bluuebunny/crossref_metadata_2025 huggingface dataset:
OR08-3 Untargeted Nuclear Receptor-Wide Screening reveals Novel Ligands From the Brain and Gut.
Authors: Campbell Jhenielle , Cummins Carolyn , Krause Henry , Liu Jiabao , Main Sridhar , Malekoltojari Ainaz , Navarre William , Peng Hui , Sahin Cigdem , Krause Henry
Published: November 2022

The 48-member family of human nuclear receptors (NRs) plays major roles in metabolic homeostasis, immunity, and inflammatory responses, largely under the control of small lipophilic molecule interactions. A critical barrier precluding major breakthroughs in the discovery of new metabolic ligands is a lack of new methods that allow comprehensive mining of the natural metabolome, most of which remains uncharacterized in terms of identity and function. To address this challenge, our group has developed and optimized an NR pulldown and untargeted metabolomics pipeline that can identify novel NR ligands from various complex mixtures, including tissues, fecal samples, microbiotic cultures, environmental waste and compound libraries. In a first proof of concept screen using brain extracts, a novel omega-3 fatty acid ligand was identified using PPARα as bait. 7(S)-HDHA was selectively isolated despite the presence of other more abundant previously published PPARα ligands. Mass spectrometric detection of 7(S)-HDHA in mouse and rat brain, time-resolved FRET analyses, and thermal shift assay results collectively show that 7(S)-HDHA is the strongest activator and highest affinity natural PPARα ligand identified to date. We also show that 7(S)-HDHA activation of PPARα in cortical neurons effectively stimulates neuronal growth and arborization, key measurements of synaptic capacity in neurons. Since many NRs are expressed in or near the gut, and the interplay between NRs and gut-derived metabolites is largely unaddressed, we have since focused the majority of our efforts on intestinal and microbiome extracts. Dozens of new ligands for xenobiotic-sensing receptors have been identified, including fatty acid, phytoestrogen, peptide, and secondary bile acid, with identities soon to be made available in a public database. A subset will be pursued in-house or with collaborators to identify bacterial sources and receptor-based outcomes. Examples of new PPARα, CAR, PXR, and/or RORα ligand-NR interactions and outcomes will be presented. These discoveries will facilitate new directions for drug development, nutritional supplements and probiotic therapies for the prevention and treatment of a wide spectrum of diseases.

Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.
OR22-1 Temporal And Spatial Cellular Heterogeneity Of Hepatocyte Metabolism
Authors: Landgraf Austin , Okada Junichi
Published: November 2022

Gene expression plays a pivotal role in the long-term regulation of gluconeogenesis and lipogenesis in the liver. Although most of the previous studies were analyzed as a whole liver, it is known that hepatocytes across the liver display specific aspects of liver function in a zonation dependent manner. Using a combination of single-cell RNA sequencing (scRNA-seq) and single molecule Fluorescence In Situ Hybridization (smFISH) technologies, we examined several novel molecular and cellular aspects of the normal regulation of hepatocyte metabolic gene expression during the transitions from the fed to fasted, and subsequent starvation states in male C57BL/6J mice. Targeted scRNA-seq was used to quantitively analyze the temporal and spatial differences of gluconeogenic and lipogenic genes following a post-prandial time course. Initially, in the fed state lipogenic genes (such as Fasn) were highly expressed in both the periportal (PP) and pericentral (PC) hepatocytes that were rapidly turned off as the mouse entered the fasted state. In contrast, gluconeogenic genes (such as Pck1) were expressed in a subset of PP hepatocytes in the fully fed state. As the mouse entered the fasted state gluconeogenic genes became activated primarily in the PP hepatocytes. However, as the mouse enters a starvation state the PC hepatocytes also increase their expression of gluconeogenic genes. Analyses by smFISH not only confirmed the scRNA-seq data but is also applicable to determine the spatial context in the native liver tissue as well as analyzing the transcriptional regulation of gluconeogenic and lipogenic genes at the single molecule resolution. In the fed state, few PP hepatocytes expressed gluconeogenic transcription sites (TS), and during a fasted time-course, over time the TS expanded outwards to the PC hepatocytes. On the other hand, lipogenic TS were expressed in both PC and PP hepatocytes in the fed state, but during a fasted time-course, TS were not detected. In summary, these data suggest that hepatocyte zonation of gluconeogenic genes is dynamic and can vary substantially depending upon the fasted and fed states. Understanding the regulation of the liver hepatocyte normal physiology will provide the molecular basis for which we can more precisely determine the dysregulation that occurs in states of insulin resistance.

Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.
OR22-6 Ovarian Cancer Cell Glucocorticoid Receptor Activity Is Associated With Cytokine Secretion Promoting Infiltration of Immunosuppressive Cells Into the Tumor Microenvironment
Authors: Taya Manisha
Published: November 2022

Immunosuppressive cells abundantly infiltrate tumors during cancer progression. Notably, immunosuppressive myeloid-derived suppressor cells (MDSCs) have recently been identified as a heterogeneous cell population that expand during tumor-associated inflammation and are significantly increased in the tumor, peripheral blood, as well as ascites of ovarian cancer patients. MDSCs contribute to tumor immune tolerance via inhibition of T-cell proliferation and activation. Signals from the tumor microenvironment in the form of soluble cytokines are proposed to lead to MDSC infiltration. It is also known that high tumor cell glucocorticoid receptor (GR) expression is associated with a relatively poor prognosis in ovarian cancer patients. We hypothesized that ovarian cancer cell GR expression and activity may modulate tumor cell cytokine secretion thereby leading to increased MDSC generation and recruitment to the tumor, thereby creating an immunosuppressive environment. Our preliminary data confirm that GR activation in two high-grade ovarian cancer cell lines (HeyA8 and SKOV3) modulates the cytokine secretome. Our results demonstrate GR-mediated secretion of several pro-tumorigenic and immunosuppressive proteins including G-CSF, M-CSF, TGF-b, and MCP-1 in those ovarian cancer models. We also observed downregulation of potent cytotoxic T-cell activating cytokines required for anti-tumor T-cell function including IL-2, IFN-g and MIP1 upon GR activation. Importantly, treatment of cells with a selective GR modulator (SGRM) reverses this immunosuppressive secretome effect. Furthermore, upon culturing healthy peripheral blood mononuclear cells (PBMCs) with tumor conditioned media from GR activated ovarian cancer cells, we show that secreted immunomodulatory factors have the capacity to promote differentiation of human MDSCs from progenitor myeloid cells. The resulting MDSC population was characterized via expression of activation markers including Arginase-1, iNOS, VEGF and TGF-b. Most importantly, the suppressive function of these MDSCs is being evaluated by determining their inhibitory potential on cytotoxic T-cell proliferation and/or activation. Based on the insight provided by these data, we propose to determine whether ovarian tumor cell-intrinsic GR activation and resulting MDSC generation contributes to earlier relapse of GR-positive ovarian cancers, and eventually whether this mechanism may be targeted to improve patient outcomes in this subset of ovarian cancers.

Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.
LBODP079 A Case of Silent Invasive Corticotroph Adenoma
Authors: Bendaram Snigdha Reddy , Kantorovich Vitaly
Published: November 2022

ACTH-secreting pituitary adenomas account for about two-thirds of cases of endogenous Cushing's syndrome and are considered the most common cause of endogenous hypercortisolemia. Silent corticotroph adenomas (SCAs) are pituitary tumors that stain positive for adrenocorticotropic hormone (ACTH) but do not produce biochemical levels of excess ACTH or cortisol. These tumors account for approximately 20% of all corticotroph adenomas and 5.5% of nonfunctioning pituitary adenomas. New immunohistochemical (IHC) techniques continue to be the gold standard in diagnosis, while having prognostic implications.

Presentation: No date and time listed
HES1 promoter activation dynamics reveal the plasticity, stemness and heterogeneity in neuroblastoma cancer stem cells
Authors: Riya Paul Ann , Basu Budhaditya , Surya Suresh , Parvathy Surendran , Lalitha Soundararajan , Jyothi Nair Pradeep , Meera Vadakkath , Jaikumar Vishnu Sunil , Sunitha Padmanabhan , Shahina Afzal , Sukumaran Rashmi , Nair Achuthsankar Sukumaran , Dhanesh Sivadasan Bindu , Jiffy John , Nelson-Sati Shijulal , Maliekal Tessy Thomas , Das Ani Venmanad , James Jackson
Published: November 2022

Notch signaling and its downstream gene target HES1 play a critical role in regulating and maintaining cancer stem cells (CSCs), similar to as they do during embryonic development. Here, we report a unique subclass of Notch-independent Hes-1 (NIHes-1)-expressing CSCs in neuroblastoma. These CSCs maintain sustained HES1 expression by activation of HES1 promoter region upstream of classical CBF-1 binding sites, thereby completely bypassing Notch receptor-mediated activation. These stem cells have self-renewal ability and potential to generate tumors. Interestingly, we observed that NIHes-1 CSCs could transition to Notch-dependent Hes-1-expressing (NDHes-1) CSCs where HES1 is expressed by Notch receptor-mediated promoter activation. We observed that NDHes-1-expressing CSCs also had the potential to transition to NIHes-1 CSCs and during this coordinated bidirectional transition, both CSCs gave rise to the majority of the bulk cancer cells, which had an inactive HES1 promoter (PIHes-1). A few of these PIHes-1 cells were capable of reverting into a CSC state. These findings explain the existence of a heterogenic mode of HES1 promoter activation within the IMR-32 neuroblastoma cell line and the potential to switch between them.

This article has an associated First Person interview with the first authors of the paper.
Analysis by metagenomic next-generation sequencing of the lung virome during mechanical ventilation
Authors: Do Vale Julien , Roux Damien , Bridier Nahmias Antoine , Salmona Maud , Mercier-Delarue Séverine , Ranger Noémie , Ricard Jean-Damien , Le Goff Jérôme , Fromentin Mélanie
Published: November 2022

Background: The lung microbiome is composed of bacteria, viruses and fungi that interplay with each other and participate in mucosal defense protecting the lungs from colonization and infection by pathogenic microorganisms. In intensive care, a change in the composition of the lung microbiome, called dysbiosis, could be associated to the occurrence of ventilator-associated pneumonia. The objective of the study was to test a method to assess the lung virome.

Methods: We applied a protocol including the same nucleic acid extraction methods as used for bacterial lung microbiome and a metagenomic next-generation sequencing (mNGS) to detect eukaryotic RNA, DNA viruses and bacteriophages.

Results: Our method was able to detect all viruses identified with multiplex polymerase chain reaction (PCR), other eukaryotic viruses not included in the multiplex PCR panel, and bacteriophages. Notably persistent viruses, mainly Herpesviridae, associated with opportunistic infections and those showing immunodepression such as Anellovirus have been identified.

Conclusions: A better description of the global composition and evolution of the lung microbiome, including viruses, could help to better understand ventilator-associated pneumonia occurrence and outcomes.
Contrast-induced nephropathy (CIN) - epidemiology, risk factors and prevention
Authors: Pierzchała Jakub Rafał , Bednarz Katarzyna , Banaś Patryk , Sobańska Natalia , Banasiak Aleksandra Paulina , Teichman Rafał , Kasprowicz Jakub , Abram Kamila , Adamus Justyna , Hyjek Michał
Published: November 2022

Introduction: Contrast-induced nephropathy is one of the most serious adverse effects of radiocontrast agents usage. It is currently listed in the literature as the third most common cause of iatrogenic acute kidney injury.
Aim of the study: The aim of this study is to provide an overview of the extent, severity and prevention of CIN. It is to shed a broader light on this disease entity and be a helpful resource in the future for other clinicians struggling with CIN.
Methods and materials: A literature review was conducted using the PubMed database, using the keywords: "contrast-induced nephropathy"; "acute kidney injury"; "contrast media".
Results: Pathogenesis of CIN is not entirely clear. There are many risk factors being e.g. diabetes, chronic kidney disease, advanced age (patients over 75 years old). Prevention methods include restricting contrast volume to a minimum, balancing the patient's volaemia before contrast administration or perioperative saline hydration to normalise volaemia.
Conclusion: CIN is a significant health problem, which can be a life threat. Despite the fact that the exact pathogenesis of the condition still remains unknown, the CIN prophylaxis becomes more and more effective due to better recognition of risk factors and the usage of adequate prevention measures appropriate to the patients' condition. More studies, with larger test groups, are needed to better define both the pathomechanism of contrast-induced acute kidney injury and new, more effective ways of prevention and treatment of this condition.
Surgical treatment of multiple plexiform schwannomas arising from the superficial radial nerve: a case report
Authors: Lee Tae-Hun , Lee Yong-Sik , Ahn Gil-Yeong , Ahn Jun-Hyeong
Published: November 2022

Schwannoma, or neurilemmoma, is a benign neoplasm that arises from Schwann cells, which surround peripheral, cranial, and autonomic nerve sheaths. Schwannoma has been reported to occur mainly as a singular lesion of the sacral nerve or sciatic nerve in young adults. Plexiform schwannoma, a subtype of schwannoma, is a rare neoplasm known to account for 2% to 5% of total schwannomas. Schwannoma of the upper extremities is relatively rare and is reported to occur mostly in the ulnar nerve. We report, with a literature review, a case of 4.2-cm and 2.8-cm symptomatic multiple plexiform schwannomas that occurred in the superficial radial nerve and were treated without neurologic sequelae by surgical resection.
Machine Learning–Based Feasibility Checks for Dynamic Time Slot Management
Authors: van der Hagen Liana , Agatz Niels , Spliet Remy , Visser Thomas R. , Kok Leendert
Published: November 2022

Online grocers typically let customers choose a delivery time slot to receive their goods. To ensure reliable service, the retailer may want to close time slots as capacity fills up. The number of customers that can be served per slot largely depends on the specific order sizes and delivery locations. Conceptually, checking whether it is possible to serve a certain customer in a certain time slot given a set of already accepted customer orders involves solving a vehicle routing problem with time windows. This is challenging in practice as there is little time available and not all relevant information is known in advance. We explore the use of machine learning to support time slot decisions in this context. Our results on realistic instances using a commercial route solver suggest that machine learning can be a promising way to assess the feasibility of customer insertions. On large-scale routing problems it performs better than insertion heuristics.

History: This paper has been accepted for the Transportation Science Special Issue on Machine Learning Methods and Applications in Large-Scale Route Planning Problems.

Funding: This research was funded by the Netherlands Organization for Scientific Research under the City Logistics Living Laboratory project [Grant 439.18.424].
Novel dual synergistic sealing ring design for a high-pressure pump – Part II
Authors: Zhang Hehui , Deng Chang , Chang Chunping , You Haolin
Published: November 2022

As simple, small, low-friction and low-cost sealing elements, O-rings are widely used in various types of pumps. When a pump's inner pressure increases, the risk of O-ring failure rises concurrently. The numerical calculations discussed in this article have been done to analyse the mode and root cause of the failure of an O-ring that is installed in a high-lift pump. A novel, dual sealing-ring design is also described.
Synthesis of Azoles in Water by Copper(I)-Catalyzed Prepared by Arc Thermal Plasma Process and a molecular Docking Study Against COVID-19
Authors: Guesmi Ahlem , Khezami Lotfi , El-Fattah Wesam Abd , Hamadi Naoufel Ben
Published: November 2022

Huisgen’s 1,3-dipolar cycloadditions in water of 6-azidohexan-1-ol dotted with terminal alkynes and catalyzed with copper nanoparticles, offering access to 1,2,3-triazoles 1,4-disubstituted. The SARS-CoV-2 coronavirus epidemic is still spreading at a fast rate worldwide. The core protease (Mpro) is a gorgeous mark for anti-COVID-19 agents. Click chemistry synthesis, catalyzed using nanoparticles, has been used to prepare the 1,2,3-triazole motif. The high docking score of the newly synthesized triazole are, may be, attributed to the presence of hydrogen bonds together with many interactions between the ligands and the active amino acid residue of the receptor. The comparison of the interactions of Taribavirin and Ribavirin drug with triazole in the largest pocket of 7JWY is also presented. Further interesting comparative docking analyses were performed. The results of this study suggest that triazole 3d may be considered for further investigation as one of the possible therapeutic agents for COVID-19.
Evaluation of Antidiarrheal Activity of Bryophyllum Pinnatum Lam. (Oken) Leaves Extracts and Isolation of Active Constituent.
Authors: Yadav Priyanka , Mishra Arun K , Singh Harpreet
Published: November 2022

Bryophyllum pinnatum Lam. (Oken) (Crassulaceae) are commonly known as miracle plant. Traditionally, this plant is used to heal wounds and to treat diarrhoea. For this reason, the main aim of the present study is to evaluate the antidiarrheal activity using castor oil-induced diarrhea model. Loperamide drug (3 mg dose, p.o.) was used as standard drug. The EAE and EE at 200mg dose and 400 mg dose, p.o. respectively produced dose-dependent protection of mice with significant P value (P < 0.001). Both extracts of plant produced dose-dependent and significant P-value (P < 0.001) towards antimotility effect compared with negative control (castor oil) group in model. EE (400 mg dose p.o.) possess better antidiarrheal potential in mice groups due to presence of flavone. 5-methyl-4,5,7- trihydroxy flavone was isolated from the ethanol extract. Finally, it can be concluded that, Bryophyllum pinnatum Lam. (Oken) leaves can be used ethnomedicinally to treat, counterbalance, bulwark, and control diarrhea.
Catalyst-Free Multicomponent Synthesis of Novel Chromene Carbonitriles from Pyrazole Aldehydes using Ethanol
Authors: Jayanthi Selvaraj , Sugumaran Thangarajan , Monisha Periyasamy , Gunasundar Kittappa , Vetriselvan Moorthy , Pramesh Manickam , Venkatachalam Ragunathan
Published: November 2022

A catalyst-free synthetic strategy to chromene carbonitriles by Multi-Component Reaction of pyrazole aldehydes, 5,5-dimethylcyclohexane-1,3-dione and malononitrile with ethanol, at room temperature is reported. Screening of solvents and purification of the compounds were also performed. The newly synthesized novel compound’s (4H-chromene-3-carbonitriles) structures were authenticated by the spectral techniques viz. (1H , 13C)Nuclear Magnetic Resonance, FT-IR, and LC-MS analysis.
Docking Studies of N-alkylated Indole Derivatives with Mycobacterium Enoyl Acyl Carrier Protein Reductase (Inh A) as Potent Antitubercular Agents
Authors: Joshi Shivam , Kawathekar Neha
Published: November 2022

The worrisome rise in multi and extensively drug-resistant Mycobacterium tuberculosis strains has prompted researchers to look for new, more effective, and safer treatments. A variety of N-alkylated indole derivatives were docked against the InhA enzyme to achieve this goal. In the present study, the flexible Ligand docking simulations were performed on 88 new compounds against the InhA protein with the PDB ID-4TZK by using Glide module. All the docks are considered as well docked as all of them were bound to Ligand binding domain of InhA. The InhA was identified through an in silico docking investigation as a possible molecular target for the N-alkylated indole derivatives. This work sought to identify possible inhibitors of the Enoyl-ACP reductase (InhA), which regulates the formation of the cell wall in mycobacterium, using in silico methods. Most of the compounds show good Glide score compare to INH as reference drug. Compound (E)-1-(4-bromo-2-hydroxyphenyl)-3-(1-butyl-1H-indol-3-yl) prop-2-en-1-one (S1R8) showed highest GLIDE score (-10.45), (S1R16-10.41), (S1R22-10.17) and (SIR24-10.10) compared to INH (-7.15). The presence of oxygen group in the ring showed hydrogen bond interactions with NAD and Tyr158 residues. Results obtained are valuable for synthesis and therefore biological screening of promising hits.
Synthesis and Properties of Transition Metal Complexes Containing Thiazole Derived Schiff Base Ligands
Authors: Kumar Kaushal , Mishra Neha , Anand Satyesh Raj , Shrivastava Satya Prakash
Published: November 2022

Although ligands containing four donor atom are tetradentate ligand of Thiazole moiety which coordinated with transition metal ions. The complex of m-NTA and m-MTA are studies by different spectral technique. Here we are synthesizing the thiazole derivatives Schiff base as a ligands, L1 = N,N'E,N,N'E)-N,N'-(1,3- phenylene bis (methanylylidene) bis (5-nitrobenzo [d] thiazo L2-amine (NTA) and L2 = N,N'E,N,N'E)-N,N'-(1,3-phenylene bis (methanylylidene) bis (5-methyl thiazo L2-amine (MTA), and coordinated with transition metals ( Co, Ni, Cu, Zn, and Cd) using lone-pair coordination method. These synthesized complexes were identified by FT-IR spectra, UV-Visible spectra, mass spectra and cyclic voltammetry and having characteristic absorption and potential high-performance CV which show a different type of stable transition metal complex. The electrochemical study was also carried out for these complexes which show the clear redox behaviour of complexes. The significant change in CV properties is exhibited by CV graphs where we can see a prominent reduction peaks M (II) to M is showing at -0.4 V . We found that in the case of L2 there is less prominent reduction peaks observed in comparison to L1.
Corrosion Inhibition Activity of Isolated Flavonoid from Andrographis echioides leaves
Authors: S. Durgadevi S. Durgadevi , Rose A. Leema , S .Vidhya S .Vidhya , Priya F. Janeeta , Kanmani P. Lydia Festus
Published: November 2022

Andrographis echioides leaves were used to isolate a flavonoid (medicarpin) that inhibited mild steel corrosion in 1M HCl. Preliminary phytochemical analysis revealed that the A.E leaves were rich in flavonoids. Following a room temperature extraction with methanol, the constituents were fractionated using a Soxhlet apparatus. Chromatographic techniques were used to isolate the constituents from the leaves of Andrographis echioides. Flavonoid compounds were characterized using Spectral studies. Weight loss and corrosion studies were investigated the inhibition activity of an isolated flavonoid (medicarpin). The inhibition efficiency of isolated flavonoid was highest (85.78 percent) at 800 ppm concentration, according to weight loss and electrochemical measurements. The influence of temperature on the corrosion activities of base metal was calculated in the temperature range 293-303K. The inhibitory activity increases with rising inhibitor concentration but decreases with rising temperature. The activation and free energies for the inhibition response sustain the method of physisorption. The adsorption of isolated flavonoid on the base metal is an endothermic process and it follows the Langmuir adsorption isotherm. The potentiostatic study illustrates that isolated flavonoid is a mixed type inhibitor. Surface Morphology examination by SEM and EDAX to reveals the adherence of isolated flavonoid on the mild steel surface.
Analytical Method Development and Validation of Obeticholic Acid Along With Stability Indicating Method by Quality by Design Approach
Authors: Trivedi Darshit , Desai Kavita , Patel Jigar
Published: November 2022

A chromatographic method was developed to determine the of assay of Obeticholic Acid with the help of Quality by design approach. QBD is a regulated technique for the process development. In Quality by Design, The method development starts with the specific intentions. A simple method was developed focusing on two critical quality attributes for development of the sturdy and polished method. The implication of self-sufficient factors was resolved using Fisher’s statistical test for Analysis of the Variance (ANOVA) model that was predicted. The aim of the present work is to develop a simple, precise, accurate method for the estimation of obeticholic acid by reverse phase chromatographic technique. Improved chromatographic conditions were observed on Thermo C18 column (150mm x 4.6mm5µm), using the mixture of Orthophosphoric acid (0.1 % OPA) and Acetonitrile (ACN) in the ratio of 55:45% v/v as mobile phase at the flow rate of 1.0mL/min. The column temperature was set at 25°C and wavelength for detection of moiety was 210nm. The system suitability parameters of the instrument used were found within acceptance criteria as per the ICH guidelines. Linearity study was carried out over a range from 100 ppm to 300 ppm and R2 value was found to be 0.9995. The precision study was calculated by injecting six samples of same concentration and the % Relative standard deviation was observed to be 0.3%. The mean percentage recoveries for 50%, 100% and 150% concentration were found to be 100.5%, 99.9% and 100.8% respectively. The percentage purity of the commercial sample assayed using the proposed method was found to be 99.8%. The developed method was validated according to ICH guidelines - Q2 (R1) and all the results were present within the acceptance criteria, Hence the proposed method can be employed for regular quality control analysis of obeticholic acid in bulk and pharmaceutical dosage forms.
Calculation of Vibrational Energies of AlH2 Using U(2) Lie Algebraic Approach
Authors: P. Suneetha P. Suneetha , J. Vijayasekhar J. Vijayasekhar
Published: November 2022

Using the U(2) Lie algebraic approach, it is determined that the vibrational energies of the aluminumdihydride (AlH2) molecule up to the fifth overtone and reported the combinational bands up to the third harmonic.In this approach, the algebraic parameters and operators are used to represent the Hamiltonian operator to calculate the vibrational energies.
The challenges of regulatory data: a case study of British charity reserves reporting
Authors: Abnett Helen , Bowles James , Clifford David
Published: November 2022

Charity reserve levels are widely used as a measure of financial vulnerability, of both individual charitable organisations and the wider sector. This paper assesses the mandated reporting of reserves by a large sample of British charities. We find that many charities are reporting figures that do not match the definition of reserves given by regulatory bodies. We therefore recommend caution when using extant reserves data, and that increased attention should be paid to the preparation of such data.
Comparative analysis of speckle-based single-pixel imaging using uniform and non-redundant optical phased arrays
Authors: Fukui Taichiro , Komatsu Kento , Nakano Yoshiaki , Tanemura Takuo
Published: November 2022

An optical phased array (OPA) is a compact high-speed wavefront modulation device that is promising for next-generation optical sensing systems. In particular, speckle-based single-pixel imaging (SSPI) using OPA is an attractive scheme since precise tuning of optical phases is unnecessary. In this work, we present a comprehensive analysis of SSPI using an OPA withNphase shifters by comparing two classes of OPAs: uniformly spaced OPA (UOPA) and non-redundant OPA (NROPA). Through singular value decomposition analysis of the illumination patterns generated from the OPA, we clarify the theoretical limit of the imaging resolution for each case. As a result, the number of resolvable points can be as large asN2−N+1for the case of NROPA. This is in clear contrast to the case of UOPA, where the number of resolvable points can only be as large as2N−1. Finally, imaging results of a test target are compared to study the impact of the array layout in OPA-based SSPI. Our work provides theoretical understanding of OPA-based SSPI and reveals the effectiveness of SSPI using NROPA.
Near-perfect ultrabroadband metal-free ultrathin THz absorber
Authors: Varshney Gaurav , Gupta Ravi Raj , Sharma Ajay K.
Published: November 2022

An ultrathin metal-free terahertz (THz) absorber is implemented and numerically analyzed. The absorber structure with a rectangular graphite resonator is designed to operate with the fundamental magnetic resonance in the lower- and higher-order magnetic resonance in the upper band. Carving the slots in the graphite resonator converts the magnetic resonance into the electric resonance at the upper frequency and merges the resonance spectra. The proposed absorber provides near-perfect flat broadband absorption of more than 99% in the 7.28–11.21 THz frequency range. Further, the absorber provides absorption of more than 90% and 80% in the 6.26–13.05 and 5.69–14.25 THz frequency range, respectively. The absorber structure utilizes a graphite-based resonator and backreflecting plane and provides the polarization insensitive response with the allowed incidence angle of more than 20° with the absorption more than 99%. The absorber response is validated through a transmission line method-based equivalent electrical circuit. Moreover, the reliability of the implemented absorber for its use in electromagnetic shields and stealth applications is calculated in terms of shielding effectiveness, which remains high in range of 50 to 250 dB.
Reconstruction error model of distributed shape sensing based on the reentered frame in OFDR
Authors: Li Sheng , Hua Peidong , Ding Zhenyang , Liu Kun , Yang Yong , Zhao Junpeng , Pan Ming , Guo Haohan , Zhang Teng , Liu Li , Jiang Junfeng , Liu Tiegen
Published: November 2022

At present, the reconstruction error of optical fiber shape sensing is commonly represented by Euclidean distance error. However, the Euclidian error of shape reconstruction will be dependent on the shape complexity, which depends on length, curvature and torsion. In this paper, we establish a reconstruction error model of distributed shape sensing in optical frequency domain reflectometry (OFDR) based on the Frenet-Serret frame and the error delivering theory, which illustrates the relationship between the reconstruction error and parameters such as curvature, torsion, fiber length and strain measurement error. We experimentally verify the feasibility and applicability of the proposed reconstruction error model by distributed optical fiber shape sensing system based on OFDR. The proposed reconstruction error model can provide a prediction of the maximal reconstruction error when the estimated range of curvature, torsion, fiber length of a shape needs to be reconstructed and strain measurement errors of OFDR system are known. It is very useful to judge whether the shape reconstruction error meets the requirement according to the shape to be reconstructed.
Underwater wireless optical communication employing polarization multiplexing modulation and photon counting detection
Authors: Gai Lei , Hei Xiaobing , Zhu Qiming , Yu Yonghe , Yang Yang , Chen Fangzhe , Gu Yongjian , Wang Guoyu , Li Wendong
Published: November 2022

Wireless optical communication is a crucial direction for improving the data transmission rate in underwater environments. In order to improve the communication performance over the water channel, this paper studies underwater wireless optical communication (UWOC) employing polarization multiplexing modulation and photon counting detection. The improvements in bit error rates and communication capacities are analyzed theoretically by constructing the communication model of polarization multiplexing modulation UWOC based on photon counting. Under specific conditions, the polarization maintenance characteristics of photons over water channels are demonstrated by measuring the Mueller matrix, the fidelity of quantum states, depolarization ratio, and calculating the ratios of ballistic photons. Based on these results, by designing and developing the experimental system of UWOC with the polarization multiplexing modulation and photon counting detection, the data transmission rates of 14.58Mbps and 7.29Mbps are realized over a water channel of 92 m by using polarization on-off keying multiplexing modulation and polarization 2-pulse-position multiplexing modulation, respectively.
Enhancement of the conversion efficiency of optical spin-orbit interactions in PT symmetric systems
Authors: Cao Yong , Zhang Zan , Ling Xiaohui
Published: November 2022

The optical spin-orbit interaction (SOI) caused by momentum-dependent Pancharatnam–Berry phase (PB) provides new opportunities in the development of spin-optical devices, but the relatively low conversion efficiency limits its application. Here, through rigorous full-wave analyses on it in a parity-time (PT) symmetric system with thickness less than a wavelength, we find that the conversion efficiency of the SOI can be enhanced in both transmission and reflection in a wide range of incidence angles. When the parameters of the PT symmetric system meet the requirement of coherent perfect absorbers-laser mode, the effective anisotropy between the TM and TE components (e.g., a difference of their Fresnel coefficients) within the beam will be amplified dramatically, which results in significantly enhanced conversion efficiency of SOIs (up to 106). These findings offer an effective way to modulate the SOIs with an ultra-thin PT symmetric system, and may exhibit applications in spin-orbit optical devices.
The Cyber Resilience Act: the EU Commission’s proposal for a horizontal regulation on cybersecurity for products with digital elements
Authors: Chiara Pier Giorgio
Published: November 2022

The EU Commission presented on 15 September 2022 the proposal for a ‘Regulation on horizontal cybersecurity requirements for products with digital elements amending Regulation (EU) 2019/1020’ (Cyber Resilience Act, CRA). This long-awaited piece of legislation would complement EU cybersecurity acquis by laying down horizontal cybersecurity requirements for all products with digital elements. This article sheds light on the ‘horizontal’ character of the CRA proposal by highlighting its main pillars. In particular, the contribution takes into account the new set of obligations placed on economic operators, the conformity assessment procedures as well as the market surveillance framework and the interplay with other legislative initiatives, both in the policy area and outside EU cybersecurity law. Against the backdrop of the sectoral regulatory approach adopted thus far by the Commission vis-à-vis cybersecurity requirements for products, horizontal intervention is needed to ensure legal certainty, avoiding duplicative obligations and further market fragmentation.
Training diversity promotes absolute-value-guided choice
Authors: Solomyak Levi , Sharp Paul B. , Eldar Eran
Published: November 2022

Many decision-making studies have demonstrated that humans learn either expected values or relative preferences among choice options, yet little is known about what environmental conditions promote one strategy over the other. Here, we test the novel hypothesis that humans adapt the degree to which they form absolute values to the diversity of the learning environment. Since absolute values generalize better to new sets of options, we predicted that the more options a person learns about the more likely they would be to form absolute values. To test this, we designed a multi-day learning experiment comprising twenty learning sessions in which subjects chose among pairs of images each associated with a different probability of reward. We assessed the degree to which subjects formed absolute values and relative preferences by asking them to choose between images they learned about in separate sessions. We found that concurrently learning about more images within a session enhanced absolute-value, and suppressed relative-preference, learning. Conversely, cumulatively pitting each image against a larger number of other images across multiple sessions did not impact the form of learning. These results show that the way humans encode preferences is adapted to the diversity of experiences offered by the immediate learning context.
Cultivating capacities in community-based researchers in low-resource settings: Lessons from a participatory study on violence and mental health in Sri Lanka
Authors: Palfreyman Alexis , Riyaz Safiya , Rizwan Zahrah , Vijayaraj Kavitha , Chathuranga I. P. R. , Daluwatte Ruwanka , Devindi W. A. T. , Eranda B. Shakila , Jayalath Vinodani , Junaid Azam , Kamal Ashra , Kannangara Shehan Koshila , Madushani K. M. G. Prasanga , Mathanakumar Laksi , Mubarak S. Ihjas , Nagalingam Vithusha , Palihawadana Sachin , Pathirana Ravishanka , Sampath V. G. Sameera , Shanmuganathan Lojini , Thrimawithana Tharindi , Vijayaratnam Priyatharshiny , Vithanage Sasith Lakshan , Wathsala R. K. K. A. Sajini , Yalini R. Mervin
Published: November 2022

Participatory methods, which rely heavily on community-based data collectors, are growing in popularity to deliver much-needed evidence on violence and mental health in low- and middle-income countries. These settings, along with local researchers, encounter the highest burden of violence and mental ill-health, with the fewest resources to respond. Despite increased focus on wellbeing for research participants and, to a lesser degree, professional researchers in such studies, the role-specific needs of community-based researchers receive scant attention. This co-produced paper draws insights from one group’s experience to identify rewards, challenges, and recommendations for supporting wellbeing and development of community-based researchers in sensitive participatory projects in low-resource settings. Twenty-one community-based researchers supporting a mixed-methods study on youth, violence and mental health in Sri Lanka submitted 63 reflexive structured journal entries across three rounds of data collection. We applied Attride-Stirling’s method for thematic analysis to explore peer researchers’ learning about research, violence and mental health; personal-professional boundaries; challenges in sensitive research; and experiences of support from the core team. Sri Lanka’s first study capturing experiences of diverse community-based researchers aims to inform the growing number of global health and development actors relying on such talent to deliver sensitive and emotionally difficult work in resource-limited and potentially volatile settings. Viewing participatory research as an opportunity for mutual learning among both community-based and professional researchers, we identify practice gaps and opportunities to foster respectful team dynamics and create generative and safe co-production projects for all parties. Intentional choices around communication, training, human and consumable resources, project design, and navigating instable research conditions can strengthen numerous personal and professional capacities across teams. Such individual and collective growth holds potential to benefit short- and long-term quality of evidence and inform action on critical issues, including violence and mental health, facing high-burden, low-resource contexts.
Management of hospital beds and ventilators in the Gauteng province, South Africa, during the COVID-19 pandemic
Authors: Alavinejad Mahnaz , Mellado Bruce , Asgary Ali , Mbada Mduduzi , Mathaha Thuso , Lieberman Benjamin , Stevenson Finn , Tripathi Nidhi , Swain Abhaya Kumar , Orbinski James , Wu Jianhong , Kong Jude Dzevela
Published: November 2022

We conducted an observational retrospective study on patients hospitalized with COVID-19, during March 05, 2020, to October 28, 2021, and developed an agent-based model to evaluate effectiveness of recommended healthcare resources (hospital beds and ventilators) management strategies during the COVID-19 pandemic in Gauteng, South Africa. We measured the effectiveness of these strategies by calculating the number of deaths prevented by implementing them. We observed differ ences between the epidemic waves. The length of hospital stay (LOS) during the third wave was lower than the first two waves. The median of the LOS was 6.73 days, 6.63 days and 6.78 days for the first, second and third wave, respectively. A combination of public and private sector provided hospital care to COVID-19 patients requiring ward and Intensive Care Units (ICU) beds. The private sector provided 88.4% of High care (HC)/ICU beds and 49.4% of ward beds, 73.9% and 51.4%, 71.8% and 58.3% during the first, second and third wave, respectively. Our simulation results showed that with a high maximum capacity, i.e., 10,000 general and isolation ward beds, 4,000 high care and ICU beds and 1,200 ventilators, increasing the resource capacity allocated to COVID- 19 patients by 25% was enough to maintain bed availability throughout the epidemic waves. With a medium resource capacity (8,500 general and isolation ward beds, 3,000 high care and ICU beds and 1,000 ventilators) a combination of resource management strategies and their timing and criteria were very effective in maintaining bed availability and therefore preventing excess deaths. With a low number of maximum available resources (7,000 general and isolation ward beds, 2,000 high care and ICU beds and 800 ventilators) and a severe epidemic wave, these strategies were effective in maintaining the bed availability and minimizing the number of excess deaths throughout the epidemic wave.
Prevalence of low birth weight and its associated factors: Hospital based cross sectional study in Nepal
Authors: Thapa Pratibha , Poudyal Amod , Poudel Rajan , Upadhyaya Dipak Prasad , Timalsina Ashish , Bhandari Rama , Baral Jijeebisha , Bhandari Rabindra , Joshi Prakash Chandra , Thapa Pratiksha , Adhikari Nabin
Published: November 2022

Low birth weight is still an important public health problem worldwide. It is a major contributor to neonatal death in developing countries, including Nepal. The government of Nepal has developed and implemented different programs to improve maternal and neonatal health, including baby’s birth weight. However, low birth weight is a major maternal and child health challenge. Maternal factors determining the birth weight of neonates have been poorly assessed in previous studies in Nepal. Thus, this study aims to assess the prevalence and risk factors associated with low birth weight in Nepal. An institution-based descriptive cross-sectional study was carried out in Paropakar Maternity Hospital and Tribhuvan University Teaching Hospital of Kathmandu district among 308 postnatal mothers. The data was collected through the face-to-face interview technique. The data was entered in EpiData 3.1 and exported to Statistical Package and Service Solutions version 21 for analysis. Multivariate logistic regression was used to obtain an adjusted odds ratio, while p-value < 0.05 with 95% Confidence Interval (CI) was considered significant. The findings showed that 15.3% of the children had low birth weight. The mean and standard deviation of childbirth weight was 2.96±0.59 kg. Mothers belonged to Dalit ethnic (AOR = 2.9, 95% CI = 1.2–7.1), Antenatal Care visited three or fewer (AOR = 2.6, 95%CI = 1.0–6.6) and did not comply with Iron and Folic Acid supplementation (AOR = 2.1, 95% CI = 1.0–4.4) were significantly associated with low birth weight. Nearly one in every six children had low birth weight. Maternal health services such as antenatal care and compliance with a recommended dose of maternal micronutrients significantly impact on birth weight. Maternal and neonatal health programs should consider these factors to reduce adverse birth outcomes in Nepal.
RASCL: Rapid Assessment of Selection in CLades through molecular sequence analysis
Authors: Lucaci Alexander G. , Zehr Jordan D. , Shank Stephen D. , Bouvier Dave , Ostrovsky Alexander , Mei Han , Nekrutenko Anton , Martin Darren P. , Kosakovsky Pond Sergei L.
Published: November 2022

An important unmet need revealed by the COVID-19 pandemic is the near-real-time identification of potentially fitness-altering mutations within rapidly growing SARS-CoV-2 lineages. Although powerful molecular sequence analysis methods are available to detect and characterize patterns of natural selection within modestly sized gene-sequence datasets, the computational complexity of these methods and their sensitivity to sequencing errors render them effectively inapplicable in large-scale genomic surveillance contexts. Motivated by the need to analyze new lineage evolution in near-real time using large numbers of genomes, we developed the Rapid Assessment of Selection within CLades (RASCL) pipeline. RASCL applies state of the art phylogenetic comparative methods to evaluate selective processes acting at individual codon sites and across whole genes. RASCL is scalable and produces automatically updated regular lineage-specific selection analysis reports: even for lineages that include tens or hundreds of thousands of sampled genome sequences. Key to this performance is (i) generation of automatically subsampled high quality datasets of gene/ORF sequences drawn from a selected “query” viral lineage; (ii) contextualization of these query sequences in codon alignments that include high-quality “background” sequences representative of global SARS-CoV-2 diversity; and (iii) the extensive parallelization of a suite of computationally intensive selection analysis tests. Within hours of being deployed to analyze a novel rapidly growing lineage of interest, RASCL will begin yielding JavaScript Object Notation (JSON)-formatted reports that can be either imported into third-party analysis software or explored in standard web-browsers using the premade RASCL interactive data visualization dashboard. By enabling the rapid detection of genome sites evolving under different selective regimes, RASCL is well-suited for near-real-time monitoring of the population-level selective processes that will likely underlie the emergence of future variants of concern in measurably evolving pathogens with extensive genomic surveillance.