bluuebunny/crossref_metadata_2025 huggingface dataset:
A Combination of Bone Marrow Mesenchymal Stem Cells with Estrogen Improves Rabbit Endometrial Injury Repair by a Mechanism Involved in an Activation of Wnt/β-catenin Signaling
Authors: Liwei Yuan , Jia Cao , Mingyue Hu , Dabao Xu , Yan Li , Shiyun Zhao , Juanjuan Yuan , Huixing Zhang , Yani Huang , He Jin , Meixia Chen , Liu Dan
Published: August 2021

Background: Although the effect of bone marrow mesenchymal stem cells (BMSCs) combined with estrogen therapy in the repair of endometrial injury has been confirmed, its underlying molecular mechanism in intrauterine adhesion (IUA) remains unclear. In this study, we aim to investigate the effect and involvement of a combination of BMSCs with estrogen in restoration of injured endometrium by applying a rabbit endometrial injury model. Method: BMSCs were isolated and labeled with PKH26 fluorescent dye. The IUA animal model was generated by a dual damage method of mechanical curettage and lipopolysaccharide infection. Rabbits were randomly assigned to the following 5 groups: sham operation group, IUA model group, E2 treatment group, BMSCs treatment group, and BMSCs combined with E2 treatment group. Bilateral uterus were obtained at different time points for the further study. HE and Masson staining were used to evaluate the number of endometrial glands and the degree of fibrosis. The expression of fibrosis and EMT related markers were observed by Immunohistochemical, immunofluorescence staining and Western blot. The expression of core molecules in the Wnt/β-catenin signaling pathway was examined by Western blot.Results: In the present study, it is found that PKH26 fluorescent dye can successfully label BMSCs and track the distribution and differentiation of transplanted BMSCs. BMSCs differentiated into endometrial epithelial cells and mainly located around the endometrial glands and extracellular matrix at 3 or 5 days post-transplantation, while BMSCs primarily differentiated into endometrial stromal cells at 7 days after orthotopic transplantation. Furthermore, after combined treatment of BMSCs and estrogen, the number of glands increased significantly, and the area of fibrosis reduced evidently, accompanied by a downregulation of mesenchymal markers and upregulation of epithelial markers when compared with each single treatment group. The expression levels of core molecules in the Wnt/β-catenin signaling pathway were higher in the BMSCs+E2 group than in the other treatment groups. Conclusions: Our study demonstrates that BMSCs combined with estrogen can improve the repair after endometrial injury by promoting the proliferation of endometrial epithelial cells and inhibiting EMT and endometrial fibrosis. This combined effect is achieved in part through activation of the Wnt/β-catenin signaling pathway.
Under-specification as the Source of Ambiguity and Vagueness in Narrative Phenotype Algorithm Definitions
Authors: Yu Jingzhi , Pacheco Jennifer A. , Ghosh Anika , Luo Yuan , Weng Chunhua , Shang Ning , Benoit Barbara , Carrell David , Carroll Robert , Dikilitas Ozan , Freimuth Robert , Gainer Vivian , Hakonarson Hakon , Hripcsak George , Kullo Iftikhar , Mentch Frank , Murphy Shawn , Peissig Peggy , Ramirez Andrea , Walton Nephi , Wei Wei-qi , Rasmussen Luke
Published: August 2021

IntroductionCurrently, one of the commonly used methods for disseminating electronic health record (EHR)-based phenotype algorithms is providing a narrative description of the algorithm logic, often accompanied by flowcharts. A challenge with this mode of dissemination is the potential for under-specification in the algorithm definition, which leads to ambiguity and vagueness. MethodsThis study examines incidents of under-specification that occurred during the implementation of 34 narrative phenotyping algorithms in the electronic Medical Record and Genomics (eMERGE) network. We reviewed the online communication history between algorithm developers and implementers within the Phenotype Knowledge Base (PheKB) platform, where questions could be raised and answered regarding the intended implementation of a phenotype algorithm. ResultsWe developed a taxonomy of under-specification categories via an iterative review process between two groups of annotators. Under-specifications that lead to ambiguity and vagueness were consistently found across narrative phenotype algorithms developed by all involved eMERGE sites. Discussion & ConclusionOur findings highlight that under-specification is an impediment to the accuracy and efficiency of the implementation of current narrative phenotyping algorithms, and we propose approaches for mitigating these issues and improved methods for disseminating EHR phenotyping algorithms.
Assessment of 5-Year Outcomes of Life Satisfaction in Acute Respiratory Distress Syndrome Survivors After Rehabilitation Programs: A Prospective, Multicenter, Randomized Controlled Trial
Authors: Rahimi-Bashar Farshid , Salesi Mahmood , Gohari-Moghadam Keivan , Pourhoseingholi Mohamad Amin , Vahedian_Azimi Amir
Published: August 2021

The use of rehabilitation program for survivors of Acute Respiratory Distress Syndrome (ARDS) could be one of the important and fundamental steps to improve the pulmonary function and health related quality of life (HRQoL) of patients. This study was carried out to evaluate the effect of two rehabilitation techniques (Family-Based Empowerment Model (FECM)/Continuing Care Model (CCM), or both of them) on pulmonary function and HRQoL in ARDS survivor. From December 2009 to October 2014, ARDS survivors from mixed medical-surgical ICUs at four academic teaching hospitals in Tehran, Iran, randomly assigned to one of three intervention groups (A, B or C) or a control group (D). Pre- and post-interventions, pulmonary functions and HRQoL status of patients in all groups were collected 48 times through clinical measurements and various questionnaires during 5 years of follow-up. Significantly improvement was seen in the intervention groups compared to the control group, and the greatest benefit was observed in patients that received mixed of FCEM and CCM rehabilitation techniques. Co-administration of FCEM and CCM can improve pulmonary function as well as the life satisfaction of ARDS survivors. As a result, the execution of the empowerment model by nurses is recommended for ARDS survivors and the participation of their families at the same time. Trial registration: NCT02787720 (ClinicalTrial.gov, 01/06/2016).
Nanoliposome-encapsulated Phenolic Rich Fraction From Alcea Rosea as a Dietary Phytobiotic in Mice Challenged by Escherichia Coli
Authors: Hassirian Niloofar , Karimi Ehsan , Oskoueian Ehsan
Published: August 2021

Background: This research was performed to evaluate the antibacterial and health-promoting potentials of the nanoliposome-encapsulated phenolic rich fraction (PRF) from Alcea rosea leaves as a dietary phytobiotic in mice challenged by enteropathogenic Escherichia coli (E. coil; O157: H7). Results: The overall results demonstrated that the nanoliposome-loaded PRF contained gallic acid, salicylic acid, pyrogallol, cinnamic acid, catechin, naringin, ferulic acid. The E. coil challenge in mice impaired the weight gain, food intake, liver enzymes, lipid peroxidation, morphometric characteristics of the ileum, up-regulated the inflammatory genes (COX2, iNOS), down-regulated the antioxidant-related genes (SOD and GPx) and increased the population of E. coil in the ileum. The dietary inclusion of nonencapsulated PRF and nanoliposome-encapsulated PRF at the concentration of 10 mg TPC/kg BW/day improved these parameters however the nanoliposome-encapsulated PRF appeared to be more effective as compared to nonencapsulated PRF in improving the health parameters in mice. Conclusion: Consequently, the nanoliposome-encapsulated PRF could play a critical role as a promising phytobiotic against E. coil infection in mice.
Pediatric Kikuchi-Fujimoto Disease Diagnosis by Ultrasound-Guided Needle Biopsy
Authors: Liang Yan , Chen Xing , Pan Min , Guo Chunyan , Liu Fengqin , Yang Juan , Ding Ning
Published: August 2021

Background

Kikuchi-Fujimoto disease (KFD) is a rare form of non-malignant and self-limited disease. It is quite susceptible to be misdiagnosed because of a lack of diagnostic guidelines. Lymph node biopsy has shown promising results to confirm KFD pathology.
Methods

This is a retrospective study of patients younger than 18 years old diagnosed with KFD between May 2016 and May 2020 in Shandong Provincial Hospital. Electronic medical records and pathological data were thoroughly reviewed. Ultrasound-guided core needle biopsy (US-CNB) method was performed in all 20 patients.
Results

A total of 20 pediatric patients were recruited to the study. There were 14 boys and 6 girls (boy:girl = 2.3:1) with a median age of 9.1 ± 3.5 years. Fever and lymphadenopathy were the most frequent complaints. The duration of fever ranged from 6 days to 70 days, with a median of 24.2 days. Leukopenia (45.0%) was more predominant than leukocytosis (10.0%) in this cohort. Laboratory findings showed elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in 13 (13/20, 65.0%), 5 (5/20, 25.0%) and 17 patients (17/20, 85.0%), respectively. Past episodes of EBV infections in 16 patients (16/18, 88.9%) were confirmed by positive EB-specific viral capsid antigen (EB-VCA) and nuclear antigen (EBNA)-specific IgG antibody tests. Elevated IgE levels were also detected in 9 patients (9/16, 56.3%). The sizes of lymph node swelling ranged from 15–34 mm in long diameter with a median of 23.2 mm. The biopsy sites were mostly selected in the left cervical lymph node (10/20, 50.0%). The histopathological subtype analysis revealed proliferative type (4/20, 20.0%), necrotizing type (13/20, 65.0%), and xanthomatous type (3/20, 15%) of lymphadenopathy. Immunohistochemical staining showed that the infiltrated histiocytes were positive for CD163 (7/20,35.0%), CD68 (15/20, 75.0%), CD123 (6/15, 40.0%) and myeloperoxidase (14/20,70.0%). Corticosteroid therapy remained effective. Patients were followed up for 1 to 4.5 years. All patients had a good prognosis. Recurrence occurred in 3 patients (3/20, 15.0%).
Conclusion

Diagnosis of KFD depends on pathological and immunohistochemical examinations. US-CNB can serve as a primary pathological diagnostic method for children and young adult patients.
Outcomes of Stroke Patients Undergoing Thrombolysis in Sri Lanka; an Observational Prospective Study From a Low-middle Income Country
Authors: Herath HMMTB , Rodrigo Chaturaka , Alahakoon AMBD , Ambawatte Sathyajith Buddhika , Senanayake Sunethra , Senanayake Bimsara , Fernando Arjuna
Published: August 2021

BackgroundStroke related deaths are relatively higher in low- and middle-income countries where only a fraction of eligible patients undergo thrombolysis. There is also limited evidence on post-thrombolysis outcomes of patients from Asian countries in these income bands. MethodsThis is a single center prospective observational study of a patient cohort with acute ischaemic stroke, undergoing thrombolysis with alteplase (low and standard dose), over a 24-month period in 2019/2020. Demographic, clinical (including scoring systems for functional impairment) and imaging data of all patients were recorded prior to thrombolysis, within 24-hours post-thrombolysis and at 3-months follow up. Incidence of symptomatic intracranial haemorrhages and all-cause mortality by 3 months was also recorded.ResultsEighty-nine patients (males – 61, 69%, mean age: 60 years ± 12.18) were recruited. Time from symptom onset to reperfusion was 174 minutes ± 56.50. Ten (11%) patients died and 19 (21%) developed symptomatic intracranial haemorrhages (sICH) by 3 months. Functional independence at 3 months (measured by Barthel index, National Institutes of Health Stroke Score – NIHSS, or modified Rankin scale - mRS) was independently associated with NIHSS on admission (p<0.05). Thrombolysis with low dose alteplase was associated with better NIHSS or mRS scores (p<0.05) at 3 months compared to standard dose.ConclusionsOn admission NIHSS is predictive of functional independence at 3 months and reducing the time from symptom onset to thrombolysis, may further improve outcomes. The preliminary observations on low dose alteplase efficacy must be confirmed by a randomized controlled trial in the local population.
Exploiting Generative Self-Supervised Learning For The Assessment of Biological Images With Lack of Annotations: A COVID-19 Case-Study
Authors: Mascolini Alessio , Cardamone Dario , Ponzio Francesco , Cataldo Santa Di , Ficarra Elisa
Published: August 2021

Computer-aided analysis of biological images typically requires extensive training on large-scale annotated datasets, which is not viable in many situations. In this paper, we present GAN-DL, a Discriminator Learner based on the StyleGAN2 architecture, which we employ for self-supervised image representation learning in the case of fluorescent biological images. We show that Wasserstein Generative Adversarial Networks combined with linear Support Vector Machines enable high-throughput compound screening based on raw images. We demonstrate this by classifying active and inactive compounds tested for the inhibition of SARS-CoV-2 infection in VERO and HRCE cell lines. In contrast to previous methods, our deep learning-based approach does not require any annotation besides the one that is normally collected during the sample preparation process. We test our technique on the RxRx19a Sars-CoV-2 image collection. The dataset consists of fluorescent images that were generated to assess the ability of regulatory-approved or late-stage clinical trials compounds to modulate the in vitro infection from SARS-CoV-2 in both VERO and HRCE cell lines. We show that our technique can be exploited not only for classification tasks but also to effectively derive a dose-response curve for the tested treatments, in a self-supervised manner. Lastly, we demonstrate its generalization capabilities by successfully addressing a zero-shot learning task, consisting of the categorization of four different cell types of the RxRx1 fluorescent images collection.
Effects of a 1-mm Difference in Bearing Thickness on Intraoperative Bearing Movement and Kinematics in Oxford Unicompartmental Knee Arthroplasty
Authors: Kawaguchi Kohei , Inui Hiroshi , Taketomi Shuji , Yamagami Ryota , Kono Kenichi , Sameshima Shin , Kage Tomofumi , Tanaka Sakae
Published: August 2021

Background: The choice of mobile bearing (MB) thickness is essential for obtaining successful results after mobile-bearing Oxford unicompartmental knee arthroplasty (UKA). This study aimed to investigate the effects of a 1-mm difference in bearing thickness on intraoperative MB movement and intraoperative knee kinematics in Oxford UKAs.Methods: We prospectively investigated the intraoperative MB movement and knee kinematics of 25 patients who underwent Oxford UKAs when surgeons didn’t know which bearing thickness to choose with 1-mm difference. A trial tibial component that was scaled every 2 mm was used to measure the intraoperative MB movement, and the tibial internal rotation relative to the femur and the knee varus angle was simultaneously evaluated using the navigation system as the knee kinematics. We separately evaluated sets of two MB thicknesses with 1-mm differences, and we compared the intraoperative parameters at maximum extension; 30º, 45º, 60º, and 90º flexion; and maximum flexion between the thicker MB (thick group) and the thinner MB (thin group).Results: The MB in the thin group was located significantly posteriorly at 90º flexion compared with that in the thick group; however, there were no differences at the other flexion angles. There was significantly less tibial internal rotation in the thin group at 90º flexion than that in the thick group; however, there were no differences at the other flexion angles. The knee varus angles in the thick group were significantly smaller than those in the thin group by approximately one degree at all angles other than at 30º and 45º flexion. Conclusion: The thicker MB could bring the less posterior MB movement and the more tibial internal rotation at 90º flexion, additionally the valgus correction angle in the thicker MB should be paid attention. These results could help surgeons to decide the thickness of MBs when they wonder the thickness of MB.
Understanding “Alexandrian” extinctions using genomic DNA from fluid-preserved museum specimens of Desmognathus salamanders
Authors: Pyron Alex , Beamer David A. , Holzheuser Chace R. , Lemmon Emily Moriarty , Lemmon Alan R. , Wynn Addison H. , O’Connell Kyle A.
Published: August 2021

Species that went extinct prior to the genomic era are typically out-of-reach for modern phylogenetic studies. We refer to these as “Alexandrian” extinctions, after the lost library of the ancient world. This is particularly limiting for conservation studies, as genetic data for such taxa may be key to understand extinction threats and risks, the causes of declines, and inform management of related, extant populations. Fortunately, continual advances in biochemistry and DNA sequencing offer increasing ability to recover DNA from historical museum specimens, including fluid-preserved natural history collections. Here, we report on success in recovering nuclear and mitochondrial data from the apparently-extinct subspecies Desmognathus fuscus carri (Neill 1951), a plethodontid salamander from spring runs in central Florida. The two specimens are 50 years old and were likely preserved in unbuffered formalin, but application of a recently derived extraction procedure yielded usable DNA and partially successful Anchored Hybrid Enrichment sequencing. These data suggest that the populations of D. f. carri from peninsular Florida are conspecific with the D. auriculatus A lineage as suggested by previous authors, but likely represented an ecogeographically distinct genetic segment that has now been lost. Genetic data from this Alexandrian extinction thus confirm the geographic extent of population declines and extirpations as well as their ecological context, suggesting a possibly disproportionate loss from sandy-bottom clearwater streams compared to blackwater swamps. Success of these methods bodes well for large-scale application to fluid-preserved natural history specimens from relevant historical populations, but the possibility of significant DNA damage and related sequencing errors in additional hurdle to overcome.
Knowledge, Attitudes, and Practice Related to COVID-19 Among Healthcare Workers in the United Arab Emirates: A Cross-sectional Study.
Authors: Marzouqi Amina M. Al , Otim Michael E. , Hijazi Heba H. , Kehail Leena S. , Kamal Ramsha A.
Published: August 2021

Objectives: The coronavirus disease-2019 (COVID-19) outbreak is a global health pandemic that continues to have an impact on many aspects of everyday life. This study investigates the Knowledge, Attitudes, and Practices (KAP) related to COVID-19 among healthcare workers in the United Arab Emirates (UAE). Methods: This study uses a cross-sectional study design. The original data were collected using an online questionnaire distributed via a Google Forms link. Participants were healthcare workers currently working in the UAE healthcare facilities and recruited using snowball sampling. The questionnaire collected information on demographic variables and COVID-19-related knowledge, attitudes, and practice.Results: In total, the sample of 107 healthcare workers completed the survey. About 92% of the participants worked in public institutions, 87% were from Dubai, and 673% were female. The majority were aged 31–40 years (34.6%), and 43% were radiographers. 66.4% held bachelor’s degrees and Indian nationalities were (28%) and the Philippinos were (28%). Most (90.7%) participants knew the absence of fever did not mean that the virus could not transmit from an infected person, and 84.1% agreed that wearing general medical masks prevented one from contracting COVID-19. However, only 36.4% strongly believed that wearing a well-fitting face mask was effective. In addition, only 15.9% reported confidently managing patients with symptoms of COVID-19, and 54.2% reported that they were afraid of contracting the virus from patients. Almost half of the participants avoided patients who had symptoms of COVID-19. Conclusion: Overall, healthcare workers’ COVID-19-related knowledge, attitudes, and practices for healthcare workers in UAE healthcare facilities was very high. However, we found gaps in awareness regarding the spread of the pandemic. Our study recommends that providing healthcare workers with education programs and counseling services would help increase their confidence in treating patients with COVID-19.
Recipient And Donor PTX3 rs2305619 Polymorphisms Increase The Susceptibility To Invasive Fungal Disease Following Haploidentical Stem Cell Transplantation: A Prospective Study
Authors: Zhao Chen , Zhao Xiao-Su , Xu Lan-Ping , Zhang Xiao-Hui , Huang Xiao-Jun , Sun Yu-Qian
Published: August 2021

Background Invasive fungal disease (IFD) is a severe complication after haploidentical stem cell transplantation (haplo-HSCT) and has a poor prognosis. It has been shown that genetic polymorphism may be one possible reason for the increased risk of IFD. This study aimed to assess the role of genetic polymorphisms in the level of susceptibility to IFD in after haplo-HSCT. Methods In this study, we prospectively enrolled 251 patients who received haplo-HSCT at the Peking University Institute of Hematology from to 2016-2018. Forty-three single nucleotide polymorphisms (SNPs) of the genomic DNA were genotyped in blood samples from both recipient and donor. Results Twenty-two patients (8.8%) were diagnosed with proven or probable IFD. The independent risk factors for IFD were grades 3-4 acute graft-versus-host disease, cytomegalovirus reactivation, and recipient and donor rs2305619 (PTX3) (P<0.05) in multivariate analysis. Meanwhile, we combined the variables to develop the IFD risk scoring system and stratified patients into low- (0), intermediate- (1-2), and high-risk (3-4) groups. The 30-day and 100-day cumulative incidence of IFD in the low-, intermediate-, and high-risk groups were 0.1%, 2.4%, 10.2% and 4.5%, 4.1%, 20.3%, respectively (P=0.015). Conclusions PTX3 rs2305619 polymorphisms increase the susceptibility of IFD after haplo-HSCT in the Chinese Han population, and the IFD scoring system could be considered as a new standard for risk stratification for IFD after HSCT.
Calcaneal Tuberosity Fracture (Beak Fracture) Fixation Using a Pre-contoured “L-form” Hook Plate: A Retrospective Study
Authors: Zhang Qiang , Zhu Chan , Wu Zongde
Published: August 2021

Background: The treatment of calcaneal tuberosity fracture (beak fracture) is very tricky. Patients’ ankle function may be badly affected by skin flap necrosis and internal fixation failure. This study presented a simple, and safe internal fixation technique which is to fix the fracture fragment with a pre-contoured “L-form” hook plate.Methods: A retrospective study was done to analyze patients with calcaneal tuberosity fracture who were treated with pre-contoured “L-form” hook plate fixation from January 2015 to February 2020. When the patients could complete single-legged heel raise tests, and when they achieved clinical healing criteria were reviewed. Functional assessment was performed according to the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot (AOFAS-AH) scores and the Visual Analogue Scale (VAS) was recommended for assessment of pain intensity (PI).Results: There were a total of 15 patients of calcaneal tuberosity fracture (beak fracture) treated with the pre-contoured “L-form” hook plate fixation technique, among which eight patients were female and the others were male, with the age ranging from 35 to 69 years (average of 55.3±9.0 years). And the mean duration of follow-up was 22.53±5.78 months (range: 12 to 36 months). 11 cases underwent emergency surgery. After the operation, there were no complications such as wound dehiscence, poor wound healing, infections, or plate exposure, no sural nerve injuries or venous thromboembolic events. Also, there was no loss of reduction or fixation failure in the follow-up. All 15 cases achieved clinical healing at 8-13 weeks (average 10.5±1.4 weeks) postoperatively. They were able to perform the test on their affected leg after 3.7±0.7 months (3-5 months) on average. The preoperative VAS and AOFAS-AH scores were 5.7±0.6 and 24.0±9.9 respectively, while the postoperative VAS and AOFAS-AH scores at the last follow-up were 1.3±0.5 and 93.8±5.2 (p<0.001).Conclusion: Emergency open reduction and internal fixation should be provided as soon as possible. For patients with Beavis type II beak fractures, the pre-contoured “L-form” hook plate fixation technique helps them restore normal ankle function. This simple, safe, and strong internal fixation technique can be one of the treatment options for avulsion fractures of the calcaneal tuberosity.
General and Illness-specific Predictors of Adaptation to Chronic Illnesses: Cognitive Appraisals and Illness-related Beliefs
Authors: Pankowski Daniel , Wytrychiewicz-Pankowska Kinga , Janowski Konrad , Pisula Ewa , Fal Andrzej Mariusz
Published: August 2021

Background
The literature indicates that cognitive appraisals and illness-related beliefs are the key cognitive factors that affect the outcomes of psychological adaptation to chronic illnesses. The main aim of the study was to identify which cognitive appraisals and illness-related beliefs are the best predictors of adaptation to living with chronic illnesses as well as which of these predictors are universal and which are illness-specific.
Methods
This study analyzed data collected online from 505 participants who reported diagnoses of rheumatoid arthritis, asthma, hypothyroidism, diabetes, and hypertension.
Results
Adaptation indicators (i.e., depressive symptoms and level of acceptance of living with the disease) differed significantly across samples with different medical diagnoses. Additionally, illness-related cognitive appraisals but not illness-related beliefs made a statistically significant specific contribution to explaining the variance in adaptation indices.
Conclusions
The predictors of adaptation to living with the disease differ between the diagnoses and the adjustment indicators. The results can contribute to a better matching of therapeutic interventions as well as social campaigns aimed at the ill people.
Dnmt3aa But Not Dnmt3ab Is Required for Maintenance of Gametogenesis in Nile Tilapia
Authors: Wang Feilong , Qin Zuliang , Li Zhiqiang , Yang Shuangyi , Gao Tian , Sun Lina , Wang Deshou
Published: August 2021

Background: Dnmt3a , a de novo methylatransferase, is essential for both male and female germ line DNA methylation. Only one Dnmt3a is identified in mammals, and homozygous mutation of Dnmt3a is lethal, while two Dnmt3a , dnmt3aa and dnmt3ab , are identified in teleosts due to the third round of genome duplication, and homozygous mutation of dnmt3aa and dnmt3ab is viable in zebrafish. Dnmt3aa and dnmt3ab were demonstrated to have essential and non-overlapped functions on modulating behavioral control, however, their function in gonadal development is unclear in fish. Results: In this study, the expression patterns of dnmt3aa and dnmt3ab in developing gonads of Nile tilapia was analyzed by quantitative real time PCR and fluorescence in situ hybridization. Both dnmt3aa and dnmt3ab displayed sexually dimorphic expression in developing gonads. Dnmt3aa was widely expressed in gonadal germ cells and somatic cells, highly expressed in oogonia, phase I and II oocytes and granulosa cells in ovaries and spermatogonia and spermatocytes in testes, while dnmt3ab was mainly expressed in ovarian granulosa cells and testicular spermatocytes. Mutation of dnmt3aa and dnmt3ab was achieved by CRISPR/Cas9 in tilapia. Lower GSI (Gonadosomatic index), increased apoptosis of oocytes and spermatocytes and significantly reduced sperm quality were observed in dnmt3aa −/− mutants, while no obvious phenotype was observed in dnmt3ab −/− mutants. Consistently, the expression of apoptotic genes was significantly increased in dnmt3aa −/− mutants. In addition, dnmt3aa and dnmt3ab were found to have certain compensatory effects in the gonads. The global DNA methylation level in ovaries and testes of dnmt3aa −/− mutants was decreased significantly, compared with that of dnmt3ab −/− mutants and WT. Conclusions: Taken together, our results suggest that dnmt3aa , not dnmt3ab , plays important roles in maintaining gametogenesis in teleost. Our results enrich the understanding of the function of DNA methyltransferases in gonads of non-mammalian vertebrates.
Knowledge, Attitude and Practices (Kap) on Diabetic Foot Care Among Patients With Diabetes in District Bahawalpur, Pakistan
Authors: Shamim Tahira , Sumreen Laila , Asif Hafiz Muhammad
Published: August 2021

Diabetes mellitus is a chronic multifactorial metabolic illness that is characterized by numerous chronic complications. Diabetes affects almost every system of the body. Among these diabetic foot is one of the major complications of diabetes mellitus. Its main objective was to investigate the knowledge, attitude and foot care practices in diabetic patients suffering from diabetic foot lesions. An institutional-based cross-sectional study was designed to be conducted at Civil Hospital, Bahawalpur, Pakistan. Total 150 diabetic patients were selected by systematic random sampling method. Ratio of Type II diabetes was 91.3% whereas 23.3% patients were having family history of diabetes. 44.35% patients were having some knowledge about diabetes related complications whereas 45.44% patients were having a positive attitude towards control and prevention of diabetes related complications. Good foot care and footwear practices were being carried out by just 33.62% of the patients. Education regarding reducing increased body weight, knowledge about foot care practices, early detection and management of peripheral neuropathy and strict glycemic control could be very helpful in decreasing the diabetic foot complication.
In Vivo Antitumor Efficacy of 17-AAG Loaded PMMA in a Multiple Myeloma Patient-Derived Xenograft Mouse Model
Authors: Shi Xiangjun , Wei Yanzhe , Yao Xingchen , Du Boran , Wu Xiaoguang , Kong Xiangyu , Du Xinru
Published: August 2021

Multiple myeloma (MM) is a monoclonal malignancy characterized by abnormal proliferation of plasma cells. Its main clinical symptoms are osteolytic damage, severe bone pain, spinal instability, and pathological fracture and are collectively referred to as multiple myeloma bone disease (MMBD). Due to its good biomechanical properties and fast curing, polymethylmethacrylate (PMMA) bone cement is widely used for bone repair after MMBD surgery. However, whether drug-loading PMMA can inhibit tumor growth and angiogenesis has not been reported. Here, we report that 17-AAG-loaded PMMA bone cement inhibits MM growth in vivo and suppresses tumor diffusion to peripheral tissues. 17-AAG-loaded PMMA promotes MM apoptosis by downregulating Bax and active Caspase-3.
Demographic factors affecting the quality of life in patients with knee osteoarthritis
Authors: Lee Tian-Shyug , Liu Hsiang-Chuan , Tsaur Wei-Guang , Lee Shih-Pin
Published: August 2021

Background

Knee osteoarthritis (OA) affects the quality of life (QOL) of elderly people, this study examines the demographic characteristics and QOL of patients with knee OA and identifies demographic characteristics that affect the QOL of these patients.
Methods

In this cross-sectional study, 30 healthy controls and 60 patients with mild-to-moderate bilateral knee OA aged between 55 and 75 years were enrolled. All participants completed a questionnaire containing questions on 10 demographic characteristics and the Medical Outcome Study 36-Item Short-Form Health Survey (SF-36), and their QOL scores in the eight dimensions of the SF-36 were evaluated.
Results

In the OA group, significant correlations were observed between monthly disposable income and physical and mental health components. Monthly disposable income was found to considerably affect the QOL of patients with knee OA.
Conclusion

Monthly disposable income is a crucial factor affecting the QOL of patients with bilateral knee OA. The findings of this study may provide a reference for formulating preventive strategies for healthy individuals and for future confirmatory research.
Trial registration:

This study was approved by the Ethics Committee of Fu Jen Catholic University (FJU-IRB NO: C107179).
Identification of Novel Variants in 8 Families With Meige Syndrome Using Whole-exome Sequencing
Authors: Wang Zhi-Bin , Qu Jian , Zhang Ying , Shu Yi , Zhou Hong-Hao , Mao Xiao-Yuan , Liu Zhao-Qian
Published: August 2021

Background: Meige syndrome is a type of cranial dystonia characterized by blepharospasm and infraorbital dystonia and may be related to movement disorders of the mandibular and facial muscles, mouth, jaw, tongue, pharynx and cervical muscles. However, the etiopathogenesis of this disease condition remains unknown. Our present study aimed to find clues to the pathogenic factors of Meige Syndrome using whole-exome sequencing. Results: The study included 13 clinically diagnosed patients with Meige syndrome, a subtype of facial dystonia, from eight families (marked as Family 1 to Family 8) and two matched controls in two of the eight families. The genomic DNA was extracted from peripheral blood for whole-exome sequencing (WES). Quality control filtering, genome repeat filtering, genomAD/1000g filtering, exonic & splicing site filtering, hazard filtering, Varsome (ACMG) filtering were used to find the genes predicted to be damaging in Meige Syndrome. Among 582,715 SNP or indel variants. One variant in PALM3 (rs374267554, NC_000019.9:g.14167249G>A) passed our analysis and detection criteria. We verified the variant site using Sanger sequencing in another 48 patients. Structural analysis of the PALM3 variant predicted its potential effects on pathogenicity.Conclusions: Our findings contribute to a better understanding of the impact of the PALM3 variant on the pathogenicity of Meige Syndrome. Sequencing PALM3 in larger Meige Syndrome cohorts and functional studies will need to be performed to further elucidate the association between PALM3 and the disease.
Acupoint Nanocomposite Hydrogel for Simulation of Acupuncture and Targeted Delivery of Triptolide Against Rheumatoid Arthritis
Authors: Ren Shujing , Liu Heng , Wang Xitong , Bi Jiquan , Lu Shengfeng , Zhu Chenqi , Li Huizhu , Chen Rui , Chen Zhipeng
Published: August 2021

BackgroundAttenuating the inﬂammatory response and relieving pain are two therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with effective targeting ability and other complementary strategies are on urgent need to be explored. To achieve this goal, an acupoint drug delivery system that can simulate acupuncture in relieving pain and targeted deliver anti-inflammatory drugs is constructed, which can co-deliver 2-chloro-N (6)-cyclopentyl adenosine (CCPA) and triptolide (TP). ResultsWe have successfully demonstrated that the nanocomposite hydrogel composed of TP-Human serum album nanoparticles (HSA NPs) and CCPA could effectively treat the RA. We found that this combination therapy can enhance analgesic effects while the mechanical pain threshold was 5.2 times compared with model group, and the thermal pain threshold was 1.4 times. Acupoint nanocomposite hydrogel could not only improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48h), but also cooperate with nanomedicine to exert synergetic improvement of inflammation and reduction of systemic toxicity. Furthermore, it can regulate inflammatory factors and restore the balance of Th17/Treg cell which provide a novel effective treatment strategy for RA.ConclusionThis novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.
Cyanidin-3-O-glucoside Inhibits the β-catenin/MGMT Pathway by Upregulating miR-214-5p to Reverse Chemotherapy Resistance in Glioma Cells
Authors: Zhou Yuan , Chen Li , Ding Deping , Li Ziheng , Cheng Li , You Qiuyun , Zhang Shunbo
Published: August 2021

Overcoming resistance to alkylating agents has important clinical significance in glioma. Cyanidin-3-O-glucoside (C3G) has a tumor-suppressive effect on tumor cells. However, whether it plays a role in temozolomide resistance in glioma is still unclear. We construct a TMZ-resistant glioma LN-18/TR cells, observe the effect of C3G on TMZ resistance in these cells, and explore the role of miR-214-5p in chemoresistance.Results show that β-catenin and MGMT were significantly upregulated in LN-18/TR cells. C3G upregulated miR-214-5p and enhanced the cytotoxic effect of temozolomide on LN-18/TR cells. C3G downregulated β-catenin and MGMT. The miR-214-5p mimic downregulated β-catenin and MGMT in LN-18/TR cells, whereas the miR-214-5p inhibitor had the opposite effect. The miR-214-5p inhibitor significantly blocked the cyanidin-3-O-glucoside-induced downregulation of β-catenin and MGMT. C3G or the miR-214-5p mimic enhanced temozolomide-induced apoptosis in LN-18/TR cells, whereas the miR-214-5p inhibitor blocked this effect. Further, C3G or miR-214-5p agomir combined with TMZ could significantly inhibit the growth of LN-18/TR tumors. Our research has discovered the potential signaling mechanism associated with C3G-mediated suppression of TMZ resistance in LN-18/TR cells through miR-214-5p, which can facilitate the treatment of MGMT-induced resistance in glioma cells.
Efficacy of Intense Pulsed Light and Meibomian Gland Expression Treatments in Meibomian Gland Dysfunction: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhou Qi , Liu Chao , Gao Zi-Qing , Li Juan
Published: August 2021

Purpose: This review aimed to evaluate the efficacy and safety of intense pulsed light treatment (IPLT) combined with meibomian gland expression treatments(MGXT) in meibomian gland dysfunction.Methods: We conducted a meta-analysis of randomized controlled trials that compared the efficacy of IPLT and MGXT in the treatment of dry eye disease (DED). The meibomian gland yielding secretion score was the primary outcome, whereas the secondary outcomes included the Meiboscore, tear breakup time in seconds, Standard Patient Evaluation for Eye Dryness and Corneal Fluorescein Staining .Results: This study consisted of 6 trials with 326 patients. Significantly greater improvement was observed in meibomian gland yielding secretion score at 1 month [MD: 13.69 (95% CI, 11.98, 15.40)] and at 3 months [MD: 11.03 (95% CI, 10.27, 11.80)], low meibomian gland yielding secretion score at 1 month [MD: 6.92 (95% CI, 5.49, 8.34)] and at 3 months MD: 6.80 (95% CI, 5.01, 8..59)], up meibomian gland yielding secretion score at 1 month [MD: 6.41 (95% CI, 4.12, 8.70)] and at 3 months [MD: 8.06 (95% CI, 5.70, 10.42)] and tear breakup time at 1 month [MD: 2.38 (95% CI, 1.83, 2.92)] and at 3 months [MD: 1.82 (95% CI, 1.48, 2.19)] in the IPL-MGX group than in the MGX group.Conclusions: IPL-MGX is safer and more efficacious as compared to the MGX alone in the treatment of patients with MGD-related dry eye. We recommend discussing the decision with the ophthalmologist for an appropriate choice.
Identification and Detection of Pathogenic Bacteria From Patients With Hospital Acquired Pneumonia in Southwest of Iran; Evaluation of Biofilm Production and Molecular Typing of Bacterial Isolates
Authors: Mazloomirad Farzad , Hasanzadeh Sajad , Sharifi Asghar , Nikbakht Gordafarin , Roustaei Narges , Khoramrooz Seyed Sajjad
Published: August 2021

BackgroundHospital acquired pneumonia (HAP) HAP is the most second nosocomial infection and the most common infection in the intensive care unit. The aim of the present study was to determine the prevalence of pathogenic bacteria, their biofilm formation and molecular typing in sputum samples from patients with HAP in southwest of Iran.MethodsIn this cross-sectional study, 58 patients with HAP were included in this study. Clinical samples including sputum andendotracheal aspirate collected from each patient under aseptic conditions and were sent to the Microbiology Laboratory.Isolation and detection of bacteria were performed by culture and polymerase chain reaction methods.Biofilm formation was evaluated using by Congo red Agar or microtiter plate assay.A rep- PCR typing method was used for typing of gram-negative bacteria. MRSA isolates were typed using SCCmec typing method. Data were analyzed by SPSS software version 15 and chi-square test.ResultsUsing culture method, bacteria identified in 52 (89.7 %) of patients. Acinetobacter baumannii was the most prevalent (37%) organism and followed by Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. All of the A. baumannii and P. aeruginosa were biofilm producer. 12 cases (80%) of S. aureus isolates were MRSA and 91.6% of MRSA were SCCmec type III. The rep -PCR analysis showed 7 different patterns in 20 A. baumannii, 6 patterns in 13 P. aeruginosa and 4 patterns in 6 E. coli. Most of the A. baumanii isolates were multi drug resistant. Conclusion﻿A. baumanii was more prevalent in VAP, while S. aureus as a major pathogen in N- VAP that maybe related to tendency of A. baumannii to the aquatic environment. Biofilm production ability in bacteria increased antibiotic resistance, development of chronic and persistent infection in HAP. Based on rep- PCR typing method we concluded that bacteria transmitted from patients or health care workers among different wards of hospital. Colistin can be used as a treatment in gram negative MDR isolates.
Intraventricular hemorrhage clot clearance rate as an outcome predictor in patients with aneurysmal subarachnoid hemorrhage: A retrospective study
Authors: Park Hae Gi , Kim Sunghan , Chung Joonho , Jang Chang Ki , Park Keun Young , Lee Jae Whan
Published: August 2021

Background
The development of intraventricular hemorrhage (IVH) in aneurysmal subarachnoid hemorrhage (aSAH) is linked with higher mortality and poor neurological recovery. Previous studies have investigated the effect of the amount and distribution of the initial IVH on the prognosis of aSAH. However, no studies have assessed the relationship between the changes in IVH over time and the prognosis of aSAH. The aim of this study was to analyze the effect of the clearance rate of IVH, which can be represented by the IVH clot clearance rate (CCR), on the outcomes of aSAH.
Methods
The IVH CCR was calculated based on the difference between the initial and follow-up modified Graeb scores (mGS), which were assessed by initial and 7-day follow-up brain computed tomography, respectively. Poor functional outcome was defined as a modified Rankin Scale score of 3–6. Univariate and multivariable analyses were performed to assess the relationships between IVH CCR and other risk factors and the prognosis of patients. Receiver operating characteristic curve analysis was performed to identify cut-off values of IVH CCR for predicting poor functional outcome.
Results
In total, 196 consecutive patients were diagnosed with aSAH between January 2014 and March 2018. According to the inclusion and exclusion criteria, 67 patients were finally included in the study. The univariate analysis revealed that a lower IVH CCR (p < 0.001), higher initial mGS (p < 0.001), older age (p < 0.001), higher initial Hunt and Hess grade (p < 0.001), presence of delayed infarction (p = 0.03), and presence of shunt-dependent hydrocephalus (p = 0.004) were significantly related to poor functional outcome. The multivariable analysis revealed that IVH CCR (odds ratio [OR] 0.941; p = 0.029), initial mGS (OR 1.632; p = 0.043), age (OR 1.561; p = 0.007), initial Hunt and Hess grade (OR 227.296; p = 0.030), and delayed infarction (OR 5310.632; p = 0.023) were independent predictors of poor functional outcome. Optimal cut-off values of IVH CCR and mGS for poor outcome were 36.27%, and 13.5, respectively (all p < 0.001).
Conclusions
The IVH CCR might have an important predictive value on poor functional outcome in patients with aSAH and IVH, along with initial mGS, age, initial Hunt and Hess grade, and delayed infarction.
Effect of Agro Waste Saline Treated Cellulose Nanofiller on Mechanical, Visco Elastic and Thermal Behaviour of Epoxy Nanocomposites
Authors: Rajan S. Thanga Kasi , J Nagarajan K , BALAJI A N , Basha K. Sathick
Published: August 2021

The authors have requested that this preprint be removed from Research Square.
A New Factor Predicting Excessive Femoral Anteversion in Patients with Recurrent Patellar Dislocation
Authors: Dong Conglei , Hao Kuo , Zhao Chao , Wang Fei
Published: August 2021

Purpose Determining a new imaging method on full-leg standing lower limb radiographs to predict excessive femoral anteversion in patients with patellar dislocation.Methods This study included 119 patients with patellar dislocation from January 2014 to January 2021. The femoral anteversion and tibial torsion were measured by CT scanning. The medial condylar angle was measured by the full-leg standing lower limb radiographs. Pearson correlation coefficient was used to evaluate the correlation between rotation parameters and medial condylar angle.Results Included patients were divided into DFO group and control group according to whether they received derotational femoral osteotomy (DFO) operation or not. There were significant statistical differences in femoral anteversion, tibial torsion and medial condylar angle between DFO group and control group (P < 0.05). This showed that there was a smaller medial condylar angle in patients undergoing DFO operation. Correlation analysis showed that the values of femoral anteversion were significantly correlated with medial condylar angle (r= -0.719, P < 0.001). Conclusion This study showed that medial condylar angle had a negative correlation with excessive femoral anteversion on the full-leg standing lower limb radiographs. The medial condylar angle can be a good predictor of femoral anteversion and can be used to guide the performance of DFO to treat patellar dislocation in clinical practice.