bluuebunny/crossref_metadata_2025 huggingface dataset:
Aβ Oligomers Alter NMDA Receptor Composition and Function in Early Stages of Alzheimer´s Disease
Authors: Ortiz-Sanz Carolina , Quintela-López Tania , Ruiz Asier , Balantzategi Uxue , Luchena Celia , Zuazo-Ibarra Jone , Capetillo-Zárate Estibaliz , Matute Carlos , Zugaza José L. , Alberdi Elena
Published: January 2021

Background Amyloid beta (Aβ)-mediated synapse dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Aβ peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in early stages of AD are unclear. Here, we show that Aβ oligomers activate PKC, phosphorylate NR2B subunit and modulate its synaptic localization and function. Methods We isolated postsynaptic fractions (PSD) of AD prefrontal cortex and hippocampus of 6-month-old 3xTg-AD mice to quantify NR2B, PSD-95 and Aβ1-42 levels. To investigate the effects of Aβ oligomers on NR2B and PSD-95 expression, we use a range of techniques including mouse intrahippocampal injections of Aβ oligomers, isolation of protein membranes by cell-surface biotinylation, and synaptosomal fractionation as well as in vivo surface immunolabeling of EGFP-NR2B. Ca2+ imaging and PKC activity were monitored by fluorescent Ca2+ indicators and FRET analysis. Results We observed that NMDAR subunit NR2B and PSD-95 levels were aberrantly upregulated and correlated with Aβ42 load in human PSD fractions from early stages of AD patients as well as in hippocampus of 3xTg-AD mice. Importantly, NR2B and PSD95 dysregulation was revealed by an increased expression of both proteins in Aβ-injected mouse hippocampi. In cultured neurons, Aβ oligomers increased NR2B-containing NMDAR density and NMDA-induced synaptic Ca2+ influx in neuronal membranes in addition to colocalization in dendrites of NR2B subunit and PSD95. Mechanistically, Aβ oligomers required integrin β1 to promote synaptic location and function of NR2B-containing NMDARs and PSD95 by phosphorylation through classic PKCs. Conclusions These results provide evidence that Aβ oligomers modify the contribution of NR2B to NMDAR composition and function in early stages of AD through an integrin β1 and PKC-dependent pathway. These data reveal a novel role of Aβ oligomers in synaptic dysfunction that may be relevant to early-stage AD pathogenesis.
Lost OTR Expression and HIF-1α Self-protection in Myometrium of Intractable Postpartum Hemorrhage
Authors: Chen Yunshan , Wang Lele , Hu Minghua , Liu Feng , Deng Mingjing , Liu Huishu
Published: January 2021

Objective: In intractable postpartum hemorrhage(IPPH), uterotonic lost efficacy in myometrum contraction formation. While the key target in uterotonic, OTR(oxytocin receptor) and internal environment in myometrum might have some changes when IPPH. Methods: Three groups of myometrial tissue at different contraction states were collected:(1) term not at labour (TNL) group(10 cases); (2) term at labour (TAL) group(10 cases);(3) intractable postpartum hemorrhage(IPPH) group(10 cases).Expressions of OTR and internal environment markers(ASIC1a ,HIF1α, GlUT, FATP and apoptosis ) were compared in 3 groups by Immunoreactivity Scores method. Results: The expression of OTR in myometrium in IPPH group was 100% negative ,compared to 30%,20% in TNL and TAL group(p < 0.05).70% positive HIF-1α expression in TNL group increased to 80% in TAL group,but decreased to 20% in IPPH group(P<0.05). While the positive expressions of ASIC1a, FATP and GLUT in three groups all had no significant difference.But the apoptosis related markers Bax,caspase-3 and caspase-9 positive expressions in IPPH were significantly all decreased(10%,10%,0%) compared to TNL and TAL group,compared to a high positive expression of Bcl-2 in 3 groups.Conclusion: OTR expression and HIF-1α self-protection might be lost in myometrium of IPPH, which could lead to uterotonic lost efficacy and conservative treatment failure.
Numerical and Experimental Demonstration of Inverse Designed Low-index Polarization-insensitive Wavelength Demultiplexer
Authors: Icli Abdullah , Alpkilic Ahmet , Yilmaz Yusuf , Yildirim Bumin , Turduev Mirbek , Kurt Hamza
Published: January 2021

The computational inverse design has paved the way for the design of highly efficient, compact, and novel nanophotonic structures beyond human intuition and trial-and-error approaches. Consequently, with this new design power, the exploration and implementation of multi-objective, complex, and functional nanophotonic devices become feasible. Herein, we used a recently emerged inverse design framework to demonstrate the design of a 1 * 2 polarization-insensitive wavelength division multiplexer (PIWDM) made of a low-refractive-index material with an index of 1.55. The designed PIWDM structure successfully steers toward the targeted channels for 1.30 mm and 1.55 mm with TE and TM polarizations, respectively. The transmission values were -2.42 and -2.18 dB for TE and -2.19 and -2.23 dB for TM polarization at the upper and lower waveguides, respectively. Taking advantage of the design with a low refractive index material, we scaled the structural dimensions corresponding to the microwave region, fabricated the compact device using a 3D printer, and conducted an experiment as a proof of concept. The experimentally verified PIWDM structure shows a power transmission efficiency of over -2.42 dB and a crosstalk value of less than -11.45 dB for the targeted wavelengths.
Development and Validation an Epigenetic Modification-related Signals for Diagnosis and Prognosis of Hepatocellular Carcinoma
Authors: Wen Diguang , Qiu Sheng , Liu Zuojin
Published: January 2021

Background: Increasing evidence has indicated that abnormal epigenetic modification such as RNAm6a modification, histone modification, DNA methylation modification, RNA binding proteins and transcription factors, is correlated with Hepatocarcinogenesis. However, it is unknown how epigenetic modification associated genes contribute to the occurrence and clinical outcome of hepatocellular carcinoma (HCC). Thus, we constructed epigenetic modification associated model that may enhance the diagnosis and prognosis of HCC.METHODS: In this study, we focused on the clinical values of epigenetic modification associated genes for HCC. Our gene expression data were collected from TCGA and a HCC datasets from GEO dataset in order to ensure the reliability of data. Their function was analyzed by bioinformatics methods. We used lasso regression, SUV, logistic regression and cox regression to construct the diagnosis and prognosis models. We also constructed a nomogram for the practicability of the above-mentioned prognosis model. The above results have been verified in an independent liver cancer dataset from ICGC database. Furthermore, we carried out pan cancer analysis to verify the specificity of the above model.RESULT: A large number of epigenetic modification associated genes were significantly different in HCC and normal liver tissues. The gene signatures showed good performance for predicting the occurrence and survival of HCC patients verified by DCA and ROC curve.CONCLUSION: Gene signatures based on epigenetic modification associated genes can be used to identify the occurrence and prognosis of liver cancer.
Combined Deep CNN–LSTM Network-based Multitasking Learning Architecture for Noninvasive Continuous Blood Pressure Estimation using Difference in ECG-PPG Features
Authors: Jeong Da Un , Lim Ki Moo
Published: January 2021

The pulse transit time (PTT), which is the difference between the R-peak time of the electrocardiogram (ECG) signal and the systolic peak of the photoplethysmography (PPG) signal, is an indicator that enables noninvasive and continuous blood pressure estimation. However, it is difficult to accurately measure the PTT from the ECG and PPG signals because they have inconsistent shapes owing to patient-specific physical characteristics, pathological conditions, and movements. Accordingly, complex preprocessing is required to estimate blood pressure based on PTT. In this paper, as an alternative solution, we propose a noninvasive continuous algorithm using the difference between the ECG and PPG as a new feature that can include PTT information. The proposed algorithm is a deep CNN–LSTM-based multitasking machine learning model that outputs simultaneous prediction results of systolic (SBP) and diastolic blood pressures (DBP). The prediction accuracies of SBP and DBP using the proposed model were 0.017±1.624 mmHg and 0.164±1.297 mmHg, respectively. This result corresponded to Grade A according to the BHS and AAMI standards, which are the validation standards for blood pressure measuring devices.
Synergy Between a Shallow Root System With a DRO1 Homologue and Localized P Application Improves Rice P Uptake 
Authors: Oo Aung Zaw , TSUJIMOTO YASUHIRO , Mukai Mana , Nishigaki Tomohiro , Takai Toshiyuki , Uga Yusaku
Published: January 2021

Improved phosphorus (P) use efficiency for crop production is needed given the depleting phosphorus ore deposits and increasing ecological concerns about its excessive use. Root system architecture (RSA) is important in efficiently capturing immobile P in soils, while agronomically, localized P application near the roots is a potential approach to address this issue. However, the interaction between genetic traits of RSA and localized P application has been little understood. Near-isogenic lines (NILs) and their parent of rice (qsor1-NIL, Dro1-NIL, and IR64, with shallow, deep, and intermediate root growth angles (RGA), respectively) were grown in flooded pots after placing P near the roots at transplanting (P-dipping). The experiment identified that the P-dipping created an available P hotspot at the soil surface; the qsor1-NIL had the greatest root biomass and root surface area in the 0–3 cm soil layer despite no genotype differences in total values; the qsor1-NIL had significantly greater biomass and P uptake than the other genotypes in the P-dipping. The superior surface root development of qsor1-NIL could have facilitated P uptakes from the P hotspot, implying that P-use efficiency in crop production can be further increased by combining genetic traits of RSA and localized P application.
Evaluation of the Effect of the Capitation Compensation Mechanism among Tuberculosis Patients with a Full Period of Treatment
Authors: hu xingyu , gao guangying
Published: January 2021

Background: To explore the compensation mechanism for pulmonary tuberculosis patients with a full period of treatment, to alleviate the financial burden of pulmonary tuberculosis patients and to provide a reference and basis for the reform of tuberculosis payment methods in other regions and countries.Methods The funding operations of medical insurance institutions and the actual operating expenses of pilot hospitals from the Dehui Tuberculosis Hospital in Jilin Province were collected from the first half of 2015 to the first half of 2018, and the operational effects were analysed through quantitative and qualitative methods.Results After implementing the compensation mechanism, the medical expenses of tuberculosis patients decreased significantly, and the economic burden of the disease was reduced; the hospital's medical service capacity was improved, and internal management was significantly improved; and the medical insurance fund did not experience overspending, thus leading to a "triple win-win" situation.Conclusion The capitation compensation mechanism with a full period of treatment is a suitable payment method for TB diagnosis and treatment, and its effect is obvious, achieving a "triple win-win" for medical insurance, hospitals and patients. It is recommended to continue to promote this model to effectively reduce the financial burden of tuberculosis patients. However, in the early stage of the implementation of the plan, due to the relatively low understanding of the reform of hospitals and patients, there will be patient loss and poor compliance. Therefore, the hospital should change the management concept, incorporate the goal of payment method reform into performance management, and require all patients to be included in the treatment path to achieve standardized management of the entire treatment process. This mechanism also provides a reference for the reform of payment methods for tuberculosis in other regions or countries.
Enrichments of Ensemble Docking Strategy Based on the Bayesian Model
Authors: Lei Yu , Guo Sheng , Liu Yi , Zuo Zhili
Published: January 2021

MotivationChallenges remained in structure-based drug discovery which include protein flexibility in binding site. Thus, concerning the flexibility of proteins, docking into an ensemble of rigid conformations (ensemble docking) have been proposed with incorporation into protein flexibility with expects that it could provide higher enrichments than rigid single receptor. Here we have developed the ensemble docking strategy by using Bayesian Model algorithms, and this method is validated by three proteins: BTK, JAK and PARP. The Bayesian Model was used to integrate independent docking runs of an ensemble of rigid crystal structures and MD simulations. ResultsThe structure of MD simulations outperforms the crystal structures in separating inhibitors from decoys in BTK and PARP. Further, the results demonstrated that the ensemble docking strategy has better performance than rigid single conformation.
How Long is Indian Coastline?
Authors: Srivast Ravi Prakash , Dimri V. P.
Published: January 2021

Coastline measurements have no explicit length if they are geometrically self-similar. It is well known that length of self-similar geometrical objects is scale dependent, and hence it is not a fixed number, rather depends on the scale used to measure it. We present a definitive approach based on a fractal method to measure the coastline of India. We propose a method to define optimum scale length, that could be used to measure the coastline. Using our method, the mainland coast measures 7567 km. There are four big inhabited islands in Andaman (North, Middle, South and Little Andaman) which accounts for 687 km of island coast, and Great Nicobar Island has 195 km of coast around it, thus coastal length of inhabited islands is 882 km. Thus the total coast length of India including major 5 inhabited islands from Andaman-Nicobar group of islands is 8391 km. There are several other small islands in Andaman-Nicobar group of islands, we observed 26 of them significant in terms of their size. Indian coast length becomes 9060 km if we account for above mentioned 26 Andaman and Nicobar Islands. According to one of the Wiki articles, there are 572 islands in Andaman-Nicobar group of islands, but many of them are very small and insignificant. This is first ever scientific study about the Indian coast length, which has global significance due to strategic and climate related coastline alterations such as sea level rise due to global warming.
Serum Calprotectin (S100A8/A9): A Promising Biomarker in Diagnosis and Follow-up in Different Subgroups of Juvenile Idiopathic Arthritis
Authors: La Céline , Lê Phu Quoc , Ferster Alina , Goffin Laurence , Spruyt Delphine , Lauwerys Bernard , Durez Patrick , Boulanger Cecile , Sokolova Tatiana , Rasschaert Joanne , Badot Valérie
Published: January 2021

BackgroundManagement of juvenile idiopathic arthritis (JIA) lacks of diagnostic and prognostic biomarkers. Therefore, this study was designed to assess the use of serum calprotectin (sCal) as a marker of disease activity and its monitoring, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. MethodsEighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 healthy controls. Enzyme-linked immunosorbent assay (ELISA) method was used to quantify sCal with a commercial kit. Mann-Whitney tests were used to compare results, correlations were assessed with Spearman’s rank correlation coefficients and Receiver Operating Characteristic curves were also generated to evaluate serum calprotectin as a prognostic tool.ResultsPatients with an active disease compared to healthy controls and to patients with inactive disease showed an 8-fold and a 2-fold increased level of sCal respectively. sCal was found to be correlated with the CRP and even more strongly with the ESR. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. As for the CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis or systemic forms. However, sCal brought an added value compared to the CRP as a prognosis marker. Indeed, patients with active disease and good responder to treatment (pediACR > 30) at 6 months following the sample test had higher sCal levels, while patients with inactive disease had higher sCal levels in case a flare was observed up to 3 to 9 months following the sample test.ConclusionsThis study confirms the potential uses of serum calprotectin as a biomarker in diagnosis and follow-up in JIA.
Additional Treatment for Digital Ulcers in Patients with Systemic Sclerosis: A Prospective, Open-Label, Multi-Arm Study for the use of Platelet-Rich Plasma-Lipofilling and Ultrasound-Based Treatments
Authors: PIRRELLO ROBERTO , SCHINOCCA CLAUDIA , SCATURRO DALILA , RIZZO CHIARA , TERRANA PIETRO , TUMMINELLI LUIGI , RUSCITTI PIERO , CORDOVA ADRIANA , GIACOMELLI ROBERTO , CICCIA FRANCESCO , MAURO GIULIA LETIZIA , GUGGINO Giuliana
Published: January 2021

Background: Local treatments such as ultraviolet-A (UVA) phototherapy, topical calcitriol, injection of autologous fat grafting, Platelet-Rich Plasma (PRP), hyaluronic acid (HA) and local ultrasound (US) treatment are considered alternative approaches for skin involvement in Systemic sclerosis (SSc).The aim of our study was to evaluate the efficacy of PRP injection and lipofilling or local ultrasound in the treatment of SSc-related digital ulcers (DUs). Methods: We enrolled 28 patients with SSc. At baseline time (T0), all patients were treated with Iloprost intravenous infusions. Then, six patients (group 1) received a first inoculation of PRP, after 15 days a second inoculation of PRP and after 15 days a third of lipofilling. Other six patients (group 2) received the three consecutive injections associated with a maintenance therapy with additional injections of PRP every 30 days for 12 months. Six patients continued only the Iloprost therapy (controls). Ten patients (group 3) underwent medical sessions with ultrasound treatment for 10 days. Clinical evaluation was assessed at baseline, after 3 and 12 months of treatment for all patients.Results: In our study have shown an improvement in cutaneous and microvascular level, in quality of life, in mobility of extremities of upper limbs and a reduction of administration of Iloprost after PRP-Lipofilling and US treatment.Conclusions: Our findings suggest that PRP, coupled with lipofilling, and ultrasound treatment in SSc patients, can be considered additional procedures in the management of DUs.
Sacubitril/valsartan Inhibits Obesity-associated Diastolic Dysfunction through Suppression of Ventricular-vascular Stiffness
Authors: Aroor Annayya R , Mummidi Srinivas , Lopez-Alvarenga Juan Carlos , Das Nitin , Habibi Javad , Jia Guanghong , Lastra Guido , Chandrasekar Bysani , Demarco Vincent G
Published: January 2021

Objective: Both cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes and serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy.Methods: Sixteen week-old male Zucker Obese rats (ZO; n=64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg-1•day-1; ZOSV); Group 3: valsartan (31 mg•kg-1•day-1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg-1•day-1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage.Results: Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val also decreased aortic stiffness and reversed impairment of nitric oxide-induced vascular relaxation seen in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective at ameliorating DD compared to val. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, proteomics revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val increased IL-4 which is increasingly been recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity associated DD.Conclusions: These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.
Down Regulation Of The Expression Of Mitochondrial Phosphopantetheinyl-Proteins In Pantothenate Kinase-Associated Neurodegeneration: Pathophysiological Consequences and Therapeutic Perspectives
Authors: Álvarez-Córdoba Mónica , Talaverón-Rey Marta , Villalón-García Irene , Povea-Cabello Suleva , Suárez-Rivero Juan M. , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Salas Joaquín J. , Sanchez-Alcazar Jose A
Published: January 2021

BackgroundNeurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.MethodsIn this manuscript, we examined the effect of PANK2 mutations on the expression levels of proteins with phosphopantetheine cofactors in fibroblast derived from PKAN patients. These proteins include cytosolic acyl carrier protein (ACP), which is integrated within the multifunctional polypeptide chain of the fatty acid synthase involved in cytosolic fatty acid biosynthesis type I (FASI); mitochondrial ACP (mtACP) associated with mitocondrial fatty acid biosynthesis type II (FASII); mitochondrial alpha-aminoadipic semialdehyde synthase (AASS); and 10-formyltetrahydrofolate dehydrogenases (cytosolic, ALD1L1, and mitochondrial, ALD1L2). ResultsIn PKAN fibroblasts the expression levels of cytosolic FAS and ALD1L1 were not affected while the expression levels of mtACP, AASS and ALD1L2 were markedly reduced, suggesting that 4′-phosphopantetheinylation of mitochondrial but no cytosolic proteins were markedly affected in PKAN patients. Furthermore, the correction of PANK2 expression levels by treatment with pantothenate in selected mutations with residual enzyme content was able to correct the expression levels of mitochondrial phosphopantetheinyl-proteins and restore the affected pathways. The positive effects of pantothenate in particular mutations were also corroborated in induced neurons obtained by direct reprograming of mutant PANK2 fibroblasts. ConclusionsOur results suggest that the expression levels of mitochondrial phosphopantetheinyl-proteins are severely reduced in PKAN cells and that in selected mutations pantothenate increases the expression levels of both PANK2 and mitochondrial phosphopantetheinyl-proteins associated with remarkable improvement of cell pathophysiology.
Genomic Insight Into 21 Hypervariable Molecular Markers in The Population of Lower Himalayan Geographical Province Himachal Pradesh, India
Authors: Sharma Arun , Srivast Ankit , Sahajpal Vivek , Kumawat R , Dixit Shivani , Chaubey Gyaneshwer , Shrivastava Pankaj
Published: January 2021

A natural geographical barrier between Tibetan plateau and south Asian countries, the Himalayan Mountain range, serves as a natural barrier between these regions for genetic flow. This has lead to vast genomic divergence among the population residing in Indian Himalayan region..This study was designed with an aim to decipher the genomic diversity and molecular characterization of 21 hypervariable molecular markers in the population of geographical province of Himachal Pradesh in the lower Himalayan region. Randomly selected 401 unrelated individuals native of the lower Himalayan geographical region were included for this study. 21 hypervariable molecular markers included in the PowerPlex® 21 system were amplified and genotyped. A total of 246 alleles and 12.3 (SE 0.927) private alleles per locus were observed. Population differentiation analysis revealed that the studied population showed a genetic affinity with the population of North India, North-west India, Central India, and Uttar Pradesh rather than the population of East India, South India, East Asia, and West Asia. Heterozygosity at the studied loci was found in the range of 0.686 to 0.920. The unite discrimination power (PD) and exclusion power (PE) was found to be 1 and 0.999999998073765 respectively. The unite value of matching probability and typical paternity index was found to be 9.33x10-26 and 5.05x108 respectively for the studied population. All the tested loci were found in Hardy Weinberg Equilibrium (HWE) expectations. Overall the studied population exhibited a great extent of genomic diversity and had a greater genetic affinity with Indo-European speakers rather than Dravidian and Tibeto-Burman speakers.
Typhoon Eye Effect Vs. Ripple Effect: the Role of Family Size on the Mental Health Under the COVID-19 Pandemic in Pakistan
Authors: Zhang Stephen X , Lateef Tooba , Chen Jiyao , Tahir Muhammad , Lateef Teba Abdul , Chen Bryan , Li Jizhen
Published: January 2021

Background: The recent outbreak of COVID-19 impacts the mental health of people worldwide. The mental conditions and the associated predictors of adults in Pakistan, the fifth most populous country in the world, during the COVID-19 remains understudied. We aim to investigate distress, anxiety, and overall mental health and their associated predictors among Pakistani adults in this pandemic. We specifically examine the mental health issues based on the distance to the epicenter, a predictor that has revealed opposing evidence in other countries based on the theories of typhoon eye effect and ripple effect. The samples consist of 601 adults who were surveyed online about 2.5 months into the outbreak across Pakistan with varying distance to the epicenter of COVID-19 of Karachi in Pakistan. Results: The results showed that 9.2% and 19.0% of the participants surpassed the cut-off of distress and anxiety disorders, respectively. Overall, the distance to the epicenter positively predicted the mental health of adults in Pakistan, and family size negatively moderated this effect. The distance to the epicenter negatively predicted distress and anxiety disorders for adults in large families, which are quite common in Pakistan. Conclusion: The evidence of the study interestingly finds the prediction of the mental health of people by their distance to the epicenter depends on the family. The evidence of this study can help to provide the initial indicator for mental health care providers to screen vulnerable groups in Pakistan, a populous country that continues struggling to cope with the COVID-19 pandemic.
Generation of Dyskeratosis Congenita-like Hematopoietic Stem Cells through the Stable Inhibition of DKC1
Authors: Carrascoso-Rubio Carlos , Zittersteijn Hidde A. , Pintado-Berninches Laura , Fernández-Varas Beatriz , Lozano M. Luz , Manguan-Garcia Cristina , Sastre Leandro , Bueren Juan A. , Perona Rosario , Guenechea Guillermo
Published: January 2021

Dyskeratosis congenita (DC) is a rare telomere biology disorder, which results in different clinical manifestations, including severe bone marrow failure. To date, the only curative treatment for bone marrow failure in DC patients is allogeneic hematopoietic stem cell transplantation. However due to the toxicity associated to this treatment, improved therapies are recommended for DC patients. Here we aimed at generating DC-like human hematopoietic stem cells in which the efficacy of innovative therapies could be investigated. Because X-linked DC is the most frequent form of the disease and is associated with an impaired expression of DKC1, we have generated DC-like hematopoietic stem cells based on the stable knock-down of DKC1 in human CD34 + cells with lentiviral vectors encoding for DKC1 short hairpin RNAs. At a molecular level, DKC1 -interfered CD34 + cells showed a decreased expression of TERC, as well as a diminished telomerase activity and increased DNA damage, cell senescence and apoptosis. Moreover, DKC1 -interfered human CD34 + cells showed defective clonogenic ability and were incapable of repopulating the hematopoiesis of immunodeficient NSG mice. The development of DC-like hematopoietic stem cells will facilitate the understanding of the molecular and cellular basis of this inherited bone marrow failure syndrome, and will serve as a platform to evaluate the efficacy of new hematopoietic therapies for DC.
Residential exposure to air pollution and access to neighborhood greenspace in relation to hair cortisol concentrations during the second and third trimester of pregnancy
Authors: Verheyen Veerle Josefa , Remy Sylvie , Lambrechts Nathalie , Govarts Eva , Colles Ann , Poelmans Lien , Verachtert Els , Lefebvre Wouter , Monsieurs Pieter , Vanpoucke Charlotte , Nielsen Flemming , Eeden Lena Van den , Jacquemyn Yves , Schoeters Greet
Published: January 2021

Background: Exposure to air pollution during pregnancy has been associated with adverse pregnancy outcomes in studies worldwide, other studies have described beneficial effects of residential greenspace on pregnancy outcomes. The biological mechanisms that underlie these associations are incompletely understood. A biological stress response, which implies release of cortisol, may underlie associations of air pollution exposure and access to neighborhood greenspaces with health. Methods: We explored residential exposure to air pollution and residential access to neighborhood greenspaces in relation to hair cortisol concentrations of participants in a prospective pregnancy cohort study in Flanders, Belgium. Hair samples were collected at the end of the second pregnancy trimester (n = 133) and shortly after delivery (n = 81). Cortisol concentrations were measured in 3-cm scalp-near hair sections, to reflect second and third pregnancy trimester cortisol secretion. We estimated long-term (3 months before sampling) residential exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC), assessed residential distance to major roads and residential access to neighborhood greenspaces (NHGS). Associations between residential exposures and hair cortisol concentrations were studied using linear regression models while adjusting for season of sampling.Results: Three-month mean residential NO2 and BC concentrations were positively associated with third pregnancy trimester hair cortisol concentrations (p = 0.008 and p = 0.017). Access to a large NHGS (10 hectares or more within 800 meters from residence) was negatively associated with third trimester hair cortisol concentrations (p = 0.019). Access to a large NHGS significantly moderated the association between residential proximity to major roads and second trimester hair cortisol concentrations (p = 0.021). Residential distance to major roads was negatively associated with second trimester hair cortisol concentrations of participants without access to a large NHGS (p = 0.003). The association was not significant for participants with access to a large NHGS. The moderation tended towards significance in the third pregnancy trimester (p < 0.10).Conclusions: Our findings suggest a positive association between long-term residential exposure to air pollution and biological stress during pregnancy, residential access to neighborhood greenspaces may moderate the association. Further research is needed to confirm our results.Trial registration: The IPANEMA study is registered under number NCT02592005 at clinicaltrials.gov.
Decreasing the leakage of continuous femoral nerve catheter fixation using 2-octyl cyanoacrylate glue (Demabond®): A randomized controlled trial
Authors: Chalacheewa Theerawat , Arnuntasupakul Vanlapa , Sangkum Lisa , Buachai Rungrawan , Chanvitayapongs Jiravud
Published: January 2021

Background: Continuous peripheral nerve catheters (CPNCs) have been used for postoperative pain relief. A common problem encountered with CPNCs is pericatheter leakage, which can lead to dressing adhesive failure. Frequent dressing changes increase the risk of catheter dislodgement and infections. Adhesive glue is effective in securing the peripheral nerve catheter and decreasing leakage around the catheter insertion site. This study aimed to evaluate the incidence of pericatheter leakage with fixation using 2-octyl cyanoacrylate glue (Dermabond®) as compared to sterile strips.Methods: Thirty patients undergoing unilateral total knee arthroplasty (TKA) with continuous femoral nerve catheter for postoperative analgesia were randomized into the catheter fixation with 2-octyl cyanoacrylate glue (Dermabond®) group or the sterile strip group. The primary outcome was the incidence of pericatheter leakage. Secondary outcomes included the frequent of catheter displacement, the difficulty of catheter removal, pain score and patient satisfaction.Results: The incidence of pericatheter leakage at 24 and 48 hours was 0% versus 93% and 0% versus 100% in the Dermabond® and sterile strip groups, respectively (P < 0.001). The incidence of displacement at 24 and 48 hours was 6.7% versus 93.3% and 6.7% versus 100% in the Dermabond® and sterile strip, respectively (P < 0.001). There was no difference in numeric rating scale, difficulty of catheter removal, or satisfaction scores between groups.Conclusion: Catheter fixation with 2-octyl cyanoacrylate glue (Dermabond®) decreased the incidence of pericatheter leakage, as well as catheter displacement, over 48 hours as compared to sterile strip fixation.
Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species
Authors: Gigout Anne , Harazin Donata , Topping Louise M. , Lindemann Sven , Brenneis Christian , Nissim Ahuva
Published: January 2021

Background: Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Cartilage degradation is mostly driven by chondrocytes which produce inflammatory mediators, proteases and oxidants. Nevertheless, the early pathogenesis events are still unclear. We employed antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA. Methods: The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed at 3, 5, 7, 14 and 28 days or anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) and were sacrificed after 1, 3, 5, 7 and 14 days. Joints were stained with toluidine blue and Saffron du Gatinais for histological scoring, anti-oxPTM-CII and anti- collagen type X antibodies (anti-CX). Results: We observed oxPTM-CII staining as early as 1 or 3 days after ACLT+pMx or DMM surgeries respectively, before overt cartilage lesions were visible. It was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes and co-localized with CX staining. Both staining were weak or absent for the lateral compartment or the contralateral knees except at later timepoints. Conclusion: The results demonstrate that oxidants production and chondrocytes hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead or radiographic changes.
Survival of silver diamine fluoride among patients treated in community dental clinics: A naturalistic study
Authors: Raskin Sarah Elaine , Tranby Eric P , Ludwig Sharity , Okunev Ilya , Frantsve-Hawley Julie , Boynes Sean
Published: January 2021

Background: Silver diamine fluoride (SDF) is a minimally-invasive preventive service used in the U.S. to avert and arrest caries since 2014. No studies document survival outcomes based in real world delivery. We analyzed 12-month survival outcomes of SDF applied independently or concurrently with other restorative procedures among a population receiving community dental care.Methods: We analyzed data on SDF applications from de-identified dental claims on Oregon Health Plan patients served by Advantage Dental in 2016, who had been seen in 2015 (patient n=2,269; teeth n=7,787). We compared survival rates of SDF alone, SDF applied with a sedative filling, and SDF with a same-day restoration. Failure was defined as a restoration or extraction of the tooth 7 to 365 days after initial application. Survival was defined as a patient returning 180 or more days after application whose tooth did not have a restoration or extraction. Differences were assessed through Wilcoxon equality of survivor function tests and log-rank equality of survivor tests to compare failure rates, Cox Proportional Hazards models to assess factors associated with survival of SDF, and Kaplan-Meier survival estimate to calculate the probability of survival over time. Results: SDF alone had an overall survival rate of 76%. SDF placed with sedative filling and with a same-day restoration had survival rates of 50% and 84% respectively, likely reflecting treatment intent. SDF alone survived exceptionally well on primary cuspids, permanent molars, and permanent bicuspids and among patients aged 10 to 20 years, with modest variation across caries risk assessment categories. A single annual application of SDF was successful in 68% of cases. Among SDF failures on permanent dentition, more than two-thirds of teeth received a minor restoration. Conclusions: SDF is a minimally invasive non-aerosolizing option that prevented non-cavitated lesions and arrested early decay among community dentistry patients when applied independently or concurrently with restorative procedures. Professional organizations, policy makers, providers, and payors should broaden optional SDF use by informing clinical guidelines, reimbursement policies, and treatment decisions. Future research should address clinical, social, service delivery, workforce, and economic outcomes using diverse population-based samples, and the mechanisms underlying single application success and caries prevention potential.
The use of dried tube specimens of Plasmodium falciparum in an external quality assessment programme to evaluate health worker performance for malaria rapid diagnostic testing in healthcare centres in Togo
Authors: DORKENOO Monique Ameyo , Kouassi Kafui Codjo , Koura Adjane K. , Adams Martin L , Gbada Komivi , Katawa Gnatoulma , Yakpa Kossi , Charlebois Remi , Milgotina Ekaterina , Merkel Michele O , Aidoo Michael
Published: January 2021

BackgroundThe use of rapid diagnostic tests (RDTs) to diagnose malaria is common in sub-Saharan African laboratories, remote primary health facilities and in the community. Currently, there is a lack of reliable methods to ascertain health worker competency to accurately use RDTs in the testing and diagnosis of malaria. Dried tube specimens (DTS) have been shown to be a consistent and useful method for quality control of malaria RDTs, however, its application in National Quality Management programmes has been limited.MethodsA Plasmodium falciparum strain was grown in culture and harvested to create DTS of varying parasite density (0, 100, 200, 500 and 1,000 parasites/µL). Using the dried tube specimens as quality control material, a proficiency testing (PT) programme was carried out in 80 representative health centres in Togo. Health worker competency for performing malaria RDTs was assessed using five blinded DTS samples, and the DTS were tested in the same manner as a patient sample would be tested by multiple testers per health centre. ResultsAll the DTS with 100 parasites/µl and 50% of DTS with 200 parasites/µl were classified as non-reactive during the pre-PT quality control step. Therefore, data from these parasite densities were not analysed as part of the PT dataset. PT scores across all 80 facilities and 235 testers was 100% for 0 parasites/µl, 63% for 500 parasites/µl and 93% for 1,000 parasites/µl. Overall, 59% of the 80 healthcare centres that participated in the PT programme received a score of 80% or higher on a set of 0, 500 and 1,000 parasites/ µl DTS samples. Sixty percent of health workers at these centres recorded correct test results for all three samples.ConclusionsThe use of DTS for a malaria PT programme was the first of its kind ever conducted in Togo. The ease of use and stability of the DTS illustrates that they this type of samples can be considered for the assessment of staff competency. The implementation of quality management systems, refresher training and expanded PT at remote testing facilities are essential elements to improve the quality of malaria diagnosis.
The radiomics features could be used to predict the distinct metastases in nasopharyngeal carcinoma patients
Authors: Li Meige , Feng Ziyou , Yang Fang , Zhan ZeJiang , Ye Haiwen , Zhang Guoyi
Published: January 2021

Background For NPC patients, distant metastasis is now the main reason for treatment failure. The patients with distinct metastases need different therapeutic regimen and have distinct prognosis. Radiomics might help us predict the type of metastases effectively.Methods The MRI data of seventy non-metastatic NPC patients who develop distant metastasis within five years after treatment were collected and 4410 radiomics features for each patient were extracted by PyRadiomics. Every radiomics feature were compared among patients with distinct metastases and tested by the receiver operating characteristic curve.Results Twenty features have significant differences between the bone metastases cohort and lung metastases cohort, two features have significant differences between the bone metastases cohort and liver metastases cohort, one feature has significant differences between the bone metastases cohort and multiple metastases cohort and sixty-seven features have significant differences between the lung metastases cohort and liver metastases cohort. Six T2WI features could identified lung metastases from bone metastases and liver metastases effectively (AUC=0.851~0.896), two T1WI features and one CE T1WI feature could respectively identified bone metastases from liver metastases and multiple metastases effectively (AUC=0.779~0.821).Conclusion The results indicate that the radiomics features could reflect some of the characteristics of distinct metastases and have potential to be used as predictor of distinct metastases.
Development of a Multi-gene-based Immune Prognostic Signature in Ovarian Cancer
Authors: cao tiefeng , shen huimin
Published: January 2021

Background： Various components of the immune system play a critical role in the prognosis and treatment response in ovarian cancer (OC). Immunotherapy has been recognized as a hallmark of cancer but the effect is contradictional. Reliable immune gene-based prognostic biomarkers or regulatory factors are necessary to be systematically explored to develop an individualized prediction signature.Methods: This study systematically explored the gene expression profiles in patients with ovarian cancer from RNA-seq data set for The Cancer Genome Atlas (TCGA). Differentially expressed immune genes and transcription factors (TFs) were identified using the collected immune genes from ImmPort dataset and TFs from Cistoma database. Survival associated immune genes and TFs were identified in terms of overall survival. The prognostic signature was developed based on survival associated immune genes with LASSO (Least absolute shrinkage and selection operator) Cox regression analysis. Further, we performed network analysis to uncover the potential regulators of immune-related genes with the help of computational biology. Results: The prognostic signature, a weighted combination of the 21 immune-related genes, performed moderately in survival prediction with AUC was 0.746, 0.735, and 0.749 for 1, 3, and 5 year overall survival, respectively. Network analysis uncovered the regulatory role of TFs in immune genes. Intriguingly, the prognostic signature reflected the immune cells landscape and infiltration of some immune cell subtypes.Conclusions: We first constructed a signature with 21 immune genes of clinical significance, which showed promising predictive value in the surveillance, and prognosis of OC patients.
Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia
Authors: Savarirayan Ravi , Tunkel David E. , Sterni Laura M. , Bober Michael B. , Cho Tae-Joon , Goldberg Michael J , Hoover-Fong Julie , Irving Melita , Kamps Shawn E. , Mackenzie William G. , Raggio Cathleen , Spencer Samantha A. , Bompadre Viviana , White Klane
Published: January 2021

Background: Recognition and appropriate management of the craniofacial manifestations of patients with skeletal dysplasia are challenging, due to the rarity of these conditions, and dearth of literature to support evidence-based clinical decision making.Methods: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, best practice guidelines in the management of craniofacial aspects of these patients.Results: After a comprehensive literature review, 23 initial statements were generated and critically discussed, with subsequent development of a list of 22 best practice guidelines after a second round voting.Conclusions: The guidelines are presented and discussed to provide context and assistance for clinicians in their decision making in this important and challenging component of care for patients with skeletal dysplasia, in order standardize care and improve outcomes.