bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting and Prosecuting IP Infringement with AICan the AI Genie Repulse the Forty Counterfeit Thieves of Alibaba?
Authors: Seng Daniel
Published: April 2021

Drawing from available quantitative and qualitative data, this chapter briefly identifies and describes the automated as well as the more sophisticated AI-driven systems deployed to detect and enforce intellectual property rights (IPR) infringement by trademark and copyright holders in the online environment. It studies the legal basis for the use of such automated systems in copyright and trademark laws, and examines how such automated systems have upended, refocused, and altered many of the issues of IPR infringement and their enforcement. This chapter will also look at the problems of non-compliant Digital Millennium Copyright Act takedown notices, opportunistic copyright trolls, and non-interventionist Internet intermediaries, review the relevant judicial and legislative treatments including those in the Directive on Copyright in the Digital Single Market, and propose possible solutions to these problems.
AI as a Legal Person?
Authors: Mik Eliza
Published: April 2021

Cyclical advancements in artificial intelligence (AI) are usually accompanied by theories advocating the granting of legal personhood to sophisticated, autonomous computers. This chapter criticizes such theories as incorrect—a possible result of legal scholars being seduced by incomprehensible technical terminology, sensationalistic stories in the popular press, and ‘creative’ photo filters that transform our faces into animals. Discussions as to when computers should be recognized as persons are, logically, outside of the scope of intellectual property law. The granting of legal personhood is not premised on the existence of consciousness, intelligence, or creativity. Recognizing an entity as a legal person is a normative choice dictated by commercial expediency, not the result of fulfilling any technical criteria. While it is necessary to acknowledge the blurring of borders between art and (computer) science, as well as the increase in the technological sophistication of the tools used by authors and inventors, it is also necessary to state that even an exponential increase in ‘computer creativity’ will not sever the link between the computer and its user. Before discarding the idea of legal personhood for ‘creative algorithms’ once and for all, the chapter explores the relationships between autonomy and creativity. In particular, it places technical terms such as ‘AI’ and ‘autonomy’ in their original context and criticizes uninformed attempts to imbue them with normative connotations.
Opt-Out to the Rescue: Organ Donation and Samaritan Duties
Authors: Midtgaard Sören Flinch , Albertsen Andreas
Published: April 2021

Deceased organ donation is widely considered as a case of easy rescue―that is, a case in which A may bestow considerable benefits on B while incurring negligent costs herself. Yet, the policy implications of this observation remain unclear. Drawing on Christopher H. Wellman’s samaritan account of political obligations, the paper develops a case for a so-called opt-out system, i.e., a scheme in which people are defaulted into being donors. The proposal’s key idea is that we may arrange people’s options in specific ways for the sake of others.
Examining Proactive and Responsive Outcomes of a Dedicated Co-Responder Team
Authors: Morabito Melissa S , Savage Jenna
Published: April 2021

The Boston Police Department (BPD) has adopted a Co-Responder approach to enhance their response to people with mental illnesses residing in the City of Boston. Because of resource constraints, the BPD does not have a dedicated car to respond to mental health-related calls. This means that while Co-Responding teams can call off on or be dispatched to calls known or suspected to have a mental health component based on nature code or a commonly visited address, they must also respond to more typical calls for service. Using grant funding, the BPD implemented a 1-month dedicated Co-Responder car pilot programme and collected data about all related encounters. Using these data, we explore the outcomes resulting from this evaluation. First, we discuss the development and implementation of the Co-Response model and dedicated car pilot in Boston. Secondly, we examine how the Co-Responder team spent its time during the dedicated car pilot programme and describe the outcomes of encounters with community members, with a focus on involuntary evaluations and commitments as well as the factors that predicted these particular outcomes. Results indicate that much of the Co-Response work is proactive and that formal dispositions, such as involuntary commitment and evaluation, are used sparingly. Finally, policy and practice implications are discussed.
Can Religiosity be Sensed with Satellite Data? An Assessment of Luminosity during Ramadan in Turkey
Authors: Livny Avital
Published: April 2021

Social scientists have long been interested in how religious beliefs and practices impact and are impacted by socio-political and economic processes. Most recently, scholarly attention has focused on the interplay between religiosity and local actors, events, and institutions. Until now, measures of religiosity have relied heavily on self-reports in surveys, but these cannot always be safely collected and tend to be costly. Even where available, survey-based measures may be too obtrusive and are rarely representative of sub-national units. Here, I propose an inexpensive method that uses satellite imagery to unobtrusively estimate religiosity across small geographic units. I hypothesize that night-lights are affected by the behavior of fasting Muslims during Ramadan, especially in places where daytime activities are otherwise unchanged (i.e., where there is no “day-night inversion”). I explore and confirm the validity of this measurement strategy in the Turkish case, using a series of high-quality surveys and electoral results, representing 973 administrative districts. I conclude with a discussion of the external validity of this method and an overview of the ethical concerns raised by the use of remote sensing to estimate religiosity, in the Muslim world and elsewhere.
Effects of the Hedgehog Signaling Inhibitor Itraconazole on Developing Rat Ovaries
Authors: Johansson Hanna Katarina Lilith , Taxvig Camilla , Olsen Gustav Peder Mohr , Svingen Terje
Published: April 2021

Early ovary development is considered to be largely hormone independent; yet, there are associations between fetal exposure to endocrine disrupting chemicals and reproductive disorders in women. This can potentially be explained by perturbations to establishment of ovarian endocrine function rather than interference with an already established hormone system. In this study we explore if Hedgehog (HH) signaling, a central pathway for correct ovary development, can be disrupted by exposure to HH-disrupting chemicals, using the antifungal itraconazole as model compound. In the mouse Leydig cell line TM3, used as a proxy for ovarian theca cells, itraconazole exposure had a suppressing effect on genes downstream of HH signaling, such as Gli1. Exposing explanted rat ovaries (gestational day 22 or postnatal day 3) to 30 µM itraconazole for 72 h induced significant suppression of genes in the HH signaling pathway with altered Ihh, Gli1, Ptch1, and Smo expression similar to those previously observed in Ihh/Dhh knock-out mice. Exposing rat dams to 50 mg/kg bw/day in the perinatal period did not induce observable changes in the offspring’s ovaries. Overall, our results suggest that HH signal disruptors may affect ovary development with potential long-term consequences for female reproductive health. However, potent HH inhibitors would likely cause severe teratogenic effects at doses lower than those causing ovarian dysgenesis, so the concern with respect to reproductive disorder is for the presence of HH disruptors at low concentration in combination with other ovary or endocrine disrupting compounds.
Role of MicroRNA in Heart Transplant
Authors: Nog Rajat , Aggarwal Gupta Chhaya , Panza Julio A
Published: April 2021

The need for noninvasive biomarkers for diagnostic, prognostic, and therapeutic purposes is increasingly being recognized in the field of heart transplantation. MicroRNAs are a class of novel biomarkers that control gene expression and influence cellular functions, including differentiation, proliferation, and functional regulation of the immune system. They can be detected in the serum, plasma, and urine and may serve as early noninvasive biomarkers for various disease processes. Despite significant advances in heart transplantation, challenges remain in the short and long term with early graft injury and dysfunction, both cellular and antibody-mediated rejection, infections of varying types and severity, and cardiac allograft vasculopathy, which require an interventional approach for diagnosis and management. In this article, we review the current knowledge on the role of microRNAs in heart transplantation and its related complications and discuss their potential impact in future strategies to manage heart transplantation.
Conventional landmark palpation versus preprocedural ultrasound for neuraxial procedures in nonobstetric patients
Authors: Onwochei Desire , Nair Ganeshkrishna , Young Bruce , Desai Neel
Published: April 2021

BACKGROUND

Central neuraxial modalities can occasionally be challenging to perform, particularly if the underlying anatomy is altered or obscured.

OBJECTIVES

To compare the efficacy, efficiency and the safety of preprocedural ultrasound to landmark palpation in the nonobstetric adult population.

DESIGN

Systematic review of randomised controlled trials with meta-analysis and trial sequential analysis.

DATA SOURCES

Systematic search of Central, CINAHL, Embase, Global Health, MEDLINE, Scopus and Web of Science to 13th February 2020.

ELIGIBILITY CRITERIA

Randomised controlled trials of nonobstetric adult patients having diagnostic and/or therapeutic neuraxial procedures using standard preprocedural ultrasound interpreted by the operator as the intervention and conventional landmark palpation as the comparator.

KEY DEFINITIONS

A skin puncture was defined as the insertion or reinsertion of the needle through the skin; needle redirection was the backward followed by the forward movement of the needle without its removal from the skin; first skin puncture referred to a single skin puncture with or without needle redirections; and first pass was a single skin puncture with no needle redirection.

RESULTS

In all, 18 randomised controlled trials with 1800 patients were included. The first pass success rate was not different between landmark and ultrasound methods [risk ratio 1.46; 95% confidence interval (CI), 0.99 to 2.16; P = 0.06, I
2 = 76%; moderate quality of evidence] and the trial sequential analysis demonstrated the futility of further randomisation of patients in modifying this finding. Preprocedural ultrasound increased the total time taken (mean difference 110.8 s; 95% CI, 31.01 to 190.65; P = 0.006; I
2 = 96%; moderate quality of evidence). Subgroup analyses revealed no influence of the predicted difficulty of the neuraxial procedure on outcomes. Compared with the landmark method, ultrasound increased the first skin puncture success rate (risk ratio 1.36; 95% CI, 1.18 to 1.57; P < 0.001; I
2 = 70%), and decreased the need for three or more skin punctures (risk ratio 0.46; 95% CI, 0.33 to 0.64; P < 0.001; I
2 = 29%) and the number of needle redirections (mean difference -1.24; 95% CI, -2.32 to -0.17; P = 0.020; I
2 = 83). The incidence of bloody tap was reduced with the use of ultrasound (risk ratio 0.61; 95% CI, 0.40 to 0.93; P = 0.020; I
2 = 42%).

CONCLUSIONS

The use of preprocedural ultrasound for neuraxial procedures in the nonobstetric adult population did not enhance the first pass success rate and increased the total time taken to a clinically insignificant extent. Improvement in secondary outcomes, including other markers of efficacy, should be interpreted with caution.
Interpersonal Continuity of Care and Its Effect on Health Care Utilizations and Expenditures for Diabetes
Authors: Ebrahimoghli Reza , Janati Ali , Sadeghi-Bazargani Homayoun , Hamishekar Hadi
Published: April 2021

We aimed to quantify continuity of care (COC) and investigate its association with health care utilizations and expenditure among patients with diabetes. This was an observational retrospective cohort study using administrative claims database of Iranian Health Insurance Organization for East Azerbaijan Province, Iran. Standard indices of COC were calculated for each patient, and their associations with utilization outcomes were determined by applying general linear regression models. A total of 32 263 patients were included (mean age: 60.9 ± 14.5 years; 64% females). Higher levels of COC were associated with a reduced number and spending of all health care service categories.
Factors that Influence Door-to-Needle Administration for Acute Stroke Patients in the Emergency Department
Authors: Davis Nicolle W. , Bailey Meghan , Buchwald Natalie , Farooqui Amreen , Khanna Anna
Published: April 2021

BACKGROUND: There is growing importance on discovering factors that delay time to intervention for acute ischemic stroke (AIS) patients, as rapid intervention is essential for better patient outcomes. The management of these patients involves a multidisciplinary effort and quality improvement initiatives to safely increase treatment with intravenous (IV) thrombolytic. The objective of this pilot study is to evaluate factors of acute stroke care in the emergency department (ED) and their impact on IV alteplase administration. METHODS: A sample of 89 AIS patients who received IV alteplase from a single academic medical institution was selected for retrospective analysis. System characteristics (presence of a stroke nurse and time of day) and patient characteristics (mode of arrival and National Institutes of Health Stroke Scale score on arrival) were analyzed using descriptive statistics and multiple regression to address the study question. RESULTS: The mean door-to-needle time is 53.74 (38.06) minutes, with 74.2% of patients arriving to the ED via emergency medical services and 25.8% having a stroke nurse present during IV alteplase administration. Mode of arrival (P = .001) and having a stroke nurse present (P = .022) are significant predictors of door-to-needle time in the ED. CONCLUSION: Although many factors can influence door-to-needle times in the ED, we did not find National Institutes of Health Stroke Scale score on arrival and time of day to be significant factors. Patients arriving to the ED by personal vehicle will have a significant delay in IV alteplase administration, therefore emphasizing the importance of using emergency medical services. Perhaps more importantly, collaborative efforts including the addition of a specialized stroke nurse significantly decreased time to IV alteplase administration for AIS patients. With this dedicated role, accelerated triage and more effective management of AIS patients is accomplished, leading to decreased intervention times and improving patient outcomes.
De Novo Human Leukocyte Antigen Allosensitization in Heartmate 3 Versus Heartmate II Left Ventricular Assist Device Recipients
Authors: Jain Rashmi , Habal Marlena V. , Clerkin Kevin J. , Latif Farhana , Restaino Susan W. , Zorn Emmanuel , Takeda Koji , Naka Yoshifumi , Yuzefpolskaya Melana , Farr Maryjane A. , Colombo Paolo C. , Sayer Gabriel T. , Uriel Nir , Topkara Veli K.
Published: April 2021

Left ventricular assist devices (LVADs) are associated with the development of antihuman leukocyte antigen (HLA) antibodies, which can create a challenge for future transplantation in these patients. The differential effects of Heartmate 3 (HM3) versus Heartmate II (HMII) on de novo HLA allosensitization remain unknown. Patients who underwent HMII or HM3 implantation and had no prior HLA antibodies by solid-phase assay (Luminex) testing were included in this study. Complement-dependent cytotoxicity (CDC) panel reactive antibody (PRA) levels and Luminex antibody profiles were followed until cardiac transplantation, device explantation, or death. Electronic medical records were reviewed to examine posttransplant outcomes. Thirty-eight HM3 and 34 HMII patients with complete data were followed for 1.5 ± 1.1 years on device support. HM3 and HMII groups had similar age at implant, female gender, ischemic heart failure etiology, bridge strategy at implant, as well as intraoperative and postoperative transfusion requirements. 39.5% of HM3 and 47.1% of HMII patients developed detectable HLA antibodies by Luminex testing (p = 0.516). Development of high-level (mean fluorescence intensity >10,000) antibodies was significantly lower in HM3 than HMII patients (5.3 vs. 20.6%, p = 0.049). CDC PRA testing showed fewer HM3 patients with a positive result (PRA > 0%) than HMII patients (39.4 vs. 70.0%, p = 0.015). Among transplanted patients, those who had developed de novo sensitization on LVAD support showed a trend toward incidence of moderate to severe grade rejection compared with unsensitized patients (23.8 vs. 4.8%, p = 0.078). HM3 is associated with lower risk of de novo HLA sensitization compared with HMII.
Utility of 18F-FDG PET/CT Imaging in Diagnosing Pulmonary Prosthetic Valve Endocarditis in a Pediatric Patient
Authors: Hardisky Dariya , Tricarico Rosamaria , Kelly John M. , Bobbey Adam J. , Stacy Mitchel R.
Published: April 2021

A 15-year-old girl with a history of complex congenital heart disease and prior pulmonary valve replacement presented with suspected endocarditis. PET/CT imaging with 18F-FDG was performed to evaluate the potential presence of intracardiac vegetations after previously inconclusive findings from CT angiography, transthoracic echocardiography, and transesophageal echocardiography. PET/CT detected heterogeneous, asymmetric, increased 18F-FDG uptake in the region of the pulmonary valve prosthesis, typical for infection, and confirmed diagnosis of bacterial infective endocarditis. This report highlights the utility of 18F-FDG PET/CT imaging to complement the Duke criteria for determining the diagnosis and therapeutic management of pediatric patients with infective endocarditis.
Fibrous Dysplasia Mimicking Skeletal Metastasis on 68Ga-FAPI PET Imaging
Authors: Song Yangmeihui , Qin Chunxia , Liu Fang , Lan Xiaoli
Published: April 2021

68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET imaging has been introduced for detecting many primary and metastatic tumors. However, false-positive uptakes have been reported in some benign lesions. Here, we presented a 68Ga-FAPI–avid lesion in the left temporal bone in a 41-year-old man with a history of signet ring cell gastric adenocarcinoma. The osseous lesion was finally distinguished as fibrous dysplasia according to the clinical and imaging findings. This case suggests that 68Ga-FAPI may have false-positive uptakes in bone benign lesions, which should be paid attention to in the diagnosis of bone lesions in patients with malignant tumors.
Memantine Alleviates Acute Lung Injury Via Inhibiting Macrophage Pyroptosis
Authors: Ding Hongdou , Yang Jie , Chen Linsong , Li Yuehua , Jiang Gening , Fan Jie
Published: April 2021

Acute lung injury (ALI) is caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis and trauma. Alveolar macrophages are the main and critical leukocytes in the airspace, and through the synthesis and release of various inflammatory mediators critically influence the development of ALI following infection and non-infectious stimuli. There is increasing recognition that inflammation and cell death reciprocally affect each other, which forms an auto-amplification loop of these two factors, and in turn, exaggerates inflammation. Therefore, pharmacological manipulation of alveolar macrophage death signals may serve as a logical therapeutic strategy for ALI. In this study, we demonstrate that memantine, a N-methyl-D-aspartic acid receptor (NMDAR) antagonist, through suppressing Ca2+ influx and subsequent ASC oligomerization inhibits macrophage Nlrp3 inflammasome activation and pyroptosis, therefore, alleviates ALI in septic mice. This finding explores a novel application of memantine, an FDA already approved medication, in the treatment of ALI, which is currently lacking effective therapy.
The smallest known heliozoans are the Erebor lineage (nom. clad. n.) inside Microheliella maris (Eukaryota, Diaphoretickes), with the amendation of M. maris diagnosis and description of Berkeleyaesol magnus gen. nov., comb. nov. (Eukaryota, incertae sedis)
Authors: Shishkin Yegor , Drachko Daria , Zlatogursky Vasily V.
Published: April 2021

A new strain of planktonic heliozoans (ZI172) belonging to the genusMicroheliella(the sister group of Cryptista in Diaphoretickes), closely related to the only one known strain ofMicroheliella maris(CCAP 1945/1), was studied with light microscopy and SSU rRNA gene sequencing. Morphometric data obtained from 127 cells and based on 254 measurements showed that this strain represents the smallest heliozoan (1.66–3.42 µm, av. 2.56 µm) in diameter known to date and one of the smallest free-living eukaryotes. We also did morphometry for strain CCAP 1945/1. Its cell body size is 3.20–6.47 µm (av. 4.15 µm;n=141;m=282). The secondary structures of hairpin 15 of the SSU rRNA molecules were reconstructed for ZI172 and CCAP 1945/1 and they were compared The possible biochemical explanation for the smaller size of the ZI172 strain, which is smaller than the CCAP 1945/1 strain, is discussed, including all published electron micrographs of CCAP 1945/1. The necessary taxonomic work is also carried out. The diagnosis ofMicroheliella marisis amended and the new infraspecific cladeEreboris described to include ZI172. The measurements and systematics of the enigmatic heliozoan ‘Raphidiophrys’magnaO’Donoghue 1922 (non 1921; the biggest known heliozoan) are also discussed and it is transferred to the new genusBerkeleyaesol.
Impact of social distancing measures on the daily number of new COVID-19 cases in Côte d’Ivoire: a retrospective cohort study
Authors: Porgo Teegwende V. , Boukar Khadidja Malloum , Djallo Ezechiel A. , Amissah Richard Quansah , Assy Coralie , Traore Adama , Sorgho Gaston
Published: April 2021

Introduction

Côte d’Ivoire is facing a second wave of the novel coronavirus disease 2019 (COVID-19). While social distancing measures (SDM) may be an option to address this wave, SDM may be devastating, especially if they have a minimal impact on the spread of COVID-19, given the other measures in place.

Methods

We conducted a cohort study involving cases that had occurred as at June 30, 2020. We used data from the Government’s situation reports. We established three study periods, which correspond to the implementation and easing of SDM, including a 10-day delay for test results: (1) the SDM (March 11 - May 24), (2) the no SDM (May 25 - June 21), and (3) the pseudo SDM (June 22 - July 10) periods. We compared the incidence rate during these periods using Poisson regression, with sex, age, and the average daily number of tests as covariates.

Results

As at July 10, there were 12,052 cases. The incidence rate was 100% higher during period 2 compared to period 1 (incidence rate ratio = 2.05, 95% confidence interval: 1.75-2.41) and 25% lower during period 3 compared to period 2 (0.75 [0.66-0.86]).

Conclusions

The easing and subsequent reinforcement of SDM had a significant impact on the spread of COVID-19 in Côte d’Ivoire. The other mitigation measures either did not compensate for the easing of the SDM during the no SDM period or were not fully effective throughout the study periods; they should be strengthened before the SDM are reimplemented.
Modeling myosin with interacting linkages
Authors: Omabegho Tosan
Published: April 2021

In this study, I describe a model in which mechanical linkages dynamically interact in a stepwise and reversible manner, and use it to model the chemical cycle and lever arm action of the biomolecular motor myosin. Myosin is emulated using a series of multivalent chemical reactions between a linkage enzyme and four reactants: a cleaveable fuel, two cleavage products, and ligand. Geometric coupling between the fuel and ligand binding sites—an analog for negative allosteric coupling—allows reaction sequences similar to nucleotide exchange to take place that in turn drive the “strokes” of the machine’s lever arm. Cyclic chemical behavior is demonstrated by stochastic simulation, and mechanical activity by a series of logical arguments. I show how a reciprocal and nonreciprocal conformational cycle emerge from the allosteric rules designed to achieve chemical cycling, and how the non-reciprocal cycle can break directional symmetry along a track like structure. A dimeric construct is used to demonstrate how directed motion can be designed by inhibition of the reciprocal cycle and reinforcement of the non-reciprocal cycle, through allosteric feedback between the units of the dimer. By showing how the chemomechanical cycle of a biomolecular motor can be recreated with simple geometric and chemical principles, this work may help advance the rational design of allosteric mechanisms, and the development of synthetic molecular motors.
Unmethylated Regions Encompass The Functional Space Within The Maize Genome
Authors: Ricci William
Published: April 2021

Delineating the functional space within genomes has been a long-standing goal shared among geneticists, molecular biologists, and genome scientists. The genome of Zea mays (maize) has served as a model for locating functional elements within the gene-distal intergenic space. A recent development has been the discovery and use of accessible chromatin as a proxy for functional regulatory elements. However, the idea has recently arisen that DNA methylation data could supplement the use of accessible chromatin data for homing in on regulatory regions. Here, I test the robustness of using DNA methylation as a proxy for functional space. I find that CHG methylation can be non-arbitrarily partitioned into hypo-methylated and hyper-methylated regions. Hypo-methylated CHG regions are stable across development and contain nearly all accessible chromatin. Note: changes that will be made in version 2: expand introduction; expand discussion; add additional analyses; expand methods; link to github scripts.
The genetic basis of structural colour variation in mimeticHeliconiusbutterflies
Authors: Brien Melanie N. , Romero Juan Enciso , Lloyd Victoria J. , Curran Emma V. , Parnell Andrew J. , Morochz Carlos , Salazar Patricio A. , Rastas Pasi , Zinn Thomas , Nadeau Nicola J.
Published: April 2021

Structural colours, produced by the reflection of light from ultrastructures, have evolved multiple times in butterflies. Unlike pigmentary colours and patterns, little is known about the genetic basis of these colours. Reflective structures on wing-scale ridges are responsible for iridescent structural colour in many butterflies, including the Müllerian mimicsHeliconius eratoandHeliconius melpomene. Here we quantify aspects of scale ultrastructure variation and colour in crosses between iridescent and non-iridescent subspecies of both of these species and perform quantitative trait locus (QTL) mapping. We show that iridescent structural colour has a complex genetic basis in both species, with offspring from crosses having wide variation in blue colour (both hue and brightness) and scale structure measurements. We detect two different genomic regions in each species that explain modest amounts of this variation, with a sex-linked QTL inH. eratobut notH. melpomene. We also find differences between species in the relationships between structure and colour, overall suggesting that these species have followed different evolutionary trajectories in their evolution of structural colour. We then identify genes within the QTL intervals that are differentially expressed between subspecies and/or wing regions, revealing likely candidates for genes controlling structural colour formation.
Pinhead antagonizes Admp to promote notochord formation
Authors: Itoh Keiji , Ossipova Olga , Sokol Sergei Y.
Published: April 2021

Dorsoventral patterning of a vertebrate embryo critically depends on the activity of Smad1 that mediates signaling by several BMP proteins, anti-dorsalizing morphogenetic protein (Admp), and their antagonists. Pinhead (Pnhd), a cystine-knot-containing secreted protein, is expressed in the ventrolateral marginal zone duringXenopusgastrulation, however, its molecular targets and signaling mechanisms have not been fully elucidated. An unbiased mass spectrometry-based screen of the gastrulasecretomeidentified Admp as a primary Pnhd-associated protein. We show that Pnhd binds Admp and inhibits its ventralizing activity by reducing Smad1 phosphorylation and suppressing its transcriptional targets. By contrast, Pnhd did not affect the signaling activity of BMP4. Importantly, the Admp gain-of-function phenotype and phospho-Smad1 levels have been enhanced after Pnhd depletion. Furthermore, Pnhd strongly synergized with Chordin and a truncated BMP4 receptor in the induction of notochord markers in ectoderm cells, and Pnhd-depleted embryos displayed notochord defects. Our findings suggest that Pnhd binds and inactivates Admp to promote notochord development. We propose that the interaction between Admp and Pnhd refines Smad1 activity gradients during vertebrate gastrulation.
The roles and regulation of MDM2 and MDMX: it is not just about p53
Authors: Klein Alyssa M. , de Queiroz Rafaela Muniz , Venkatesh Divya , Prives Carol
Published: April 2021

Most well studied as proteins that restrain the p53 tumor suppressor protein, MDM2 and MDMX have rich lives outside of their relationship to p53. There is much to learn about how these two proteins are regulated and how they can function in cells that lack p53. Regulation of MDM2 and MDMX, which takes place at the level of transcription, post-transcription, and protein modification, can be very intricate and is context-dependent. Equally complex are the myriad roles that these two proteins play in cells that lack wild-type p53; while many of these independent outcomes are consistent with oncogenic transformation, in some settings their functions could also be tumor suppressive. Since numerous small molecules that affect MDM2 and MDMX have been developed for therapeutic outcomes, most if not all designed to prevent their restraint of p53, it will be essential to understand how these diverse molecules might affect the p53-independent activities of MDM2 and MDMX.
Seismic responses to an earthquake source in stratified transversely isotropic porous media
Authors: Sun Junhua , Gao Yongxin , Tong Ping , He Xiao , Wang Wei , Geng Shuwei
Published: April 2021

In this paper, we study seismic responses to an earthquake source in horizontally stratified transversely isotropic porous media with a vertical axis of symmetry that is, transversely isotropic porous media. We present a semi‐analytical method to simulate the three‐dimensional time–space–domain seismic wavefields. We obtain the solution in the frequency–wavenumber domain by the global matrix method and transform it to the time–space domain by the discrete wavenumber method and fast Fourier transform. Our method incorporates the moment tensor source so that it allows simulating seismic responses to an earthquake. We validate our method by degenerating the transversely isotropic porous media into the isotropic porous media and transversely isotropic solid media, respectively, and compare the results with the corresponding reference solutions. We then investigate the characteristics of seismic wavefields in the transversely isotropic porous media by considering an explosive source, a shear‐wave source and a double‐couple source. The results reveal interesting observations in the transversely isotropic porous media versus the isotropic porous media. For example, the wave can have a response to the pore pressure during its propagation in a transversely isotropic porous medium while the shear‐wave does not generate any disturbance of the pore pressure. Our method is semi‐analytical and computationally efficient and it can be used for rapid evaluation of the seismic responses in transversely isotropic porous media.
Intense nocturnal warming alters growth strategies, colouration and parasite load in a diurnal lizard
Authors: Rutschmann Alexis , Dupoué Andréaz , Miles Donald B. , Megía‐Palma Rodrigo , Lauden Clémence , Richard Murielle , Badiane Arnaud , Rozen‐Rechels David , Brevet Mathieu , Blaimont Pauline , Meylan Sandrine , Clobert Jean , Le Galliard Jean‐François
Published: April 2021

In the past decades, nocturnal temperatures have been playing a disproportionate role in the global warming of the planet. Yet, they remain a neglected factor in studies assessing the impact of global warming on natural populations.

Here, we question whether an intense augmentation of nocturnal temperatures is beneficial or deleterious to ectotherms. Physiological performance is influenced by thermal conditions in ectotherms and an increase in temperature by only 2°C is sufficient to induce a disproportionate increase in metabolic expenditure. Warmer nights may expand ectotherms' species thermal niche and open new opportunities for prolonged activities and improve foraging efficiency. However, increased activity may also have deleterious effects on energy balance if exposure to warmer nights reduces resting periods and elevates resting metabolic rate.

We assessed whether warmer nights affected an individual's growth, dorsal skin colouration, thermoregulation behaviour, oxidative stress status and parasite load by exposing yearling common lizards (Zootoca vivipara) from four populations to either ambient or high nocturnal temperatures for approximately 5 weeks.

Warmer nocturnal temperatures increased the prevalence of ectoparasitic infestation and altered allocation of resources towards structural growth rather than storage. We found no change in markers for oxidative stress. The thermal treatment did not influence thermal preferences, but influenced dorsal skin brightness and luminance, in line with a predicted acclimation response in colder environments to enhance heat gain from solar radiation.

Altogether, our results highlight the importance of considering nocturnal warming as an independent factor affecting ectotherms' life history in the context of global climate change.

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Patterns of striped skunk scavenging on human remains
Authors: Smith Alexander
Published: April 2021

Scavenging is a known behavior of striped skunks (Mephitis mephitis), though it is rarely documented. Striped skunks were observed and documented scavenging nine human donors at the Forensic Investigation Research Station (FIRS) in Whitewater, Colorado from October 2017 through September 2019. Human remains are placed on the surface, outdoors, in a fenced area, and monitored daily through notes, photographs, and multiple systems for scoring decomposition. Motion‐activated game cameras are strategically positioned to monitor potential scavenger activity within the facility. When scavenging occurred, game camera images were temporally correlated to daily photographs and notes to confirm the source of observed defects. Striped skunks at the FIRS scavenged the soft tissue of the arms, legs, genitals, and torso. Game camera images documented skunks digging, climbing on top of remains, repositioning limbs, and using their paws to manipulate tissue. These activities impacted soft tissue, bone, and the surrounding environment. Scavenging patterns varied seasonally, with higher frequency and lower selectivity in the winter. Striped skunks are common throughout most of North America and are likely to scavenge human remains when available. Understanding patterns and behaviors of specific scavengers can help investigators accurately interpret defects found on and around human remains.
Linkage and linkage disequilibrium among the markers in the forensic MPS panels
Authors: Li Ran , Budowle Bruce , Sun Hongyu , Ge Jianye
Published: April 2021

For the past two to three decades, forensic DNA evidence has been analyzed with a limited number of short tandem repeats (STRs), and these STRs are usually assumed to be independent for statistical calculations. With the development and implementation of the MPS technologies, more autosomal markers, both single nucleotide polymorphisms (SNPs) and STRs, can be analyzed. A number of these markers are physically very close to each other, and it may not be appropriate to assume all these markers are genetically unlinked or in linkage equilibrium. In this study, publicly accessible genomic data from five representative populations were used to evaluate the genetic linkage and linkage disequilibrium (LD) between autosomal markers represented in six major commercial panels (in total, 362 markers). Among the 3041 syntenic marker pairs, 1524 pairs had sex‐average genetic distances <50 cM, and thus, these marker pairs can be considered as genetically linked. Among the 143 marker pairs with physical distances <1 Mb, 19 LD haplotype blocks (comprising 39 SNPs in total) were detected for at least one of the tested populations. Statistical methods for interpreting linked markers and/or markers in LD were suggested for various case scenarios.
Using hot steam exposure to reveal mechanical properties of spaghetti beams and columns
Authors: Akbar Fathan , Abdullah Mikrajuddin
Published: April 2021

We demonstrate that the bending evolution of spaghetti beams and columns by hot steam reveals several food‐related properties: time‐dependent Young modulus, the diffusion coefficient of steam molecules penetrating the material, the partial Fickian behavior of molecule diffusion, and a logistic‐like evolution of the column‐bending angle. The time‐lapse images of the spaghetti strands were recorded for estimating the strand's curvatures and, from these estimates, the strand's Young's moduli were calculated. Freely hung cantilever spaghetti beams and columns were exposed to hot steam from boiling water so that the images were recorded in real time while the beam or column bent undisturbedly. It is observed that the Young modulus decreased exponentially with time after an appropriate considerable period of exposure. The diffusion coefficient of water molecules can be estimated from the bending evolution, and our data matched with the experimental data reported by others. The method presented in this paper provides an alternative method for estimating the diffusion coefficient of vapor molecules penetrating the materials.

Practical Application

The elastic modulus is estimated by merely measuring the angle made by the spaghetti's free end in the form of a cantilever beam or column. The measurement is performed remotely. Using a simple calculation, the error of estimation is less than 5%. The chef can use the simulated result for estimating the “doneness” of the spaghetti being boiled or steamed by clamping a piece of spaghetti horizontally and guessing the angle of the free end.
Health‐related quality of life and work impairment in idiopathic inflammatory myopathies in South Australia
Authors: Xu Alan , Sun Caitlyn , Metcalf Robert , Limaye Vidya
Published: April 2021

Aim

The idiopathic inflammatory myopathies (IIM) are rare autoimmune diseases that are usually chronic and often present with skeletal muscle inflammation and weakness. We sought to examine the impact of IIM in a cohort of 50 South Australian patients on health‐related quality of life (HRQOL) and work productivity (WP). We uniquely categorized patients across gender, IIM subtypes, employment status, and also whether there was extramuscular involvement from IIM.

Methods

Multiple modalities were used, as recommended by the International Myositis Assessment and Clinical Studies Group (IMACS), to assess the impact of IIM, including manual muscle strength testing (MMT‐8), the Physician and Patient Global Activity Assessments (PHGAA, PTGAA), Myositis Disease Activity Assessment Tool (MDAAT), and serum creatinine kinase (CK) levels. The impacts of IIM on HRQOL and WP were analyzed using the Medical Outcomes Study 36‐items Short Form (SF‐36) and Work Productivity and Activity Impairment (WPAI) questionnaires, respectively.

Results

We found significantly lower HRQOL outcome scores in most of the SF‐36 domains when compared to the most recent population norms (P ≤ .01). Physical health was predominantly affected with relative preservation of emotional health. There were also significant associations between MMT‐8, PHGAA and PTGAA scores and HRQOL and WP.

Conclusions

Our findings highlight the significant impact of IIM on HRQOL and WP in a well‐characterized cohort of patients with IIM within Australia, and therefore the importance of a holistic approach to the management of these patients.
Association of FOXP3 rs3761548 polymorphism and its reduced expression with unexplained recurrent spontaneous abortions: A South Indian study
Authors: Dirsipam Kethora , Ponnala Deepika , Madduru Dhatri , Bonu Rajeswari , Jahan Parveen
Published: April 2021

Problem: Fork Head Box Protein 3 (FOXP3) is an X‐linked gene, codes for a master transcription regulatory protein that controls the development and function of immunosuppressive T regulatory (Treg) cells. They are crucial mediators of maternal foetal tolerance and successful pregnancy outcome. The aim of the study is to evaluate the association of FOXP3 rs3761548 functional polymorphism and to assess the serum concentrations of full‐length FOXP3 protein in Unexplained Recurrent Spontaneous Abortions (URSA) patients of Southern India.

Method of study: The study included blood samples from 150 URSA patients and 150 healthy, pregnant parous women. Polymerase Chain Reaction‐Restriction Fragment Length Polymorphism was done for rs3761548 FOXP3 genotyping. Serum concentrations of full‐length FOXP3 protein were estimated by enzyme‐linked immunosorbent assay.

Results: The frequencies of mutant A allele, CA and AA genotypes of rs3761548 functional polymorphism were significantly elevated in patients compared to healthy, pregnant parous women and exhibited a two, three and twofold increased risk respectively towards URSA. Serum concentrations of full‐length FOXP3 protein were high in controls compared to patients (10.14 ± .30 vs. 8.84 ± 1.73 ng/ml; p < .05).

Conclusion: Our results advocate an association of FOXP3 rs3761548 polymorphism and reduced expression of full‐length FOXP3 protein with URSA.
Laparoscopic surgery using 8 K ultra‐high‐definition technology: Outcomes of a phase II study
Authors: Tsukamoto Shunsuke , Kuchiba Aya , Moritani Konosuke , Shida Dai , Katayama Hiroshi , Yorikane Eiko , Kanemitsu Yukihide
Published: April 2021

Introduction

Currently, laparoscopic surgery generally relies on 2 K high‐definition image quality. The National Cancer Center Hospital, Olympus Corporation, and NHK Engineering System Inc. recently developed a new laparoscopic system with an 8 K ultra‐high‐definition (UHD) camera that provides images with a high‐resolution, wide color range, high frame rate, and high dynamic range. This study aimed to investigate the effectiveness and safety of a new laparoscopic system which uses an 8 K UHD camera system (8K UHD system).

Methods

This phase II study enrolled 23 patients with colon or rectosigmoid cancer who were indicated for radical resection with laparoscopic colectomy using the 8 K UHD system. The primary endpoint was the proportion of patients with ≥30 mL of intraoperative blood loss.

Results

Of the 23 patients, 22 completed laparoscopic surgery with the 8 K UHD system. One patient was converted to the 2 K high‐definition laparoscopic system due to technical difficulties with the 8 K UHD system during surgery. The median amount of intraoperative blood loss was 14 mL (range, 2‐71 mL), and number of patients with intraoperative blood loss ≥30 mL was four (17.4%). None of the patients had >100 mL of intraoperative blood loss. No intraoperative complications were noted, and four (17.4%) patients developed postoperative complications. Pathological complete resection was achieved in all patients, and no conversion to open surgery was required.

Conclusions

Laparoscopic surgery using the 8 K UHD system appears to be both safe and effective. However, further refinements may be necessary to improve usability.
Feature screening with large‐scale and high‐dimensional survival data
Authors: Yi Grace Y. , He Wenqing , Carroll Raymond. J.
Published: April 2021

Data with a huge size present great challenges in modeling, inferences, and computation. In handling big data, much attention has been directed to settings with “largepsmalln”, and relatively less work has been done to address problems withpandnbeing both large, though data with such a feature have now become more accessible than before, whereprepresents the number of variables andnstands for the sample size. The big volume of data does not automatically ensure good quality of inferences because a large number of unimportant variables may be collected in the process of gathering informative variables. To carry out valid statistical analysis, it is imperative to screen out noisy variables that have no predictive value for explaining the outcome variable. In this paper, we develop a screening method for handling large‐sized survival data, where the sample sizenis large and the dimensionpof covariates is of non‐polynomial order of the sample sizen, or the so‐called NP‐dimension. We rigorously establish theoretical results for the proposed method and conduct numerical studies to assess its performance. Our research offers multiple extensions of existing work and enlarges the scope of high‐dimensional data analysis. The proposed method capitalizes on the connections among useful regression settings and offers a computationally efficient screening procedure. Our method can be applied to different situations with large‐scale data including genomic data.
“Blepharophimosis‐plus” syndromes: Frequency of systemic genetic disorders that also include blepharophimosis
Authors: Landau Prat Daphna , Nguyen Brian J. , Strong Alanna , Katowitz William R. , Katowitz James A.
Published: April 2021

Background

To determine the frequency of isolated blepharophimosis‐ptosis‐epicanthus inversus syndrome (BPES) versus systemic genetic disorders in patients presenting with blepharophimosis.

Methods

Retrospective clinical records review. The records of all patients with blepharophimosis seen in the Division of Ophthalmology at the Children's Hospital of Philadelphia during a 12‐year‐period (2009‐2020) were reviewed for medical history, clinical examination findings and results of genetic analyses.

Results

The 135 patients identified with blepharophimosis included 72 females (53%) and 63 males (47%) whose mean ± standard deviation age at first visit was 3.5 ± 6.4 years (range 0‐39.8 years). Sixty‐seven of the patients (50%) had undergone genetic testing for FOXL2 gene mutation. Fifty‐four (81%) harboured FOXL2 gene mutations and 13 (19%) did not. Altogether, 126 patients (93%) had a final diagnosis of isolated BPES. The remaining nine (7%) had syndromic diagnoses (“blepharophimosis‐plus”), including Dubowitz syndrome (n = 2), Ohdo syndrome (n = 1), 22q11.2 duplication (n = 1) and 3q22 deletion (n = 2). Three patients with multiple congenital anomalies remain undiagnosed.

Conclusions

Blepharophimosis is an eyelid feature occurring most commonly in isolation due to FOXL2 gene mutation, but can also be a harbinger of multisystem disease not exclusive to isolated BPES, as observed in 7% of cases in this series. The ophthalmologist is often the first to recognise these unique features, and must consider and rule out non‐BPES syndromes before establishing a diagnosed classic BPES. A comprehensive genetic evaluation is, therefore, indicated in all cases.