bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel targeted co-delivery nanosystem for enhanced ovarian cancer treatment via multidrug resistance reversion and mTOR-mediated signaling pathway
Authors: Wang Xueqin , Xiong Tiandi , Cui Miao , Li Na , Li Qin , Zhu Li , Duan Shaofeng , Wang Yunlong , Guo Yuqi
Published: December 2021

Background

Multidrug resistance (MDR) is the main challenge of successful chemotherapy for ovarian cancer patients, with 50% to 75% of ovarian cancer patients eventually relapsed due to it. One of the effective strategies for treating MDR and improving therapeutic efficiency of ovarian cancer is to use nanotechnology-based targeted drug delivery systems. In this study, a novel nano targeted co-delivery system modified by hyaluronic acid (HA) was developed by using gold nanorods coated with functionalized mesoporous silica nanoparticles (HA-PTX/let-7a-GNR@MSN) for combined delivery of hydrophobic chemotherapy drug Paclitaxel (PTX) andlethal-7a(let-7a), a microRNA (miR), to overcome MDR in ovarian cancer. Furthermore, we also analyzed the molecular mechanism of this nanotherapeutic system in the treatment of ovarian cancer.

Results

HA-modified nanocomplexes can specifically bind to the CD44 receptor, which is highly expressed in SKOV3/SKOV3TRcells, achieving effective cell uptake and 150% enhancement of tumor site permeability. The nanosystem realized the stable combination and protective transportation of PTX and miRs. Analysis of drug-resistant SKOV3TRcells and an SKOV3TRxenograft model in BALB/c-nude mice showed significant downregulation of P-glycoprotein in heterogeneous tumor sites, PTX release, and subsequent induction of apoptosis. More importantly, this nanosystem could synergistically inhibit the growth of ovarian tumors. Further studies suggest that mTOR-mediated signaling pathways play an important role in reversing drug resistance and inducing apoptosis.

Conclusions

To sum up, these data provide a model for overcoming PTX resistance in ovarian cancer.

Graphical Abstract
Combined integrin αvβ3 and lactoferrin receptor targeted docetaxel liposomes enhance the brain targeting effect and anti-glioma effect
Authors: Qi Na , Zhang Shangqian , Zhou Xiantai , Duan Wenjuan , Gao Duan , Feng Jianfang , Li Aimin
Published: December 2021

The integrin αvβ3 receptor and Lactoferrin receptor (LfR) are over-expressed in both cerebral microvascular endothelial cells and glioma cells. RGD tripeptide and Lf can specifically bind with integrin αvβ3 receptor and LfR, respectively. In our study, RGD and Lf dual-modified liposomes loaded with docetaxel (DTX) were designed to enhance the brain targeting effect and treatment of glioma. Our in vitro studies have shown that RGD-Lf-LP can significantly enhance the cellular uptake of U87 MG cells and human cerebral microvascular endothelial cells (hCMEC/D3) when compared to RGD modified liposomes (RGD-LP) and Lf modified liposomes (Lf-LP). Free RGD and Lf competitively reduced the cellular uptake of RGD-Lf-LP, in particular, free RGD played a main inhibitory effect on cellular uptake of RGD-Lf-LP in U87 MG cells, yet free Lf played a main inhibitory effect on cellular uptake of RGD-Lf-LP in hCMEC/D3 cells. RGD-Lf-LP can also significantly increase penetration of U87 MG tumor spheroids, and RGD modification plays a dominating role on promoting the penetration of U87 MG tumor spheroids. The results of in vitro BBB model were shown that RGD-Lf-LP-C6 obviously increased the transport of hCMEC/D3 cell monolayers, and Lf modification plays a dominating role on increasing the transport of hCMEC/D3 cell monolayers. In vivo imaging proved that RGD-Lf-LP shows stronger targeting effects for brain orthotopic gliomas than that of RGD-LP and Lf-LP. The result of tissue distribution confirmed that RGD-LF-LP-DTX could significantly increase brain targeting after intravenous injection. Furthermore, RGD-LF-LP-DTX (a dose of 5 mg kg−1 DTX) could significantly prolong the survival time of orthotopic glioma-bearing mice. In summary, RGD and LF dual modification are good combination for brain targeting delivery, RGD-Lf-LP-DTX could enhance brain targeting effects, and is thus a promising chemotherapeutic drug delivery system for treatment of glioma.

Graphical abstract
Pharmaceutical subsidy policy in Iran: a qualitative stakeholder analysis
Authors: Olyaaeemanesh Alireza , Jaafaripooyan Ebrahim , Abdollahiasl Akbar , Davari Majid , Mousavi Seyyed Meysam , Delpasand Mansoor
Published: December 2021

Background

Over the past three decades, allocation of foreign currency subsidies has been the primary strategy of various administrations in Iran to improve access to medicines. This strategy has resulted in several challenges, including stakeholder conflicts of interest.

Objective

To identify the power, interest, and role of the stakeholders in allocating foreign currency subsidies to medicines in the Iranian health system.

Methods

In this qualitative study, 39 semi-structured interviews were conducted. Key informants were recruited using a purposive sampling technique. The theoretical framework adopted by Varvasovszky and Brugha was employed. The data were analysed using directed content analysis.

Results

The foreign currency subsidy for medicines included 21 stakeholders in five main categories: governmental organizations, Iranian Parliament, general population, nongovernmental organizations (NGOs), and the pharmaceutical industry. Stakeholders varied in their level of participation and support in the policy-making process. Among them, the Iranian Government, Planning and Budget Organization, the Ministry of Health and Medical Education (MoHME), and Iran Food and Drug Administration (IFDA) were the most important stakeholders, with highly supportive positions, while domestic drug manufacturers were the strongest opponents of this policy. The Government of Iran is the most powerful institution with regard to the ability to allocate foreign currency subsidies to medicines, followed by the MoHME and the IFDA.

Conclusion

This study demonstrated that identifying and analysing the stakeholders involved in allocating foreign currency subsidies to medicines can provide valuable information for policy-makers to enable a more comprehensive understanding and better capacity to determine whether or not to eliminate these subsidies. Moreover, decision-making in this process is a long-term issue that requires consensus among all stakeholders. Because of the political and social consequences of eliminating foreign currency subsidies, the necessary political will is not institutionalized. We recommend a step-by-step approach in eliminating foreign currency subsidies if the requirements are met (i.e., those related to the consequences of such interventions). Therefore, revision of the current policy along with these requirements, in addition to financial transparency and enhanced efficiency, will facilitate progress towards achieving the Sustainable Development Goals by improving access to medicines.
Tracking macrophages in diabetic neuropathy with two-color nanoemulsions for near-infrared fluorescent imaging and microscopy
Authors: Nichols James M. , Crelli Caitlin V. , Liu Lu , Pham Hoang Vu , Janjic Jelena M. , Shepherd Andrew J.
Published: December 2021

Background

The incidence of diabetes and diabetic peripheral neuropathy continues to rise, and studies have shown that macrophages play an important role in their pathogenesis. To date, macrophage tracking has largely been achieved using genetically-encoded fluorescent proteins. Here we present a novel two-color fluorescently labeled perfluorocarbon nanoemulsion (PFC-NE) designed to monitor phagocytic macrophages in diabetic neuropathy in vitro and in vivo using non-invasive near-infrared fluorescent (NIRF) imaging and fluorescence microscopy.

Methods

Presented PFC-NEs were formulated with perfluorocarbon oil surrounded by hydrocarbon shell carrying two fluorescent dyes and stabilized with non-ionic surfactants. In vitro assessment of nanoemulsions was performed by measuring fluorescent signal stability, colloidal stability, and macrophage uptake and subsequent viability. The two-color PFC-NE was administered to Leprdb/db and wild-type mice by tail vein injection, and in vivo tracking of the nanoemulsion was performed using both NIRF imaging and confocal microscopy to assess its biodistribution within phagocytic macrophages along the peripheral sensory apparatus of the hindlimb.

Results

In vitro experiments show two-color PFC-NE demonstrated high fluorescent and colloidal stability, and that it was readily incorporated into RAW 264.7 macrophages. In vivo tracking revealed distribution of the two-color nanoemulsion to macrophages within most tissues of Leprdb/db and wild-type mice which persisted for several weeks, however it did not cross the blood brain barrier. Reduced fluorescence was seen in sciatic nerves of both Leprdb/db and wild-type mice, implying that the nanoemulsion may also have difficulty crossing an intact blood nerve barrier. Additionally, distribution of the nanoemulsion in Leprdb/db mice was reduced in several tissues as compared to wild-type mice. This reduction in biodistribution appears to be caused by the increased number of adipose tissue macrophages in Leprdb/db mice.

Conclusions

The nanoemulsion in this study has the ability to identify phagocytic macrophages in the Leprdb/db model using both NIRF imaging and fluorescence microscopy. Presented nanoemulsions have the potential for carrying lipophilic drugs and/or fluorescent dyes, and target inflammatory macrophages in diabetes. Therefore, we foresee these agents becoming a useful tool in both imaging inflammation and providing potential treatment in diabetic peripheral neuropathy.
Evaluating the presence of Mycoplasma hyorhinis, Fusobacterium nucleatum, and Helicobacter pylori in biopsies of patients with gastric cancer
Authors: Nascimento Araujo Camila do , Amorim Aline Teixeira , Barbosa Maysa Santos , Alexandre Julieta Canjimba Porto Lucas , Campos Guilherme Barreto , Macedo Cláudia Leal , Marques Lucas Miranda , Timenetsky Jorge
Published: December 2021

Background

Gastric cancer is the third leading cause of cancer-related deaths worldwide and has been associated with infections that may promote tumour progression. Accordingly, we analysed the presence of Mollicutes, Mycoplasma hyorhinis, Fusobacterium nucleatum and Helicobacter pylori in gastric cancer tissues and evaluated their correlation with clinicopathological factors.

Methods

Using a commercial kit, DNA were extracted from 120 gastric samples embedded in paraffin: 80 from patients with gastric cancer and 40 from cancer free patients, dating from 2006 to 2016. Mollicutes and H. pylori were detected by PCR; F. nucleatum and M. hyorhinis were detected by qPCR, together with immunohistochemistry for the latter bacteria.

Results

Mollicutes were detected in the case and control groups (12% and 2.5%) and correlated with the papillary histologic pattern (P = 0.003), likely due to cell transformation promoted by Mollicutes. M. hyorhinis was detected in the case and control group but was not considered a cancer risk factor. H. pylori was detected at higher loads in the case compared to the control group (8% and 22%, P = 0.008) and correlated with metastasis (P = 0.024), lymphatic invasion (P = 0.033), tumour of diffused type (P = 0.028), and histopathological grading G1/G2 (P = 0.008). F. nucleatum was the most abundant bacteria in the case group, but was also detected in the control group (26% and 2.5%). It increased the cancer risk factor (P = 0.045, OR = 10.562, CI95% = 1.057–105.521), and correlated with old age (P = 0.030) and tumour size (P = 0.053). Bacterial abundance was significantly different between groups (P = 0.001).

Conclusion

Our findings could improve the control and promote our understanding of opportunistic bacteria and their relevance to malignant phenotypes.
The mediating role of internalizing and externalizing symptoms in the relationship between childhood trauma and suicidality among adolescents: a structural equation model
Authors: Kim Gangsan , Shin Jiyoon , Kim Jae-Won
Published: December 2021

Background

The objective of this study is to investigate the direct and indirect effects of childhood trauma, internalizing symptoms, and externalizing symptoms on suicidality among adolescents, thereby establishing a structural equation model.

Methods

The present study uses a cross-sectional descriptive design. Among 147 adolescents aged 12–17, 93 outpatients diagnosed with major depressive disorder and 54 controls were included in the study. They completed the Early Trauma Inventory Self-Report (Short Form) and Columbia Suicidality Severity Rating Scale. Their parents completed the Child Behavior Checklist. Analyses were performed using Pearson’s correlation and structural equation modelling.

Results

Childhood trauma had both direct and indirect effects, via internalizing symptoms and externalizing symptoms, on suicidality. Internalizing symptoms had a direct effect on suicidality. Meanwhile, externalizing symptoms were not directly associated with suicidality, but indirectly associated via internalizing symptoms.

Conclusions

Findings provide in-depth understanding of the mediating role of internalizing symptoms and externalizing symptoms in the relationship between childhood trauma and suicidality, suggesting that the therapeutic interventions for both internalizing symptoms and externalizing symptoms may be important to prevent suicide in adolescents with childhood trauma.
Assessment of FDA-approved drugs against Strongyloides ratti in vitro and in vivo to identify potentially active drugs against strongyloidiasis
Authors: Keiser Jennifer , Häberli Cécile
Published: December 2021

Background

Infections with Strongyloides stercoralis belong to the most neglected helminth diseases, and research and development (R&D) efforts on novel drugs are inadequate.

Methods

A commercially available library containing 1600 FDA-approved drugs was tested in vitro against Strongyloides ratti larvae (L3) at 100 µM. Hits (activity > 70%) were then evaluated against S. ratti adult worms at 10 µM. Morantel, prasterone, and levamisole were tested in the S. ratti rat model using dosages of 1–100 mg/kg.

Results

Seventy-one of the 1600 compounds tested against S. ratti L3 revealed activity above 70%. Of 64 compounds which progressed into the adult screen, seven compounds achieved death of all worms (benzethonium chloride, cetylpyridinium chloride, Gentian violet, methylbenzethonium chloride, morantel citrate, ivermectin, coumaphos), and another eight compounds had activity > 70%. Excluding topical and toxic compounds, three drugs progressed into in vivo studies. Prasterone lacked activity in vivo, while treatment with 100 mg/kg morantel and levamisole cured all rats. The highest in vivo activity was observed with levamisole, yielding a median effective dose (ED50) of 1.1 mg/kg.

Conclusions

Using a drug repurposing approach, our study identified levamisole as a potential backup drug for strongyloidiasis. Levamisole should be evaluated in exploratory clinical trials.

Graphical Abstract
Complete genome sequencing of SARS-CoV-2 strains: A pilot survey in Palestine reveals spike mutation H245N
Authors: Al-Jawabreh Amer , Ereqat Suheir , Dumaidi Kamal , Al-Jawabreh Hanan , Nasereddin Abedelmajeed
Published: December 2021

Objectives

SARS-CoV-2, severe respiratory syndrome coronavirus-2, is an RNA virus that emerged from China sweeping the globe in the form of a pandemic that became an international public health concern. This pilot study aimed to describe the genetic variation and molecular epidemiology of SARS-CoV-2 in Palestine in fall 2020.

Results

To achieve these aims, whole genome sequencing of SARS-CoV-2, phylogenetic analysis, haplotype networking and genetic diversity analysis were performed. These analyses revealed a unique spike mutation H245N that has never been reported before. The phylogenetic analysis depicted that three clusters existed in Palestinian SARS-CoV-2 genome sequences, in which cluster-I comprised the majority of clusters by 90%. Congruently, the haplotype network analysis depicted the same three clusters with a total of 39 haplotypes. The genetic diversity analysis showed that Cluster-I is highly diverse as confirmed by statistically significant mutation rate indices, Tajima’s D and Fu-Li’s-F tests (− 2.11 and 2.74, respectively), highest number of mutations (Eta = 120), highest number of haplotypes (h = 17), and highest average number of nucleotide differences between any two sequences (S = 118). The study confirmed the high genetic diversity among the Palestinian of SARS-CoV-2 which possessed high number of mutations including one which was reported for the first time.
Spatial and temporal genetic variation in Ethiopian barley (Hordeum vulgare L.) landraces as revealed by simple sequence repeat (SSR) markers
Authors: Dido Allo A. , Degefu Dawit T. , Assefa Ermias , Krishna M. S. R. , Singh B. J. K. , Tesfaye Kassahun
Published: December 2021

Background

Ethiopia is considered as center of diversity for barley (Hordeum vulgare L.) and it is grown across different agro-ecologies of the country. Unraveling population structure and gene flow status on temporal scales assists an evaluation of the consequences of physical, demographic and overall environmental changes on the stability and persistence of populations. This study was to examine spatial and temporal genetic variation within and among barley landrace samples collected over a period of four decades, using simple sequence repeat markers.

Results

Results from STRUCTURE, neighbor joining tree and discriminant analysis of principal component (DAPC) analysis revealed presence low-to-high genetic diversity among the landraces and grouped the landraces into three clusters. The cluster analysis revealed a close relationship between landraces along geographic proximity with genetic distance increases along with geographic distance. From analysis of molecular variance (AMOVA) in terms of collection year, it was observed that within-population genetic diversity much higher than between population and that the temporal differentiation is considerably smaller. The low-to-high genetic differentiation between landraces could be attributed to gene flow across the region as a consequence of seed exchange among farmers.

Conclusion

The results demonstrate that this set of SSRs was highly informative and useful in generating a meaningful classification of barley germplasms. Furthermore, results obtained from this study also suggest that landraces are a source of valuable germplasm for sustainable agriculture in the context of future climate change and in situ conservation strategies following adaptation to local environments.
Challenges in the control of COVID-19 outbreaks caused by the delta variant during periods of low humidity: an observational study in Sydney, Australia
Authors: Ward Michael P. , Liu Yuanhua , Xiao Shuang , Zhang Zhijie
Published: December 2021

Background

Since the appearance of severe acute respiratory coronavirus 2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) pandemic, a growing body of evidence has suggested that weather factors, particularly temperature and humidity, influence transmission. This relationship might differ for the recently emerged B.1.617.2 (delta) variant of SARS-CoV-2. Here we use data from an outbreak in Sydney, Australia that commenced in winter and time-series analysis to investigate the association between reported cases and temperature and relative humidity.

Methods

Between 16 June and 10 September 2021, the peak of the outbreak, there were 31,662 locally-acquired cases reported in five local health districts of Sydney, Australia. The associations between daily 9:00 am and 3:00 pm temperature (°C), relative humidity (%) and their difference, and a time series of reported daily cases were assessed using univariable and multivariable generalized additive models and a 14-day exponential moving average. Akaike information criterion (AIC) and the likelihood ratio statistic were used to compare different models and determine the best fitting model. A sensitivity analysis was performed by modifying the exponential moving average.

Results

During the 87-day time-series, relative humidity ranged widely (< 30–98%) and temperatures were mild (approximately 11–17 °C). The best-fitting (AIC: 1,119.64) generalized additive model included 14-day exponential moving averages of 9:00 am temperature (P < 0.001) and 9:00 am relative humidity (P < 0.001), and the interaction between these two weather variables (P < 0.001). Humidity was negatively associated with cases no matter whether temperature was high or low. The effect of lower relative humidity on increased cases was more pronounced below relative humidity of about 70%; below this threshold, not only were the effects of humidity pronounced but also the relationship between temperature and cases of the delta variant becomes apparent.

Conclusions

We suggest that the control of COVID-19 outbreaks, specifically those due to the delta variant, is particularly challenging during periods of the year with lower relative humidity and warmer temperatures. In addition to vaccination, stronger implementation of other interventions such as mask-wearing and social distancing might need to be considered during these higher risk periods.

Graphical Abstract
APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study
Authors: Kurki Samu N. , Kantonen Jonas , Kaivola Karri , Hokkanen Laura , Mäyränpää Mikko I. , Puttonen Henri ,   FinnGen, Martola Juha , Pöyhönen Minna , Kero Mia , Tuimala Jarno , Carpén Olli , Kantele Anu , Vapalahti Olli , Tiainen Marjaana , Tienari Pentti J. , Kaila Kai , Hästbacka Johanna , Myllykangas Liisa
Published: December 2021

Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.
Numerical validation of pressure and flow characteristics across a control valve in a feed line
Authors: Suri Nikhil , K. S. Venkateswaran , T. Ramesh
Published: December 2021

This work is intended to understand the variation of pressure and flow at the pump inlet of liquid rocket engine. The opening and closure of the valve upstream of the pump features complex phenomenon. The opening and  closing of the valve cause pressure and flow variations at the pump inlet which may lead to combustion instabilities in combustion chamber of engine, hydraulic transients in feedlines, and off-design operation of turbo-pumps which are fundamental to the efficient testing and operation of engine. A numerical model to predict the pressure and flow transients across a control valve for different rate of opening in fluid feed systems has been developed using first-order finite difference technique. In case of flow in pipes, the velocity and pressure is governed by momentum and continuity equations. A computer code for the prediction of fluid transients is developed based on method of characteristics for one-dimensional fluid flow in pipelines and compared with test data for validation. The control valve is considered to be in-line with the feed line and modeled based on the valve coefficient vs. percent opening of valve. This model can subsequently be used to predict the effect of opening/closing time of the valve on pressure surges across the control valve and corresponding flow rate in the feedline for different opening of the valve.
Scalable Science Education via Online Cooperative Questioning
Authors: Hilton Courtney B. , Goldwater Micah B. , Hancock Dale , Clemson Matthew , Huang Alice , Denyer Gareth
Published: December 2021

How can the scalable powers of peer learning and online technologies be most effectively used to support conceptual understanding in science education? This paper reviews cognitive science research on how people learn via question answering and authoring and evaluates a promising novel learning design that applies these principles.
Peculiarities of magnetic moment switching in the φ
0-junction
Authors: Belgibayev T. , Shukrinov Yu. M. , Plecenik A. , Pechousek J. , Burdik C.
Published: December 2021

We have investigated the dynamics of magnetization under a current pulse in a

-junction with a direct coupling between the magnetic moment and the superconducting current. The correspondence between the magnetization value at the end of the pulse

and the realization of the magnetization reversal along the easy axis of the ferromagnetic is considered. The crucial influence of the ratio w of the ferromagnetic frequency to the characteristic frequency of the Josephson junction on the results of reversal predictions is demonstrated. The effect of the w magnitude on the manifestation of periodicity bands in the

dependence on the model parameters is shown. There is a critical value of the Gilbert damping, above which the magnetization reversal is not realized. It is shown that at small w the magnitude

can be considered as a criterion of magnetization reversal. I.e., if

, the magnetization reversal would happen with 100 percent probability. The results can be used in various areas of superconducting spintronics, in particular, to create a memory element based on the Josephson

-junction.
An interview with Scott Fraser
Authors: Grewal Seema
Published: December 2021

Scott Fraser is a Provost Professor, and the Director of Science Initiatives, at the University of Southern California, USA. Scott has had a long-standing interest in applying the tools of chemistry, engineering and physics to problems in biology and medicine. Amongst other things, Scott is best known for his contributions to developing microscopes and tools to image developing embryos. Earlier this year, Scott was awarded the SDB's 2021 Edwin G. Conklin Medal, which aims to recognize ‘a developmental biologist who has made and is continuing to make extraordinary research contributions to the field, and is an excellent mentor who has helped train the next generation of outstanding scientists’. We caught up with Scott to find out more about his interdisciplinary research and his approach to mentoring.
Behavioural responses of threespine stickleback with lateral line asymmetries to experimental mechanosensory stimuli
Authors: Planidin Nicholas P. , Reimchen Thomas E.
Published: December 2021

Behavioural asymmetry, typically referred to as laterality, is widespread among bilaterians and is often associated with asymmetry in brain structure. However, the influence of sensory receptor asymmetry on laterality has undergone limited investigation. Here we used threespine stickleback (Gasterosteus aculeatus) to investigate the influence of lateral line asymmetry on laterality during lab simulations of three mechanosensation-dependent behaviours: predator evasion, prey localization and rheotaxis. We recorded the response of stickleback to impacts at the water surface and water flow in photic conditions and low-frequency oscillations in the dark, across four repeat trials. We then compared individuals' laterality with asymmetry in the number of neuromasts on either side of their body. Stickleback hovered with their right side against the arena wall 57% of the time (P<0.001) in illuminated surface impact trials and 56% of the time (P=0.085) in dark low-frequency stimulation trials. Light regime modulated the effect of neuromast count on laterality, as fish with more neuromasts were more likely to hover with the wall on their right during illumination (P=0.007) but were less likely to do so in darkness (P=0.025). Population-level laterality diminished in later trials across multiple behaviours and individuals did not show a consistent side bias in any behaviours. Our results demonstrate a complex relationship between sensory structure asymmetry and laterality, suggesting that laterality is modulated by multiple sensory modalities and is temporally dynamic.
RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type
Authors: Medhi Ragini , Price Jonathan , Furlan Giulia , Gorges Beronia , Sapetschnig Alexandra , Miska Eric A.
Published: December 2021

The human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyze the additions of uridines at the 3′ end of RNAs, including the precursors of the tumor suppressor miRNA let-7 upon recruitment by the oncoprotein LIN28A. As a consequence, let-7 family miRNAs are down-regulated. Disruption of this TUT4/7 activity inhibits tumorigenesis. Hence, targeting TUT4/7 could be a potential anticancer therapy. In this study, we investigate TUT4/7-mediated RNA regulation in two cancer cell lines by establishing catalytic knockout models. Upon TUT4/7 mutation, we observe a significant reduction in miRNA uridylation, which results in defects in cancer cell properties such as cell proliferation and migration. With the loss of TUT4/7-mediated miRNA uridylation, the uridylated miRNA variants are replaced by adenylated isomiRs. Changes in miRNA modification profiles are accompanied by deregulation of expression levels in specific cases. Unlike let-7s, most miRNAs do not depend on LIN28A for TUT4/7-mediated regulation. Additionally, we identify TUT4/7-regulated cell-type-specific miRNA clusters and deregulation in their corresponding mRNA targets. Expression levels of miR-200c-3p and miR-141-3p are regulated by TUT4/7 in a cancer cell-type-specific manner. Subsequently, BCL2, which is a well-established target of miR-200c is up-regulated. Therefore, TUT4/7 loss causes deregulation of miRNA–mRNA networks in a cell-type-specific manner. Understanding of the underlying biology of such cell-type-specific deregulation will be an important aspect of targeting TUT4/7 for potential cancer therapies.
Likely community transmission of COVID-19 infections between neighboring, persistent hotspots in Ontario, Canada
Authors: Mucaki Eliseos J. , Shirley Ben C. , Rogan Peter K.
Published: December 2021

Introduction: This study aimed to produce community-level geo-spatial mapping of confirmed COVID-19 cases in Ontario Canada in near real-time to support decision-making. This was accomplished by area-to-area geostatistical analysis, space-time integration, and spatial interpolation of COVID-19 positive individuals.

Methods: COVID-19 cases and locations were curated for geostatistical analyses from March 2020 through June 2021, corresponding to the first, second, and third waves of infections. Daily cases were aggregated according to designated forward sortation area (FSA), and postal codes (PC) in municipal regions Hamilton, Kitchener/Waterloo, London, Ottawa, Toronto, and Windsor/Essex county. Hotspots were identified with area-to-area tests including Getis-Ord Gi*, Global Moran’s I spatial autocorrelation, and Local Moran’s I asymmetric clustering and outlier analyses. Case counts were also interpolated across geographic regions by Empirical Bayesian Kriging, which localizes high concentrations of COVID-19 positive tests, independent of FSA or PC boundaries. The Geostatistical Disease Epidemiology Toolbox, which is freely-available software, automates the identification of these regions and produces digital maps for public health professionals to assist in pandemic management of contact tracing and distribution of other resources. 

Results: This study provided indicators in real-time of likely, community-level disease transmission through innovative geospatial analyses of COVID-19 incidence data. Municipal and provincial results were validated by comparisons with known outbreaks at long-term care and other high density residences and on farms. PC-level analyses revealed hotspots at higher geospatial resolution than public reports of FSAs, and often sooner. Results of different tests and kriging were compared to determine consistency among hotspot assignments. Concurrent or consecutive hotspots in close proximity suggested potential community transmission of COVID-19 from cluster and outlier analysis of neighboring PCs and by kriging. Results were also stratified by population based-categories (sex, age, and presence/absence of comorbidities).

Conclusions: Earlier recognition of hotspots could reduce public health burdens of COVID-19 and expedite contact tracing.
Nurse staffing and patient care outcomes: protocol for an umbrella review to identify evidence gaps for low and middle-income countries
Authors: Imam Abdulazeez , Obiesie Sopuruchukwu , Aluvaala Jalemba , Maina Michuki , Gathara David , English Mike
Published: December 2021

Background: Adequate staffing is key to the delivery of nursing care and thus to improved inpatient and health service outcomes. Several systematic reviews have addressed the relationship between nurse staffing and these outcomes. Most primary studies within each systematic review are likely to be from high-income countries which have different practice contexts to low and middle-income countries (LMICs), although this has not been formally examined. We propose conducting an umbrella review to characterise the existing evidence linking nurse staffing to key outcomes and explicitly aim to identify evidence gaps in nurse staffing research in LMICs.

Methods and analysis: This protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA-P). Literature searching will be conducted across Ovid Medline, Embase and EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Two independent reviewers will conduct searching and data abstraction and discordance will be handled by discussion between both parties. The risk of bias of the individual studies will be performed using the AMSTAR-2.

Ethics and dissemination: Ethical permission is not required for this review as we will make use of already published data. We aim to publish the findings of our review in peer-reviewed journals.

PROSPERO registration number:CRD42021286908
Archaeological settlement research for the late Middle Ages in Poland
Authors: Marciniak-Kajzer Anna
Published: December 2021

Archaeological settlement research in Poland has to date not been conducted on a large scale. The remains of medieval villages have usually been excavated when rescue works were required by construction projects – usually along the routes of planned highways. Traces of farming have been discovered only by chance, and research on the distribution of land uses has mainly been carried out by geographers. In a few cases, survey excavations of rural settlements have been carried out in the vicinity of defensive structures being investigated. In cities, even long-term studies have basically been limited to researching only the densely built-up zone, the market square, and defensive walls. Neither agricultural land owned by townsfolk nor the zones outside the city proper that they used economically have been examined. The surface research resulting from the campaign Archeologiczne Zdjęcie Polski – AZP (Polish Archaeological Record) is of little use for the late Middle Ages, firstly because artefacts from that period were not collected at the beginning of the research, and also because of a specific aspect of cultivation (fertilisation), which saw a considerable carrying of movable cultural artefacts out from built-up areas. These weaknesses resulted from various factors. First of all, there was a lack of interest in such research among not only historical preservation services but also archaeologists themselves. However, the main factor was the significant financial outlays that such research requires.
Currently, archaeology has many techniques at its disposal that allow large areas to be studied and that thus allow archaeological sites to be identified and preliminarily investigated. Aerial laser scanning and ground-based geophysical methods provide much valuable data and, above all, allow places requiring excavation to be accurately identified. Unfortunately, deeming such methods to sufficiently record sites can sometimes mean that they constitute the first and only archaeological survey of a site. Then there are problems of dating such sites and, of course, we do not acquire many of the movable cultural objects that research on medieval society demands.
Wooden sacral architecture in Greater Poland. An interdisciplinary case study of the church in Domachowo
Authors: Różański Artur , Jurek Tomasz , Marciniak Piotr , Łobodzińska Patrycja , Schaaf Ulrich
Published: December 2021

Sacred wooden architecture in Poland is a huge and still unrecognised research problem. It covers a number of issues of interdisciplinary character: from the properties of building materials and carpentry techniques, through constructionand architectural-spatial solutions, to cultural and natural conditions. Hence, the best way to study this problem is interdisciplinary research. The necessity of cooperation of representatives of various scientific disciplines became the basis for creating a team to study the wooden church of St Michael the Archangel in Domachowo, so far dated to 1568. As researchers representing various disciplines (including archaeology, history, art history, history of architecture, architecture, architectural conservation), we cite sources and research that allow us to formulate a thesis that the past of the Domachowo church dates back to the 14th century. Moreover, we present the research and methodological problems inscribed in the aforementioned church building, understood as a whole. Such a multifaceted approach allows us to redefine the current knowledge about the church in Domachowo.
Barczewko – a cemetery of the first settlers in Southern Warmia against the background of medieval inhumation necropolises in Teutonic Prussia
Authors: Koperkiewicz Arkadiusz
Published: December 2021

Barczewko is located near Olsztyn, in the Warmian-Masurian province (north-eastern Poland). The site on Lake Wadąg was the place of the first location of today’s Barczewo (Ger. Wartenburg). Urban settlement with the castle/watchtower was erectedon the initiative of the bishop of Warmia at the end of the 1320s. The development of the young urban colony was interrupted in 1354 when it was invaded by Lithuanian troops, burned down and abandoned. The village that was later established nearbywas called Alt Wartenberg. The hill behind the village, referred to as the Old Town, has never been built on. The place is a specific time capsule, preserving the remains of buildings and the basic elements of the town’s spatial arrangement. In the years 2013–2019, a Polish-German research project was carried out here. After a series of non-invasive tests, the cellars of dwelling buildings with artefacts abandoned on the day of the raid, fortifications, market square buildings, central place of craft and trade nature (the so-called mercatorio) and the settlers’ cemetery, as well as the remains of the victims of the raid, were uncovered by excavation. It is a unique complex which provides a lot of information about the pioneering phases of town  formation in the state of the Teutonic Order, and about the everyday life of settlers coexisting most likely with the Old Prussian population. The excavations reveal details of the dramatic events related to the fall of the town, thus confirming written sources. This text presents for the first time the preliminary results of the research on the cemetery of the first settlers in southern Warmia. The necropolis provides evidence for the presence of the Old Prussian indigenous population who played a significant role in this process.
Brakowanie dokumentacji niearchiwalnej i gospodarka makulaturą w urzędzie na przykładzie przepisów Ministerstwa Leśnictwa w Warszawie z lat 1951 i 1952
Authors: Dąbrowski Adam Grzegorz
Published: December 2021

W maju 1951 r. zatwierdzona została uchwała Prezydium Rządu w sprawie gospodarki makulaturą, której zapisy w znacznej mierze odnosiły się do urzędów administracji państwowej. Rozwinięciem uchwały rządowej były wytyczne Naczelnej Dyrekcji Archiwów Państwowych z lutego 1952 r. w sprawie trybu postępowania przy przekazywaniu akt urzędów i instytucji państwowych na makulaturę. Artykuł prezentuje wymienione wyżej normatywy, próbę ich wdrożenia oraz skutki nowego stanu prawnego dla mechanizmu brakowania dokumentacji niearchiwalnej na przykładzie Ministerstwa Leśnictwa w Warszawie.
 W efekcie w składnicy akt Ministerstwa przeprowadzono podział akt na kategorie A oraz B, następnie przygotowano stosowne spisy akt przeznaczonych na brakowanie i wystąpiono do właściwych władz archiwalnych o wydanie zgody na przekazanie ich na makulaturę. Niestety, proces ten objął tylko niewielkie ilość dokumentacji niearchiwalnej z zasobu składnicy akt Ministerstwa, a do selekcji archiwaliów resortu powrócono dopiero po kilku latach (być może z powodu trudności w prawidłowej kwalifikacji poszczególnych materiałów do kategorii A bądź B, o czym świadczyły protokoły z kontroli przebiegu takiej kwalifikacji).
XXII Ogólnopolski Zjazd Studentów Archiwistyki w Siedlcach 16–17 kwietnia 2021 r.
Authors: Czyż Piotr
Published: December 2021

Sprawozdanie z XXII Ogólnopolskiego Zjazdu Studentów Archiwistyki w Siedlcach 16–17 kwietnia 2021 r.
The Defects of Nigeria’s Secured Transactions in Movable Assets Act 2017 and Their Potential Repercussions on Access to Credit: a Comparative Analysis and Lessons from the Anglo-American Law
Authors: Iheme Williams Chima
Published: December 2021

It has been sufficiently established in law and finance literature that an effective legal framework that governs non-possessory security transactions is a key component in the realization of financial inclusion and affordable access to credit in market economies. Recently, the Nigerian lawmakers enacted the Secured Transactions in Movable Assets Act 2017 (STMA), which was modelled after the United States’ Article 9 of the Uniform Commercial Code (UCC Article 9) and its unitary-functional approach to security interests. Arguably, some of the STMA’s provisions are defective: they do not reflect the local conditions in Nigeria and are likely to frustrate its section 1 aim of broadening access to credit for individuals and small businesses. The STMA recognizes registration as the main method of perfection: yet there are multiple but unlinked movable collateral registries in Nigeria which ultimately constitute a breeding ground for secret liens. This article argues that the relegation of other perfection methods, such as ‘possession’ and ‘control’, will diminish the economic success of the reformed law. It calls for a reconsideration of the rules governing publicity and the perfection of security interests under the STMA with insights and lessons from the UCC Article 9 and its underlying case law.
Better to Explain or to Testify? The Position of the Accused as a Source of Oral Evidence in a Criminal Trial in a Comparative Perspective
Authors: Kuczyńska Hanna
Published: December 2021

In this article the position of the accused as a source of personal evidence in three different European legal systems: Poland, Germany, and England, will be presented. This analysis will be oriented to understand the way of functioning of the two different models of giving statements of fact by the accused at a criminal trial. The main difference is that in the common law model of criminal trial the accused may only present evidence by testifying as a witness speaking about what happened, whereas in the continental model the accused gives a specific personal type of evidence (that in the Anglo-Saxon literature is rather described as “oral evidence”) that is known as explanations. From this differentiation several consequences arise: among others, the possibility of presenting untruthful explanations and presenting many versions of events in the continental model which have to be assessed by the judges. At the same time, the same right of the accused to silence and not to give incriminating evidence applies in both models of criminal trial – however, in two different shapes and with different types of limitations.
Three Different Legal Attitudes Towards Non-Marital Cohabitation in Europe
Authors: Kabza Ewa
Published: December 2021

The rising number of people “just living together”, people who are neither married nor in registered partnerships, clearly demonstrates that non-marital unions can no longer be ignored. To obtain an accurate picture of the situation of non-marital partners it was essential to conduct comparative research of multiple legal orders. This analysis threw a new light (at least from the Polish standpoint) on possible solutions to the problem of the regulation of legal aspects of “living together”. It appears that three different legal attitudes towards non-marital cohabitation may be distinguished in Europe. Firstly, there are legal orders in which by virtue of an explicit reference by the legislator – the regulations on marriage are applied to cohabitation (quasi-marriage cohabitation). Secondly, there also exist countries in which a law was adopted regulating selected aspects of actual cohabitation (implied model of cohabitation). And thirdly, there are legal orders in which any cohabitant-oriented legal regime exists.
Access to Internet as a Human Right – Justification and Comparative Study
Authors: Mehrotra Abhinav
Published: December 2021

This paper advances a human rights perspective to the understanding of internet access by viewing it through a comparative lens with reference to countries in Europe, and the USA, India, and China. The question that is explored is: does internet access warrant recognition as a stand-alone human right, or is it sufficient that access is so bound up with one or more existing rights that formal recognition is unnecessary? Through this paper an effort has been made to analyse whether having a right to internet access as a human right is possible and to argue for the need to recognise such a right given the importance such a right holds, as can be seen especially during the ongoing pandemic when every aspect of life has been shifted to the online mode.