bluuebunny/crossref_metadata_2025 huggingface dataset:
Lenograstim-Induced Nodal Extramedullary Hematopoiesis
Authors: Leroy-Freschini Benjamin , Nicolae Alina , Iltis-Roux Aurore
Published: September 2020

We report the case of a 23-year-old man with nodal EMH (extramedullary hematopoiesis) occurring during treatment for a stage IIA “gray-zone” lymphoma. Although it is often related to myeloproliferative bone marrow disease, benign etiologies such as lenograstim treatment after chemotherapy can also induce EMH and be responsible for false-positive 18F-FDG PET/CT examinations. In this respect, GLUT overexpression in hematopoietic lineages and macrophages of the inflammatory environment are responsible for increased 18F-FDG uptake. Histopathologic confirmation of new hypermetabolic lesions on follow-up PET/CT may be required when the new lesions do not conform with the treatment responses in the preexisting lesions.
PET/CT-Guided Tissue Sampling in Patients With a Failed or Inconclusive CT-Guided Procedure
Authors: Kumar Rakesh , Sharma Anshul , Thulkar Sanjay , Iyer Venkateswaran K. , Sharma Atul
Published: September 2020

Background

CT-guided tissue sampling is a very effective tool. However, false-negative results are obtained when regions such as necrotic core or surrounding reactive fibrosis and inflammation are sampled. PET/CT-guided sampling can circumvent these limitations.

Purpose

The aim of this study was to analyze the effectiveness of PET/CT-guided sampling in patients with at least 1 instance of failed or inconclusive CT-guided procedure and factors determining the accurate sampling and complications.

Methods

One hundred eleven patients were prospectively included. After feasibility analysis in a diagnostic 18F-FDG PET/CT, sampling was performed in 106 patients (45 women, 61 men; mean age, 48.09 ± 15.42 years; biopsy in 80 and fine-needle aspiration cytology [FNAC] in 26 patients), using robotic arm and a lower IV injection dose of 74 to 111 MBq (2–3 mCi) 18F-FDG. In all patients, final check scans revealed needle at the target site. Using planned needle path as reference, deviations in first check scan were measured. Patient (n = 30) and respiratory motion (n = 57) were also recorded.

Results

Accurate lesion targeting was achieved in 81 cases (63 positive lesions, 12 confounding lesions, and 7 inadequate samples). Lesion was missed in 5 instances, and blood/necrotic tissue sampled in 19. Overall 18F-FDG–avid lesions were accurately targeted in 77.36% of patients (86.25% [biopsy] + 50% [FNAC]). Significant variables affecting targeting were needle gauge, deviation from intended entry point, procedure duration, procedure type, and patient movement. Using binomial regression, the significant parameters were procedure type (biopsy vs FNAC; odds ratio [OR], 5.916; P = 0.002), patient movement (OR, 0.275; P = 0.023), and procedure duration (OR, 1.195; P = 0.011). Overall complication rate was 21.70%, with 4.71% major complications. It was dependent on target depth (mean depth, 69.74 ± 20.29 mm [complications] vs 47.18 ± 22.60 mm; P < 0.001). Positive correlation was seen between the target depth and distance of needle from the intended target (Spearman ρ = 0.307; P = 0.001). In 28 procedures, the physician was asked to wear a pocket dosimeter, who received a mean dose of 2.52 (SD, 3.10) μSv.

Conclusions

PET/CT-guided sampling should be considered where CT-guided biopsy has failed or is inconclusive. The outcome is impacted by needle gauge and patient movement, and complication rate is dependent on target depth.
Dose Calculations and Dose-Effect Relationships in 177Lu-PSMA I&T Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer
Authors: Barna Sandra , Haug Alexander R. , Hartenbach Markus , Rasul Sazan , Grubmüller Bernhard , Kramer Gero , Blaickner Matthias
Published: September 2020

Introduction

Dose response of 22 patients experiencing mCRPC (metastatic castration-resistant prostate cancer) to 177Lu-PSMA I&T radionuclide therapy was investigated. Dosimetry calculations are used to assess correlations between dosimetric quantities and biomarker values.

Methods

The patients’ age range was 74 ± 7 years at the time of the investigated treatment cycle, and the mean injected activity was 7416 ± 218 MBq. Planar images at several time points postinjection were used for evaluation of absorbed doses to organs and lesion. 68Ga-PSMA PET/CT follow-up imaging enabled the determination of individual tumor molecular volume (TMV) shrinkage. Changes in 7 different biomarkers after the first treatment cycle were correlated with the calculated absorbed organ and TMV doses, resulting in a total number of 259 investigated correlations.

Results

Sixty-three TMVs were identified in the bone, lymph node, and liver tissue with an average reduction of 32.3%, 84.7%, and 72.9%, respectively. Absorbed doses per unit of administered activity for organs and lesions show good agreement with previous works (0.77, 0.71, and 0.27 mGy/MBq for parotid gland, kidneys, and liver as well as 4.38, 5.47, and 4.95 mGy/MBq for bone, lymph node, and liver malignancies, respectively). Only 37 of 259 possible correlations turned out to be statistically significant, 26 of which are associated with the absorbed dose of an organ and the decrease of alkaline phosphatases.

Conclusions

Although treatment with 177Lu-PSMA I&T leads to a big reduction of TMV in patients with mCRPC, the lack of correlations calls for studies using voxel-wise dosimetry based on SPECT/CTs.
Dual Thyroid Ectopia and Heterotopic Thyroid Autotransplantation
Authors: Palaniswamy Shanmuga Sundaram , Subramanyam Padma
Published: September 2020

Ectopic thyroid gland can be detected at any age. It is a developmental defect that results from abnormal migration of the primitive thyroid bud. Dual ectopia is very rare, and only a few cases have been reported in literature. Patients with thyroid ectopia may be either euthyroid or hypothyroid. Concept of thyroid autotransplantation is based on restoring euthyroidism and is an attempt to preserve the autoregulatory mechanism of hormone production. This is a case of dual ectopia who underwent heterotopic thyroid autotranplantation. Images demonstrate hypertrophy of the transplanted thyroid tissue with gradual restoration of thyroid trapping function.
68Ga-DOTATOC PET for Treatment Efficacy Evaluation of Cardiac Sarcoidosis
Authors: Imperiale Alessio , Poindron Vincent , Martinez Matias , Ohlmann Patrick , Schindler Thomas H. , El Ghannudi Soraya
Published: September 2020

Cardiac sarcoidosis (CS) has a poor prognosis related to life-threating arrhythmias and heart failure. Treatment includes anti-inflammatory therapies and implantable pacemaker and/or cardioverter defibrillator. The presence of cardiac devices and physiologic myocardial glucose uptake are major limitations of both cardiac magnetic resonance and 18F-FDG PET/CT, reducing their diagnostic value. Somatostatin-based PET/CT has been proposed to detect active CS. Contrarily to 18F-FDG uptake, which reflects nonspecific leukocyte infiltration, 68Ga-DOTATOC may identify active granulomatosis. Herein, we underline the specificity of 68Ga-DOTATOC PET in challeging clinical situations including refractory CS, and chronic CS in patients with cardiac device, or false-positive 18F-FDG PET/CT results.
A Case of Primary Sacral Lymphoma Evaluated by 18F-FDG PET/CT
Authors: Xu Tingting , Fu Wenhui , Zhang Xinyi , Chen Yue
Published: September 2020

Primary sacral lymphoma is an unusual bone malignant tumor that poses a diagnostic challenge. Herein, we report a rare case of primary sacral lymphoma, which was initially assessed as suspicious bone metastasis. The subsequent histology and immunohistochemistry of the sacral biopsy confirmed the diagnosis of diffuse large B-cell lymphoma.
Graft-Versus-Host Disease Presenting as a Myositis and Myonecrosis
Authors: Patel Dhruv M. , Newallo Domnique S. , Barron Bruce
Published: September 2020

Graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation. Polymyositis with myonecrosis is a rare manifestation of GVHD. Here, we report the case of a 32-year-old man with acute myeloid leukemia who developed GVHD after transplant. He subsequently developed polymyositis, which was diagnosed on PET/CT and confirmed on pathology. Treatment with corticosteroids resulted in the resolution of the symptoms. Abnormal muscular FDG uptake resolved on the follow-up PET/CT.
Widespread Metastatic Gastric Signet-Ring Cell Carcinoma Shown by 68Ga-FAPI PET/CT
Authors: Fan Chunlei , Guo Wei , Su Guoqiang , Chen Bo , Chen Haojun
Published: September 2020

The present study compared 68Ga-FAPI and 18F-FDG PET/CT in a patient with GSRCC (gastric signet-ring cell carcinoma). In this case, 68Ga-FAPI PET/CT shows much higher tumor-to-background contrast of primary tumor and reveals more metastatic lesions than 18F-FDG PET/CT. This case demonstrates that 68Ga-FAPI PET/CT outperforms 18F-FDG in identifying both primary and metastatic lesions in GSRCC.
Pembrolizumab Exacerbates Thyroid Diseases Shown on FDG PET/CT
Authors: Wang Xuezhu , Wang Jingnan , Yang Xu , Zhao Haitao , Huo Li
Published: September 2020

A 51-year-old woman with a history of sarcomatoid hepatocellular carcinoma, status post resection, underwent FDG PET/CT. In addition to abnormal activity elsewhere, the images showed focal activity in the isthmus of the thyroid, suggestive of malignant involvement, and diffuse mild activity in the left lobe of the thyroid, suggestive of thyroiditis. After a 10-week anti–PD-1 pembrolizumab therapy, the follow-up FDG PET/CT scan demonstrated much more intense activity in both the isthmus and the left lobe of the thyroid. Pathological examination revealed papillary thyroid cancer in the isthmus and thyroiditis in the left lobe of the thyroid.
68Ga-FAPI Outperforms 18F-FDG PET/CT in Identifying Bone Metastasis and Peritoneal Carcinomatosis in a Patient With Metastatic Breast Cancer
Authors: Pang Yizhen , Zhao Liang , Chen Haojun
Published: September 2020

A 60-year-old woman, previously treated for breast cancer, was referred to gastroenterologists due to persistent abdominal distension. 18F-FDG PET/CT revealed multiple abnormal foci at the skeleton including the bilateral ilium, peritoneum, and omentum. 68Ga-FAPI PET/CT was performed for further detecting the primary lesion, which showed a greater number of bone metastases and higher uptake in peritoneal carcinomatoses than 18F-FDG. Biopsy at the left ilium and omentum indicated metastases from breast cancer. This case highlighted that 68Ga-FAPI may outperforms 18F-FDG PET/CT in identifying bone metastasis and peritoneal carcinomatosis.
Clinical and Striatal Dopamine Transporter Predictors of Mild Behavioral Impairment in Drug-Naive Parkinson Disease
Authors: Yoo Han Soo , Lee Sangwon , Chung Seok Jong , Ye Byoung Seok , Sohn Young H. , Yun Mijin , Lee Phil Hyu
Published: September 2020

Purpose

Neuropsychiatric symptoms are important and frequent nonmotor features in Parkinson disease (PD). We explored mild behavioral impairment (MBI) in drug-naive patients with PD and its clinical and dopamine transporter (DAT) correlates.

Methods

We recruited 275 drug-naive patients with PD who had undergone Unified Parkinson’s Disease Rating Scale, a neuropsychological battery, Neuropsychiatric Inventory, and N-(3-[18F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) PET within 6 months. Patients with PD were divided into groups without MBI (PD-MBI−, n = 186) and with MBI (PD-MBI+, n = 89) according to the Neuropsychiatric Inventory. We performed comparative analysis of DAT availability, cognitive function, and motor deficits between the groups.

Results

Mild behavioral impairment was found in 32.4% of PD patients at the time of diagnosis, and affective dysregulation and decreased motivation were the 2 most common neuropsychiatric domains. Dopamine transporter availability in the anterior caudate (odds ratio, 0.60; P = 0.016) and anterior putamen (odds ratio, 0.58; P = 0.008) was associated with the development of MBI in PD. PD-MBI+ group had a lower z-score in memory-related tests and Stroop color reading test than PD-MBI− group. PD-MBI+ group had a higher Unified Parkinson’s Disease Rating Scale motor score after controlling for DAT availability in the posterior putamen than PD-MBI− group (P = 0.007).

Conclusions

This study suggests that early behavioral impairment is associated with more pathological involvement in the anterior striatum, memory and frontal dysfunction, and motor deficits, which could be regarded as a different phenotype in PD.
Left Ventricular Infected Thrombus Detected by 18F-FDG PET/CT and MRI in Disseminated Staphylococcus Infection
Authors: García Vicente Ana María , Villar García Miguel , Blanch Sancho José Javier , Soriano Castrejón Ángel
Published: September 2020

We present the case of a 61-year-old woman with fever and acute meningitis. Clinical evaluation revealed maculopapular rash, right gluteus cellulitis, and centered retinal hemorrhages. In the intensive care unit, persistent Staphylococcus bacteremia was detected. However, transesophageal echocardiography did not reveal pathologic features. 18F-FDG PET/CT and cardiac MRI diagnosed a left ventricular infected thrombus, an extremely rare condition especially in patients without structural cardiopathy.
Primary Inferior Vena Cava Leiomyosarcoma With Hepatic Metastases on FDG PET/CT
Authors: Zou Sijuan , Zhou Jianyuan , Tang Ming , Wang Ziqing , Zhu Xiaohua
Published: September 2020

Leiomyosarcomas originating from the inferior vena cava are very rare malignant tumors with an extremely poor prognosis. We report FDG PET/CT findings of pathology-proven hepatic metastases from leiomyosarcoma originating from the inferior vena cava in a young woman whose initial presentation was worsening abdominal and chest pain.
Bilateral Epiphora as Only Presenting Sign of Total Paranasal Sinus Aplasia
Authors: Yagci Buket , Mangan Mehmet Serhat , Toslak Iclal Erdem , Balik Ayse Ozlem , Ozogul Murat
Published: September 2020

A 20-year-old female patient was presented with a bilateral epiphora. She had no history of infection or trauma related to the sinus areas. On examination, her facial appearance was abnormal and fullness on the face was observed. The fluorescein dye disappearance test was positive in both eyes. The lacrimal system irrigation was patent nasolacrimal duct. However, the dacryoscintigraphy imaging scan demonstrated bilateral obstruction at the nasolacrimal duct-inferior meatus junction. Nasal endoscopy did not reveal any pathologic findings, and lateral nasal wall, septum, and nasal cavities were normal. The patient was referred to the radiology department for a computed tomography of the paranasal sinus as a preoperative diagnostic imaging for lacrimal intervention. Computed tomography revealed the absence of all paranasal sinuses on both sides as well as absence of the ostiomeatal complex and ethmoidal air cells. Both bony lacrimal canal was narrow. Epiphora may be initial sign of total paranasal sinus aplasia.
Meta-analysis reveals materiomic relationships in major ampullate silk across the spider phylogeny
Authors: Craig Hamish C. , Piorkowski Dakota , Nakagawa Shinichi , Kasumovic Michael M. , Blamires Sean J.
Published: September 2020

Spider major ampullate (MA) silk, with its combination of strength and extensibility, outperforms any synthetic equivalents. There is thus much interest in understanding its underlying materiome. While the expression of the different silk proteins (spidroins) appears an integral component of silk performance, our understanding of the nature of the relationship between the spidroins, their constituent amino acids and MA silk mechanics is ambiguous. To provide clarity on these relationships across spider species, we performed a meta-analysis using phylogenetic comparative methods. These showed that glycine and proline, both of which are indicators of differential spidroin expression, had effects on MA silk mechanics across the phylogeny. We also found serine to correlate with silk mechanics, probably via its presence within the carboxyl and amino-terminal domains of the spidroins. From our analyses, we concluded that the spidroin expression shifts across the phylogeny from predominantly MaSp1 in the MA silks of ancestral spiders to predominantly MaSp2 in the more derived spiders' silks. This trend was accompanied by an enhanced ultimate strain and decreased Young's modulus in the silks. Our meta-analysis enabled us to decipher between real and apparent influences on MA silk properties, providing significant insights into spider silk and web coevolution and enhancing our capacity to create spider silk-like materials.
Nonlinear phenomena in models of the circadian clock
Authors: van Soest Inge , del Olmo Marta , Schmal Christoph , Herzel Hanspeter
Published: September 2020

The mammalian circadian clock is well-known to be important for our sleep–wake cycles, as well as other daily rhythms such as temperature regulation, hormone release or feeding–fasting cycles. Under normal conditions, these daily cyclic events follow 24 h limit cycle oscillations, but under some circumstances, more complex nonlinear phenomena, such as the emergence of chaos, or the splitting of physiological dynamics into oscillations with two different periods, can be observed. These nonlinear events have been described at the organismic and tissue level, but whether they occur at the cellular level is still unknown. Our results show that period-doubling, chaos and splitting appear in different models of the mammalian circadian clock with interlocked feedback loops and in the absence of external forcing. We find that changes in the degradation of clock genes and proteins greatly alter the dynamics of the system and can induce complex nonlinear events. Our findings highlight the role of degradation rates in determining the oscillatory behaviour of clock components, and can contribute to the understanding of molecular mechanisms of circadian dysregulation.
Multi-stability in cellular differentiation enabled by a network of three mutually repressing master regulators
Authors: Duddu Atchuta Srinivas , Sahoo Sarthak , Hati Souvadra , Jhunjhunwala Siddharth , Jolly Mohit Kumar
Published: September 2020

Identifying the design principles of complex regulatory networks driving cellular decision-making remains essential to decode embryonic development as well as enhance cellular reprogramming. A well-studied network motif involved in cellular decision-making is a toggle switch—a set of two opposing transcription factors A and B, each of which is a master regulator of a specific cell fate and can inhibit the activity of the other. A toggle switch can lead to two possible states—(high A, low B) and (low A, high B)—and drives the ‘either-or' choice between these two cell fates for a common progenitor cell. However, the principles of coupled toggle switches remain unclear. Here, we investigate the dynamics of three master regulators A, B and C inhibiting each other, thus forming three-coupled toggle switches to form a toggle triad. Our simulations show that this toggle triad can lead to co-existence of cells into three differentiated ‘single positive' phenotypes—(high A, low B, low C), (low A, high B, low C) and (low A, low B, high C). Moreover, the hybrid or ‘double positive' phenotypes—(high A, high B, low C), (low A, high B, high C) and (high A, low B, high C)—can coexist together with ‘single positive' phenotypes. Including self-activation loops on A, B and C can increase the frequency of ‘double positive' states. Finally, we apply our results to understand cellular decision-making in terms of differentiation of naive CD4
+
T cells into Th1, Th2 and Th17 states, where hybrid Th1/Th2 and hybrid Th1/Th17 cells have been reported in addition to the Th1, Th2 and Th17 ones. Our results offer novel insights into the design principles of a multi-stable network topology and provide a framework for synthetic biology to design tristable systems.
Wound healing: cellular mechanisms and pathological outcomes
Authors: Wilkinson Holly N. , Hardman Matthew J.
Published: September 2020

Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. Derangement in wound-linked cellular behaviours, as occurs with diabetes and ageing, can lead to healing impairment and the formation of chronic, non-healing wounds. These wounds are a significant socioeconomic burden due to their high prevalence and recurrence. Thus, there is an urgent requirement for the improved biological and clinical understanding of the mechanisms that underpin wound repair. Here, we review the cellular basis of tissue repair and discuss how current and emerging understanding of wound pathology could inform future development of efficacious wound therapies.
Growth of carbon nanofibres on molybdenum carbide nanowires and their self-decoration with noble-metal nanoparticles
Authors: Vengust Damjan , Vilfan Mojca , Mrzel Aleš
Published: September 2020

High specific surface area makes carbon nanofibres suitable for catalyst support. Here we report on optimization of carbon nanofibre (CNF) growth on molybdenum carbide nanowires (MoCNW) by direct carburization of

Mo

6

S

2

I

8

nanowire bundles. Typical CNFs obtained by this method are several hundreds of nanometres long at a diameter of 10–20 nm. We show that nanofibre growth does not depend on the initial morphology of the nanowires: nanofibres grow on individual bundles of MoCNW, on dense networks of nanowires deposited on silicon substrate, and on free-standing nanowire foils. We find that carbon nanofibres remain firmly attached to the nanowires even if they are modified into

Mo

2

C

and further into

Mo

S

2

nanowires. The method thus enables production of a novel hybrid material composed of

Mo

S

2

nanowires densely covered with carbon nanofibres. We have additionally shown that the obtained CNFs can easily be self-decorated with platinum nanoparticles with diameters of several nanometres directly from water solution at room temperature without reducing agents. Such efficient synthesis and decoration process yield hybrid platinum/CNF/molybdenum-based NW materials, which are a promising material for a wide range of possible future applications, including sensitive sensorics and improved catalysis.
Evolutionary game theory modelling to represent the behavioural dynamics of economic shutdowns and shield immunity in the COVID-19 pandemic
Authors: Kabir K. M. Ariful , Tanimoto Jun
Published: September 2020

The unprecedented global spread of COVID-19 has prompted dramatic public-health measures like strict stay-at-home orders and economic shutdowns. Some governments have resisted such measures in the hope that naturally acquired shield immunity could slow the spread of the virus. In the absence of empirical data about the effectiveness of these measures, policymakers must turn to epidemiological modelling to evaluate options for responding to the pandemic. This paper combines compartmental epidemiological models with the concept of behavioural dynamics from evolutionary game theory (EGT). This innovation allows us to model how compliance with an economic lockdown might wane over time, as individuals weigh the risk of infection against the certainty of the economic cost of staying at home. Governments can, however, increase spending on social programmes to mitigate the cost of a shutdown. Numerical analysis of our model suggests that emergency-relief funds spent at the individual level are effective in reducing the duration and overall economic cost of a pandemic. We also find that shield immunity takes hold in a population most easily when a lockdown is enacted with relatively low costs to the individual. Our qualitative analysis of a complex model provides evidence that the effects of shield immunity and economic shutdowns are complementary, such that governments should pursue them in tandem.
Measuring friction at an interface using ultrasonic response
Authors: Li X. , Dwyer-Joyce R. S.
Published: September 2020

Friction between sliding surfaces is a fundamental phenomenon prevalent in many aspects of engineering. There are many sliding contact tribometers that measure friction force in a laboratory environment. However, the transfer of laboratory data to real machine elements is unreliable. Results depend on the specimen configuration, surface condition and environment. In this work, a method has been developed that uses the nonlinear response of a high-power ultrasonic wave to deduce friction coefficientin situat an interface. When the high-power shear wave strikes a frictional interface, relative slip can occur. It imposes a nonlinear response and causes generation of higher-order odd frequency components in received ultrasonic signals. The amplitude of the harmonics depends on contact stress and local friction coefficient. This nonlinear ultrasonic response has been investigated both numerically and experimentally. A simple one-dimensional model has been used to predict nonlinearity generation. This model has been compared with experiments conducted on aluminium rough surfaces pressed together under increasing loads. Two strategies have been used to estimate the friction coefficient by correlating experimental and numerical third-order nonlinearity. It has proved possible to determine the friction coefficientin situat the interface; values in the range of 0.22 to 0.61 were measured for different surface configurations.
Axisymmetric bending analysis of functionally graded one-dimensional hexagonal piezoelectric quasi-crystal circular plate
Authors: Li Yang , Li Yuan , Qin Qinghua , Yang Lianzhi , Zhang Liangliang , Gao Yang
Published: September 2020

Within a framework of the state space method, an axisymmetric solution for functionally graded one-dimensional hexagonal piezoelectric quasi-crystal circular plate is presented in this paper. Applying the finite Hankel transform onto the state space vector, an ordinary differential equation with constant coefficients is obtained for the circular plate provided that the free boundary terms are zero and an exponential function distribution of material properties is assumed. The ordinary differential equation is then used to obtain the stress, displacement and electric components in the physical domain of the elastic simply supported circular plate through the use of the propagator matrix method and the inverse Hankel transform. The numerical studies are carried out to show the validity of the present solution and reveal the influence of material inhomogeneity on the axisymmetric bending of the circular plate with different layers and loadings, which provides guidance for the design and manufacture of functionally graded one-dimensional hexagonal piezoelectric quasi-crystal circular plate.
Do novel insecticides pose a threat to beneficial insects?
Authors: Siviter Harry , Muth Felicity
Published: September 2020

Systemic insecticides, such as neonicotinoids, are a major contributor towards beneficial insect declines. This has led to bans and restrictions on neonicotinoid use globally, most noticeably in the European Union, where four commonly used neonicotinoids (imidacloprid, thiamethoxam, clothianidin and thiacloprid) are banned from outside agricultural use. While this might seem like a victory for conservation, restrictions on neonicotinoid use will only benefit insect populations if newly emerging insecticides do not have similar negative impacts on beneficial insects. Flupyradifurone and sulfoxaflor are two novel insecticides that have been registered for use globally, including within the European Union. These novel insecticides differ in their chemical class, but share the same mode of action as neonicotinoids, raising the question as to whether they have similar sub-lethal impacts on beneficial insects. Here, we conducted a systematic literature search of the potential sub-lethal impacts of these novel insecticides on beneficial insects, quantifying these effects with a meta-analysis. We demonstrate that both flupyradifurone and sulfoxaflor have significant sub-lethal impacts on beneficial insects at field-realistic levels of exposure. These results confirm that bans on neonicotinoid use will only protect beneficial insects if paired with significant changes to the agrochemical regulatory process. A failure to modify the regulatory process will result in a continued decline of beneficial insects and the ecosystem services on which global food production relies.
Lineage-specific patterns of chromosome evolution are the rule not the exception in Polyneoptera insects
Authors: Sylvester Terrence , Hjelmen Carl E. , Hanrahan Shawn J. , Lenhart Paul A. , Johnston J. Spencer , Blackmon Heath
Published: September 2020

The structure of a genome can be described at its simplest by the number of chromosomes and the sex chromosome system it contains. Despite over a century of study, the evolution of genome structure on this scale remains recalcitrant to broad generalizations that can be applied across clades. To address this issue, we have assembled a dataset of 823 karyotypes from the insect group Polyneoptera. This group contains orders with a range of variations in chromosome number, and offer the opportunity to explore the possible causes of these differences. We have analysed these data using both phylogenetic and taxonomic approaches. Our analysis allows us to assess the importance of rates of evolution, phylogenetic history, sex chromosome systems, parthenogenesis and genome size on variation in chromosome number within clades. We find that fusions play a key role in the origin of new sex chromosomes, and that orders exhibit striking differences in rates of fusions, fissions and polyploidy. Our results suggest that the difficulty in finding consistent rules that govern evolution at this scale may be due to the presence of many interacting forces that can lead to variation among groups.
Fisheries-induced selection against schooling behaviour in marine fishes
Authors: Guerra Ana Sofia , Kao Albert B. , McCauley Douglas J. , Berdahl Andrew M.
Published: September 2020

Group living is a common strategy used by fishes to improve their fitness. While sociality is associated with many benefits in natural environments, including predator avoidance, this behaviour may be maladaptive in the Anthropocene. Humans have become the dominant predator in many marine systems, with modern fishing gear developed to specifically target groups of schooling species. Therefore, ironically, behavioural strategies which evolved to avoid non-human predators may now actually make certain fish more vulnerable to predation by humans. Here, we use an individual-based model to explore the evolution of fish schooling behaviour in a range of environments, including natural and human-dominated predation conditions. In our model, individual fish may leave or join groups depending on their group-size preferences, but their experienced group size is also a function of the preferences of others in the population. Our model predicts that industrial fishing selects against individual-level behaviours that produce large groups. However, the relationship between fishing pressure and sociality is nonlinear, and we observe discontinuities and hysteresis as fishing pressure is increased or decreased. Our results suggest that industrial fishing practices could be altering fishes’ tendency to school, and that social behaviour should be added to the list of traits subject to fishery-induced evolution.
Morphological convergence obscures functional diversity in sabre-toothed carnivores
Authors: Lautenschlager Stephan , Figueirido Borja , Cashmore Daniel D. , Bendel Eva-Maria , Stubbs Thomas L.
Published: September 2020

The acquisition of elongated, sabre-like canines in multiple vertebrate clades during the last 265 Myr represents a remarkable example for convergent evolution. Due to striking superficial similarities in the cranial skeleton, the same or similar skull and jaw functions have been inferred for sabre-toothed species and interpreted as an adaptation to subdue large-bodied prey. However, although some sabre-tooth lineages have been classified into different ecomorphs (dirk-tooths and scimitar-tooths) the functional diversity within and between groups and the evolutionary paths leading to these specializations are unknown. Here, we use a suite of biomechanical simulations to analyse key functional parameters (mandibular gape angle, bending strength, bite force) to compare the functional performance of different groups and to quantify evolutionary rates across sabre-tooth vertebrates. Our results demonstrate a remarkably high functional diversity between sabre-tooth lineages and that different cranial function and prey killing strategies evolved within clades. Moreover, different biomechanical adaptations in coexisting sabre-tooth species further suggest that this functional diversity was at least partially driven by niche partitioning.
Cardiovascular disease and severe hypoxemia associated with higher rates of non-invasive respiratory support failure in COVID-19
Authors: Wang Jing Gennie , Liu Bian , Percha Bethany , Pan Stephanie , Goel Neha , Mathews Kusum S. , Gao Cynthia , Tandon Pranai , Tomlinson Max , Yoo Edwin , Howell Daniel , Eisenberg Elliot , Naymagon Leonard , Tremblay Douglas , Chokshi Krishna , Dua Sakshi , Dunn Andrew , Powell Charles , Bose Sonali
Published: September 2020

Rationale

Acute hypoxemic respiratory failure (AHRF) is the major complication of coronavirus disease 2019 (COVID-19), yet optimal respiratory support strategies are uncertain.

Objectives

To describe outcomes with high-flow oxygen delivered through nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) in COVID-19 AHRF and identify individual factors associated with failure.

Methods

We performed a retrospective cohort study of hospitalized adults with COVID-19 treated with HFNC and/or NIPPV to describe rates of success (live discharge without endotracheal intubation (ETI)), and identify characteristics associated with failure (ETI and/or in-hospital mortality) using Fine-Gray sub-distribution hazard models.

Results

A total of 331 and 747 patients received HFNC and NIPPV as the highest level of non-invasive respiratory support, respectively; 154 (46.5%) in the HFNC cohort and 167 (22.4%) in the NIPPV cohort were successfully discharged without requiring ETI. In adjusted models, significantly increased risk of HFNC and NIPPV failure was seen among patients with cardiovascular disease (subdistribution hazard ratio (sHR) 1.82; 95% confidence interval (CI), 1.17-2.83 and sHR 1.40; 95% CI 1.06-1.84), respectively, and among those with lower oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio at HFNC and NIPPV initiation (sHR, 0.32; 95% CI 0.19-0.54, and sHR 0.34; 95% CI 0.21-0.55, respectively).

Conclusions

A significant proportion of patients receiving non-invasive respiratory modalities for COVID-19 AHRF achieved successful discharge without requiring ETI, with lower success rates among those with cardiovascular disease or more severe hypoxemia. The role of non-invasive respiratory modalities in COVID-19 related AHRF requires further consideration.
Functional immunoparalysis characterized by elevated Interleukin-10 and Interleukin-10- to-Lymphocyte Count Ratio is associated with severe disease and poor outcomes in coronavirus disease 2019 (COVID-19)
Authors: Henry Brandon Michael , Benoit Stefanie W. , Vikse Jens , Berger Brandon A. , Pulvino Christina , Hoehn Jonathan , Rose James , de Oliveira Maria Helena Santos , Lippi Giuseppe , Benoit Justin L.
Published: September 2020

Objectives

Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state, called cytokine storm. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response which if severe may lead to a state of functional immunoparalysis. The aim of this study was to evaluate the anti-inflammatory response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with patient outcomes.

Methods

Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was peak COVID-19 severity within 30 days of index ED visit. Additional endpoints included COVID-19 severity at ED disposition, development of severe acute kidney injury (AKI) or secondary bacterial infections.

Results

A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease at both time points (all p<0.05), as well as in those who developed severe AKI and secondary bacterial infection (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 was associated with 42% increased odds of severe COVID-19 (p=0.031), whilst a one-unit increase IL-10/lymphocyte ratio was also associated with 32% increase in odds of severe COVID-19 (p=0.013).

Conclusions

The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of secondary bacterial infections. IL-10 and IL-10/lymphocyte ratio at ED presentation were independent predictors of COVID-19 severity. Functional immunoparalysis in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.
Deubiquitinase UCHL1 Maintains Protein Homeostasis through PSMA7-APEH-Proteasome Axis in High-Grade Serous Ovarian Carcinoma
Authors: Tangri Apoorva , Lighty Kinzie , Loganathan Jagadish , Mesmar Fahmi , Podicheti Ram , Zhang Chi , Iwanicki Marcin , Nakshatri Harikrishna , Mitra Sumegha
Published: September 2020

High-grade serous ovarian cancer (HGSOC) is characterized by chromosomal instability, DNA damage, oxidative stress, and high metabolic demand, which exacerbate misfolded, unfolded and damaged protein burden resulting in increased proteotoxicity. However, the underlying mechanisms that maintain protein homeostasis to promote HGSOC growth remain poorly understood. In this study, we report that the neuronal deubiquitinating enzyme, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is overexpressed in HGSOC and maintains protein homeostasis. UCHL1 expression was markedly increased in HGSOC patient tumors and serous tubal intraepithelial carcinoma (HGSOC precursor lesions). High UCHL1 levels correlated with higher tumor grade and poor patient survival. UCHL1 inhibition reduced HGSOC cell proliferation and invasion through the outer layers of omentum as well as significantly decreased thein vivometastatic tumor growth in ovarian cancer xenografts. Transcriptional profiling of UCHL1 silenced HGSOC cells revealed the down-regulation of genes implicated with proteasome activity along with the upregulation of endoplasmic reticulum (ER) stress-induced genes. Reduced expression of proteasome subunit alpha 7 (PSMA7) and acylaminoacyl peptide hydrolase (APEH) resulted in a significant decrease in proteasome activity, impaired protein degradation, and abrogated HGSOC growth. Furthermore, the accumulation of polyubiquitinated proteins in the UCHL1 silenced cells led to attenuation of mTORC1 activity and protein synthesis, and induction of terminal unfolded protein response. Collectively, these results indicate that UCHL1 promotes HGSOC growth by mediating protein homeostasis through the PSMA7-APEH-proteasome axis.

Abstract Figure

Implications

This study identifies the novel links in the proteostasis network to target protein homeostasis in HGSOC. It recognizes the potential of inhibiting UCHL1 and APEH to sensitize cancer cells to proteotoxic stress and as novel alternative therapeutic approaches.
Insertional mutagenesis defines drivers and evolutionary relationships in pancreatic cancer metastasis
Authors: Govindaraju Suman , Maurin Michelle , Newberg Justin Y. , Jones Devin J. , Lee Hubert , Markovitz Judit E. , Mann Michael B. , Black Michael A. , Mann Karen M.
Published: September 2020

Metastasis is a defining feature of pancreatic cancer, impacting patient quality of life and therapeutic outcomes. While recurrent mutations inKRASandTP53play important roles in primary tumor development and persist in metastases, the contributions of other genes to the metastatic process is understudied. Here, we define a network of metastasis-promoting genes and uncover positively selected genes in metastatic lesions from ourSleeping Beautymouse model of pancreatic cancer using our recently described SB Driver Analysis statistical pipeline. We show that loss of single genesDLG1, PARD3, PKP4andPTPRKpromote pancreas cancer progression in a context-specific manner. Finally, we define clonal and sub-clonal insertion events that distinguish primary and individual metastatic tumors and use single cell sequencing to gain insight into the evolutionary relationships between sub-regions of primary pancreatic tumors and related metastases, which has important implications for pancreatic disease progression and therapeutic opportunities for patients.
Pathway dynamics can delineate the sources of transcriptional noise in gene expression
Authors: Ham Lucy , Jackson Marcel , Stumpf Michael P.H.
Published: September 2020

Single-cell expression profiling has opened up new vistas on cellular processes. Among other important results, one stand-out observation has been the confirmation of extensive cell-to-cell variability at the transcriptomic and proteomic level. Because most experimental analyses are destructive we only have access to snapshot data of cellular states. This loss of temporal information presents significant challenges in inferring dynamics, as well as causes of cell-to-cell variability. In particular, we are typically unable to separate dynamic variability from within individual systems (“intrinsic noise”) from variability across the population (“extrinsic noise”). Here we mathematically formalise this non-identifiability; but we also use this to identify how new experimental set-ups coupled to statistical noise decomposition can resolve this non-identifiability. For single-cell transcriptomic data we find that systems subject to population variation invariably inflate the apparent degree of burstiness of the underlying process. Such identifiability problems can, in principle, be remedied by dual-reporter assays, which separates total gene expression noise into intrinsic and extrinsic contributions; unfortunately, however, this requires pairs of strictly independent and identical gene reporters to be integrated into the same cell, which is difficult to implement experimentally in most systems. Here we demonstrate mathematically that, in some cases decomposition of transcriptional noise is possible with non-identical and not-necessarily independent reporters. We use our result to show that generic reporters lying in the same biochemical pathways (e.g. mRNA and protein) can replace dual reporters, enabling the noise decomposition to be obtained from only a single gene. Stochastic simulations are used to support our theory, and show that our “pathway-reporter” method compares favourably to the dual-reporter method.
Crystal structure and Hirshfeld surface analysis of (E)-3-[(4-methylbenzylidene)amino]-5-phenylthiazolidin-2-iminium bromide N,N-dimethylformamide monosolvate
Authors: Duruskari Gulnara Sh. , Khalilov Ali N. , Mammadova Gunay Z. , Çelikesir Sevim Türktekin , Akkurt Mehmet , Akobirshoeva Anzurat A. , Maharramov Abel M.
Published: September 2020

In the cation of the title salt, C17H18N3S+·Br−·C3H7NO, the central thiazolidine ring adopts an envelope conformation with puckering parameters Q(2) = 0.310 (3) Å and φ(2) = 42.2 (6)°. In the crystal, each cation is connected to two anions by N—H... Br hydrogen bonds, forming an R
4
2(8) motif parallel to the (10\overline{1}) plane. van der Waals interactions between the cations, anions and N,N-dimethylformamide molecules further stabilize the crystal structure in three dimensions. The most important contributions to the surface contacts are from H...H (55.6%), C...H/H...C (17.9%) and Br...H/H...Br (7.0%) interactions, as concluded from a Hirshfeld analysis.
Crystal structure and Hirshfeld surface analysis of 2-(1H-indol-3-yl)ethanaminium acetate hemihydrate. Corrigendum
Authors: Rajeswari Balakrishnan , Santhi Radhakrishnan , Sivajeyanthi Palaniyappan , Balasubramani Kasthuri
Published: September 2020

In the paper by Rajeswari et al. [Acta Cryst. (2019), E75, 451–455], the affiliations were not given correctly.
rac-(E,trans)-4-Bromo-10,10-dimethyl-9,11-dioxabicyclo[6.3.0]undec-4-ene
Authors: Schollmeyer Dieter , Heidrich Maximilian , Detert Heiner
Published: September 2020

In the title compound, a cyclooctene ring in a twist-boat conformation and a dioxolane ring with a distorted envelope conformation are annulated in a trans configuration. Alternating strands of single enantiomers build up the crystal. Within the strands, the molecules are connected by weak C—H...O hydrogen bonds.
Implementing quality assurance system for open and distance learning in three Asian open universities: Philippines, Indonesia and Pakistan
Authors: Zuhairi Aminudin , Raymundo Maria Rowena Del Rosario , Mir Kamran
Published: September 2020

Purpose

Quality assurance (QA) in open and distance learning (ODL) has always become universal concerns of stakeholders. The quality of ODL has been confronted with challenges in terms of the diversity of inputs, processes, the complex supply chain management of ODL and recent paradigm shift into online learning. Assuring the quality of ODL are daunting tasks at individual, institution and system levels. Completed before the beginning of the COVID-19 outbreak, this study aims to better understand the implementation of QA system in three Asian open universities (OUs), namely University of the Philippines Open University (UPOU), Universitas Terbuka (UT), Indonesia and Allama Iqbal Open University (AIOU), Pakistan.

Design/methodology/approach

A qualitative method was employed involving analysis of documents of the three Asian OUs and focus group discussions and interviews with management and staff. Data collected were then analyzed to draw conclusions and possible recommendations.

Findings

Findings of this study presented good practices, challenges and rooms for improvement of the QA system in the three Asian OUs. Focusing on students and stakeholders in their QA effort, this study has revealed that quality begins with inner self and is multidimensional. QA is principally viewed as continuous improvement, as mechanism and assessment and as effort at exceeding expectations of students and stakeholders. The recent challenge for QA is to embrace a delicate process of ODL transformation into online digital system. The recent COVID-19 outbreak has further implications and challenged QA implementation in ODL in higher education into the next level of complexity.

Practical implications

This study revealed the diversities in how OUs met the societal needs of their respective stakeholders and addressed the challenges ahead for QA in ODL.

Originality/value

These findings were expected to enhance the understanding of the theory and practice of QA in ODL and to contribute to quality improvement of ODL programs.