bluuebunny/crossref_metadata_2025 huggingface dataset:
Global status of tetracycline resistance among clinical isolates of Vibrio cholerae: a systematic review and meta-analysis
Authors: Ahmadi Mohammad Hossein
Published: August 2021

Background

There has been an increasing resistance rate to tetracyclines, the first line treatment for cholera disease caused byV. cholerastrains, worldwide. The aim of the present study was to determine the global status of resistance to this class of antibiotic amongV. choleraisolates.

Methods

For the study, electronic databases were searched using the appropriate keywords including: ‘Vibrio’, ‘cholera’, ‘Vibrio cholerae’, ‘V. cholerae’, ‘resistance’, ‘antibiotic resistance’, ‘antibiotic susceptibility’, ‘antimicrobial resistance’, ‘antimicrobial susceptibility’, ‘tetracycline’, and ‘doxycycline’. Finally, after some exclusion, 52 studies from different countries were selected and included in the study and meta-analysis was performed on the collected data.

Results

The average resistance rate for serogroup O1 to tetracycline and doxycycline was 50% and 28%, respectively (95% CI). A high level of heterogeneity (I2 > 50%,p-value < 0.05) was observed in the studies representing resistance to tetracycline and doxycycline in O1 and non-O1, non-O139 serogroups. The Begg’s tests did not indicate the publication bias (p-value > 0.05). However, the Egger’s tests showed some evidence of publication bias in the studies conducted on serogroup O1.

Conclusions

The results of the present study show that the overall resistance to tetracyclines is relatively high and prevalent amongV. choleraeisolates, throughout the world. This highlights the necessity of performing standard antimicrobial susceptibility testing prior to treatment choice along with monitoring and management of antibiotic resistance patterns ofV. choleraestrains in order to reduce the emergence and propagation of antibiotic resistant strains as well as the failure of treatment.
LncRNA-TUG1 promotes the progression of infantile hemangioma by regulating miR-137/IGFBP5 axis
Authors: Zhou Lili , Jia Xiao , Yang Xiangzheng
Published: August 2021

Background

Previous studies indicated that lncRNA taurine upregulated gene 1 (TUG1) played essential roles in human cancers. This study aimed to investigate its function in infantile hemangioma (IH).

Methods

A total of 30 pairs of clinical infantile specimens were used in this study. The expression of TUG1 in IH tissues was assessed by quantitative reverse transcriptase PCR (qRT-PCR). Two short hairpin RNA targeting TUG1 (sh-TUG1-1 and sh-TUG1-2) were transfected into hemangioma-derived endothelial cells, HemECs, to block its expression. The effects of TUG1 on HemECs were evaluated by Cell Counting Kit-8 (CCK-8), colony formation assay, wound healing assay, and Transwell assay. The underlying molecular mechanism of TUG1 was investigated by Starbase prediction and luciferase reporter assay and further determined by loss- and gain-of-function approaches. In addition, the role of TUG1 on tumorigenesis of HemECs was confirmed in an in vivo mouse model.

Results

TUG1 was significantly upregulated in infant hemangioma tissues compared with normal adjacent subcutaneous tissues. The loss- and gain-of-function approaches indicated that TUG1 overexpression promoted proliferation, migration, and invasion of HemECs in vitro, and TUG1 knockdown inhibited the tumorigenesis of HemECs in vivo. Specifically, TUG1 could compete with IGFBP5 for miR137 binding. Rescue experiments further confirmed the role of the TUG1/miR137/IGFBP5 axis in HemECs.

Conclusion

TUG1 was closely associated with the progression of IH by regulating the miR-137/IGFBP5 axis, which might be a potential target for IH treatment.
Determinants of the uptake of intermittent preventive treatment of malaria in pregnancy with sulphadoxine pyrimethamine in Sabatia Sub County, Western Kenya
Authors: Mutanyi Joshua A. , Onguru Daniel O. , Ogolla Sidney O. , Adipo Lawrence B.
Published: August 2021

Background

Annually, 125.2 million pregnant women worldwide risk contracting malaria, including 30.3 million and 1.5 million in Sub-Saharan Africa and Kenya respectively. At least three doses of sulphadoxine pyrimethamine for intermittent preventive treatment of malaria in pregnancy (IPTp-SP) is recommended for optimal benefit. Kenya recorded low IPTp-SP optimal uptake in 2015. This study investigated the prevalence of and factors influencing IPTp-SP optimal uptake in Sabatia Sub County, Western Kenya.

Methods

A cross-sectional study was conducted in Sabatia Sub County from April to October 2020. Using a validated semi-structured questionnaire, data were obtained from 372 randomly sampled post-delivery women aged 15–49 years with live birth within one year preceding the study. Women on cotrimoxazole prophylaxis during pregnancy were excluded. Pearson Chi-square and Fisher’s Exact test were measures of association used. Binary logistic regression analysed predictors of optimal IPTp-SP uptake.

Results

Optimal IPTp-SP uptake was 79.6%, 95% CI 75.5%–83.7%. Predictors of IPTp-SP optimization were gestational age at first antenatal care (ANC) visit (P = 0.04), frequency of ANC visits (P < 0.001), maternal knowledge of IPTp-SP benefits (P < 0.001), maternal knowledge of optimal sulphadoxine pyrimethamine (SP) dose (P = 0.03) and SP administration at ANC clinic (P = 0.03). Late ANC initiators were less likely to receive optimal IPTp-SP (aOR = 0.4, 95% CI 0.2–0.9). Odds of optimizing IPTp-SP increased among women with ≥ 4 ANC visits (aOR = 16.7, 95% CI 7.9–35.3), good knowledge of IPTp-SP benefits (aOR = 2.4, 95% CI 1.3–4.5) and good knowledge of optimal SP dose (aOR = 1.9, 95% CI 1.1–3.4). Women who never missed being administered SP were highly likely to receive optimal IPTp-SP (aOR = 2.9, 95% CI 1.1–7.2)

Conclusions

This study has found high IPTp-SP optimal uptake in the study area. Efforts should be directed towards early and more frequent ANC visits. Intensive and targeted health education is required. It’s fundamental to adequately stock and consistently administer SP. Future studies considering larger samples and health workers’ perspectives of the health system delivery factors are recommended.

Graphical abstract
Standardization and validation of assay of selected omega-3 and omega-6 fatty acids from phospholipid fraction of red cell membrane using gas chromatography with flame ionization detector
Authors: Gupta Ruby , Dhatwalia Savita , Chaudhry Monica , Kondal Dimple , Stein Aryeh D. , Prabhakaran Dorairaj , Tandon Nikhil , Ramakrishnan Lakshmy , Khandelwal Shweta
Published: August 2021

Background

Docosahexaenoic acid (DHA) is an important structural component of human brain and retina. Evidence exists linking nutritional status of pregnant mothers and cognitive functions of their born infants. The DHANI (Maternal DHA Supplementation and Offspring Neurodevelopment in India) trial was implemented to evaluate the effect of maternal supplementation with DHA during pregnancy and for 6 months following delivery on motor and mental development of infants at 1 and 12 months. We describe here the standardization and validation of an assay for measurement of selected omega-3 and omega-6 fatty acids from the phospholipid fraction of red blood cells to assess their status in mothers at baseline, delivery and 6 months post-delivery and for infants in cord blood and at 1 and 12 months of age. The validated method has been used for the analysis of samples for DHANI.

Methods

Lipids were extracted from a pool of red blood cells, separated using thin layer chromatography. The phospholipid fraction was esterified, and fatty acids were separated by gas chromatography using a flame ionization detector.

Result

The method accuracy for DHA was between 97 - 98% and between 91 - 95% for arachidonic acid (AA) at three different concentrations. The intra-assay and inter-assay coefficient of variation for the fatty acids ranged from 1.19 to 5.7% and 0.78 to 13.0% respectively. Intraclass correlation (ICC), as a measure of reproducibility, ranged between 0.689 and 0.996. A good linearity was observed for all the fatty acids between concentrations of 0.2–4 μg/ml.

Conclusion

The standardized and validated method is suitable for implementation in large epidemiological studies for evaluation of fatty acids and in nutritional trials for assessment of fatty acid content of various lipid classes.
DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice
Authors: Zhu Ying , Wang Xinru , Zhou Xiaoyun , Ding Lexi , Liu Dan , Xu Huizhuo
Published: August 2021

Background

Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR.

Methods

Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model. DR mouse model was established by streptozotocin injection, and then received 5-Aza-2-deoxycytidine (DAC; DNA methyltransferase inhibitor) treatment. Hematoxylin–eosin staining was performed to assess retinal tissue damage. PPARα methylation was examined by Methylation-Specific PCR. Flow cytometry and DCFH-DA fluorescent probe was used to estimate apoptosis and reactive oxygen species (ROS). The interaction between DNA methyltransferase-1 (DNMT1) and PPARα promoter was examined by Chromatin Immunoprecipitation. Quantitative real-time PCR and western blot were performed to assess gene and protein expression.

Results

HG treatment enhanced the methylation levels of PPARα, and repressed PPARα expression in HRCPs. The levels of apoptotic cells and ROS were significantly increased in HRCPs in the presence of HG. Moreover, DNMT1 was highly expressed in HG-treated HRCPs, and DNMT1 interacted with PPARα promoter. PPARα overexpression suppressed apoptosis and ROS levels of HRCPs, which was rescued by DNMT1 up-regulation. In DR mice, DAC treatment inhibited PPARα methylation and reduced damage of retinal tissues.

Conclusion

DNMT1-mediated PPARα methylation promotes apoptosis and ROS levels of HRCPs and aggravates damage of retinal tissues in DR mice. Thus, this study may highlight novel insights into DR pathogenesis.
Percutaneous transhepatic biliary puncture simulator: a cord network prototype
Authors: Lopez Benítez Rubén , Reyes del Castillo Tomás , Benz David , Fechner Carsten , Szabo Lorant , Kara Levent , Monnard Etienne , Kostrzewa Michael , Roos Justus E.
Published: August 2021

Background

The aim of this study was to present a percutaneous transhepatic biliary puncture simulator that can be used without radiation exposure and that reflects the conventional anatomy of the biliary ducts and its vicinity structures.

Methods

An anatomically based model of the biliary tree was developed using a cord network fixed to a wooden frame. The skin, ribs, intercostal muscles, and right lower lobe pleura were simulated using foam sponge, plastic tubes, a polystyrene foam panel, and an air pad, respectively. For the puncture, we used a 20-G Chiba needle and a wire with distal double arches; these were used to troll a cord, simulating the successful puncture of a bile duct. A camera was also placed above the model to allow the trainees to train eye-hand coordination while viewing the image on a monitor in real time. The simulator was tested with 60 radiology residents to evaluate the confidence and skills transferability of the training model.

Results

After receiving an introduction of the system and 5 min of training under tutor surveillance, all participants were able to troll a cord of the biliary simulator by themselves in less than 4 min. Only one participant punctured the simulated pleura. The participants’ evaluations showed positive results, with increased user confidence and skills transferability after the training session.

Conclusions

This proposed simulator can be an effective tool to improve a trainee’s confidence and competence while achieving procedural and non-procedural interventional radiology skills related to the liver.

Trial registration

Retrospectively registered
Derivation and Validation of the Cancer READMIT Score: A Readmission Risk Scoring System for Patients With Solid Tumor Malignancies
Authors: Manzano Joanna-Grace M. , Lin Heather , Zhao Hui , Halm Josiah , Suarez-Almazor Maria E.
Published: August 2021

PURPOSE:

Readmissions for the medical treatment of cancer have traditionally been excluded from readmission measures under the Hospital Readmissions Reduction Program. Patients with cancer often have higher readmission rates and may need heightened support to ensure effective care transitions after hospitalization. Estimating readmission risk before discharge may assist in discharge planning efforts and help promote care coordination at time of discharge.

PATIENTS AND METHODS:

We developed and validated a readmission risk scoring system among a cohort of adult cancer patients with solid tumor admitted at a comprehensive cancer center. Multivariate logistic regression analysis was used to develop the model. The model's discriminative capacity was evaluated through a receiver operating characteristic curve analysis. We further compared the performance of the developed score with existing risk scores for 30-day readmission.

RESULTS:

The 30-day unplanned readmission rate in the total cohort was 16.0% (n = 1,078 of 6,720). After multivariate analysis, Cancer site, Recent emergency room visit within 30 days, non-English primary language, Anemia defined as hemoglobin < 10 g/dL, > 4 Days length of stay during the index admission, unmarried Marital status, Increased white blood cell count > 11 × 109/L, and distant Tumor spread were significantly associated with risk of unplanned 30-day readmission. The derived score, which we call the Cancer READMIT score, had modest discriminatory performance in predicting readmissions (area under the curve for the model receiver operating characteristic curve = 0.647).

CONCLUSION:

The Cancer READMIT score was able to predict 30-day unplanned readmissions to our institution with fairly modest performance. External validation of our derived risk scoring system is recommended.
Invariants of disordered semimetals via the spectral localizer
Authors: Schulz-Baldes Hermann , Stoiber Tom
Published: August 2021

The spectral localizer consists in placing the Hamiltonian in a Dirac trap. For topological insulators its spectral asymmetry is equal to the topological invariants, providing a highly efficient tool for numerical computation. Here this technique is extended to disordered semimetals and allows to access the number of Dirac or Weyl points as well as weak invariants. These latter invariants imply the existence of surface states.
Tricks of the Light
Authors: Mitchell Gregory , Blanchette Thaddeus
Published: August 2021

While there is a growing literature focusing on clients in sexual economies, much of this relies on heteronormative and/or unproven assumptions about masculinity and men’s motivations for purchasing sex. This collaborative ethnographic research takes a comparative approach by studying performances of masculinity in heterosexual and homosexual commercial sex venues in Rio de Janeiro. The authors argue that masculine performances not only are about homosocial male bonding between clients but also are aspirational performances in which actors must work within and across particular class- and race-based structures to jockey for position within the local hierarchy of hegemonic masculinity. They conclude that the connection between masculinity in heterosexual and homosexual venues is fractal, refractive, and coconstituitive. That is, even though the performances of masculinity look different in outward appearance, they actually operate within a shared ideology of gender and are coconstructed through actors’ own pretensions toward class distinction.
The oncogenic transcription factor FUS-CHOP can undergo nuclear liquid–liquid phase separation
Authors: Owen Izzy , Yee Debra , Wyne Hala , Perdikari Theodora Myrto , Johnson Victoria , Smyth Jeremy , Kortum Robert , Fawzi Nicolas L. , Shewmaker Frank
Published: August 2021

Myxoid liposarcoma is caused by a chromosomal translocation resulting in a fusion protein comprised of the N terminus of FUS (fused in sarcoma) and the full-length transcription factor CHOP (CCAAT/enhancer-binding protein homologous protein, also known as DDIT3). FUS functions in RNA metabolism, and CHOP is a stress-induced transcription factor. The FUS-CHOP fusion protein causes unique gene expression and oncogenic transformation. Although it is clear that the FUS segment is required for oncogenic transformation, the mechanism of FUS-CHOP-induced transcriptional activation is unknown. Recently, some transcription factors and super enhancers have been proposed to undergo liquid–liquid phase separation and form membraneless compartments that recruit transcription machinery to gene promoters. Since phase separation of FUS depends on its N terminus, transcriptional activation by FUS-CHOP could result from the N terminus driving nuclear phase transitions. Here, we characterized FUS-CHOP in cells and in vitro, and observed novel phase-separating properties relative to unmodified CHOP. Our data indicate that FUS-CHOP forms phase-separated condensates that colocalize with BRD4, a marker of super enhancer condensates. We provide evidence that the FUS-CHOP phase transition is a novel oncogenic mechanism and potential therapeutic target for myxoid liposarcoma.

This article has an associated First Person interview with the first author of the paper.
Visualizing endogenous Rho activity with an improved localization-based, genetically encoded biosensor
Authors: Mahlandt Eike K. , Arts Janine J. G. , van der Meer Werner J. , van der Linden Franka H. , Tol Simon , van Buul Jaap D. , Gadella Theodorus W. J. , Goedhart Joachim
Published: August 2021

Rho GTPases are regulatory proteins, which orchestrate cell features such as morphology, polarity and movement. Therefore, probing Rho GTPase activity is key to understanding processes such as development and cell migration. Localization-based reporters for active Rho GTPases are attractive probes to study Rho GTPase-mediated processes in real time with subcellular resolution in living cells and tissue. Until now, relocation Rho biosensors (sensors that relocalize to the native location of active Rho GTPase) seem to have been only useful in certain organisms and have not been characterized well. In this paper, we systematically examined the contribution of the fluorescent protein and Rho-binding peptides on the performance of localization-based sensors. To test the performance, we compared relocation efficiency and specificity in cell-based assays. We identified several improved localization-based, genetically encoded fluorescent biosensors for detecting endogenous Rho activity. This enables a broader application of Rho relocation biosensors, which was demonstrated by using the improved biosensor to visualize Rho activity during several cellular processes, such as cell division, migration and G protein-coupled receptor signaling. Owing to the improved avidity of the new biosensors for Rho activity, cellular processes regulated by Rho can be better understood.

This article has an associated First Person interview with the first author of the paper.
The role of single nucleotide polymorphisms of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) on susceptibility to herniated nucleus pulposus
Authors: Azharuddin Azharuddin , Ilmawan Muhammad , Fajar Jonny Karunia , Fahriani Marhami , Mamada Sukamto S. , Maliga Helnida Anggun , Nainu Firzan , Dhama Kuldeep , Harapan Harapan , Magetsari Rahadyan
Published: August 2021

Background: The pathogenesis of herniated nucleus pulposus (HNP) is complex and may involve the wide variety of gene polymorphism. However, the reports from the existing studies are inconclusive. The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL-1A), tumor necrosis factor-alpha (TNF-A), and vitamin D receptor (VDR) genes on the susceptibility to herniated nucleus pulposus (HNP).

Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test.

Results: We screened 3,067 unique studies for eligibility and three, two and nine case-control studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations.

Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.
Marine plant mediated green synthesis of silver nanoparticles using mangrove Rhizophora stylosa: Effect of variable process and their antibacterial activity
Authors: Willian Nancy , Syukri Syukri , Zulhadjri Zulhadjri , Arief Syukri
Published: August 2021

Background: Most natural plants used in the synthesis of silver nanoparticles are limited to marine plants. To carry out applications, colloidal silver nanoparticles (AgNps) should have appropriate properties such as homogeneous shapes, small and narrow particle size distribution, and long time stability. This study aims to determine the effects of a variable process of AgNps mediated mangrove Rhizophora stylosa (RS) leaf extract, and antibacterial activity. 

Methods: Synthesis of AgNps was carried out by stirring silver nitrate solution with aqueous extract. The characterization of AgNps was carried out using UV-Vis spectrophotometry, X-ray diffraction (XRD), Dynamic Light Scattering (DLS) zetasizer and Transmission Electron Microscopy (TEM). Evaluation of antibacterial activity was carried out on Escherichia coli and Staphylococcus aureus. Reaction conditions such as the concentration of metal ions (0.001 M, 0.005 M, and 0.01 M), extracts (1%, 3%, and 5% v/v), and the reaction time on the size and stability of nanoparticles were also explored.

Results: The UV-Vis spectroscopy showed an absorption of colloidal AgNps in a wavelength range of 403–443 nm.  TEM analysis showed that as-synthesized AgNps were spherical in shape with a size range of 5–87 nm. The use of 0.001 M and 0.005 M of Ag+ resulted in a smaller diameter than the synthesized AgNps, using 0.01 M Ag+, in the same extract concentration. The range of zeta potential was -24.9 mV to -27.7 mV. The as-synthesized AgNps were stable for more than one month. The XRD analysis showed four peaks, which were attributed to the face centered cubic crystal structure of metallic silver. The results of the silver nanoparticles synthesis showed good activity on Escherichia coli and Staphylococcus aureus, with an inhibition zone between 4.1–7.2 mm.

Conclusions: The AgNps synthesized with RS leaf extract, which is a reducing agent, showed good potential as an antibacterial component.
Im bann der Würgerin – Kamadme, Lamaštu und Lilith in der Hellas?
Authors: Jagiełło Mieszek
Published: August 2021

The following paper explores some possible connections between Greek and Mesopotamian child-killing demons. First, the main Sumerian/Akkadian demoness Kamadme Lamaštu is being characterized and set in comparison with the lil-demons and their singularisation Lilith. Briefly, their modus operandi is being studied with a focus on strangulation. It is being proposed that the reoccurring meme of children being strangled by these demons comes from a misinterpretation of the anatomy of the human body which manifested in the belief in a rāṭu in Mesopotamia or ὁδός in Greece. This organ was believed to be a “channel” that connects women’s genital system with the respiratory tract. With that in mind, some Greek and Roman demons are being considered as potentially being derived from the aforementioned ancient Near Eastern supernatural beings. Hence, the proposal is put forward that the Greek Hesperides, the Theban Sphinx, the Lesbian Gello as well as the Greco-Roman Stri(n)x have in fact been adopted by the Occident from the East.
Theology of Carl Schmitt
Authors: Geréby György
Published: August 2021

The paper addresses the theology of Carl Schmitt. Schmitt often stresses his ‘natural born Catholicism.’ At the same time he also claims repeatedly not to be a theologian in the professional sense. On the other hand, his main ideas like the concept of the political (Der Begriff des Politischen), the public character of the church (Römischer Katholizimus und politische Form), and finally, his Politische Theologie II in reaction to Erik Peterson’s refutation of Politische Theologie I show that Schmitt’s ideas imply deep and problematic theological positions. The role of the katechon, or the Grand Inquisitor and his criticism of Peterson’s patristic arguments, especially the rejection of the anti-Arian reasoning of Gregory Nazianzen show a markedly unorthodox theological stance reminiscent of Charles Maurras’ political Catholicism. Schmitt’s transcends patristic orthodoxy in order to apply his historically conditioned 19th-century theology to sacralizing his idea of the political.
Traditional Revolt against the Modern Science (Philosophy in the Inter-war Period)
Authors: Jedliński Marek
Published: August 2021

The article presents the views of traditionalists of the interwar period on science and education. Traditionalist philosophy is characterized by a turn to the past and a desire to return to the old world; the modern era is severely criticized. From this perspective, traditionalists contest the science of the modern world. According to them, it is characterized by a one-sided development, which has also affected the Western education system. Traditionalist philosophy denounces the rationalism and pragmatism inherent in modern science, proposing an alternative vision of traditional science based on wisdom rather than expert knowledge. According to traditionalists, science based on the affirmation of novelty and the unknown can threaten tradition – the transmission of the highest values, ideas and goals, without which no culture can survive.
Dispute over the Guardian of the Constitution. Hans Kelsen, Carl Schmitt and the Weimar Case
Authors: Górnisiewicz Arkadiusz
Published: August 2021

The paper discusses one of the most important debates on the meaning of constitutional adjudication in the 20th century that engaged two eminent legal and political thinkers Hans Kelsen and Carl Schmitt. The paper focuses on the constitutional dispute over the guardianship of the constitution in the final years of Weimar’s Germany and reconstructs the arguments of the two major protagonists in this dispute concerning the Weimar constitution and the fundamental question whether the guardian of the constitution is (or should be) the constitutional court or the president of the Reich. The debate highlights the complexity of the political problems of a democratic state, as well as the intricate relationship between law and state and has retained high level of topicality. The paper also pays attention to the philosophical-political premises that underlined the distinctly different views on the relationship between law and politics in the thought of Hans Kelsen and Carl Schmitt.
Quality improvement in practice—part 1: creating learning systems
Authors: Shah Amar
Published: August 2021

Applying quality improvement methods to solve complex quality issues involves people deeply. People discover solutions, test and adapt ideas, thereby giving them autonomy and control over the system in which they work. Focusing quality improvement on what matters most for staff and service users creates the opportunity to bring a deeper sense of meaning and connection to purpose, both of which are integral to joy in work. When applying quality improvement at scale within large organisations or systems, bringing teams together in learning systems can provide a critical structure to build skills, collaborate and learn from one another. This article describes the core elements of learning systems designed to support quality improvement and joy in work, illustrated through two examples. The framework can be applied at different levels of a system, including the individual, the team and the organisation, or even to a large improvement effort across organisational boundaries. The next article in this series will discuss the application of the joy in work framework to healthcare settings.
Predicting Density and Moisture Content of Populus xiangchengensis and Phyllostachys edulis using the X-Ray Computed Tomography Technique
Authors: Wang Qingping , Liu Xing'e , Yang Shumin
Published: August 2021

Density (D) and moisture content (MC) are two important physical properties of wood and bamboo, which are highly correlated with many other physical and mechanical properties. In this study, the X-ray computed tomography (CT) technique was used to determine the D and MC of poplar (Populus xiangchengensis) and bamboo (Phyllostachys edulis). There was a statistically significant difference in the CT-measured numbers for D and MC between these species. The D-CT and MC-CT linear models for both species were independently established: Dpoplar = 0.00098 × H + 1.02603, Dbamboo = 0.00118 × H + 0.98684, MCpoplar = 0.00309 × H + 1.89982, and MCbamboo = 0.00131 × H + 0.31488, where H is the CT number. The determination coefficients, R2, of the models were all higher than 0.97. Additionally, the R2 values obtained for model validation were also all higher than 0.97. These results indicated that it is feasible to reliably determine D and MC of wood and bamboo using the X-ray CT technique. This study aims to provide reference data for CT detection of the D and MC of wood and bamboo.
Treatment with LEDs at a wavelength of 642 nm enhances skin tumor proliferation in a mouse model
Authors: Goo Hyeyoon , Mo SangJoon , Park Hyeong Ju , Lee Min Young , Ahn Jin-Chul
Published: August 2021

Photobiomodulation (PBM) is attracting increased attention in the fields of dermatology and cosmetics. PBM with a variety of light parameters has been used widely in skin care, but can cause certain types of unwanted cells to proliferate in the skin; this can lead to skin tumors, such as papillomas and cancers. We constructed a mouse model of human skin tumors using DMBA as an initiator and TPA as a promoter, and confirmed that LEDs with a wavelength of 642 nm (red light) increased tumor size, epidermal thickness, and systemic proinflammatory cytokine levels. These results indicated that skin tumor cell proliferation may result from the use of 642 nm LEDs, suggesting the need for regulation of skin care based on LED light therapy.
Three-dimensional localization refinement and motion model parameter estimation for confined single particle tracking under low-light conditions
Authors: Lin Ye , Sharifi Fatemeh , Andersson Sean B.
Published: August 2021

Confined diffusion is an important model for describing the motion of biological macromolecules moving in the crowded, three-dimensional environment of the cell. In this work we build upon the technique known as sequential Monte Carlo - expectation maximization (SMC-EM) to simultaneously localize the particle and estimate the motion model parameters from single particle tracking data. We extend SMC-EM to handle the double-helix point spread function (DH-PSF) for encoding the three-dimensional position of the particle in the two-dimensional image plane of the camera. SMC-EM can handle a wide range of camera models and here we assume the data was acquired using a scientific CMOS (sCMOS) camera. The sensitivity and speed of these cameras make them well suited for SPT, though the pixel-dependent nature of the camera noise presents a challenge for analysis. We focus on the low signal setting and compare our method through simulation to more standard approaches that use the paradigm of localize-then-estimate. To localize the particle under the standard paradigm, we use both a Gaussian fit and a maximum likelihood estimator (MLE) that accounts for both the DH-PSF and the pixel-dependent noise of the camera. Model estimation is then carried out either by fitting the model to the mean squared displacement (MSD) curve, or through an optimal estimation approach. Our results indicate that in the low signal regime, the SMC-EM approach outperforms the other methods while at higher signal-to-background levels, SMC-EM and the MLE-based methods perform equally well and both are significantly better than fitting to the MSD. In addition our results indicate that at smaller confinement lengths where the nonlinearities dominate the motion model, the SMC-EM approach is superior to the alternative approaches.
Low-pass filtering based polarimetric dehazing method for dense haze removal
Authors: Liang Jian , Ren Liyong , Liang Rongguang
Published: August 2021

Polarimetric dehazing method is very promising in enhancing the quality of images captured in the scattering media. However, it is found that the dehazing results calculated by hazy images are very sensitive to the noise, which may cause the method unstable or even invalid. To overcome this drawback and enhance the capability and stability of the polarimetric dehazing method, digital image processing algorithms or bias parameters need to be added into the method, however, they will make the algorithm complex and time consuming. In this paper, using low pass filter to suppress the noise of the hazy images, a novel polarimetric dehazing method is proposed to enhance the visibility of hazy images, especially for dense haze removal. Experimental results demonstrate that this method is totally automatic and very effective in dense haze processing. This method may have great potential usage in many applications, such as optical surveillance, underwater imaging, and bio-tissue imaging, etc.
Generating starting points for designing freeform imaging optical systems based on deep learning
Authors: Chen Wenchen , Yang Tong , Cheng Dewen , Wang Yongtian
Published: August 2021

Deep learning is an important aspect of artificial intelligence and has been applied successfully in many optics-related fields. This paper proposes a generalized framework for generation of starting points for freeform imaging optical design based on deep learning. Compared with our previous work, this framework can be used for highly nonrotationally symmetric freeform refractive, reflective, and catadioptric systems. The system parameters can be advanced and the ranges of these system parameters can be wide. Using a special system evolution method and a K-nearest neighbor method, a full dataset consisting of the primary and secondary parts can be generated automatically. The deep neural network can then be trained in a supervised manner and can be used to generate good starting points directly. The convenience and feasibility of the proposed framework are demonstrated by designing a freeform off-axis three-mirror imaging system, a freeform off-axis four-mirror afocal telescope, and a freeform prism for an augmented reality near-eye display. The design framework reduces the designer’s time and effort significantly and their dependence on advanced design skills. The framework can also be integrated into optical design software and cloud servers for the convenience of more designers.
Underwater image restoration via feature priors to estimate background light and optimized transmission map
Authors: Zhou Jingchun , Wang Yanyun , Zhang Weishi , Li Chongyi
Published: August 2021

Underwater images frequently suffer from color casts and poor contrast, due to the absorption and scattering of light in water medium. To address these two degradation issues, we propose an underwater image restoration method based on feature priors inspired by underwater scene prior. Concretely, we first develop a robust model to estimate the background light according to feature priors of flatness, hue, and brightness, which can effectively relieve color distortion. Next, we compensate the red channel of color corrected image to revise the transmission map of it. Coupled with the structure-guided filter, the coarse transmission map is refined. The refined transmission map preserves the edge information while improving the contrast. Extensive experiments on diverse degradation scenes demonstrate that our method achieves superior performance against several state-of-the-art methods.
Achieving high-performance in situ fabricated FAPbBr3 and electroluminescence
Authors: Liu Zhenjie , Xue Xulan , Kang Zhihui , Wang Rong , Zhang Han , Ji Wenyu
Published: August 2021

Currently, metal halide perovskite films still encounter the issues of inferior film quality and interfacial electrical properties when they were constructed electroluminescence devices. Herein, efficient and pinhole-free perovskite emissive film was obtained on the poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) layer modified by an ultrathin LiF layer. Owing to the synergetic effect of the LiF interlayer, including better regulation of the perovskite film and a more balanced charge injection capability, an efficient green light-emitting diode based on the perovskite film was achieved with a maximum current efficiency of 25.6 cd/A, which is 58% higher than that of the control device with a plasma-treated PEDOT:PSS layer. Our results not only provide a facile strategy for acquiring efficient perovskite films but also circumvent the expensive and time-consuming plasma treatment process commonly used to improve the wetting properties of the underlying films.
High-performance III-V photodetectors on a monolithic InP/SOI platform
Authors: Xue Ying , Han Yu , Tong Yeyu , Yan Zhao , Wang Yi , Zhang Zunyue , Tsang Hon Ki , Lau Kei May
Published: August 2021

Integrating light emission and detection functionalities using
efficient III-V materials on Si wafers is highly desirable for
Si-based photonic integrated circuits. To fulfill the need of
high-performance photodetectors (PDs) monolithically integrated on Si
for Si photonics, we demonstrate III-V PDs directly grown on a
InP/Si-on-insulator (SOI) platform parallel to the Si device layer in
a variety of device dimensions. Device characteristics including a
3 dB bandwidth beyond 40 GHz, open eye diagrams at 40 Gb/s, a dark
current of 0.55 nA, a responsivity of 0.3 A/W at 1550 nm, and 0.8 A/W
at 1310 nm together with a 410 nm operation wavelength span from
1240 nm to 1650 nm are achieved. We further simulate the feasibility
of interfacing the III-V PDs with the Si waveguide by designing
waveguide-coupled PDs with butt coupling schemes. These results point
to a practical solution for the monolithic integration of III-V active
components and Si-based passive devices on a InP/SOI platform in the
future.
Characterization of Tumor-immune Microenvironment by High-throughput Image Analysis of CD8 Immunohistochemistry Combined With Modified Masson’s Trichrome
Authors: Havnar Charles , Lau Shari , Hung Jeffrey , Eastham-Anderson Jeff , Espiritu Carmina , Rangell Linda , Koeppen Hartmut , Ziai James , Foreman Oded
Published: August 2021

With the advent of checkpoint inhibitors, there is increasing need to study the dynamics of CD8+ T-cells in the tumor microenviroment. In this article, we describe a semi-automated method to quantify and interrogate spatial relationships between T-cells and collagenous stroma in human and mouse tissue samples. The assay combines CD8 immunohistochemistry with modified Masson’s trichrome. Slides are scanned and digital images are analyzed using an adjustable MATLAB algorithm, allowing for high-throughput quantification of cytotoxic T-cells and collagen. This method provides a flexible tool for unbiased quantification of T-cells and their interactions with tumor cells and tumor microenvironment in tissue samples.
PhyloFisher: A phylogenomic package for resolving eukaryotic relationships
Authors: Tice Alexander K. , Žihala David , Pánek Tomáš , Jones Robert E. , Salomaki Eric D. , Nenarokov Serafim , Burki Fabien , Eliáš Marek , Eme Laura , Roger Andrew J. , Rokas Antonis , Shen Xing-Xing , Strassert Jürgen F. H. , Kolísko Martin , Brown Matthew W.
Published: August 2021

Phylogenomic analyses of hundreds of protein-coding genes aimed at resolving phylogenetic relationships is now a common practice. However, no software currently exists that includes tools for dataset construction and subsequent analysis with diverse validation strategies to assess robustness. Furthermore, there are no publicly available high-quality curated databases designed to assess deep (>100 million years) relationships in the tree of eukaryotes. To address these issues, we developed an easy-to-use software package, PhyloFisher (https://github.com/TheBrownLab/PhyloFisher), written in Python 3. PhyloFisher includes a manually curated database of 240 protein-coding genes from 304 eukaryotic taxa covering known eukaryotic diversity, a novel tool for ortholog selection, and utilities that will perform diverse analyses required by state-of-the-art phylogenomic investigations. Through phylogenetic reconstructions of the tree of eukaryotes and of the Saccharomycetaceae clade of budding yeasts, we demonstrate the utility of the PhyloFisher workflow and the provided starting database to address phylogenetic questions across a large range of evolutionary time points for diverse groups of organisms. We also demonstrate that undetected paralogy can remain in phylogenomic “single-copy orthogroup” datasets constructed using widely accepted methods such as all vs. all BLAST searches followed by Markov Cluster Algorithm (MCL) clustering and application of automated tree pruning algorithms. Finally, we show how the PhyloFisher workflow helps detect inadvertent paralog inclusions, allowing the user to make more informed decisions regarding orthology assignments, leading to a more accurate final dataset.
SiGMoiD: A super-statistical generative model for binary data
Authors: Zhao Xiaochuan , Plata Germán , Dixit Purushottam D.
Published: August 2021

In modern computational biology, there is great interest in building probabilistic models to describe collections of a large number of co-varying binary variables. However, current approaches to build generative models rely on modelers’ identification of constraints and are computationally expensive to infer when the number of variables is large (N~100). Here, we address both these issues with Super-statistical Generative Model for binary Data (SiGMoiD). SiGMoiD is a maximum entropy-based framework where we imagine the data as arising from super-statistical system; individual binary variables in a given sample are coupled to the same ‘bath’ whose intensive variables vary from sample to sample. Importantly, unlike standard maximum entropy approaches where modeler specifies the constraints, the SiGMoiD algorithm infers them directly from the data. Due to this optimal choice of constraints, SiGMoiD allows us to model collections of a very large number (N>1000) of binary variables. Finally, SiGMoiD offers a reduced dimensional description of the data, allowing us to identify clusters of similar data points as well as binary variables. We illustrate the versatility of SiGMoiD using multiple datasets spanning several time- and length-scales.
Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development
Authors: Kuil Laura E. , MacKenzie Katherine C. , Tang Clara S. , Windster Jonathan D. , Le Thuy Linh , Karim Anwarul , de Graaf Bianca M. , van der Helm Robert , van Bever Yolande , Sloots Cornelius E. J. , Meeussen Conny , Tibboel Dick , de Klein Annelies , Wijnen René M. H. , Amiel Jeanne , Lyonnet Stanislas , Garcia-Barcelo Maria-Mercè , Tam Paul K. H. , Alves Maria M. , Brooks Alice S. , Hofstra Robert M. W. , Brosens Erwin
Published: August 2021

Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo.

This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes located within CN losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution of UFD1L, TBX2, SLC8A1, and MAPK8 to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expression and between reduced Ret and Tubb5 expression in vivo. Rare large CN losses—often de novo—contribute to HSCR in HSCR-AAM patients. We proved the involvement of six genes in enteric nervous system development and Hirschsprung disease.