and was particularly pronounced in more challenging conditions with larger visual disturbances.

Conclusions
Substituting otherwise missing foot pressure feedback with vibrotactile signals can improve postural stability for people with lower-limb amputations. The design of the mapping between the foot–ground interaction force and the tactile signals is essential for the user to utilize the surrogated tactile signals for postural control, especially for situations that their postural control is challenged.
Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers
Authors: Mihashi Yasuhito , Kimura Shoichi , Iwasaki Hiromi , Oshiro Yumi , Takamatsu Yasushi , Kawauchi Shigeto , Shimajiri Shohei , Ishizuka Kenji , Takeshita Morishige 
Published: November 2021

Abstract
Background
The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated.

Methods
Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs.

Results
Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01).

Conclusion
Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.
Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems
Authors: Richter Anne , Wegener Sonja , Breuer Kathrin , Razinskas Gary , Weick Stefan , Exner Florian , Bratengeier Klaus , Flentje Michael , Sauer Otto , Polat Bülent 
Published: November 2021

Abstract
Background
To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans.

Methods
For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom.

Results
The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans.

Conclusions
For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.
LncRNA NONHSAT030515 promotes the chondrogenic differentiation of human adipose-derived stem cells via regulating the miR-490-5p/BMPR2 axis
Authors: Yang Qinqin , Guo Jiajia , Ren Zhijing , Li Bo , Huang Haifeng , Yang Zhen 
Published: November 2021

Abstract
Background
Chondrogenic differentiation of human adipose-derived stem cells (hADSCs) is important for cartilage generation and degradation. LncRNAs play an essential role in stem cell differentiation. However, the role and mechanism of lncRNA in hADSCs remain unclear. Our previous study showed that miR-490-5p was downregulated during chondrogenic differentiation of hADSCs. In this study, we investigated the effect and mechanism of lncRNA NONHSAT030515 interacting with miR-490-5p on chondrogenic differentiation of hADSCs.

Methods
Alcian blue staining was used to assess the deposition of chondromatrix proteins following chondrogenic differentiation of human adipose stem cells. Immunohistochemistry was used to evaluate the expression of collagenII. TargetScan, miRTarBase and miRDB database analyses were applied to find the miRNA and target genes of lncRNA NONHSAT030515. A dual luciferase experiment was conducted to identify the direct target of NONHSAT030515. pcDNA3.1- NONHSAT030515 transfection and sh- NONHSAT030515 treatment were conducted to verify the role of lncRNA NONHSAT030515 in chondrogenic differentiation. The levels of Aggrecan, SOX9 and COL2A1 were analyzed by qRT-PCR and Western blot assay.

Results
Alcian blue staining, immunocytochemical, qRT-PCR, and Western blot have determined that lncRNA NONHSAT030515 can promote the chondrogenic differentiation of hADSCs. MiR-490- 5p was the direct target of NONHSAT030515, while BMPR2 was the target gene. This result was confirmed by luciferase reporter assay. Up-regulation of NONHSAT030515 promoted BMPR2 protein expression and promoted chondrogenic differentiation, whereas down-regulation of NONHSAT030515 caused completely opposite results.

Conclusion
LncRNA NONHSAT030515 promotes the chondrogenic differentiation of hADSCs through increasing BMPR2 expression by regulating miR-490- 5p.
Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway
Authors: Zhou Yu-hu , Xie Qiang 
Published: November 2021

Abstract
Background
Osteoporosis (OP) is a well-known chronic degenerative disease, with impaired mesenchymal stem cells (MSCs) function and suppressed osteogenic differentiation. Total glycosides from Eucommia ulmoides seed (TGEUS) was a Chinese medicine and have rich pharmacological effects. This study was designed to explore the mechanism of TGEUS in promoting osteogenic differentiation and bone formation in ovariectomized (OVX) rats.

Methods
Adipose‐derived mesenchymal stem cells (ADSCs) were isolated and treated with different concentration of TGEUS. Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Osteogenic capacity was identified by ALP staining and ARS staining. Moreover, RNA sequencing between control and TGEUS treated ADSCs were further performed to reveal the mechanism of TGEUS in promoting osteogenic differentiation. The expression of Jag1, Lfng and Hey1 were measured using quantitative real-time polymerase chain reaction (qRTPCR). Osteogenic markers were further assessed by western blot. DAPT and NICD were further used to identify whether Notch signaling pathway involved into TGEUS promoting osteogenic differentiation of ADSCs. Ovariectomy-induced bone loss rats model was established and divided into three groups: sham, OVX and OVX + TGEUS groups. HE staining and immunohistochemical staining were further performed to identify whether TGEUS could promote bone formation.

Results
TGEUS treatment significantly enhanced the cell viability and ALP activity than control group, the optimal dose of TGEUS was 5 μM. We selected 5 μM TGEUS for further study. TGEUS significantly enhanced ALP activity and calcium deposition than that of control group. Activation of Notch signaling fully blocked TGEUS-induced osteogenic differentiation of ADSCs. Following TGEUS treatment, the trabecular bone of the rats was significantly increased, thickened, and more connected compared to the OVX group. With the treatment of TGEUS, the expression of Osterix (Osx), Osteocalcin (OCN) and RUNX Family Transcription Factor 2 (RUNX2) increased than OVX group.

Conclusion
TGEUS enhanced osteogenic differentiation of ADSCs and promoted bone formation in ovariectomy-induced bone loss rats. Our study broadened the understanding of TGEUS as a therapeutic target against osteoporosis.
LncRNA SCIRT is downregulated in atherosclerosis and suppresses the proliferation of human aortic smooth muscle cells (HAOSMCs) by sponging miR-146a in cytoplasm
Authors: Gao Wenhui , Li Rong , Yu Jingjing , He Xijie , Xu Duo , Zhong Hai , Dong Wenwen , Cui Hanbin 
Published: November 2021

Abstract
Background
SCIRT has been characterized as a key player in cancer biology, while its role in other human diseases is unclear. This study explored its role in atherosclerosis, with a specific focus on its interaction with SCIRT and miR-146a.

Methods
The expression of SCIRT and miR-146a in atherosclerosis-affected tissues and healthy tissues from 56 atherosclerosis patients were analyzed by RT-qPCR. The expression of SCIRT in nuclear and cytoplasm samples was detected by RNA fractionation assay. The direct interaction between SCIRT and miR-146a was detected by RNA pull-down assay. SCIRT and miR-146a were overexpressed in human aortic smooth muscle cells (HAOSMCs) to study the crosstalk between them. The role of SCIRT and miR-146a in the proliferation of HAOSMCs was analyzed with BrdU assay.

Results
SCIRT was downregulated by atherosclerosis, while miR-146a was upregulated by atherosclerosis. SCIRT was detected in both cytoplasm and nuclear samples, and it directly interacted with miR-146a. In HAOSMCs, overexpression of SCIRT and miR-146a did not affect the expression of each other. Interestingly, SCIRT suppressed the proliferation of HAOSMCs and reduced the enhancing effects of miR-146a on cell proliferation.

Conclusion
Therefore, SCIRT is downregulated in atherosclerosis and it suppresses the proliferation of HAOSMCs by sponging miR-146a in cytoplasm.
An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
Authors: Zhang Yan , Wang Jian-Ying , Wang Hao , Chen Xiao-Yun , Zhang Lei , Yuan Ying 
Published: November 2021

Abstract
Background
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease dominated by synovial hyperplasia and bone destruction. The male flower of Eucommia ulmoides Oliv. (EF) has been shown to exert effects on the inflammation caused by RA. However, how EF affects synoviocyte apoptosis and bone destruction on RA have not been investigated thoroughly. The effects of EF on apoptosis of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells, osteoclast differentiation of RAW264.7 cells, and bone destruction in a collagen-induced arthritis (CIA) model in rats were explored.

Methods
First, the main components of EF were identified by high-performance liquid chromatography. In vitro, we investigated the anti-proliferative and pro-apoptotic effects of EF on HFLS-RA cells by immunofluorescence assays, flow cytometry, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting; we also investigated how EF influenced the differentiation of RAW264.7 cells into osteoclasts. In vivo, we used a rat model of CIA to investigate the effects of EF on anti-arthritis activity, toe swelling, Arthritis Score, serum levels of metabolic bone factors, and pathologic conditions. Micro-computed tomography was used to scan ankle joints. mRNA and protein expression of factors related to the nuclear factor-kappa B (NF-κB) pathway were determined by RT-qPCR and western blotting, respectively.

Results
EF inhibited synoviocyte proliferation and promoted apoptosis in a dose-dependent manner. EF inhibited osteoclast differentiation by inhibiting activation of the NF-κB pathway. EF reduced articular inflammation in CIA rats, inhibited the expression of pro-angiogenic factors, and delayed the destruction of articular cartilage and bone. Our data indicated that EF acted via a mechanism related to bone metabolism induced by the NF-κB pathway.

Conclusions
EF exerts a potential therapeutic effect upon RA. Our research will help to elucidate the potential pharmacologic mechanisms associated with the beneficial effects of EF, and provide an experimental basis for EF application in clinical treatments.

Graphical Abstract