bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous monocyte myeloid-derived suppressor cells ameliorate immune imbalance, neuroinflammation and cognitive impairment in 5xFAD mice infected with Porphyromonas gingivalis
Authors: Cheng Xiao , Chi Li , Lin Tianqiong , Liang Fengyin , Pei Zhong , Sun Jianbo , Teng Wei 
Published: March 2023

Abstract
Background
Periodontitis is closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, has been reported in our recent study to cause immune-overreaction and induce cognitive impairment. Monocytic myeloid-derived suppressor cells (mMDSCs) possess potent immunosuppressive function. It is unclear whether mMDSCs-mediated immune homeostasis is impaired in AD patients with periodontitis, and whether exogenous mMDSCs could ameliorate immune-overreaction and cognitive impairment induced by Pg.

Methods
To explore the influence of Pg on cognitive function, neuropathology and immune balance in vivo, 5xFAD mice were treated with live Pg by oral gavage, three times a week for 1 month. The cells of peripheral blood, spleen and bone marrow from 5xFAD mice were treated with Pg to detect the proportional and functional alterations of mMDSCs in vitro. Next, exogenous mMDSCs were sorted from wild-type healthy mice and intravenously injected into 5xFAD mice that were infected with Pg. We used behavioral tests, flow cytometry and immunofluorescent staining to evaluate whether exogenous mMDSCs could ameliorate the cognitive function, immune homeostasis and reduce neuropathology exacerbated by Pg infection.

Results
Pg exacerbated cognitive impairment in 5xFAD mice, with the deposition of amyloid plaque and increased number of microglia in the hippocampus and cortex region. The proportion of mMDSCs decreased in Pg-treated mice. In addition, Pg reduced the proportion and the immunosuppressive function of mMDSCs in vitro. Supplement of exogenous mMDSCs improved the cognitive function, and enhanced the proportions of mMDSCs and IL-10+ T cells of 5xFAD mice infected with Pg. At the same time, supplement of exogenous mMDSCs increased the immunosuppressive function of endogenous mMDSCs while decreased the proportions of IL-6+ T cells and IFN-γ+ CD4+ T cells. In addition, the deposition of amyloid plaque decreased while the number of neurons increased in the hippocampus and cortex region after the supplement of exogenous mMDSCs. Furthermore, the number of microglia increased with an increase in the proportion of M2 phenotype.

Conclusions
Pg can reduce the proportion of mMDSCs, induce immune-overreaction, and exacerbate the neuroinflammation and cognitive impairment in 5xFAD mice. Supplement of exogenous mMDSCs can reduce the neuroinflammation, immune imbalance and cognitive impairment in 5xFAD mice infected with Pg. These findings indicate the mechanism of AD pathogenesis and Pg-mediated promotion of AD, and provide a potential therapeutic strategy for AD patients.
A comprehensive immunohistochemical analysis of 26 markers in 250 cases of serous ovarian tumors
Authors: Němejcová Kristýna , Šafanda Adam , Bártů Michaela Kendall , Michálková Romana , Drozenová Jana , Fabian Pavel , Hausnerová Jitka , Laco Jan , Matěj Radoslav , Méhes Gábor , Škapa Petr , Stružinská Ivana , Dundr Pavel 
Published: March 2023

Abstract
Background
We examined a large cohort of serous tubo-ovarian tumors with 26 immunohistochemical markers, with the aim to assess their value for differential diagnosis and prognosis.

Methods
Immunohistochemical analyses with 26 immunomarkers were performed on 250 primary tubo-ovarian tumors including 114 high grade serous carcinomas (HGSC), 97 low grade serous carcinomas (LGSC), and 39 serous borderline tumors (micropapillary variant, mSBT). The associations of overall positivity with clinicopathological characteristics were evaluated using the chi-squared test or Fisher’s Exact test.

Results
We found significantly different expression of p53, p16, ER, PR, PTEN, PAX2, Mammaglobin, RB1, Cyclin E1, stathmin, LMP2, L1CAM, CD44, and Ki67 in HGSCs compared to LGSCs. No significant differences were found between LGSC and mSBT. None of the other included markers (PAX8, ARID1A, HNF1B, Napsin A, CDX2, SATB2, MUC4, BRG1, AMACR, TTF1, BCOR, NTRK) showed any differences between the investigated serous tumors. Regarding the prognosis, only PR and stathmin showed a statistically significant prognostic meaning in LGSCs, with better overall survival (OS) and recurrence-free survival (RFS) in cases positive for PR, and worse outcome (RFS) for stathmin. None of the study markers showed prognostic significance in HGSCs.

Conclusion
We provided an extensive immunohistochemical analysis of serous ovarian/tubo-ovarian tumors. Although we found some differences in the expression of some markers in HGSCs compared to LGSCs, only p53, p16, and Ki67 seem to be useful in real diagnostic practice. We also suggested the best discriminative cut-off for Ki67 (10% of positive tumor cells) for distinguishing HGSC from LGSC. We found prognostic significance of PR and stathmin in LGSCs. Moreover, the high expression of stathmin could also be of predictive value in ovarian carcinomas as target-specific anti-stathmin effectors are potential therapeutic targets.
A new biotechnology for in-planta gene editing and its application in promoting flavonoid biosynthesis in bamboo leaves
Authors: Sun Huayu , Wang Sining , Zhu Chenglei , Yang Kebin , Liu Yan , Gao Zhimin 
Published: March 2023

Abstract
Background
Bamboo is a perennial and renewable biomass forest resource and its leaf flavonoid is an antioxidant for biological and pharmacological research. The established genetic transformation and gene editing systems in bamboo are significantly limited by the dependence on bamboo regeneration capability. The way to improve the flavonoid content in bamboo leaves through biotechnology is still not feasible.

Results
Here, we developed an in-planta, Agrobacterium-mediated gene expression method for exogenous genes via wounding and vacuum in bamboo. We demonstrated that the RUBY served as a reporter efficiently expressed in bamboo leaves and shoots, albeit unable to integrate into the chromosome. We have also developed a gene editing system by creating an in situ mutant of the bamboo violaxanthin de-epoxidase (PeVDE) gene in bamboo leaves, with lower NPQ values under the fluorometer, which can serve as a native reporter for gene editing. Furthermore, the bamboo leaves with increased flavonoid content were achieved by knocking out the cinnamoyl-CoA reductase genes.

Conclusions
Our method can be applied for the functional characterization of novel genes in a short time and is helpful for bamboo leaf flavonoid biotechnology breeding in the future.
Nesfatin-1 suppresses autophagy of chondrocytes in osteoarthritis via remodeling of cytoskeleton and inhibiting RhoA/ROCK signal pathway
Authors: Jiang Lifeng , Moqbel Safwat Adel Abdo , Zhu Junxiong , Fu Qiangchang , Lai Jiabin , Lin Changjian , Wu Lidong 
Published: March 2023

AbstractAutophagy and cytoskeleton integrity of chondrocytes are a considered as major factors in the progression of osteoarthritis (OA) involving excessive chondrocyte apoptosis and senescence. Nesfatin-1, an adipokine, has been reported to be closely related to cell autophagy and cytoskeleton malfunction. Our previous study found that nesfatin-1 was highly correlated with OA progress in OA patient, and the expression of nesfatin-1 rises in knee articular tissue, serum and chondrocytes. In current study, we aimed to explore the therapeutic effect of nesfatin-1 on OA and its molecular mechanism related to chondrocyte autophagy and cytoskeleton malfunction. We firstly demonstrated that nesfatin-1 effectively suppressed excessive autophagy of OA chondrocytes at both gene and protein levels. Meanwhile, we also found that nesfatin-1 significantly improved cytoskeleton integrity by showing higher F-actin/G-actin ratio, as well as more organized actin fiber structure. Mechanistically, utility of RhoA activator and inhibitor revealed that regulation of autophagy and cytoskeleton integrity via nesfatin-1 was realized via RhoA/ROCK pathway. We also confirmed that nesfatin-1 significantly ameliorated IL-1β induced cartilage degeneration via destabilization of the medial meniscus (DMM) model. Overall, our study indicates that nesfatin-1 might be a promising therapeutic molecule for OA intervention.
Analysis of the cost-efficiency of the vascular impulse technology (VIT) in the perioperative management of complex ankle fractures: results of a prospective randomised controlled trial
Authors: El Barbari Jan S. , Schnetzke Marc , Swartman Benedict , Grützner Paul A. , Franke Jochen 
Published: March 2023

Abstract
Introduction
Posttraumatic swelling causes a delay in surgery, a prolonged hospital stay and a higher risk of complications. Thus, soft tissue conditioning following complex ankle fractures is of central importance in their perioperative management. Since the clinical benefit of VIT usage on the clinical course has been shown, it should now be investigated whether it is also cost-efficient in doing so.

Materials and methods
Included are published clinical results of the prospective, randomised, controlled, monocentric VIT study that have proven the therapeutic benefit in complex ankle fractures. Participants were allocated in a 1:1 ratio into the intervention group (VIT) and the control group (elevation). In this study, the required economic parameters of these clinical cases were collected on the data of the financial accounting and an estimation of annual cases had been performed to extrapolate the cost-efficiency of this therapy. The primary endpoint was the mean savings (in €).

Results
Thirty-nine cases were studied in the period from 2016 to 2018. There was no difference in the generated revenue. However, due to lower incurred costs in the intervention group, there were potential savings of about €2000 (pITT = 0.073) to 3000 (pAT = 0.008) per patient compared to the control group with therapy costs decreasing as the number of patients treated increases from €1400 in one case to below €200 per patient in 10 cases. There were 20% more revision surgeries in the control group or 50 min more OR time, respectively, and an increased attendance by staff and medical personnel of more than 7 h.

Conclusions
VIT therapy has been shown to be a beneficial therapeutic modality, but it is so not only in regard to soft-tissue conditioning but also cost efficiency.
The promotive role of USP1 inhibition in coordinating osteogenic differentiation and fracture healing during nonunion
Authors: Huang Jun , Zhou Hongxiang , He Liang , Zhong Lin , Zhou Ding , Yin Zongsheng 
Published: March 2023

Abstract
Background
Nonunion is a failure of fracture healing and a major complication after fractures. Ubiquitin-specific protease 1 (USP1) is a deubiquitinase that involved in cell differentiation and cell response to DNA damage. Herein we investigated the expression, function and mechanism of USP1 in nonunion.

Methods and results
Clinical samples were used to detect the USP1 expression in nonunion. ML323 was selected to inhibit USP1 expression throughout the study. Rat models and mouse embryonic osteoblasts cells (MC3T3-E1) were used to investigate the effects of USP1 inhibition on fracture healing and osteogenesis in vivo and in vitro, respectively. Histological changes were examined by micro-computerized tomography (Micro-CT), hematoxylin & eosin (H&E) staining and Masson staining. Alkaline phosphatase (ALP) activity detection and alizarin red staining were used for osteogenic differentiation observation. The expression of related factors was detected by quantitative real-time PCR, western blot or immunohistochemistry (IHC). It was shown that USP1 was highly expressed in nonunion patients and nonunion rats. USP1 inhibition by ML323 promoted fracture healing in nonunion rats and facilitated the expression of osteogenesis-related factors and the signaling of PI3K/Akt pathway. In addition, USP1 inhibition accelerated osteogenic differentiation and promoting PI3K/Akt signaling in MC3T3-E1 cells.

Conclusions
USP1 inhibition plays a promotive role in coordinating osteogenic differentiation and fracture healing during nonunion. PI3K/Akt may be the downstream pathway of USP1.
Evidence-based informed consent form for total knee arthroplasty
Authors: Pai Satvik N. , Jeyaraman Madhan , Maffulli Nicola , Jeyaraman Naveen , Migliorini Filippo , Gupta Ashim 
Published: March 2023

Abstract
Introduction
Informed consent documentation is often the first area of interest for lawyers and insurers when a medico-legal malpractice suit is concerned. However, there is a lack of uniformity and standard procedure about obtaining informed consent for total knee arthroplasty (TKA). We developed a solution for this need for a pre-designed, evidence-based informed consent form for patients undergoing TKA.

Materials and methods
We extensively reviewed the literature on the medico-legal aspects of TKA, medico-legal aspects of informed consent, and medico-legal aspects of informed consent in TKA. We then conducted semi-structured interviews with orthopaedic surgeons and patients who had undergone TKA in the previous year. Based on all of the above, we developed an evidence-based informed consent form. The form was then reviewed by a legal expert, and the final version was used for 1 year in actual TKA patients operated at our institution.

Results
Legally sound, evidence-based Informed Consent Form for Total Knee Arthroplasty.

Conclusion
The use of legally sound, evidence-based informed consent for total knee arthroplasty would be beneficial to orthopaedic surgeons and patients alike. It would uphold the rights of the patient, promote open discussion and transparency. In the event of a lawsuit, it would be a vital document in the defence of the surgeon and withstand the scrutiny of lawyers and the judiciary.
Radiological features accompanying peroneus brevis split rupture revealed on magnetic resonance imaging – a cohort study
Authors: Huuskonen Michael , Borkmann Simon , Bengtsson Alexander , Sobecki Piotr , Józwiak Rafał , Solidakis Nektarios , Szaro Paweł 
Published: March 2023

AbstractBackgroundPeroneal split tears are an underrated cause of ankle pain. While magnetic resonance imaging (MRI) is useful for diagnosis, split tears are challenging to identify. The aim of the study was to investigate the association of peroneus brevis split rupture with abnormalities of the superior peroneal retinaculum (SPR), anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), joint effusion, morphology of the malleolar groove, presence of the bone marrow oedema and prominent peroneal tuberculum.MethodsAnkle MRI cases were assessed by independent observers retrospectively in two groups: one with peroneus brevis split tears (n = 80) and one without (control group, n = 115). Two observers evaluated the soft tissue lesions, and three graded the bone lesions. Fisher's exact test and Pearson correlation were used for analysis. The Bonferroni‐Holm method (B‐H) was used to adjust for multiple comparisons.ResultsOnly bone marrow edema in the posterior part of the lateral malleolus was significantly (p < 0.05) more common in the split tear group after applying B‐H. SPR total rupture was seen only in the experimental group. No differences in incidence of ATFL and CFL lesions or other SPR lesions were noticed (p < 0.05).ConclusionBone marrow edema in the posterior part of the lateral malleolus is associated with peroneus split tears on MRI.
Improving vasopressor use in cardiac arrest
Authors: Perkins Gavin D. , Couper Keith 
Published: March 2023

AbstractThe Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early defibrillation. Most patients, however, remain in cardiac arrest despite these interventions. Drug treatments, particularly the use of vasopressors, have been included in resuscitation algorithms since their inception. This narrative review describes the current evidence base for vasopressors and reports that adrenaline (1 mg) is highly effective at achieving return of spontaneous circulation (number needed to treat 4) but is less effective on long-term outcomes (survival to 30 days, number needed to treat 111) with uncertain effects on survival with a favourable neurological outcome. Randomised trials evaluating vasopressin, either as an alternative to or in addition to adrenaline, and high-dose adrenaline have failed to find evidence of improved long-term outcomes. There is a need for future trials to evaluate the interaction between steroids and vasopressin. Evidence for other vasopressors (e.g. noradrenaline, phenylephedrine) is insufficient to support or refute their use. The use of intravenous calcium chloride as a routine intervention in out of hospital cardiac arrest is not associated with benefit and may cause harm. The optimal route for vascular access between peripheral intravenous versus intraosseous routes is currently the subject of two large randomised trials. Intracardiac, endobronchial, and intramuscular routes are not recommended. Central venous administration should be limited to patients where an existing central venous catheter is in situ and patent.
Prevalence of diabetic retinopathy in Brazil: a systematic review with meta-analysis
Authors: Chagas Thiago Alves , dos Reis Mateus Augusto , Leivas Gabriel , Santos Lucas Porto , Gossenheimer Agnes Nogueira , Melo Gustavo Barreto , Malerbi Fernando Korn , Schaan Beatriz D. 
Published: March 2023

Abstract
Aims
To evaluate the prevalence of diabetic retinopathy (DR) in Brazilian adults with diabetes mellitus via a systematic review with meta-analysis.

Methods
A systematic review using PubMed, EMBASE, and Lilacs was conducted, searching for studies published up to February 2022. Random effect meta-analysis was performed to estimate the DR prevalence.

Results
We included 72 studies (n = 29,527 individuals). Among individuals with diabetes in Brazil, DR prevalence was 36.28% (95% CI 32.66–39.97, I2 98%). Diabetic retinopathy prevalence was highest in patients with longer duration of diabetes and in patients from Southern Brazil.

Conclusion
This review shows a similar prevalence of DR as compared to other low- and middle-income countries. However, the high heterogeneity observed—expected in systematic reviews of prevalence—raises concerns about the interpretation of these results, suggesting the need for multicenter studies with representative samples and standardized methodology.
Disruption of early visual processing in amyloid-positive healthy individuals and mild cognitive impairment
Authors: Javitt Daniel C. , Martinez Antigona , Sehatpour Pejman , Beloborodova Anna , Habeck Christian , Gazes Yunglin , Bermudez Dalton , Razlighi Qolamreza R. , Devanand D. P. , Stern Yaakov 
Published: March 2023

Abstract
Background
Amyloid deposition is a primary predictor of Alzheimer’s disease (AD) and related neurodegenerative disorders. Retinal changes involving the structure and function of the ganglion cell layer are increasingly documented in both established and prodromal AD. Visual event-related potentials (vERP) are sensitive to dysfunction in the magno- and parvocellular visual systems, which originate within the retinal ganglion cell layer. The present study evaluates vERP as a function of amyloid deposition in aging, and in mild cognitive impairment (MCI).

Methods
vERP to stimulus-onset, motion-onset, and alpha-frequency steady-state (ssVEP) stimuli were obtained from 16 amyloid-positive and 41 amyloid-negative healthy elders and 15 MCI individuals and analyzed using time–frequency approaches. Social cognition was assessed in a subset of individuals using The Awareness of Social Inference Test (TASIT).

Results
Neurocognitively intact but amyloid-positive participants and MCI individuals showed significant deficits in stimulus-onset (theta) and motion-onset (delta) vERP generation relative to amyloid-negative participants (all p < .01). Across healthy elders, a composite index of these measures correlated highly (r =  − .52, p < .001) with amyloid standardized uptake value ratios (SUVR) and TASIT performance. A composite index composed of vERP measures significant differentiated amyloid-positive and amyloid-negative groups with an overall classification accuracy of > 70%.

Discussion
vERP may assist in the early detection of amyloid deposition among older individuals without observable neurocognitive impairments and in linking previously documented retinal deficits in both prodromal AD and MCI to behavioral impairments in social cognition.
Using participatory epidemiology to investigate women’s knowledge on the seasonality and causes of acute malnutrition in Karamoja, Uganda
Authors: Catley Andy , Arasio Raphael Lotira , Hopkins Charles 
Published: March 2023

AbstractThe Karamoja region of northeast Uganda had been characterized by high levels of acute malnutrition (AM) for decades, despite substantial aid investment in nutrition programmes. Participatory epidemiology (PE) was used to understand the seasonality of child AM from the perspective of women agro-pastoralists and understand their knowledge and prioritization of the causes of child AM. Women provided highly plausible descriptions and analysis of monthly variations in the occurrence of AM, livelihood factors related to the temporal variation in AM occurrence, the root causes of AM and relationships between these causes. Overall, AM was strongly attributed to declining livestock ownership and access to cow milk and normalized gender discrimination. Monthly calendars revealed important monthly patterns in AM, births and women’s workload that had not been previously reported. There was significant agreement (p < 0.01) between independent women’s groups (n = 16) for the monthly calendars and causal diagrams, indicating strong reproducibility of the methods. Triangulation indicated good validity of the monthly calendar method. The PE approach demonstrated that agro-pastoralist women with limited formal education could describe and analyse the seasonality of AM and related factors and identify and prioritize the causes of AM. Indigenous knowledge should be valued and respected, and nutrition programmes should shift the emphasis towards far more participatory and community-based approaches. The timing of conventional nutrition surveys in agro-pastoral settings should be based on an understanding of the seasonality of livelihoods.
Activation of the Hedgehog signaling pathway leads to fibrosis in aortic valves
Authors: Gu Dongsheng , Soepriatna Arvin H. , Zhang Wenjun , Li Jun , Zhao Jenny , Zhang Xiaoli , Shu Xianhong , Wang Yongshi , Landis Benjamin J. , Goergen Craig J. , Xie Jingwu 
Published: March 2023

Abstract
Background
Fibrosis is a pathological wound healing process characterized by excessive extracellular matrix deposition, which interferes with normal organ function and contributes to ~ 45% of human mortality. Fibrosis develops in response to chronic injury in nearly all organs, but the a cascade of events leading to fibrosis remains unclear. While hedgehog (Hh) signaling activation has been associated with fibrosis in the lung, kidney, and skin, it is unknown whether hedgehog signaling activation is the cause or the consequence of fibrosis. We hypothesize that activation of hedgehog signaling is sufficient to drive fibrosis in mouse models.

Results
In this study, we provide direct evidence to show that activation of Hh signaling via expression of activated smoothened, SmoM2, is sufficient to induce fibrosis in the vasculature and aortic valves. We showed that activated SmoM2 -induced fibrosis is associated with abnormal function of aortic valves and heart. The relevance of this mouse model to human health is reflected in our findings that elevated GLI expression is detected in 6 out of 11 aortic valves from patients with fibrotic aortic valves.

Conclusions
Our data show that activating hedgehog signaling is sufficient to drive fibrosis in mice, and this mouse model is relevant to human aortic valve stenosis.