bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-215-5p Promotes Proliferation, Invasion, And Inhibits Apoptosis In Liposarcoma Cells By Targeting MDM2-P53 Signaling Pathways
Authors: Song Zhengnan , Bai Jingping , Jiang Renbing , Wu Junshen , Yang Wenpeng
Published: February 2022

Liposarcoma (LPS) is one of the most common soft tissue malignancies in adults, and LPS is characterized by dysregulation of multiple signaling pathways including MDM2 amplification.MicroRNAs (miRNAs) are involved in tumor progression by regulating gene expression through incomplete complementary pairing with the 3 'untranslated region of mRNAs.In this study, we showed that miR-215-5p could target and promote MDM2 expression, and promote LPS cell proliferation, invasion, and inhibit apoptosis.QRT-PCR showed that the expression of MDM2 was significantly higher when miR-215-5p was overexpressed (2.85 ± 0.48), and dual-luciferase reporter gene showed that the fluorescence intensity ratio decreased in the overexpression group (0.72 ± 0.02), and cell phenotype assay revealed that the proliferation activity increased in the overexpression group, with cell proliferation rates of 104 ± 0.04 (%), 116 ± 0.01 (%), and 120 ± 0.01 (%), increased apoptosis rate (1.47 ± 0.33 (%)), increased colony formation rate (85.10 ± 2.85 (%)), increased cell healing area ratio (30.08 ± 2.00 (%)), and increased cell invasion number (138 ± 3.60) at 24 h, 48 h, and 72 h, respectively; FISH revealed that miR-215-5p colocalized with MDM2, and MDM2 expression increased in the overexpression group, WB suggested that Bax expression decreased, PCNA, Bcl-2, and MDM2 expression increased, and P53 and p21 expression decreased in the overexpression group;These data suggest that miR-215-5p can promote LPS progression through the MDM2-P53 signaling pathway, and targeting miR-215-5p may be a novel therapeutic strategy for the treatment of LPS.
Inequalities in mortality associated with housing conditions in Belgium between 1991 and 2020
Authors: OTAVOVA Martina , FAES Christel , BOULAND Catherine , DE CLERCQ Eva , VANDENINDEN Bram , EGGERICKX Thierry , SANDERSON Jean-Paul , DEVLEESSCHAUWER Brecht , MASQUELIER Bruno
Published: February 2022

BackgroundPoor housing conditions have been associated with increased mortality. Our main objective is to investigate association between housing inequality and increased mortality and to estimate the number of deaths that could be prevented if the population of Belgium faced the mortality rates of the least deprived housing deprivation decile.MethodsWe utilized individual-level mortality data extracted from the National Register in Belgium and relative to deaths that occurred between Jan 1, 1991 and Dec 31, 2020. Spatial and time-specific housing deprivation indices (1991, 2001, and 2011) were created at the level of the smallest geographical unit in Belgium, assigning these units into deciles from the most to least deprived. We calculated mortality attributable to housing inequality as the difference between the observed and expected deaths by applying mortality of the least deprived decile to other deciles. We also used standard life table calculations to estimate the potential years of life lost due housing inequality. Results18.5% (95% CI 17.7-19.3) of all deaths between 1991 and 2020 were attributable to housing inequality, corresponding to 584,875 deaths. Over time, life expectancy at birth increased for the most and least deprived deciles by about 3.5 years. The gap in life expectancy between the two deciles remained high, on average 4.6 years. Life expectancy in Belgium is reduced by approximately 3 years lost due to housing inequality. Conclusions Thousands of deaths in Belgium could be avoided if housing inequality was reduced. Hotspots of housing inequalities need to be localized and targeted with tailored public actions.
Adjoint-based Limit Cycle Oscillation Instability Sensitivity and Suppression
Authors: He Sicheng , Jonsson Eirikur , Martins Joaquim R. R. A.
Published: February 2022

Limit cycle oscillations (LCO) can be supercritical or subcritical. The supercritical response is benign, while the subcritical response can be destructive. It is desirable to avoid subcritical responses by enforcing LCO stability through design optimization constraints. However, there is a need for a computational approach that can model this instability and can handle hundreds or thousands of design variables. We propose a simple metric to determine the LCO stability using a fitted bifurcation diagram slope to address this need. We develop an adjoint-based formula to compute the stability derivative efficiently with respect to many design variables. To evaluate the stability derivative, we only need to compute the time-spectral adjoint equation three times no matter the number of design variables in the optimization problem. The proposed adjoint method is verified with finite differences, achieving a five-digit agreement between the two approaches. We consider a stability-constrained LCO parameter optimization problem and demonstrate that the optimizer can suppress the instability. Finally, we consider a more realistic LCO speed and stability-constrained mass minimization problem for an airfoil. The proposed method can be extended to optimization problems with a PDE-based model, opening the door to applications where high-fidelity models are needed.
Prevalence, Incidence and Clinical Outcomes of Epicardial Coronary Artery Disease Among Transthyretin Amyloidosis Cardiomyopathy Patients
Authors: Hassan Rana , Miller Robert J. H. , Howlett Jonathan G. , White James A. , Fine Nowell M.
Published: February 2022

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients are often older and may be at risk for obstructive epicardial coronary artery disease (oeCAD). While ATTR-CM may cause small vessel coronary disease, the prevalence and clinical significance of oeCAD is not well described.Methods and Results: The prevalence and incidence of oeCAD and its association with all-cause mortality and hospitalization among 133 ATTR-CM patients with ≥1-year follow-up was evaluated. The mean age was 78±9 years, 119 (89%) were male, 116 (87%) had wild-type and 17 (13%) had hereditary subtypes. Seventy-two (54%) patients underwent oeCAD investigations, with 30 (23%) receiving a positive diagnosis. Among these patients, 23 (77%) were diagnosed prior to ATTR-CM diagnosis, 6 (20%) at the time of ATTR-CM diagnosis, and 1 (3%) after ATTR-CM diagnosis. Baseline characteristics between patients with and without oeCAD were similar. Among patients with oeCAD, only 2 (7%) required additional investigations, intervention or hospitalization after ATTR-CM diagnosis. After a median follow-up of 27 months there were 37 (28%) deaths occurring in 5 patients with oeCAD (17%) and 32 patients without oeCAD (31%). Fifty-six (42%) patients required hospitalization, including 10 patients with oeCAD (33%) and 46 patients without oeCAD (45%). There was no significant difference in the rates of death or hospitalization among ATTR-CM patients with and without oeCAD, and oeCAD was not significantly associated with either outcome by regression analysis.Conclusions: While oeCAD is prevalent in ATTR-CM patients, this diagnosis is frequently known at time of ATTR-CM diagnosis and is not associated with subsequent death or hospitalization.
Cough presentation and cough-related healthcare utilization in tertiary care: analysis of routinely collected academic institutional database
Authors: An Jin , Lee Ji-Hyang , Won Ha-Kyeong , Kang Yewon , Kwon Hyouk-Soo , Lee Jae-Seung , Lee Sei Won , Kim Tae-Bum , Oh Yeon-Mok , Cho You Sook , Lee Sang-Do , Moon Hee-Bom , Song Woo-Jung
Published: February 2022

Background: Most knowledge on cough epidemiology was obtained from questionnaire surveys of general populations or small focused studies of patients visiting specialist clinics. Routinely collected data (RCD) from electronic health records (EHR) are useful sources for studying disease epidemiology, but their use was limited in chronic cough. The present study aimed to investigate cough presentation and cough-related healthcare utilization, using the RCD of patients referred with cough.Methods: This is a retrospective cohort study utilizing an academic institutional EHR database. Cough cases were identified using the text search for the chief complaint indicating “cough” in the structured case report form. Using the information, we constructed a retrospective cohort of patients with subacute or chronic cough. Baseline demographics, medical history, concomitant symptoms, and diagnostic tests were analyzed. Healthcare utilization during 1 year since the baseline visit was assessed for drug prescriptions, additional diagnostic tests, outpatient visits, and hospitalization.Results: Among a total of 28,312 new referrals, cough was the chief complaint in 13,223 cases (46.7%). Based on the selection criteria, 3,810 subacute and 7,150 chronic cough patients were finally included. A common demographic profile was middle-aged woman (mean age 52.1 years, and female 63%). Patients had a median three accompanying symptoms (interquartile range: 2–5). Abnormal throat sensation (globus, tickling, or dryness) was the most common (about 70%), but symptoms suggesting nasal diseases, asthma, or acid reflux were also frequent. During the first year, both of subacute and chronic cough patients required multiple drug prescriptions, diagnostic tests, and outpatient visits, but the degree of utilization was higher in patients with chronic cough. Codeine-containing drugs were given to 21.5% of patients with chronic cough, and oral antibiotics to 23.7% and oral steroids to 9.9%.Conclusions: Cough is a common chief complaint among new referrals to tertiary specialist clinics. Cough is accompanied by multiple symptoms and is associated with healthcare utilization, particularly more in patients with chronic cough. Further studies are needed to understand their long-term health outcomes and reduce the disease burden.
Multispectral Beam Splitter from Visible to MWIR
Authors: MAHENDRA ROUCHIN , Chandra Ramesh
Published: February 2022

Electro-optical/infrared multispectral systems are being developed for a variety of defence and commercial systems applications. An ability to detect and recognize the low-contrast and distance targets in a complex environment is of great importance for many applications. The development of such systems requires special optical filters which can separate the different bands as per the requirement. We have designed and simulated these two beam splitters at 45O angle of incidence that will be applied to separate the bands from visible to MWIR. For such an optical system, the beam splitter must separate the MWIR (3600-4900nm), SWIR bands (900-1700nm) and, visible (400-700nm). In this paper, we have reported thin film coating design and simulation of these two beamsplitters. The first beam splitter is used to separate MWIR from visible and SWIR. The MWIR is in the reflection channel and the other two bands are in the transmission channel. The second beam splitter separates the remaining two bands, visible and SWIR. The visible is in the reflection channel and the SWIR is in the transmission channel.
Predictors of Happiness Among Hemodialysis Patients
Authors:   1.	Seyedeh . Ameneh Motalebi,   2.	Bahareh Yousefi,   3.	Fatemeh Hosseinpoor,   4.	Seyedehzahra Hosseinigolafshani
Published: February 2022

BackgroundPromoting happiness in hemodialysis patients is associated with positive physical and psychological health outcomes. Therefore, the current study aimed to determine the predictors for happiness among hemodialysis patients.MethodsThis descriptive cross-sectional study was conducted among 200 patients who referred to the hemodialysis ward of Booali Sina Hospital in Qazvin, Iran, in 2020. Samples were selected through a convenience sampling method based on inclusion and exclusion criteria. The socio demographic checklist, the Oxford Happiness Questionnaire, and the Schneider's Life Expectancy Questionnaire were used for collecting the data. Multivariate regression model was used to determine the predictors of happiness.ResultsThe participants’ mean age was 59.23±14.43. The majority of the participants were male (n=122, 61.0%) and married (n=134, 67.0%). A majority of them (69%) reported moderate levels of happiness. The results of multivariate regression model showed that educational level (β=0.248, p≤0.001), marital status (β=-0.268, p≤0.001), hemodialysis adequacy (β=0.268, p≤0.001), and hope (β=0.231, p≤0.001) significantly predicted happiness among hemodialysis patients. Finally, the variables explained 47.2% of the variance in happiness among the patients.ConclusionsBased on the results of the current study, managers, planners and nurses of the hemodialysis ward can play an effective role in promoting happiness and vitality in this group of patients by considering effective interventions in their daily interactions with the aim of promoting hope, emphasizing on the study and valuable outcomes of higher educational level, striving for dialysis adequacy and helping to solve common life challenges.
Simple Febrile Seizures: New Cut Off for the Duration of the Crises
Authors: Falsaperla Raffaele , Vitaliti Giovanna , Bonadies Anna , Domenica Marino Simona , Piero Pavone , Catia Romano , Fabio Savoia , Camilla Calì , Ruggieri Martino , Riccardo Lubrano , Vincenzo Tipo
Published: February 2022

Background: Our study aimed to identify a new cut-off for febrile seizure (FS) with a good prognosis, thereby replacing the 15 min described in the standard definition of simple febrile seizure (SFS).Methods: Our study was a retrospective observational study (from January 2016 to December 2016) on children admitted to the Pediatric emergency room of the Santobono-Pausilipon Hospital, Naples, Italy, and Policlinico-Vittorio-Emanuele University Hospital, Catania, Italy, for fever, which developed SFS during the hospitalization. All included patients had their seizures classified as SFS according to the international criteria for epilepsy. We assumed a cut-off of 5 min duration, and we analyzed the EEG results, neurological follow up at 12 months, and the recurrence of the febrile seizures the following year. Then, with another calculation, we identify an optimal cut-off of 6 min. Finally, we divided the population into two groups: children with seizures having a duration greater than or less than 6 min.Results: We found that the population with FS with a duration greater than 6 min presented EEG alteration at follow up visits, neurological disorders, and a recurrence of FS during the following year.Conclusions: We suggest to introduce a new cut-off for the duration of FS that better represents the benign nature of a simple febrile event.
Evaluation of the BioMérieux VIDAS® HIV Duo Quick and Anti-HCV Assays for Dried Blood Spot Based Serosurveillance
Authors: Cholette François , Farmer Braedy , Balakireva Olga , Pavlova Daria , Lopatenko Anna , Chukhalova Iryna , Bargan Svitlana , Mishra Sharmistha , Becker Marissa , Lee Emma R. , Kim John , Sandstrom Paul
Published: February 2022

Serosurveillance is central to monitoring our progress towards HIV and HCV elimination targets proposed for 2030. However, serosurveillance systems are ineffective without reliable serological assays for the detection of HIV and HCV antibodies. Assays should also be compatible with dried blood spot (DBS) samples to facilitate biological sample collection. The VIDAS® HIV Duo Quick and Anti-HCV assays are sold as reagents strips and processed by the automated VIDAS® benchtop immunoanalyser. While both assays have shown excellent performance in serum and plasma, performance data in DBS samples is lacking. In our study, we evaluate the performance of the VIDAS® HIV Duo Quick and Anti-HCV assays in DBS (n = 725) collected during a cross-sectional serosurvey (the Transitions study). The VIDAS® HIV Duo quick had a sensitivity and specificity of 94.5% (95% CI: 85.1%, 98.5%) and 95.7% (95% CI: 93.9%, 97.0%) respectively. Likewise, the VIDAS® Anti-HCV had a sensitivity and specificity of 95.6% (95% CI: 91.6%, 97.8%) and 95.6% (95% CI: 93.5%, 97.0%) respectively. These assays are unlikely to be helpful in low-prevalence settings due to sub-optimal performance, but their performance could likely be improved by optimizing DBS elution protocols which was, unfortunately, not possible during our study.
Assessing the potential determinates of national vitamin A supplementation in Ethiopia.
Authors: Lucha Tadele Abate , Ketsela Admassu , Engida Teklu Assefa
Published: February 2022

Background: Vitamin A is a nutrient that is required in a small amount for normal visual system function, growth and development, epithelia’s cellular integrity, immune function, and reproduction. Vitamin A has a significant and clinically important effect since it has been associated with a reduction in all-cause and diarrhea mortality. The aim of this study was to determine factors associated with national vitamin A supplementation among children aged 6-35 months by using data from the 2019 Ethiopia Mini Demographic and Health Survey.Method: The study used a population-based cross-sectional study design to assess factors associated with vitamin A supply among children aged 6 to 35 months in the six months before the survey's start. Descriptive statistics were used to identify the proportion of children who had taken vitamin A supplements, after which multivariable logistic regression analysis was carried out to determine the predictors of vitamin A supplementation. Result: The overall coverage of vitamin A supplementation among children aged 6-35 months for the survey included was 46 %. In the multivariable analysis, children who resided in urban areas [AOR = 1.34 (95 % CI: 1.00, 1.81)] were more likely to receive vitamin A supplementation than children living in rural areas. Postnatal care recipients were 1.5 times more likely than non-recipients to obtain vitamin A capsules for their children [AOR = 1.54 (95 % CI: 1.20, 1.97)]. Mothers [AOR = 1.26, 95% CI: 1.029, 1.57] who delivered at health facilities were 26% more likely to receive vitamin A capsules for their children than those who delivered at home. Other factors that were associated with higher a likelihood of vitamin A supplementation were: number of antenatal visits, age of child, and household wealth index.Conclusion: The coverage of vitamin A supplementation set by the Ethiopia ministry of health remains low and it is strongly associated with antenatal visit, postnatal checkups and place of delivery. Expanding institutional delivery and maternal health services like ANC and PNC should be prioritized.
Morphometric description of the koala humerus using microcomputed tomography
Authors: Hawkins Jason , Basa Rachel M , Norton Matthew J , Johnson Kenneth A
Published: February 2022

Background: The current prognosis for successful return to function in koalas with appendicular fractures is poor despite being the most common fracture type to result in successful rehabilitation. The forelimb, particularly the humerus, plays a critical role in stabilisation and support while climbing trees. Successful rehabilitation therefore requires adequate internal stabilisation to promote bone healing and faster return to function. Current knowledge of koala limb bone morphometry is lacking and would provide useful clinical insight for future orthopaedic research, particularly with regards to recommendations regarding implant size and type. In this study microcomputed tomography (micro-CT) was used to describe bone length, internal and external diameters, and cortical thickness at five transverse levels along the humerus of skeletally mature koala cadavers. Qualitative descriptions were also made regarding bone features deemed clinically relevant to potential fracture repair techniques. Results: Mean humeral length was 114.3 mm (95% CI 107.29 – 121.31 mm). Mediolateral diameters were greater than craniocaudal diameters at each measurement level, and the diaphysis has a distally tapering medullary cavity. Diaphyseal cortices were relatively homogenous with slight distal thickening, and medial cortices were thickest along the entire bone. The bone protuberances of the deltoid and supinator ridges projected most of the way down the lateral surface of the bone while the medial surface remained relatively uniform. Distal to the deltoid ridge the humerus curved caudally, terminating at a craniocaudally flattened distal epiphysis. Conclusion: Morphometric descriptions provided in this study will serve as a useful reference for future research, guiding orthopaedic surgery and improving prognosis of koala humeral fractures.
Distinct CD8 T Cell Populations with Differential Exhaustion Profiles Associate with Secondary Complications in Common Variable Immunodeficiency
Authors: Klocperk Adam , Friedman David , Schlaak Emilia Alexandra , Unger Susanne , Parackova Zuzana , Goldacker Sigune , Sediva Anna , Bengsch Bertram , Warnatz Klaus
Published: February 2022

Purpose
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, with heterogeneous clinical presentation. Our goal here was to analyze CD8 T cell homeostasis in patients with infection only CVID, compared to those with dysregulatory and autoimmune phenomena.
Methods
Flow and mass cytometry evaluation of peripheral blood of 40 patients with CVID and 17 healthy donors.
Results
CD8 T cells are skewed in patients with CVID, with loss of naïve and increase of effector memory stages, expansion of cell clusters with high functional exhaustion scores, and a highly activated population of cells with immunoregulatory features, producing IL-10. These findings correlate to clinically widely used B-cell-based EURO classification. CD127, TIGIT and PD1 expression in CD8 T cells are strongly associated with interstitial lung disease and autoimmune cytopenias, whereas HLA-DR and CD38 predict non-infectious diarrhea.
Conclusion
We demonstrate features of advanced differentiation, exhaustion, activation and immunoregulatory capabilities within CD8 T cells of CVID patients. CD8 T cells assessment may allow further stratification of CVID patients and provide new insights into CVID pathogenesis, including a better understanding of mechanisms underlying T cell exhaustion.
Towards Defining Morphologic Parameters of Normal Parous and Nulliparous Breast Tissues by Artificial Intelligence
Authors: Ogony Joshua , de Bel Thomas , Radisky Derek C. , Kachergus Jennifer , Thompson E. Aubrey , Degnim Amy C. , Ruddy Kathryn J. , Hilton Tracy , Stallings-Mann Melody , Vachon Celine , Hoskin Tanya L. , Heckman Michael G. , Vierkant Robert A. , White Launia J. , Moore Raymond M. , Carter Jodi , Jensen Matthew , Pacheco-Spann Laura , Henry Jill E. , Storniolo Anna Maria , Winham Stacey J. , Laak Jeroen van der , Sherman Mark E.
Published: February 2022

Background:Breast terminal duct lobular units (TDLUs), the source of most breast cancer (BC) precursors, are shaped by age-related involution, a gradual process, and postpartum involution (PPI), a dramatic inflammatory process that restores baseline microanatomy after weaning. Dysregulated PPI is implicated in the pathogenesis of postpartum BCs. We propose that assessment of TDLUs in the postpartum period may have value in risk estimation, but characteristics of these tissues in relation to epidemiological factors are incompletely described.Methods: Using validated Artificial Intelligence and morphometric methods, we analyzed digitized images of tissue sections of normal breast tissues stained with hematoxylin and eosin from donors <45 years from the Komen Tissue Bank (180 parous and 545 nulliparous). Metrics assessed by AI, included: TDLU count; adipose tissue fraction; mean acini count/TDLU; mean dilated acini; mean average acini area; mean “capillary” area; mean epithelial area; mean ratio of epithelial area versus intralobular stroma; mean mononuclear cell count (surrogate of immune cells); mean fat area proximate to TDLUs and TDLU area. We compared epidemiologic characteristics collected via questionnaire by parity status and race, using a Wilcoxon rank sum test or Fisher’s exact test. Histologic features were compared between nulliparous and parous women (overall and by time between last birth and donation [ recent birth: ≤5 years versus remote birth: >5 years]) using multivariable regression models.Results:Normal breast tissues of parous women contained significantly higher TDLU counts and acini counts, more frequent dilated acini, higher mononuclear cell counts in TDLUs and smaller acini area per TDLU than nulliparas (all multivariable analyses p<0.001). Differences in TDLU counts and average acini size persisted for >5 years postpartum whereas increases in immune cells were most marked <5 years of a birth. Relationships were suggestively modified by several other factors, including demographic and reproductive characteristics, ethanol consumption and breastfeeding duration. Conclusions:Our study identified sustained expansion of TDLU numbers and reduced average acini area among parous versus nulliparous women and notable increases in immune responses within five years following childbirth. Further, we show that quantitative characteristics of normal breast samples vary with demographic features and BC risk factors.
Chloroplast Genome of Lithocarpus Dealbatus: Identification of Hotspots for Sequence Variability and Phylogeny Analysis in Quercoideae, a Sub-family of Fagaceae
Authors: Shelke Rahul , Banerjje Rudra , Joshi Babita , Singh Prem Prakash , Tiwari Gopal Ji , Adhikari Dibyendu , Jena Satya Narayan , Barik Saroj Kanta
Published: February 2022

BackgroundThere has been phylogenetic ambiguity and species delimitation problem in Lithocarpus genus and the sub-family Quercoideae (Family: Fagaceae). Lithocarpus dealbatus is the dominant genus among the Quercoideae in India. Although several studies have been conducted on regeneration, ecological and economic significance of the species, limited information is available at genome scale. We sequenced and assembled the complete chloroplast genome of L. dealbatus and compared with other Quercoideae members to understand the sequence variations, rearrangements and its phylogenetic lineage in the Quercoideae.ResultsWe assembled the 161,476 bp chloroplast genome of L. dealbatus, which has a large single-copy section of 90,732 bp and a small single-copy region of 18,987 bp, separated by a pair of inverted repeat regions of 25,879 bp. There were 133 genes in the cp-genome, including 86 protein coding genes, 39 transfer RNAs, and eight ribosomal RNAs. Analysis of repeat elements and RNA editing sites revealed inter-specific similarities within Lithocarpus genus. DNA diversity analysis identified highly diverged coding and non-coding hotspot regions in the genera Lithocarpus, Quercus, Castanea, and Castanopsis. These hot spots can be used as polymorphic barcodes to resolve the phylogenetic relationship at species level. We discovered five barcodes that could aid in species delimitation across the four genera of Quercoideae. The phylogenetic analysis among the Quercoideae established a monophyletic origin of Lithocarpus, and a closer evolutionary lineage with many Quercus species.ConclusionsOur findings provide insights into the chloroplast genome of L. dealbatus, the mutational hotspot regions and repeat elements. These could be utilized as molecular markers/barcodes for detailed studies in population genetics.
High-Normal Alanine Aminotransferase as a Predictor of Significant Liver Histological Injury in Chronic Hepatitis B Virus Infection with Different HBV DNA Levels
Authors: shan Ren , Junfeng Lu , Kefei Wang , Lina Ma , Yanhong Zheng , Sujun Zheng , Xinyue Chen
Published: February 2022

Objective
We aimed to assess significant liver histological injury(SLHI) of chronic hepatitis B (CHB) patients with normal ALT in order to select clinical threshold of ALT.
Methods
We retrospectively examined 347 patients who underwent liver biopsy in Beijing You an hospital, Capital Medical University from January 2018 to January 2021. Univariate analysis of the clinical parameters versus inflammation and fibrosis was carried out.
Results
Of these 347 patients met the inclusion criteria, 174(50.1%) patients had SLHI totally.The AUROC of the ALT associated with the diagnosis of SLHI was 0.572 for female and 0.6 for male with a cut-off value of 20U/L and 25U/L, respectively (p = 0.04, p = 0.013).Among HBeAg-positive patients,the proportion of SLHI in the high-normal ALT group (ALT > 20 U/L for female,>25 U/L for male) with low HBV DNA loads(< 7log10 IU/ml)was higher(66.7% vs 33.3%, p < 0.001); also the proportion in the HBeAg-negative with high-normal ALT and HBV DNA ≧ 2000 IU/ml was significantly higher(70% vs 37.7%, p < 0.001).
Conclusion
Clinical threshold of ALT to distinguish SLHI was 25U/L for male and 20U/L for female.The CHB patients with high-normal ALT and certain HBV DNA level ( ≧ 2000 IU/ml for HBeAg-negative and < 7log10 IU/ml for HBeAg-positive) were suggested to perform liver biopsy or noninvasive methods for histopathology assessment, then to be determined for antiviral therapy.
ALX1-transcribed LncRNA AC132217.4 Promotes Osteogenesis and Bone Healing via IGF-AKT Signaling in Mesenchymal Stem Cells
Authors: Zhang cui , Wu Shali , Chen Erman , Yu Luyang , Wang Jinfu , Wu Mengrui
Published: February 2022

The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) is critical for bone formation and regeneration. A high non-/delayed-union rate of fracture healing still occurs in specific populations, implying an urgent need to discover novel targets for promoting osteogenesis and bone regeneration. Long non-coding (lnc)RNAs are emerging regulators of multiple physiological processes, including osteogenesis. Based on differential expression analysis of RNA sequencing data, we found that lncRNA AC132217.4, a 3'UTR-Overlapping lncRNA of insulin growth factor 2 (IGF2), was highly induced during osteogenic differentiation of BMSCs. Afterward, both gain-of-function and loss-of-function experiments proved that AC132217.4 promotes osteoblast development from BMSCs. As for its molecular mechanism, we found that AC132217.4 binds with IGF2 mRNA to regulate its expression and downstream AKT activation to control osteoblast maturation and function. We also identified two splicing factors from RNA-pull-down assay, serine and arginine-rich splicing factor 2 (SRSF2) and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) regulates AC132217.4 biogenesis at post-transcriptional level. Furthermore, we identified a transcription factor, ALX1, regulates AC132217.7 expression at transcriptional level to promote osteogenesis. Importantly, in-vivo over-expression of AC132217.4 essentially promotes the bone healing process in a murine tibial drill-hole model. Altogether, our study demonstrates that lncRNA AC132217.4 is a novel anabolic regulator of BMSC osteogenesis and could be a plausible therapeutic target for improving bone regeneration.
Road to entire insulation for resonances
Authors: Cao Qingjie , Zhu Guangnan , Wang Zhenkun , Zhang Yuntian , Chen Yushu , Woo Ko-Choong
Published: February 2022

The effective solution to avoid machinery damage caused by resonance has been perplexing the field of engineering as a core research direction since the resonance phenomenon was discovered by Leonhard Euler in 1750. Numerous attempts have been performed to reduce the influence of resonance since the middle of last century, by introducing a nonlinear structure or a closed-loop control system. However, the existed methodologies cannot eliminate the resonance completely even extra problems were introduced inevitably, which means the technical choke-point of resonance-free remains unsolved. Here we propose an inverse method based upon the requirements of dynamic characteristics of the supporting system to construct a passive archetypal model with zero-stiffness within a designable distance to avoid the resonance. The reliability of the inverse method is demonstrated theoretically and experimentally, which indicate that the constructed system with zero-stiffness can outright eliminate the mechanical resonance by completely isolating the energy transfer between the load and environment. The distinctive geometric characteristics of the zero-stiffness system leads to a new inspiration for the design of resonance-free passive mechanisms or metamaterials, and the inverse method can even adapt the design for a more targeted application based on an arbitrary complex dynamic requirement.
On the prevalence of Forest Fires in Spain
Authors: Boccard Nicolas
Published: February 2022

We study the prevalence of forest fires in Spain in the long run by computing the probability that a forest tree, as opposed to shrub or bush, will be lost to fire over the course of the year. Climate change is first shown to increase the likelihood of this event. Next, we document how risk grew dramatically from 1961 up to the democratic era (c. 1980) and has since receded to less than 2 trees lost per thousand. We bring together the socio-economic drivers identified for this trend reversal. Our finding is commensurate with the evolution of the same risk in neighboring Mediterranean countries.
Lnc-FSD2-31:1 in Pancreatic ductal adenocarcinoma promotes ATG7-mediated proliferation and fibrosis of cancer associated fibroblasts via exosome miR-4736
Authors: Geng Xinglong , Li Le , Luo Yan , Hu Jisheng , Zhao Zhongjie , Cheng Chundong , Zhang Tao , Yang Wenbo , Zhang Yangyang , Liu Liwei , Xie Yu , Li Guanqun , Liu Danxi , Bai Xuewei , Wang Gang , Chen Hua , Sun Bei , Chen Hongze
Published: February 2022

Background
Long non-coding RNA (lncRNA) is closely related to the occurrence of Pancreatic ductal adenocarcinoma (PDAC). Intercellular interactions between cancer associated fibroblasts (CAFs) and cancer cells influence malignant proliferation and chemotherapy resistance of PDAC in a variety of ways. We performed the global expression profiles of lncRNA between longevity and short survival PDAC patients’ pancreatic tissues, to identify molecular mechanism of PDAC.
Method
Tissue microarray (TMA) was used to explore survival related lncRNA in PDAC. The localization of lncRNA was conform by RNA fluorescence in-situ hybridization (FISH) analysis. Functional assays were introduced to demonstrate the anti-tumor effects of lncRNA in vitro and in vivo. Exosomes and primary CAFs were isolated from PDAC cell lines and patient tissues. Bioinformatics and 3D co-culture model were used to find the downstream targets. KPC transgenic mouse model and human cytokine array were also applied to detect the mechanism of PDAC.
Results
We found that lnc-FSD2-31:1 was elevated significantly in longevity survival patients. Lnc-FSD2-31:1 suppressed PDAC proliferation, invasion, and metastasis in vitro and in vivo. Lnc-FSD2-31:1 also act as a competing endogenous RNA (ceRNA) to inhibit miR-4736 expression in PDAC cells. Exosome miR-4736 secreted by PDAC was transported to CAFs. We found miR-4736 inhibited the proliferation, autophagy and promoted the fibrosis of CAFs by binding to the 3’-untranslated region(3’-UTR) of ATG7. Under the stimulatory of miR-4736, CAFs particularly secreted IL-32α, IL-1β, IL-1ra, G-CSF, IL-2, IL-4. Furthermore, miR-4736 antagomir intraperitoneally injected can suppressed tumor growth in KPC mice. Exosome miR-4736 of plasma might be a biomarker of PDAC.
Conclusions
Lnc-FSD2-31:1 suppress PDAC progression and act as a competing endogenous RNA (ceRNA) to inhibit miR-4736 expression in PDAC cells. Exosome miR-4736 released by PDAC inhibit autophagy and promote fibrosis of CAFs via targeting ATG7. miR-4736 might be a promising biomarker and treatment target of PDAC.
Feasibility and acceptability of a multicomponent, group psychological intervention for adolescents with psychosocial distress in public schools of Pakistan: A feasibility cluster randomized controlled trial (cRCT)
Authors: Hamdani Syed Usman , Huma Zill-e- , Tamizuddin-Nizami Asad , Baneen Um-ul- , Suleman Nadia , Javed Hashim , Malik Aiysha , Wang Duolao , Mazhar Samra , Khan Shahzad Alam , Minhas Fareed Aslam , Rahman Atif
Published: February 2022

Background
Child and adolescent mental health problems are a global public mental health priority. However, there is a lack of evidence-based scalable psychological interventions for adolescents living in low resource settings. This trial was designed to evaluate the feasibility and acceptability of delivering the World Health Organization’s Early Adolescent Skills for Emotions (EASE) intervention at public schools in a rural sub-district in Rawalpindi, Pakistan.
Methods
A two arm, single blinded, feasibility cluster randomized controlled trial with mixed-methods evaluation was conducted with 59 adolescents and their caregivers from 8 public schools. In the 4 intervention arm schools, 6 non-specialist facilitators delivered the culturally-adapted EASE group sessions to the adolescents (n = 29) and their caregivers with desired fidelity under the supervision of in-country supervisors.
Results
The participation rate of adolescents in the intervention sessions was 83%. The intervention strategies were implemented by the adolescents. However, attending biweekly sessions at schools was challenging for caregivers with only 50% caregivers attending the sessions.
Conclusions
The results of this study support the feasibility and acceptability of delivering this culturally adapted intervention through non-specialist facilitators in school settings in Pakistan and pave the way to conduct a fully powered cluster randomized controlled trial to test the effectiveness of intervention to improve psychological outcomes in adolescents.
Trial registration:
Trial registered with Clinicaltrials.gov prospectively; NCT04254393
Development of a digitally-obtainable 10-year all-cause mortality risk score based on data from 497,712 UK Biobank participants
Authors: Colombo Michele , Dolezalova Nikola , Despotovic Aleksa , Reed Angus B. , Morelli Davide , Aral Mert , Plans David
Published: February 2022

Background
All-cause mortality (ACM) scores are a useful tool for identifying individuals with decreased life expectancy. An interpretable score consisting of smartphone-obtainable variables could allow for long-term management of individual health and support the next generation of healthcare monitoring and preventative practices. The aim of this study was to develop a 10-year ACM risk score using the UK Biobank dataset, using only digitally-obtainable variables.
Methods
The models were developed using the full UK Biobank cohort comprising nearly 500,000 individuals. We extracted 399 features from the dataset and, through a data-driven feature selection process with subsequent clinical review, identified 34 features for the final model. As part of the study, we compared two survival analysis approaches: Cox proportional hazards model and DeepSurv, a deep learning-based survival analysis algorithm.
Results
Before feature selection, Cox performed similarly to DeepSurv, achieving a c-index of 0.771 (95% CI 0.770–0.772) and 0.774 (95% CI 0.772–0.775) on the test dataset, respectively. Using the selected 34 features, the c-index of Cox decreased slightly to 0.770 (95% CI 0.769–0.770) and DeepSurv to 0.758 (95% CI 0.755–0.762). The models show excellent calibration at 10 years.
Discussion
This study describes a smartphone-compatible ACM score, with excellent predictive ability. The score described here improves on a previous smartphone-compatible score, C-Score, by incorporating non-modifiable factors in addition to variables which can be actively modified to reduce risk.
Conclusion
We have developed a smartphone-compatible ACM score that is comprehensive, easily interpretable and actionable, and as such, could provide a powerful tool for preventative healthcare.
First-in-human demonstration of functional task performance using a sonomyographic prosthesis
Authors: Engdahl Susannah M. , Acuña Samuel A. , King Erica L. , Bashatah Ahmed , Sikdar Siddhartha
Published: February 2022

Ultrasound-based sensing of muscle deformation, known as sonomyography, has shown promise for accurately classifying the intended hand grasps of individuals with upper limb loss in offline settings. Building upon this previous work, we present the first-in-human demonstration of real-time prosthetic hand control using sonomyography to perform functional tasks. An individual with congenital bilateral limb absence was fitted with sockets containing a low-profile ultrasound transducer placed over forearm muscle tissue in the residual limbs. A classifier was trained using linear discriminant analysis to recognize ultrasound images of muscle contractions for three discrete hand configurations (rest, tripod grasp, index finger point) under a variety of arm positions designed to cover the reachable workspace. A prosthetic hand mounted to the socket was then controlled using this classifier. Using this real-time sonomyographic control, the participant was able to complete three functional tasks that required selecting different hand grasps in order to grasp and move one-inch wooden blocks over a broad range of arm positions. Additionally, these tests were successfully repeated without retraining the classifier across three hours of prosthesis use and following simulated donning and doffing of the socket. This study supports the feasibility of using sonomyography to control upper limb prostheses in real-world applications.
Perivascular Epithelioid Cell Tumor (PEComa) of the Liver: a Report of Two Cases
Authors: Li Yi-xiang , Lv Wei-long , Wang Li-li , Qu Meng-meng , Zhu Yuan-hui , Lei Jun-qiang
Published: February 2022

Background: Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor of mesenchymal origin which can arise at a variety of visceral and soft tissue sites. It most often occurs in the uterus, but develops in the liver very infrequently, only 8% of PEComa cases.Here, we present two pathologically proven cases of PEComa of the liver, retrospectively discuss the clinical, imaging and histological features.Case presentation: Case1:A 54-year-old female patient with intermittent epigastric discomfort for 2 years and aggravated for 5 days.The laboratory examinations were normal.Computed tomography (CT) showed the lesions were located on the right lobe The discomfort had resolved after surgery and PEComa was diagnosed after pathological examination of the surgical specimen. The patient has been followed-up for 5 years without recurrence.Case2:A 30-year-old woman was found to have a mass of liver incidentally during regular physical examination after breast cancer surgery. On contrast enhancement CT, a well demarcated mass was found. After operation, pathological diagnosis was established as malignant PEComa of the right liver. Neither primary recurrence nor metastasis was found during the 2-year follow-up.Conclusions: The imaging manifestations of liver PEComa have certain characteristics. When the tumor density is not uniform or contains fat, and thickening vascular shadow appears around the lesion, combined with clinical and laboratory examination, suggestive diagnosis can be made.
Case Report : Primary Mediastinal Leiomyoma
Authors: Lam Ngoc My , Cappello Matteo , Foucart Annick , Remmelink Myriam
Published: February 2022

Background : The presence of leiomyoma in the anterior mediastinum is uncommun and less than 20 cases were described in the literature. Herein we report a 44-year-old woman with an asymptomatic anterior mediastinal mass who underwent complete surgical tumor resection. Methods : Imaging techniques, anatomopathological analysis and immunohistochemical stains were performed to find the diagnosis.Results : The proposed pathological diagnosis is primary mediastinal leiomyoma.Conclusions : Primary mediastinal leiomyoma is a rare benign tumor. It develops from smooth muscle fibers of large vessels or esophagus. Total surgical resection is the treatment of choice.
Confidence Bands and Hypothesis Tests for Hit Enrichment Curves
Authors: Ash Jeremy R , Hughes-Oliver Jacqueline M
Published: February 2022

In virtual screening for drug discovery, hit enrichment curves are widely used to assess the performance of ranking algorithms with regard to their ability to identify early enrichment. Unfortunately, researchers almost never consider the uncertainty associated with estimating such curves before declaring differences between performance of competing algorithms. Appropriate inference is complicated by two sources of correlation that are often overlooked: correlation across different testing fractions within a single algorithm, and correlation between competing algorithms. Additionally, researchers are often interested in making comparisons along the entire curve, not only at a few testing fractions. We develop inferential procedures to address both the needs of those interested in a few testing fractions, as well as those interested in the entire curve. For the former, four hypothesis testing and (pointwise) confidence intervals are investigated, and a newly developed EmProc approach is found to be most effective. For inference along entire curves, EmProc-based confidence bands are recommended for simultaneous coverage and minimal width. While we focus on the hit enrichment curve, this work is also appropriate for lift curves that are used throughout the machine learning community. Our inferential procedures trivially extend to enrichment factors, as well.
Application of Novel Quantitative Measurement of Iris Angiography in Diabetic Retinopathy
Authors: Zhang Longli , Chai Yue , Zhang Luyuan , Hei Kaiwen , Li Xiaorong
Published: February 2022

Introduction: The purpose of this study was to explore the application of a novel quantitative measurement of iris angiography (IA) in diabetic retinopathy (DR). Methods: This was a single-center, cross-sectional prospective study. Totally 168 consecutive patients with diabetic mellitus (DM) were involved into this study from May 2016 to December 2020, 168 subjects were devided into 3 groups, 32 non-retinopathy patients,96 non-proliferative diabetic retinopathy patients(NPDR), and 40 proliferative diabetic retinopathy (PDR) patients. All patients underwent ophthalmologic examination, such as best corrected visual acuity, intraocular pressure, slit-lamp microscopy, gonioscopy, ultra-wide-field fundus photography, fluorescein angiography of the iris (IFA), and indocyanine green angiography of the iris (IIGA). The starting of iris vascular leakage time(LT) was recorded, and the range of pupil fluorescein leakage was measured by a novel measurement. Results: LT of iris in non-retinopathy, non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups were 33.14 ± 3.03s, 32.45 ± 5.17s, and 25.67 ± 5.03s, respectively. The LT in the PDR group was significantly faster than those in the NPDR and non-retinopathy groups (P=0.000). The iris pupil leakage range (LR) of the non-retinopathy, NPDR, and PDR groups were 21.21 ± 30.06, 62.48 ± 42.17, and 141.31 ± 73.61°, and LR in PDR groups were largest among all groups (P=0.000). Neovascularization of the iris (NVI) was detected in 8 eyes (26.7%) in the PDR group. No NVI was found in non-retinopathy and NPDR groups.Conclusions: The novel quantitative measurement of IA can be used to evaluate the severity of diabetic iridopathy (DI) accurately and detect invisible NVI as early as possible to provide a basis for the formulation of personalized treatment for DR patients.