bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary exosomal hsa_circ_0001250 as a novel diagnostic biomarker of idiopathic membranous nephropathy
Authors: Li Qianyu , Xu Mingzhu , Zhang Zhiping , Yin Min , Zhang Yucheng , Liu Feng 
Published: December 2022

Abstract
Aims
Idiopathic membranous nephropathy (IMN) is a common cause of adult nephrotic syndrome. Currently, the diagnosis of IMN mainly depends on renal biopsy, which is invasive. What’s more, markers already known for the clinical diagnosis of IMN are not sensitive enough. The present study aims to investigate the profiling of urinary exosomal circular RNAs (circRNAs) of IMN, and to look for a potential biomarker for diagnosis of IMN.

Methods
Urine exosomes were collected from patients with IMN and idiopathic nephrotic syndrome (INS), as well as healthy controls (HCs) by ultracentrifuge. A pairwise comparison between 5 IMN and 5 HC was performed by high-throughput sequencing. Enrichment analysis were performed to explore the potential functions of differentially expressed circRNAs in IMN. Among three differentially expressed circRNAs which may be involved in signaling pathways of pathogenesis of IMN and matched conserved mouse circRNAs, hsa_circ_0001250 was selected as the target circRNA after quantitative polymerase chain reaction among 23 IMN, 19 INS and 23HC. Sanger sequencing and RNase R digestion assay were performed to validated the ring-structure and sequence of hsa_circ_0001250. ROC (Receiver Operating Characteristic) curve correlation analysis was used to further validate the potential utility of hsa_circ_0001250 as a diagnostic biomarker of IMN. A circRNA-miRNA-mRNA network was constructed to reflect the relationship between hsa_circ_0001250 and its target miRNAs and mRNAs.

Results
766 up-regulated and 283 down-regulated circRNAs were identified in IMN patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed signaling pathways of pathogenesis of IMN which the different expressed circRNAs may participate in. The ring-structure and the sequence of hsa_circ_0001250 were confirmed, the expression of hsa_circ_0001250 was validated significantly increased in IMN, relevant with high level of proteinuria. A circRNA-miRNA-mRNA network reflected that hsa_circ_0001250 may play a role in the pathogenesis of IMN by target hsa-miR-639 and hsa-miR-4449.

Conclusion
We revealed the expression and functional profile of differentially expressed urinary exosomal circRNAs of IMN patients. Urinary exosomal hsa_circ_0001250 was tested as a potential biomarker of IMN and a predicted circRNA-miRNA-mRNA network was constructed.
Superior capsule reconstruction, partial cuff repair, graft interposition, arthroscopic debridement or balloon spacers for large and massive irreparable rotator cuff tears: a systematic review and meta-analysis
Authors: Davies Andrew , Singh Prashant , Reilly Peter , Sabharwal Sanjeeve , Malhas Amar 
Published: December 2022

AbstractBackgroundMultiple non-arthroplasty surgical techniques are described for the management of large and massive irreparable rotator cuff tears. There is currently no consensus on the best management strategy. Our aim was to compare clinical outcomes following arthroscopic debridement, arthroscopic partial cuff repair, superior capsule reconstruction, balloon spacers or graft interposition for the management of large and massive irreparable rotator cuff tears.MethodsA comprehensive search was performed of the following databases: Medline, Embase, CINAHL and Cochrane Database of Systematic Reviews. Data were extracted from relevant studies published since January 2000 according to the pre-specified inclusion criteria. The primary outcome was the post-operative improvement in shoulder scores. Meta-analysis of the primary outcome was performed. Secondary outcomes included retear rates and complications.ResultsEighty-two studies were included reporting the outcomes of 2790 shoulders. Fifty-one studies were included in the meta-analysis of the primary outcome. The definition of an irreparable tear varied. All procedures resulted in improved shoulder scores at early follow-up. Shoulder scores declined after 2 years following balloon spacers, arthroscopic debridement and partial cuff repair. High retear rates were seen with partial cuff repairs (45%), graft interposition (21%) and superior capsule reconstruction (21%).ConclusionsLarge initial improvements in shoulder scores were demonstrated for all techniques despite high retear rates for reconstructive procedures. Shoulder scores may decline at mid- to long-term follow-up.
Incidence and risk factors for surgical site infection following volar locking plating (VLP) of unstable distal radius fracture (DRF)
Authors: Meng Hongyu , Xu Bin , Xu Yi , Niu Haiyun , Liu Ning 
Published: December 2022

Abstract
Purpose
Volar locking plating (VLP) is the mainstay of treatment for distal radius fracture (DRF) but may be compromised by postoperative surgical site infection (SSI). This study aimed to identify the incidence and the risk factors for SSI following VLP of DRF.

Methods
This retrospective study identified consecutive patients who underwent VLP for closed unstable DRFs in our institution between January 2015 and June 2021. Postoperative SSI was identified by inquiring the medical records, the follow-up records or the readmission medical records for treatment of SSI. The potential factors for SSI were extracted from the medical records. Univariate and multivariate logistic regression analyses were performed to identify the independent factors.

Results
There were 930 patients included, and 34 had an SSI, representing an incidence of 3.7% (95% CI 2.4–4.9%). Patients with an SSI had threefold extended hospitalization stay (44.1 ± 38.2 versus 14.4 ± 12.5 days) as did those without. In univariate analysis, 18 variables were tested to be statistically different between SSI and non-SSI group. In multivariate analysis, 6 factors were identified as independently associated with SSI, including sex (male vs. female, OR 3.5, p = 0.014), ASA (III and IV vs. I, OR 3.2, p = 0.031), smoking (yes vs. no, OR 2.4, p = 0.015), bone grafting (OR 4.0, p = 0.007), surgeon volume (low vs. high, OR 2.7, p 0.011) and operation at night-time (vs. day-time, OR 7.8, p < 0.001).

Conclusion
The postoperative SSI of VLP of DRF was not uncommon, and the factors identified in this study, especially those modifiable, would help identify individual SSI risk, target clinical surveillance and inform patient counseling.
Prolonging the time of progesterone supplementation to improve the pregnancy outcomes of single day 6 blastocyst transfer in frozen-thawed cycles: study protocol for a randomized controlled trial
Authors: Xu Manlin , Yan Yuan , Shen Xiaoyue , Sun Haixiang , Yan Guijun , Kong Na , Jiang Yue 
Published: December 2022

Abstract
Background
Infertility is one of the most important and underappreciated reproductive health problems in developing countries. Currently, in vitro fertilization and embryo transfer is the most effective treatment strategy for infertility. In a frozen-thawed cycle, single-blastocyst transfer can not only ensure relatively higher pregnancy and live birth rates but also effectively reduce the risk of maternal and neonatal complications. In frozen-thawed cycles, progesterone is initiated to promote the final phase of endometrial preparation prior to embryo transfer. However, the optimal duration of exposure to progesterone has remained inconclusive. Therefore, we designed a randomized controlled trial (RCT) to compare the effects of different prolonged progesterone transformation times (P+6 and P+7) on the pregnancy outcomes of D6 single blastocyst transfer in a frozen-thawed cycle.

Methods
This is a single-center, prospective, randomized controlled clinical trial involving 900 patients with single blastocyst transfer in the frozen-thawed cycle, aged from 20 to 38 years, with less than three transfers, and with HRT-cycle single D6 blastocyst transfer in the current cycle. Participants will be randomly assigned (1:1) into two parallel groups: the transfer of day 6 blastocysts on the 7th day of progesterone supplementation and the transfer of day 6 blastocysts on the 6th day of progesterone supplementation. The primary outcome measure is the clinical pregnancy rate. Secondary outcome measures include the miscarriage rate and live birth rate.

Discussion
This is the first randomized controlled trial to compare the transfer of day 6 blastocysts on the 6th and 7th day of progesterone supplementation. The results of this study will provide evidence for whether to prolong the duration of exposure to progesterone prior to embryo transfer.

Trial registration
ClinicalTrials.gov, ID: NCT04938011. Registered on 19 June 2021.
DNA methylation patterns associated with konzo in Sub-Saharan Africa
Authors: Kocher Kristen , Bhattacharya Surajit , Bramble Matthew S. , Okitundu-Luwa Daniel , Ngoyi Dieudonne Mumba , Tshala-Katumbay Desire , Vilain Eric 
Published: December 2022

AbstractKonzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks, is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic-sensitive regions of the genome, providing the first study of epigenomic alterations associated with a clinical phenotype of konzo.
Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children
Authors: Surgent Olivia , Riaz Ali , Ausderau Karla K. , Adluru Nagesh , Kirk Gregory R. , Guerrero-Gonzalez Jose , Skaletski Emily C. , Kecskemeti Steven R. , Dean III Douglas C , Weismer Susan Ellis , Alexander Andrew L. , Travers Brittany G. 
Published: December 2022

AbstractBackgroundElevated or reduced responses to sensory stimuli, known as sensory features, are common in autistic individuals and often impact quality of life. Little is known about the neurobiological basis of sensory features in autistic children. However, the brainstem may offer critical insights as it has been associated with both basic sensory processing and core features of autism.MethodsDiffusion-weighted imaging (DWI) and parent-report of sensory features were acquired from 133 children (61 autistic children with and 72 non-autistic children, 6–11 years-old). Leveraging novel DWI processing techniques, we investigated the relationship between sensory features and white matter microstructure properties (free-water-elimination-corrected fractional anisotropy [FA] and mean diffusivity [MD]) in precisely delineated brainstem white matter tracts. Follow-up analyses assessed relationships between microstructure and sensory response patterns/modalities and analyzed whole brain white matter using voxel-based analysis.ResultsResults revealed distinct relationships between brainstem microstructure and sensory features in autistic children compared to non-autistic children. In autistic children, more prominent sensory features were generally associated with lower MD. Further, in autistic children, sensory hyporesponsiveness and tactile responsivity were strongly associated with white matter microstructure in nearly all brainstem tracts. Follow-up voxel-based analyses confirmed that these relationships were more prominent in the brainstem/cerebellum, with additional sensory-brain findings in the autistic group in the white matter of the primary motor and somatosensory cortices, the occipital lobe, the inferior parietal lobe, and the thalamic projections.LimitationsAll participants communicated via spoken language and acclimated to the sensory environment of an MRI session, which should be considered when assessing the generalizability of this work to the whole of the autism spectrum.ConclusionsThese findings suggest unique brainstem white matter contributions to sensory features in autistic children compared to non-autistic children. The brainstem correlates of sensory features underscore the potential reflex-like nature of behavioral responses to sensory stimuli in autism and have implications for how we conceptualize and address sensory features in autistic populations.
Targeting regulation of VEGF by BPTF in non-small cell lung cancer and its potential clinical significance
Authors: Dai Meng , Hua Chunyu , Wang Mingqin , Gao Li , Jiang Ling , Liu Yuan 
Published: December 2022

Abstract
Purpose
VEGF facilitates tumor angiogenesis, and bevacizumab targeting VEGF is used in anti-tumor therapy. It is meaningful to clarify the upstream regulatory mechanism of VEGF. BPTF is important in chromosomal remodeling, and promotes the progression of tumors. However, its role in promoting tumor angiogenesis by targeting VEGF has not been fully reported. This study aims to elucidate the expression regulation of VEGF by BPTF and its clinical significance in NSCLC.

Methods
1. BPTF siRNA and shRNA plasmids were used to reduce the expression of BPTF by transfection in vivo and in vitro. BPTF, VEGF and CD144 expressions were examined by immunofluorescence and Western Blot. 2. The expressions of BPTF, VEGF, CD144 and CD31 were detected in lung adenocarcinoma samples by immunofluorescence, Western blot and immunohistochemical staining. 3. 26 lung adenocarcinoma patients treated by bevacizumab were divided into 2 groups according to the treatment efficacy. BPTF and VEGF expressions were analyzed.

Results
1. BPTF knockdown inhibited the expression of VEGF and CD144 in vivo and in vitro. 2. Compared with para-cancer tissues, BPTF, VEGF, CD144 and CD31 were highly expressed in lung adenocarcinoma. 3. In 75 lung adenocarcinoma specimens, BPTF and VEGF overexpression was correlated with lymph node metastasis and clinical stage. The 5-year survival rate of patients with BPTF and VEGF low expression was higher, and BPTF expression was positively correlated with VEGF expression. 4. Among 26 patients treated with bevacizumab, the patients with BPTF overexpression are more sensitive to the treatment.

Conclusions
BPTF positively regulates VEGF expression and its high expression predicts a better efficacy of bevacizumab treatment in NSCLC.
Cognitively impaired aged Octodon degus recapitulate major neuropathological features of sporadic Alzheimer’s disease
Authors: Tan Zhiqun , Garduño B. Maximiliano , Aburto Pedro Fernández , Chen Lujia , Ha Nicole , Cogram Patricia , Holmes Todd C. , Xu Xiangmin 
Published: December 2022

AbstractThe long-lived Chilean rodent (Octodon degus) has been reported to show spontaneous age-dependent neuropathology and cognitive impairments similar to those observed in human AD. However, the handful of published papers on degus of differing genetic backgrounds yield inconsistent findings about sporadic AD-like pathological features, with notably differing results between lab in-bred degus versus outbred degus. This motivates more extensive characterization of spontaneously occurring AD-like pathology and behavior in degus. In the present study, we show AD-like neuropathological markers in the form of amyloid deposits and tau abnormalities in a cognitively impaired subset of aged outbred degus. Compared to the aged degus that show normal burrowing behavior, the age-matched degus with burrowing behavior deficits correlatively exhibit detectable human AD-like Aβ deposits and tau neuropathology, along with neuroinflammatory markers that include enhanced microglial activation and higher numbers of reactive astrocytes in the brain. This subset of cognitively impaired aged degus also exhibits cerebral amyloid angiopathy and tauopathy. We find robust neurodegenerative features in behaviorally deficient aged degus, including hippocampal neuronal loss, altered parvalbumin and perineuronal net staining in the cortex, and increased c-Fos neuronal activation in the cortex that is consistent with the neural circuit hyperactivity reported in human AD patients. By focusing on the subset of aged degus that show AD-like behavioral deficits and correlative neuropathology, our findings establish outbred degus as a natural model of sporadic AD and demonstrate the potential importance of wild-type outbred genetic backgrounds for AD pathogenesis.
On the interplay of borderline personality features, childhood trauma severity, attachment types, and social support
Authors: Schulze Anna , Cloos Leonie , Zdravkovic Monika , Lis Stefanie , Krause-Utz Annegret 
Published: December 2022

AbstractBackgroundAdverse childhood experiences (ACE) have consistently been associated with borderline personality disorder (BPD). Still, it is not yet entirely understood if and how different types of ACE (emotional, physical, sexual abuse, neglect) relate to different BPD subdomains (affective instability, identity disturbance, negative relationships, self-harm). Insecure attachment and lower perceived social support are associated with both ACE and BPD and may therefore contribute to their relationship. No study so far integrated all these variables in one model, while accounting for their mutual influence on each other. We investigated the interplay of BPD subdomains, ACE, attachment, and perceived social support using a graph-theoretical approach.MethodsAn international sample of 1692 participants completed the Childhood Trauma Questionnaire (CTQ), the Borderline Feature Scale from the Personality Assessment Inventory (PAI-BOR), the Adult Attachment Scale (AAS), and Multidimensional Scale of Perceived Social Support (MSPSS) via an online survey. We estimated a partial correlation network including subscales of the CTQ and the PAI-BOR as nodes. We extended the network by including subscales of the AAS and MSPSS as additional nodes.ResultsEmotional abuse was the most central node in both networks and a bridge between other types of ACE and BPD features. All domains of BPD except affective instability were associated with emotional abuse. Identity disturbances was the most central node in the BPD network. The association between ACE and BPD features was partly but not fully explained by attachment and social support.ConclusionOur findings suggest that emotional abuse is an important link in the association between ACE and BPD features, also when taking attachment and social support into account. Findings further suggest an outstanding role of identity disturbance, linking emotional abuse to affective instability and being strongly associated with attachment anxiety.
Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media
Authors: Kim Jun Yong , Rhim Won-Kyu , Cha Seung-Gyu , Woo Jiwon , Lee Joo Youn , Park Chun Gwon , Han Dong Keun 
Published: December 2022

AbstractHuman mesenchymal stem cells (hMSCs)-derived extracellular vesicles (EVs) have been known to possess the features of the origin cell with nano size and have shown therapeutic potentials for regenerative medicine in recent studies as alternatives for cell-based therapies. However, extremely low production yield, unknown effects derived from serum impurities, and relatively low bioactivities on doses must be overcome for translational applications. As several reports have demonstrated the tunability of secretion and bioactivities of EVs, herein, we introduced three-dimensional (3D) culture and cell priming approaches for MSCs in serum-free chemically defined media to exclude side effects from serum-derived impurities. Aggregates (spheroids) with 3D culture dramatically enhanced secretion of EVs about 6.7 times more than cells with two-dimensional (2D) culture, and altered surface compositions. Further modulation with cell priming with the combination of TNF-α and IFN-γ (TI) facilitated the production of EVs about 1.4 times more than cells without priming (9.4 times more than cells with 2D culture without priming), and bioactivities of EVs related to tissue regenerations. Interestingly, unlike changing 2D to 3D culture, TI priming altered internal cytokines of MSC-derived EVs. Through simulating characteristics of EVs with bioinformatics analysis, the regeneration-relative properties such as angiogenesis, wound healing, anti-inflammation, anti-apoptosis, and anti-fibrosis, for three different types of EVs were comparatively analyzed using cell-based assays. The present study demonstrated that a combinatory strategy, 3D cultures and priming MSCs in chemically defined media, provided the optimum environments to maximize secretion and regeneration-related bioactivities of MSC-derived EVs without impurities for future translational applications.
Mild hypothermia combined with dexmedetomidine reduced brain, lung, and kidney damage in experimental acute focal ischemic stroke
Authors: Battaglini Denise , da Silva Adriana Lopes , Felix Nathane Santanna , Rodrigues Gisele , Antunes Mariana Alves , Rocha Nazareth Novaes , Capelozzi Vera Luiza , Morales Marcelo Marcos , Cruz Fernanda Ferreira , Robba Chiara , Silva Pedro Leme , Pelosi Paolo , Rocco Patricia Rieken Macedo 
Published: December 2022

Abstract
Background
Sedatives and mild hypothermia alone may yield neuroprotective effects in acute ischemic stroke (AIS). However, the impact of this combination is still under investigation. We compared the effects of the combination of mild hypothermia or normothermia with propofol or dexmedetomidine on brain, lung, and kidney in experimental AIS. AIS-induced Wistar rats (n = 30) were randomly assigned, after 24 h, to normothermia or mild hypothermia (32–35 °C) with propofol or dexmedetomidine. Histologic injury score and molecular biomarkers were evaluated not only in brain, but also in lung and kidney. Hemodynamics, ventilatory parameters, and carotid Doppler ultrasonography were analyzed for 60 min.

Results
In brain: (1) hypothermia compared to normothermia, regardless of sedative, decreased tumor necrosis factor (TNF)-α expression and histologic injury score; (2) normothermia + dexmedetomidine reduced TNF-α and histologic injury score compared to normothermia + propofol; (3) hypothermia + dexmedetomidine increased zonula occludens-1 expression compared to normothermia + dexmedetomidine. In lungs: (1) hypothermia + propofol compared to normothermia + propofol reduced TNF-α and histologic injury score; (2) hypothermia + dexmedetomidine compared to normothermia + dexmedetomidine reduced histologic injury score. In kidneys: (1) hypothermia + dexmedetomidine compared to normothermia + dexmedetomidine decreased syndecan expression and histologic injury score; (2) hypothermia + dexmedetomidine compared to hypothermia + propofol decreased histologic injury score.

Conclusions
In experimental AIS, the combination of mild hypothermia with dexmedetomidine reduced brain, lung, and kidney damage.