bluuebunny/crossref_metadata_2025 huggingface dataset:
Fixel-Based Analysis of White Matter Alterations in Early- Stage Cerebral Small Vessel Disease
Authors: Petersen Marvin , Frey Benedikt M. , Mayer Carola , Kühn Simone , Gallinat Jürgen , Hanning Uta , Fiehler Jens , Borof Katrin , Jagodzinski Annika , Gerloff Christian , Thomalla Götz , Cheng Bastian
Published: August 2021

Cerebral small vessel disease (CSVD) is a common cause of morbidity and cognitive decline in the elderly population. However, characterizing the disease pathophysiology and its association with potential clinical sequelae in early stages is less well explored. We applied fixel-based analysis (FBA), a novel framework of investigating microstructural white matter integrity by diffusion-weighted imaging, to data of 921 participants of the Hamburg City Health Study, comprising middle-aged individuals with increased cerebrovascular risk in early stages of CSVD. In individuals in the highest quartile of white matter hyperintensity loads (n=232, median age 63 years; IQR 15.3 years), FBA detected significantly reduced axonal density and increased atrophy of transcallosal fiber tracts, the bilateral superior longitudinal fasciculus, and corticospinal tracts compared to participants in the lowest quartile of white matter hyperintensities (n=228, mean age 55 years; IQR 10 years). Analysis of all participants (N=921) demonstrated a significant association between reduced fiber density and worse executive functions operationalized by the Trail Making Test. Findings were confirmed by complementary analysis of diffusion tensor metrics.
Familial Hypocalciuric Hypercalcemia: The Challenge of Diagnosis
Authors: Taïeb David , Lasbleiz Adele , Paladino Nunzia Cinzia , Romanet Pauline , Castinetti Frédéric , Cuny Thomas , Sebag Frédéric
Published: August 2021

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant genetic disorder classically characterized by lifelong mild-to-moderate asymptomatic hypercalcemia with inappropriately normal to elevated serum parathyroid hormone (PTH) concentrations and hypocalciuria, best expressed by a urine calcium-to-creatinine clearance ratio (CCCR)<0.01[1,2]. FHH prevalence is estimated between 1:10 000 to 1:100 000[3,4]. In 60% of cases, FHH is due to CASR inactivating mutation[5]. More rarely FHH is due to AP2S1 or GNA11 inactivating mutation, both genes encoding for proteins involved downstream of CASR activation[6]. These molecular alterations are found in all parathyroid cells, explaining disease persistence following partial parathyroidectomy and the ineffective surgical management of these patients. FHH phenotypes could however overlap with primary hyperparathyroidism (PHPT). Indeed, even if patients with FHH are currently asymptomatic, some of them present chondrocalcinosis, kidney stones or bone fracture and very high level of PTH or calcemia[7]. Nonetheless, the distinction has to be adressed since the therapeutic approach significantly differs between these two conditions. Surgery is usually recommended for PHPT[8] while follow-up is preferred in the latter case[9,10]. We report and discuss 7 cases, 6 out 7 being operated for a presumed PHPT.
5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer’s Disease
Authors: Chen Lei , Xu Shunliang , Shen Qianqian , Yu Hongzhuan , Pei Shengjie , Zhang Yangting , He Xin , Wang QiuZhen , Li Duo
Published: August 2021

Background: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in nervous system. It has been reported that 5hmC is significant associated with Alzheimer’s disease (AD). Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. However, there is no research about genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD to date. Methods: We carried out a case-control study and used a highly sensitive and selective high-throughput sequencing of chemical labels to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in AD patients and the control. Results: We detected a significant difference of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls. AD patients can be well distinguished from cognitively normal controls by differentially hydroxymethylated regions (DhMRs) in cfDNA. Specially, we found 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) had prediction diagnostic potential based on their significant correlations with MMSE and MoCA scores. Conclusions: The present results suggest that 5hmC markers derived from plasma cfDNA can be served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100042537, registered 13 January 2021-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120582.
Blocking lncRNA-SNHG16 Sensitizes Gastric Cancer Cells to 5-Fu Through Targeting the miR-506-3p-PTBP1-Mediated Glucose Metabolism
Authors: Ding Yan , Gao Sujie , Zheng Jiabin , Chen Xuebo
Published: August 2021

Gastric cancer (GC) is one of the most human malignancies. The 5-fluorouracil (5-Fu) is a first-line anti-gastric cancer chemotherapeutic agent. However, a large number of GC patients developed 5-Fu resistance. Currently, the biological roles and molecular mechanisms of lncRNA-SNHG16 in 5-Fu resistant gastric cancer still remain elusive. Here we report SNHG16 as well as PTBP1 are positively associated with 5-Fu resistance of gastric cancer. SNHG16 and PTBP1 are significantly upregulated in gastric tumors and cell lines. Silencing SNHG16 or PTBP1 effectively sensitized GC cells to 5-Fu. Furthermore, the glucose metabolism was remarkedly elevated in 5-Fu resistant GC cells. Under low glucose supply, 5-Fu resistant cells displayed higher vulnerability than parental GC cells. Bioinformatical analysis and luciferase assay demonstrated that SNHG16 downregulated miR-506-3p by sponging it. We identified PTBP1 was a direct target of miR-506-3p in GC cells. RNA-seq results indicated PTBP1 positively regulated multiple glycolysis enzymes expressions, including GLUT1, HK2 and LDHA. Bioinformatics analysis illustrated the 3’UTRs of glycolysis enzymes contained multiple PTBP1 binding sites, which were further verified by RNA-pull down and RNA immunoprecipitation assays. Consequently, we demonstrated PTBP1 upregulated the mRNAs of glycolysis enzymes via promoting the mRNAs stabilities. Finally, in vivo xenograft experiments validated that blocking the SNHG16-mediated miR-506-3p-PTBP1 axis effectively sensitized xenograft tumors to 5-Fu treatments. Summarily, our study reports biological roles and molecular mechanisms underlying the lncRNA SNHG16-mediated 5-Fu resistance in GC through modulating the miR-506-3p-PTBP1-glycolysis axis, presenting a promising prospect in improvement of 5-Fu therapy for chemoresistant GC patients.
Incidence of Ocular, Adnexal and Orbital Trauma at Different Tertiary Care Centers of Karachi.
Authors: Qidwai Nazia , Alkhairy Saba , Masood Nausheen
Published: August 2021

The authors have requested that this preprint be removed from Research Square.
Electrochemical Crystallization for Recovery of Phosphorus and Potassium from Urine as K-Struvite, with A Sacrificial Magnesium Anode
Authors: Shan Jinhua , Liu Hongbo , Zhang Haodong , Long Shiping , Lichtfouse Eric
Published: August 2021

Declining earth resources, rising ore cost and pollution call for better recycling of wastewater in the context of the circular economy. In particular, urine is a potential huge source of phosphorus (P) and potassium (K) agricultural nutrients, yet the efficiency of actual methods for P and K recovery are limited. Here we designed a electrochemical crystallization system using sacrificial magnesium anodes to recover P and K in the form of K-struvite (MgKPO4·6H2O) from simulated urine at low (P/K=0.25) and high (P/K=0.6) phosphate levels, respectively. Results show optimal recoveries of 88.5% for P and 35.4% for K in the form of rod-shaped K-struvite at 3.5 mA/cm2, yet higher current density reduced recovery due to side reactions and pH increase. Adding phosphate to urine increased K recovery to 35.4% versus 15.0% without phosphate. Adding prefabricated struvite crystals at 1.6 g/L into urine enhanced the recovery of K by 14.7% and of P by 23.7% compared to the control group. Overall, our findings show that electrochemical crystallization is promising for the recovery of K-struvite fertilizers.
A specific relationship between musical sophistication and auditory working memory
Authors: Lad Meher , Billig Alexander J. , Kumar Sukhbinder , Griffiths Timothy D.
Published: August 2021

Musical engagement may be associated with better listening skills, such as the perception of and working memory for notes, in addition to the appreciation of musical rules. The nature and extent of this association is controversial. In this study we assessed the relationship between musical engagement and both sound perception and working memory. We developed a task to measure auditory perception and working memory for sound using a behavioural measure for both, precision. We measured the correlation between these tasks and musical sophistication based on a validated measure (the Goldsmiths Musical Sophistication Index) that can be applied to populations of both musicians and non-musicians. The data show that musical sophistication accounts for 21% of the variance in the precision of working memory for frequency in an analysis that accounts for age and non-verbal intelligence. Musical sophistication was not significantly associated with the precision of working memory for amplitude modulation rate or with the precision of perception of either acoustic feature. The work supports a specific association between musical sophistication and working memory for sound frequency.
Global Diversity of the Gene Encoding the Pfs25 Protein - A Plasmodium Falciparum Transmission-Blocking Vaccine Candidate
Authors: Sookpongthai Pornpawee , Utayopas Korawich , Sitthiyotha Thassanai , Pengsakul Theerakamol , Kaewthamasorn Morakot , Wangkanont Kittikhun , Harnyuttanakorn Pongchai , Chunsrivirot Surasak , Pattaradilokrat Sittiporn
Published: August 2021

Background: Vaccines against the sexual stages of the malarial parasite Plasmodium falciparum are indispensable for controlling malaria and abrogating the spread of drug-resistant parasites. Pfs25, a surface antigen of the sexual stage of P. falciparum, is a leading candidate for transmission-blocking vaccine development. While clinical trials have reported that Pfs25-based vaccines are safe and effective in inducing transmission-blocking antibodies, the extent of the genetic diversity of Pfs25 in malaria endemic populations has been rarely studied. Thus, this study aimed to investigate the global diversity of Pfs25 in P. falciparum populations.Methods: A database of 307 Pfs25 sequences of P. falciparum was established. Population genetic analyses were performed to evaluate haplotype and nucleotide diversity, analyze haplotypic distribution patterns of Pfs25 in different geographical populations, and construct a haplotype network. Neutrality tests were conducted to determine evidence of natural selection. Homology models of the Pfs25 haplotypes were constructed, subjected to molecular dynamics (MD), and analyzed in terms of flexibility and percentages of secondary structures.Results: Pfs25 of P. falciparum comprised 11 unique haplotypes. Of these, haplotype 1 (H1) and H2, the major haplotypes, represented 70% and 22% of the population, respectively. H1 and H2 were dominant in Asia, whereas H1 was dominant in Africa, Central America, and South America. Other haplotypes were rare and region-specific, resulting in unique distribution patterns in different geographical populations. The diversity in Pfs25 originated from 10 single nucleotide polymorphism (SNP) loci located in EGF-like domains and anchor domain. Of these, an SNP at position 392 (GGA/GCA), resulting in amino acid substitution 131 (Gly/Ala), defined the two major haplotypes. MD results showed that structures of H1 and H2 variants were relatively similar. Limited polymorphism in Pfs25 could be likely due to negative selection. Conclusions: The study successfully established a Pfs25 sequence database that can become an essential tool for monitoring vaccine efficacy, designing assays for detecting malaria carriers, and conducting epidemiological studies of P. falciparum. The discovery of the two major haplotypes, H1 and H2, and their conserved structures suggests that the current Pfs25-based vaccines could be globally used for malaria control.
Dielectric Properties of Polyvinyl Alcohol/ Polyacrylamide Blend Film Filled with Carbon Nanospheres
Authors: Adoor Rashmi , Ayachit Narasimha , Upadhyaya Kishor , Bhajantri R.F. , Anandalli Mallikarjun
Published: August 2021

Carbon nanosphere / Polyvinyl alcohol/Polyacrylamide (CNS/PVA/PAM) nanocomposite films prepared via a solution casting method were studied for their structural and dielectric properties. Scanning Electron Microscopy (SEM) images of the CNS/PVA/PAM blends reveal the formation of circular islands of CNS and uniform blending with PVA/PAM matrix. XRD pattern shows a higher value with increase in blending ratio of PVA with CNS. The interaction of the dispersed and preformed CNS particles with the PVA/PAM chain was confirmed by the corresponding vibrational signaturing of PVA/PAM through FTIR. The dielectric constant increased from [K = 134, 2K Hz, 305 Kelvin] to [K = 438, 2KHz, 333 Kelvin] and the composite films exhibited a high increase in the energy storage efficiency upto 75% (at 2KHz) in the case of 4%CNS /PVA/PAM 50:50 sample.
Epicardial Adipose Tissue Radiodensity Is Associated With All-cause Mortality in Patients Undergoing Hemodialysis
Authors: Kwon Seong Soon , Choi Kyoungjin , Nam Bo Da , Lee Haekyung , Cho Nam-Jun , Park Byoung Won , Kim Hyoungnae , Noh Hyunjin , Jeon Jin Seok , Han Dong Cheol , Oh Sujeong , Kwon Soon Hyo
Published: August 2021

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm3) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range: 16.67–44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR]: 1.055; 95% confidence interval [CI]: 1.015–1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis.
Predicting Anesthetic Infusion Events Using Machine Learning
Authors: Miyaguchi Naoki , Takeuchi Koh , Kashima Hisashi , Morita Mizuki , Morimatsu Hiroshi
Published: August 2021

Recently, research has been conducted to automatically control anesthesia using machine learning, with the aim of alleviating the shortage of anesthesiologists. In this study, we address the problem of predicting decisions made by anesthesiologists during surgery using machine learning; specifically, we formulate a decision making problem by increasing the flow rate at each time point in the continuous administration of analgesic remifentanil as a supervised binary classification problem. The experiments were conducted to evaluate the prediction performance using six machine learning models: logistic regression, support vector machine, random forest, LightGBM, artificial neural network, and long short-term memory (LSTM), using 210 case data collected during actual surgeries. The results demonstrated that when predicting the future increase in flow rate of remifentanil after 1 min, the model using LSTM was able to predict with scores of 0.659 for sensitivity, 0.732 for specificity, and 0.753 for ROC-AUC; this demonstrates the potential to predict the decisions made by anesthesiologists using machine learning. Furthermore, we examined the importance and contribution of the features of each model using shapley additive explanations—a method for interpreting predictions made by machine learning models. The trends indicated by the results were partially consistent with known clinical findings.
Two Short Low Complexity Regions (LCRs) are Hallmark Sequences of the Delta SARS-CoV- 2 Variant Spike Protein
Authors: Becerra Arturo , Muñoz-Velasco Israel , Aguilar-Cámara Abelardo , Cottom-Salas Wolfgang , Cruz-González Adrián , Vázquez-Salazar Alberto , Hernández-Morales Ricardo , Jácome Rodrigo , Campillo-Balderas José Alberto , Lazcano Antonio
Published: August 2021

Low complexity regions (LCRs) are protein sequences formed by a set of compositionally biased residues. LCRs are extremely abundant in cellular proteins and have also been reported in viruses, where they may partake in evasion of the host immune system. Here we report four novel extremely conserved LCRs in the spike proteins of several SARS-CoV-2 variants. With the exception of Iota, where it is absent, the Spike LCR-1 is present in the signal peptide of 80.57% of the Delta variant, and in other variants of concern and interest. The Spike LCR-2 is highly prevalent (79.87%) in Iota. Two distinctive LCRs are present in the Delta spike protein. The Delta Spike LCR-3 is present in 99.19% of the analyzed sequences, and the Delta Spike LCR-4 in 98.3% of the same set of proteins. These two LCRs are present in the furin cleavage site and HR1 domain, respectively, and may be considered hallmark traits of the Delta variant. The presence of two medically-important point mutations, P681R and D950N, in these LCRs, combined with the extraordinary conservation of these regions, suggests that they may be a trait associated with the rapid spread of the highly contagious Delta lineage.
Neuroblastoma in Children: Intraoperative Goal Directed Therapy, Intraoperative And Postoperative Outcomes
Authors: Kumba Claudine
Published: August 2021

Background
Neuroblastoma is the most common tumor in children. Anesthetic management can be challenging due to the localization, catecholamine-secreting characteristic of the tumor. We undertook a secondary analysis in a previously study to describe patients who underwent neuroblastoma resection.
Objective
To describe intraoperative and postoperative outcomes in patients who underwent neuroblastoma resection and to propose optimal intraoperative management for postoperative outcome improvement.
Methods
Secondary analysis of children who had neuroblastoma resection in the initial retrospective study.
Results
There were 16 patients with a mean age of 39.3±22.1 months. Seven (43.8%) patients presented with intraoperative or postoperative complications. One (6.3%) patient had intraoperative broncho-laryngospasm and difficult intubation respectively. Two (12.5%) patients had intraoperative hemorrhagic shock. One patient (6.3%) had postoperative renal failure. Two patients (12.5%) had postoperative respiratory failure and 3 (18.8%) patients had postoperative cardiocirculatory failure. One (6.3%) had postoperative pulmonary sepsis and septicemia respectively. Thirteen (81.3%) patients were intraoperatively transfused. There was no in-hospital mortality.
Conclusion
Neuroblastoma surgery can be a challenging situation where cardiovascular instability, high blood loss and transfusion requirements can be encountered. Consequently, preoperative preparation, intraoperative optimal management with validated means in children are necessary for a better postoperative outcome in this surgical setting.
Outcome of Topiramate in Migraine Prophylaxis
Authors: Ibrahim Etedal Ahmed A. , Elhardallo Wadia Abdalla Balla , Ahmed Khabab Abbasher Hussien Mohamed , Omer Mohammed Eltahier Abdalla
Published: August 2021

Background: Topiramate is an anti epileptic medication originally and one of the first line drugs for migraine prophylaxis.Objective: To assess outcome of Topiramate in migraine prophylaxis by evaluating reduction in frequency and/or severity of attacks and address most common adverse affect associated with it.Methods: A Descriptive, prospective hospital based study was conducted at Ibrahim Malik Hospital, National center of neurological disease and sciences within the period of October 2018 –May 2019. Data entered, cleaned, analyzed using SPSS version 25.0.Results: This study covered 32 study participants; the mean age (33 ± 10) years, with female predominance by 27 (84%).Nearly, half of them 15(47%) migraine triggered by weather changes, 13 (41%) menstruation. 17(53%) was suffering from headache > 24 months, and most of them 26(81%) used the OTC medications in the acute pain headache.Mean of frequency of attacks per month was reduce (6.1 base line to 3.2), in severity mean was (6.9 turn to 5). Reduction in Frequency of attacks there was significant in both number and severity (p value < 0.001) with no significant difference in (50 mg and 100mg dose). Concerning adverse effects 5(15.6%) didn’t complain of any, more than third 12(38%) experienced weight loss, 7(22%) both Abdominal/GIT symptoms and Dizziness, 5(16%) mood changes, 4(13%) both parathesia and decreased memory, 3(9%) both Anorexia and sleepiness.Conclusion: Topiramate is effective in reducing headache frequency and reasonably well tolerated in adult Sudanese patients with episodic migraine. This may provide good evidence to support its use in routine clinical management.
Depth dependence of climatic controls on soil microbial community activity and composition
Authors: Dove Nicholas , Barnes Morgan , Moreland Kimber , Graham Robert , Berhe Asmeret , Hart Stephen
Published: August 2021

Subsoil microbiomes play important roles in soil carbon and nutrient cycling, yet our understanding of the controls on microbial communities in the subsoil is limited. Here, we investigate the direct (mean annual temperature and precipitation) and indirect (soil chemistry) effects of climate on microbiome composition and activity throughout the soil profile across two elevation-bioclimatic gradients in central California, USA. We show that microbiome composition changes and activity decreases with depth. Across these sites, the direct influence of climate on microbiome composition and activity was relatively lower at depth. Furthermore, we find that certain microbial taxa change in relative abundance over large temperature and precipitation gradients only in specific soil horizons, highlighting the depth dependence of the climatic controls on microbiome composition. Our finding that the direct impacts of climate are muted at depth suggests that deep soil microbiomes may lag in their acclimation to new temperatures with a changing climate.
The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Randomized Trial
Authors: Chávez-Iñiguez Jonathan S. , Ibarra-Estrada Miguel , Sánchez-Villaseca Sergio , Romero-González Gregorio , Font-Yañez Jorge J. , Torre-Quiroga Andrés De la , de Quevedo Andrés Aranda-G , Romero-Muñóz Alexia , Maggiani-Aguilera Pablo , Gómez-Fregoso Juan , Garcia-Garcia Guillermo
Published: August 2021

Aim:The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF).Methods: In a double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion.Results:From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p= 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53).ConclusionIn patients with SCR-1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results of renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 in June 2017 retrospectively registered.
Quasi-hedge funds market in Poland in view of their performance persistence
Authors: Aspadarec Waldemar
Published: August 2021

Performance persistence analysis is important as it has a decisive influence on investor allocation decisions. Investors can use quasi-hedge funds’ persistence to build effective investment strategies. Thus, the paper explores performance persistence of quasi-hedge funds operating at the Polish capital market. The methodology is based on constructing the new market performance index intended only for absolute return funds. It is validated regarding absolute returns of Polish quasi-hedge funds. The Absolute Return Index (ARI) is used to rate quasi-hedge funds’ performance persistence in assessing their fundamental purpose: to deliver consistently positive returns in all market conditions. For this, their quarterly return rates are used. All 53 funds operating for at least 36 months and representing 48.2% of the entire segment of absolute return funds are analyzed. The use of ARI allows examining quasi-hedge funds’ performance persistence in terms of market changes and the assessment of their purpose. In the short term (6 months) profitability remained persistent, while in the long term (12 months) such a hypothesis could be refuted. More than 40% of funds showed positive persistence within six months; only positive persistence occurred in the short term. 9.4% of funds repeatedly obtained negative returns, so absolute return funds’ negative performance persisted neither in the short nor long term. Closed-ended investment funds showed much stronger persistence of above-average positive returns, which additionally tended to avoid repeating negative returns in two-quarter and four-quarter series. This confirms the assumption that in this respect the Polish market is similar to the developed ones.
Does intrapreneurship increase work spirit and performance of village credit institutions?
Authors: I Ketut Merta  , Wayan Gede Supartha I , Made Artha Wibawa I , Bagus Ketut Surya Ida
Published: August 2021

This study aims to analyze the influence of intrapreneurship on improving village credit institution (VCI) performance with the work spirit as a mediation variable. The study was conducted at 108 village credit institutions in Karangasem Regency, Bali Province, Indonesia. Respondents were representatives of the management of village credit institutions (heads, treasurers, and secretaries). Sampling was done by proportional random sampling. A quantitative approach was used. Data were analyzed by the partial least square with SmartPLS 2.0 M3 program. The results found that intrapreneurship had a significant positive effect on the VCI performance. In addition, intrapreneurship had a significant positive effect on the work spirit, work spirit had a significant positive effect on the VCI performance, and work spirit significantly mediated the effect of intrapreneurship on VCI performance. Findings described the relationships among intrapreneurship, work spirit, and VCI performance in Karangasem Regency. VCI performance is more influenced by the work spirit than intrapreneurship with a coefficient of 0.645; VCI performance is partially influenced by intrapreneurship with a coefficient of 0.383; work spirit is also partially influenced by intrapreneurship with a coefficient of 0.353. Work spirit with a coefficient of 0.227 can act as partial mediation of the VCI performance in Karangasem Regency, Bali Province, Indonesia.
Interpretation of some criminal law aspects of the right to respect for private life
Authors: Timofeyeva Yuriivna
Published: August 2021

The article considers some issues of interpretation of the right to privacy in the practice of the ECtHR and its impact on the criminal law of Ukraine.
Numerous violations of the articles of the Convention require systematic response of the state and appropriate changes in both legislation and changes in law enforcement practices. The violations relate in particular to problems of interpretation of the provisions of the Convention. Provisions of Art. 8 of the Convention are related to other provisions of the Convention and the development of the case law of the European Court of Human Rights on certain issues.
It is noted that the Convention is dynamic, it changes under the influence of society, its provisions change in the process of development and acquire new meanings. In particular, the ECtHR recognizes a violation of Art. 8 (right to respect for private life) in those contexts in which he has not previously recognized. In particular, interpretation of Art. 8 of the Convention in the context of the right to environmental safety in case significant harm to the persons health (cases Dubetska and others v. Ukraine, Grymkivska v. Ukraine), the right to beg in the context of the right to freedom of expression (Lakatush v. Switzerland).
It is established that the development of these provisions requires analysis and consideration in the development of a new Criminal Code. At the same time, care must be taken to maintain a balance between freedoms and human rights and the security of society and the state. It is important that the rights enshrined in the Convention remain fundamental and do not go beyond the interests and needs of the individual. In addition, it is also necessary to take into account the national characteristics of the state.
Lecture on the topic: "Conviction: the concept, features, legal consequences, repayment and removal of convictions" (Articles 88-91 of the Criminal Code of Ukraine)
Authors: Tiutiuhin Volodymyr Illich
Published: August 2021

The lecture focuses on the main issues of the institute of criminal record. In particular, the following issues are considered: 1) the concept and features of a criminal record; 2) negative legal consequences caused by a person's criminal record; 3) preconditions, grounds, procedure for calculating the terms of repayment of a criminal record; 4) conditions for removal of a criminal record.
Criminal law and criminological threats in the Internet during a pandemic
Authors: Kalinina Alina Vladyslavivna , Shramko Sabriie Seitzheliivna
Published: August 2021

A general description of criminal law and criminological threats on the Internet, which have become particularly common or arose during the pandemic in Ukraine and the world have been analyzed in the scientific paper. It is noted that during this pandemic people began to rely more than ever on computer systems, mobile devices and the Internet for remote working, education, communication, shopping, sharing and receiving information, minimization the influence of the social distancing, etc. Increasing of the number of Internet users and the time spent them online, combined with the feelings of confusion, anxiety and fear has become an enabling environment for criminal activity in the cyber space.
The risks associated with the digitalization of health care in Ukraine and abroad have been identified. It is noted, that Interpol has identified three the most common types of cyberattacks at the international level, which affected individuals and legal entities during the pandemic: 1) the functioning of malicious domains; 2) distribution of malicious software; 3) download extortion programs.
Phishing and other types of cyber fraud, related to COVID-19, were analyzed. It is emphasized, that the perception of fake information (depending on its content) can lead to the panic spreading among the population, the formation of aggression against certain groups of people and so on.
It was determined, that during the COVID-19 pandemic, the increasing of the amount of "screen time" among both adults and children contributed to the intensification of actions aimed at sexual abuse of children on the Internet, cyberbullying, incitement to risky online behavior, distribution of potentially dangerous content.
It is stated, that according to experts opinion, the implementation of criminal law and criminological threats on the Internet in 2020 caused losses of more than 1% of world GDP.
Arrays of Copper Microelectrodes from Disposable Chips: Fabrication and Characterization
Authors: Higino Giane , Machado Ítalo , Nascimento Gabriel , Pedrotti Jairo
Published: August 2021

A simple, fast, and low-cost process to fabricate arrays of copper microelectrodes (CuMEs) based on disposable electronic microchips is described. Arrays with 8 to 20 CuMEs were characterized by energy-dispersive X-ray spectroscopy and cyclic voltammetry techniques. The closest interelectrode distance in the arrays is 358 ± 22 μm, and the minor radius ranged from 10.6 to 13.5 μm. The microchips with CuMEs were sealed in epoxy resin to fabricate the rod and flat-shaped platforms, allowing the CuMEs to be addressed separately. Glucose, hydrazine, and nitrate were used as analyte models for voltammetric and amperometric detection at CuMEs arrays, showing excellent performance in batch and flow-through cells. Glucose measurements carried out with flow injection analysis system with amperometric detection at an array of 20 CuMEs showed a wide linear range (0.020-4.0 mmol L-1), high sensitivity (734.1 μA L mmol-1 cm-2), and a limit of detection of 1.7 μmol L-1.
Evolution characteristics and relationship of meteorological and hydrological droughts from 1961 to 2018 in Hanjiang River Basin, China
Authors: Wang Lin , Zhang Jianyun , Elmahdi Amgad , Shu Zhangkang , Wu Yinghui , Wang Guoqing
Published: August 2021

In the context of global warming and increasing human activities, the acceleration of the water cycle will increase the risk of basin drought. In this study, to analyze the spatial and temporal evolution characteristics of hydrological and meteorological droughts over the Hanjiang River Basin (HRB), the Standardized Precipitation Index (SPI) and Standardized Runoff Index (SRI) were selected and applied for the period 1961–2018. In addition, the cross-wavelet method was used to discuss the relationship between hydrological drought and meteorological droughts. The results and analysis indicated that: (1) the meteorological drought in the HRB showed a complex cyclical change trend of flood-drought-flood from 1961 to 2018. The basin drought began to intensify from the 1990s and eased in the 2010s. The characteristics of drought evolution in various regions are different based on scale. (2) During the past 58 years, the hydrological drought in the HRB has shown a significant trend of intensification, particularly in autumn. Also, the hydrological droughts had occurred frequently since the 1990s, and there were also regional differences in the evolution characteristics of drought in various regions. (3) Reservoir operation reduces the frequency of extreme hydrological drought events. The effect of reducing the duration and intensity of hydrological drought events by releasing water from the reservoir is most obvious at Huangjiagang Station, which is the nearest to Danjiangkou Reservoir. (4) The hydrological drought and meteorological drought in the HRB have the strongest correlation on the yearly scale. After 1990, severe human activities and climate change have not only reduced the correlation between hydrological drought and meteorological drought in the middle and lower reaches of the basin, but also reduced the lag time between them. Among them, the hydrological drought in the upper reaches of the basin lags behind the meteorological drought by 1 month, and the hydrological drought in the middle and lower reaches of the basin has changed from 2 months before 1990 to 1 month lagging after 1990.
Comercio internacional entre Alianza del Pacífico y ANSEA: un análisis comparativo
Authors: González-Ayala Flavio Rafael , Lechuga-Cardozo Jorge Isaac
Published: August 2021

El presente artículo tiene como objetivo mostrar evidencia del comportamiento de la balanza comercial, exportaciones e importaciones entre la Alianza del Pacífico - AP y la Asociación de Naciones del Sudeste Asiático - ANSEA de forma comparativa, en el período 2002 a 2018. Se definió un estudio cuantitativo de tipo correlacional, descriptivo, no experimental y transeccional. Se aceptan las hipótesis de que existen diferencias significativas entre la media de crecimiento de exportaciones, importaciones y balanza comercial de la Alianza del Pacífico, y la media de crecimiento de exportaciones, importaciones y balanza comercial de ANSEA; y se rechaza la hipótesis de que no existen diferencias significativas (iguales) entre la media de crecimiento de exportaciones e importaciones de la Alianza del Pacífico y la media de crecimiento, exportaciones e importaciones de ANSEA. Lo anterior no explica el comportamiento de la balanza de pagos ya que existen diferencias significativas entre el crecimiento de las exportaciones e importaciones de AP y ANSEA.
Análisis de la generación de rentas propias por el municipio de Ocaña en el periodo 2009-2017
Authors: Sánchez-Becerra Carlos Andrés , Rodríguez Alex Mauricio
Published: August 2021

La presente investigación incorpora elementos teóricos del federalismo fiscal, estructuras y niveles de gobierno, descentralización, información y determinación de necesidades en lo local, y tipos de ingresos y gastos locales. Así mismo, busca conocer cómo ha sido el proceso de descentralización fiscal en el municipio de Ocaña desde la perspectiva de la capacidad para generar sus propios ingresos con base en las rentas que la Constitución y la ley le han otorgado y cuya reglamentación se encuentra en al acuerdo municipal 042 de 2009 “Estatuto Tributario del Municipio de Ocaña”. También, se dispone de la información contable pública disponible en el Consolidador de Hacienda e Información Pública (CHIP) y las resoluciones de la Contaduría General de la Nación sobre categorización de municipios. Con esta información se realizaron análisis comparativos de los recaudos y sus pesos relativos sobre los ingresos, comprendiendo el desempeño de la hacienda municipal para gestionar y recaudar sus rentas propias en el periodo 2009- 2017. Se resalta que, aunque el recaudo fiscal ha tenido un crecimiento significativo, su desempeño es inferior a otros municipios de similares características poblacionales.
Recent Progress Towards Vaccines and Antibody-based Therapies Against
Alzheimer's Disease
Authors: Ji Wenbo , Gong Baofeng , Jin Hong , Chen Xiaohan , Li Peng , Cheng Wenbin , Zhao Yuchen , He Bin , Zhuang Jianhua , Gao Jie , Yin You
Published: August 2021

:

Alzheimer's disease (AD), one of the progressive neurodegenerative disorders, is characterized
by clinical features such as memory loss, acquired skill loss, apraxia, and interpersonal and
social communication disorders. The AD hallmarks at the neuropathological level include intracellular
neurofibrillary tangles constituted by the hyperphosphorylated tau protein as well as the senile
extracellular plaques dominated by the amyloid-β (Aβ) deposits. At present, AD treatment that
mainly targeted towards improving symptoms and effective drugs to delay or stop disease progression
is lacking. Vaccines and antibody-based therapies are a type of natural, synthetic, and gene recombinant
biological product that treat or prevent disease progression by stimulating specific or
non-specific immune responses. Compared with traditional targeted drugs, vaccines and antibodybased
therapies have better safety and effectiveness and can even maintain the expression and stability
of Aβ and Tau proteins in patients for a long time. Logically, vaccines and antibody-based therapies
are somewhat different from traditional drugs because these drugs can achieve the therapeutic
effect of AD by activating immune cells and regulating the immune system of patients themselves,
thereby clearing disease-related proteins and long-term survival. Complete cure is also observed in
some patients after receiving the immunotherapy. Currently available vaccines and antibody-based
therapies mainly target Aβ and phosphorylated tau proteins. There are 44 vaccines and antibodybased
therapies for AD, among which nine drugs are discontinued, three drugs are inactive, eleven
drugs are in clinical phase 1, twelve drugs are in clinical phase 2, and seven drugs are in clinical
phase 3. Currently, no vaccines and antibody-based therapies have been approved for AD treatment.
In this paper, we review and analyse the research progress of vaccines and antibody-based therapies
that are used to treat AD.
Formulation and Evaluation of Hydroxypropylmethylcellulose-dicyclomine
Microsponges for Colon Targeted Drug Delivery: In Vitro and In
Vivo Evaluation
Authors: Sher Muhammad , Bukhari Syed Nasir Abbas , Sarfaraz Rai Muhammad , Iqbal Sadia , Hussain Muhammad Ajaz , Naeem-ul Hassan Muhammad , Hassan Faiza
Published: August 2021

Objective:

The objective of the present study was to design novel colon targeted delivery
of Dicyclomine Hydrochloride (DCH) microsponges.

Methods:

Microsponges (MS1-MS4) based on different ratios of Hydroxypropylmethylcellulose
(HPMC) and DCH were prepared by quasi-emulsion solvent diffusion method. Micro-sponges
were analyzed by determining percent yield, encapsulation efficiency, drug content, drug-polymer
compatibility and thermal stability. Kinetic analysis of thermal stability data was done by Chang
method, Friedman method and Broido method. In vitro dissolution study was carried out at pH 1.2,
pH 6.8 and pH 7.4 at different time intervals.

Results:

Results showed that there was no chemical interaction between DCH and HPMC in all microsponge
formulations. Production yield, drug content and encapsulation efficiency were enhanced
on increasing the drug-polymer ratio. Thermal stability of all the micro-sponges was
greater than that of pure drug. In vitro drug release was decreased on increasing the polymer concentration
at different pH levels. The newly prepared micro-sponges based on HPMC were confirmed
as a promising means of colon-targeted delivery of DCH. An HPLC method was developed
and validated for the bioequivalence study of newly designed microsponges. Pharmacokinetics parameters
were calculated using the linear trapezoidal method after single oral administration of microsponges
in white albino rabbits. Pharmacokinetics results indicate an enhancement in the value
of t1/2, tmax, Cmax and AUC0-t of DCH in the microsponges as compared to standard DCH showing enhanced
bioavailability of the drug after microsponges formation.

Conclusion:

The current study shows a new approach for colon-specific delivery of DCH based on
microsponges.
Molecular Epidemiology of HIV-1 Virus in Egypt: A Major Change in the Circulating Subtypes
Authors: Amer Ahmed Noby , Gaballah Ahmed , Emad Rasha , Ghazal Abeer , Attia Nancy
Published: August 2021

Background:

Human immunodeficiency virus type 1 (HIV-1) is characterized by high
genetic diversity due to its high mutation and recombination rates. Although, there is an increasing
prevalence of Circulating Recombinant Forms (CRFs) worldwide, subtype B is still recognized as
the predominant subtype in the Middle East and North Africa (MENA) region. There is a limited
sampling of HIV in this region due to its low prevalence. The main purpose of this study is to provide
a summary of the current status of the resident HIV subtypes and their distribution among
Egyptian patients.

Methodology:

Forty-five HIV-1 patients were included in this study. Partial pol gene covering the
protease (PR) and Reverse Transcriptase (RT) was successfully amplified in 21 HIV patients using
nested PCR of cDNA of the viral genomic RNA, then sequenced. The sequence data were used for
viral HIV-1 subtyping by 5 online subtyping tools: NCBI viral genotyping tool, Stanford University
HIV database (HIVDB) subtyping program, REGA tool, Context-Based Modeling for Expeditious
Typing (COMET) tool, and Recombinant Identification Program (RIP) tool. The final subtype
assignment was based on molecular phylogenetic analysis.

Results:

Unexpectedly, non-B subtypes are dominating, with the most common circulating one is
CRF02_AG (57.1%) followed by subtype B (14.3%), subtype BG recombinant (9.5%), CRF35_
AD (9.5%), subtype A1 and CRF06_cpx (4.8% each).

Conclusion:

To the best of our knowledge, this is the first study to tackle HIV-1 subtyping among
the group of HIV-1 patients in Egypt. CRF02_AG is the most prevalent subtype in Egypt.
Plant Extract-Assisted Green Synthesis of 2-Arylimidazo [1,2-A] Pyridine and Benzimidazole Derivatives
Authors: Veer Babita , Singh Ram
Published: August 2021

A green and efficient method for the synthesis of 2-arylimidazo [1, 2-a] pyridine (3)
and benzimidazole (8) derivatives has been developed using plant extracts. The different plant
part extracts of Terminalia chebula, Punica granatum, and Aegle marmelos have been studied.
The aqueous fruit extract of Terminalia chebula gave better results. The synthetic method has
been optimized with respect to plant extract quantity, pH of the reaction, and yield. The developed
protocol showed several advantages like mild reaction conditions, short reaction time, high yield,
and reduced environmental impact.
Synthetic Methods and Pharmacological Potential of Different Oxazine
Analogs
Authors: Asif Mohammad , Imran Mohd.
Published: August 2021

:

Oxazine analog is a vital class of heterocyclic compounds and has attracted synthetic interest
owing to their wide range of biological activities. Oxazine analogs are valuable in medicinal
organic chemistry and exhibit different varieties of biological activities such as antimicrobial, anticancer,
antimalarial, antitubercular, sedative, anticonvulsant, analgesic, anti-inflammatory, antipyretic,
etc. Oxazine can be derived from benzene by appropriate substitution of carbon atoms of the ring
by nitrogen and oxygen atoms. Nowadays, the development of drug resistance is a key problem, and
to defeat this problem, it is crucial to synthesize novel compounds. So, novel oxazine analogs may
play a crucial role to overcome these problems. Oxazine analogs are prepared by reaction of chalcone
derivatives with thiourea in the presence of alcohol and sodium hydroxide. The present aims of
this review are to give an outline of some different synthetic methods and different types of biological
activities of oxazine analogs. We hope that this review will be motivating for researchers concerned
with oxazine analogs.