bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity Scoring Cutoff for MLPA and Its Diagnostic Yield in 332 North Indian Children with Developmental Delay
Authors: Srivastava Priyanka , Kaur Parminder , Daniel Roshan , Chaudhry Chakshu , Kaur Anit , Seth Saurabh , Kumari Divya , Kaur Anupriya , Panigrahi Inusha
Published: October 2022

Chromosomal aberrations/rearrangements are the most common cause of intellectual disability (ID), developmental delay (DD), and congenital malformations. Traditionally, karyotyping has been the investigation of choice in such cases, with the advantage of being cheap and easily accessible, but with the caveat of the inability to detect copy number variations of sizes less than 5 Mb. Chromosomal microarray can solve this problem, but again the problems of expense and poor availability are major challenges in developing countries. The purpose of this study is to find the utility of multiplex ligation-dependent probe amplification (MLPA) as a middle ground, in a resource-limited setting. We also attempted to establish an optimum cutoff for the de Vries score, to enable physicians to decide between these tests on a case-to-case basis, using only clinical data. A total of 332 children with DD/ID with or without facial dysmorphism and congenital malformations were studied by MLPA probe sets P245. Assessment of clinical variables concerning birth history, facial dysmorphism, congenital malformations, and family history was done. We also scored the de Vries scoring for all the patients to find a suitable cutoff for MLPA screening. In our study, the overall detection rate of MLPA was 13.5% (45/332). The majority of patients were DiGeorge's syndrome with probe deletion in 22q11.21 in 3.3% (11/332) followed by 15q11.2 del in 3.6% (12/332, split between Angelman's and Prader–Willi's syndromes). Also, 3.0% (10/332) of patients were positive for Williams–Beuren's syndrome 7q11.23, 1.8% (6/332) for Wolf–-Hirschhorn's syndrome 4p16.3, 1.2% (4/332) for 1p36 deletion, and 1% for each trichorhinophalangeal syndrome type I 8q23.3 duplication syndrome and cri du chat syndrome. The optimum cutoff of de Vries score for MLPA testing in children with ID and/or dysmorphism came out to be 2.5 (rounded off to 3) with a sensitivity of 82.2% and specificity of 66.7%. This is the largest study from India for the detection of chromosomal aberrations using MLPA common microdeletion kit P245. Our study suggests that de Vries score with a cutoff of 3 or more can be used to offer MLPA as the first tier test for patients with unexplained ID, with or without facial dysmorphism and congenital malformations.
Arterial Embolization and Methylene Blue Injection into the Aberrant Artery in Two Infants with Intralobar Sequestration
Authors: Accarain Anna Ayako , Laureys Marc , Joyeux Luc , Damry Nasroola , Steyaert Henri , Reusens Helena
Published: October 2022

Bronchopulmonary sequestration is a rare congenital lung dysplasia. An intralobar sequestration (ILS) is a nonfunctional mass within the lung parenchyma without bronchial communication and with aberrant systemic arterial blood supply. Surgical resection or close observation can be proposed in the management of asymptomatic and low-risk ILS, but there is a lack of consensus. Endovascular embolization before thoracoscopic resection of ILS has been described to limit perioperative bleeding. Another technique previously reported is the injection of methylene blue in the feeding artery to macroscopically mark the sequestration from the healthy lung. In that way, a nonanatomical resection can be performed instead of a lobectomy without the risk of leaving abnormal lung tissue in place. We describe the first two cases of these two techniques combined: a 3-year-old girl with an ILS in the right lower lobe with an artery originating from the abdominal aorta, and a 14-month-old girl with an ILS in the right lower lobe with an artery coming from the celiac trunk.

The combination of embolization and injection of methylene blue in the aberrant artery leads to a clear macroscopic demarcation of the blue-colored ILS from the healthy lung parenchyma and allowed safe nonanatomical resection of the ILS without risk of bleeding or compromising normal lung tissue.
Intraluminal Migration of a Penrose Drain Presented with Hematochezia, after Lower Gastrointestinal Surgery
Authors: Mourelatou Roza , Liatsos Christos , Bistaraki Angeliki , Nikou Efstathios
Published: October 2022

Background Although surgical drains are widely used after lower gastrointestinal (GI) procedures, complications may occur. Specifically, sporadic cases of drain migration into a hollow viscus, most commonly regarding active drains and treated with surgical removal, have been reported. Herein, we present a case of a passive drain (penrose) migration into the colon, after segmental sigmoidectomy with primary anastomosis, presented with hematochezia.

Methods A 37-year-old male patient suffering from colovesical fistula, due to sigmoid diverticulitis, underwent resection of the fistula, the involved sigmoid segment and the bladder opening, followed by primary anastomosis of the colon and primary closure of the bladder. A penrose catheter was positioned near the anastomosis.

Results On 8th postoperative day (POD) the patient had three episodes of hematochezia and blood in the drain collection bag, followed by relative improvement. On 15th POD gas was observed on the drain's collection bag and a new episode of hematochezia led him to sigmoidoscopy. The endoscopy revealed the presence of the penrose drain intraluminally, protruding via an ulcer at the level of the anastomosis. The penrose repositioned outside the lumen and metallic clips were used to approximate the defect. The patient was then fully recovered, discharged, and the drain removed on follow-up.

Conclusion To our knowledge this is the first report of drain migration presented with hematochezia, after lower GI surgery, avoided reoperation, and resolved with removal of the drain under direct endoscopic vision.
Führung im Gesundheitswesen: Gerade in Krisen gilt: Kurs halten
Authors: Gocke Peter
Published: October 2022

Krisen verleiten dazu, den Blick von den Herausforderungen abzuwenden – und Krisen gibt es genug: Die Pandemie ist nicht überwunden, der Krieg in der Ukraine belastet, führt zu Energiekrise, Lieferkettenproblemen und drohenden Preissteigerungen nicht abschätzbaren Ausmaßes.Dies verursacht vielerorts Unsicherheit, sie ist fast greifbar und lähmt. Dabei benötigen wir weiter alle Kraft, um die Herausforderungen zu bewältigen, vor denen wir sowieso schon stehen: Demografischer Wandel, Fachkräftemangel und Kostendruck nehmen unverändert zu.
Preisexplosion: Der perfekte Sturm
Authors: Doelfs Guntram
Published: October 2022

Die steigende Inflation und explodierende Energiekosten bringen derzeit selbst rentable Kliniken in eine gefährliche Schieflage. Weil gleichzeitig die Erlöse stagnieren, sinkt die Liquidität bedenklich. Während die DKG rasche Hilfe in Milliardenhöhe fordert, warnen andere vor Hilfen nach dem Gießkannen-Prinzip und fordern eine schnelle Umsetzung der geplanten Klinikreform.
Künstliche Intelligenz: Wegweisende Technologie
Authors: Lang Michael
Published: October 2022

Forscherinnen und Forscher aus München, Bonn und London haben einen föderalen und selbstlernenden Algorithmus entwickelt, der Hirntumore erkennen kann.
Rollout des E-Rezepts: Ein holpriger Start
Authors: Lang Michael
Published: October 2022

Der stufenweise Rollout des E-Rezepts zum 1. September hat mit einem Eklat begonnen. Die Kassenärztliche Vereinigung Schleswig-Holstein nimmt nach Bedenken der zuständigen Datenschützer nicht wie geplant an der Einführung des E-Rezepts teil. Auch sonst läuft vieles nicht rund in diesem Projekt.
Energieerzeugung im Krankenhaus: Vom Erdgas zum Wasserstoff
Authors: Kucera Martin
Published: October 2022

Angesichts gestiegener Kosten für fossile Energien zahlt es sich für Kliniken aus, bereits frühzeitig in eine umweltschonende Energieerzeugung investiert zu haben. Neben dem großflächigen Einsatz von Solarenergie und der effizienten Nutzung von Erdgas gibt es bereits einen Vorreiter, der in die Produktion von Wasserstoff einsteigen wird.
Energiekrise: Kliniken am Gas-Tropf mit wenig Alternativen
Authors: Reisinger Kathrin
Published: October 2022

Die deutschen Städte und Landtage bereiten sich auf drohenden Gasmangel vor. Auch der Gesundheitssektor ist gefordert, Sparmaßnahmen zu erarbeiten. Doch für effiziente Sparmaßnahmen wurde in den letzten Jahren in der Branche zu wenig investiert. Kurzfristig wird nun nach Alternativen zum Gas gesucht, um die Energieversorgung der Krankenhäuser sicherzustellen.
Microfluidic system for immune cell activation and inflammatory cytokine profiling: Application to screening of dietary supplements for anti-inflammatory properties
Authors: Ramadan Qasem , Alawami Hawra , Zourob Mohammed
Published: October 2022

A versatile and reconfigurable microfluidic chip has been fully in-house fabricated and tested for immune cell culture, activation, and quantification of multi-cytokine secretion. The chip comprises three vertically stacked fluidic layers for perfusion, cell culture and cytokine capture, and quantification, respectively. The perfused media were separated from the cell culture by employing a biomimetic membrane as a model of the intestinal epithelial layer. Time-resolved detection and quantification of several secreted cytokines were enabled by an array of parallel channels, which are interfaced with the cell culture by a porous membrane. Each channel hosts magnetic beads conjugated with a specific antibody against the cytokine of interest. Magnetic bead-assisted agitation enables homogenization of the cell culture supernatant and perfusion of the cytokines through the bottom immune assay channels. As a proof of concept, THP-1 monocytic cells and their induced macrophages were used as a model of immune-responsive cells. The cells were sequentially stimulated by lipopolysaccharides and two dietary supplements, namely, docosahexaenoic acid (DHA) and curcumin, which are known to possess inflammasome-modulating activity. Both DHA and curcumin have shown anti-inflammatory effects by downregulating the secretion of TNFα, IL-6, IL-1β, and IL-10. Treatment of the cells with DHA and curcumin together lowered the TNFα secretion by ∼54%. IL-6 secretion was lowered upon cell treatment with curcumin, DHA, or DHA and curcumin co-treatment by 69%, 78%, or 67%, respectively. IL-1β secretion was lowered by 67% upon curcumin treatment and 70% upon curcumin and DHA co-treatment. IL-10 secretion was also lowered upon treating the cells with DHA, curcumin, or DHA and curcumin together by 7%, 53%, or 54%, respectively. The limit of the detection of the assay was determined as 25 pg/ml. Four cytokine profiling was demonstrated, but the design of the chip can be improved to allow a larger number of cytokines to be simultaneously detected from the same set of cells.
Skin health in northern Australia
Authors: Thomas Hannah M. M. , Enkel Stephanie , McRae Tracy , Cox Victoria , Kessaris Heather-Lynn , Ford Abbey J. , Famlonga Rebecca , Newton Rebekah , Amgarth-Duff Ingrid , Whelan Alexandra , Bowen Asha C.
Published: October 2022

Achieving healthy skin requires the prevention of infectious diseases that affect the skin. Prevention activities range from environmental health improvements to address inequities in living situations, through to community-wide treatment programs to reduce transmission and improve skin health. In this paper we discuss the pathogens that cause and conditions that arise when skin is infected, the burden of disease in northern Australia, and some of the current research underway to address this high burden, which predominantly affects remote-living Aboriginal and Torres Strait Islander children and families.
Advantages and limitations of diagnostic methods for avian metapneumovirus
Authors: Tamehiro Claudia Yurika , Filho Hiran Castagnino Kunert , Cavalli Lissandra Souto , Grassotti Tiela Trapp , Carvalho Daiane , de Brito Benito Guimarães , Otutumi Luciana Kazue , de Brito Kelly Cristina Tagliari
Published: October 2022

Respiratory tract diseases are responsible for major economic losses in the poultry industry. Avian metapneumovirus is a pathogen that causes acute infections in the upper airways of turkeys and chickens, is associated with Swollen Head Syndrome, and generates variable morbidity between 1% and 20% in chickens. Turkey Rhinotracheitis has a morbidity of up to 100%. The frequent presence of secondary agents or infections associated with other microorganisms can aggravate the syndrome. The clinical diagnosis itself is not sufficient to determine metapneumovirus infections since the disease can be confused with other respiratory problems. Serological methods such as seroneutralisation, immunofluorescence and ELISA, immunohistochemistry, virus isolation from embryonated eggs or tissue cultures and PCR are the main techniques used in the diagnosis of avian metapneumovirus infections. Therefore, a laboratory diagnosis confirming the presence of this pathogen is necessary. Currently, several methods are available, with varying applications and sensitivity. This work describes the current diagnostic methods and presents their advantages and limitations.
Possibilities for probabilities
Authors: Page Don N.
Published: October 2022

In ordinary situations involving a small part of the universe, Born's rule seems to work
well for calculating probabilities of observations in quantum theory. However, there are a number
of reasons for believing that it is not adequate for many cosmological purposes. Here a number of
possible generalizations of Born's rule are discussed, explaining why they are consistent with the
present statistical support for Born's rule in ordinary situations but can help solve various
cosmological problems.
Generalization properties of restricted Boltzmann machine for short-range order
Authors: Timirgazin M A , Arzhnikov A K
Published: October 2022

A biased sampling algorithm for the restricted Boltzmann machine (RBM) is proposed, which allows generating configurations with a conserved quantity. To validate the method, a study of the short-range order in binary alloys with positive and negative exchange interactions is carried out. The network is trained on the data collected by Monte–Carlo simulations for a simple Ising-like binary alloy model and used to calculate the Warren–Cowley short-range order parameter and other thermodynamic properties. We demonstrate that the proposed method allows us not only to correctly reproduce the order parameters for the alloy concentration at which the network was trained, but can also predict them for any other concentrations.
Disturbances in North American boreal forest and Arctic tundra: impacts, interactions, and responses
Authors: Foster Adrianna C , Wang Jonathan A , Frost Gerald V , Davidson Scott J , Hoy Elizabeth , Turner Kevin W , Sonnentag Oliver , Epstein Howard , Berner Logan T , Armstrong Amanda H , Kang Mary , Rogers Brendan M , Campbell Elizabeth , Miner Kimberley R , Orndahl Kathleen M , Bourgeau-Chavez Laura L , Lutz David A , French Nancy , Chen Dong , Du Jinyang , Shestakova Tatiana A , Shuman Jacquelyn K , Tape Ken , Virkkala Anna-Maria , Potter Christopher , Goetz Scott
Published: October 2022

Ecosystems in the North American Arctic-Boreal Zone (ABZ) experience a diverse set of disturbances associated with wildfire, permafrost dynamics, geomorphic processes, insect outbreaks and pathogens, extreme weather events, and human activity. Climate warming in the ABZ is occurring at over twice the rate of the global average, and as a result the extent, frequency, and severity of these disturbances are increasing rapidly. Disturbances in the ABZ span a wide gradient of spatiotemporal scales and have varying impacts on ecosystem properties and function. However, many ABZ disturbances are relatively understudied and have different sensitivities to climate and trajectories of recovery, resulting in considerable uncertainty in the impacts of climate warming and human land use on ABZ vegetation dynamics and in the interactions between disturbance types. Here we review the current knowledge of ABZ disturbances and their precursors, ecosystem impacts, temporal frequencies, spatial extents, and severity. We also summarize current knowledge of interactions and feedbacks among ABZ disturbances and characterize typical trajectories of vegetation loss and recovery in response to ecosystem disturbance using satellite time-series. We conclude with a summary of critical data and knowledge gaps and identify priorities for future study.
Navigation Robot Covid With 3D LiDAR Using RTAB-MAP Method
Authors: Wibowo Muhamad Ardiansyah Putra , Ramadhan Sami Fauzan , Turnip Arjon
Published: October 2022

The current pandemic has had a profound impact on people’s daily lives. This is because the COVID-19 virus is spread through the air. Technology such as autonomous robots can be the best solution to contain the spread of COVID-19. This study aims to develop an autonomous robot using 3D LiDAR to obtain 3D mapping. The method used is to use RTAB-MAP, namely the 3D SLAM method to get the mapping results. The result of this paper is that 3D LiDAR using RTAB-MAP gets good results when 3D LiDAR conditions are at a height of 150cm and 180cm with 18W lamp lighting.
The potential of rice bran waste (Oryza sativa L.) and shrimp shell waste as chitin nanowhisker with glycerol plasticizer in the production of bioplastic
Authors: Setiawan J V , Adhitama R , Goeltom M T , Askitosari T D , Yang D C , Sukweenadhi J
Published: October 2022

Bioplastics are plastics made from biopolymers as an alternative to commercial plastics to reduce environmental pollution. Starch from rice bran waste is an essential biopolymer material, and chitin from shrimp shell waste; can be converted into chitin nanowhiskers (CNWs) that can strengthen biopolymer materials. A glycerol plasticizer was added to improve its elasticity. This research aims to determine the potential of starch from rice bran waste and CNWs from shrimp shell waste as ingredients in the production of bioplastics with the addition of glycerol plasticizer and its degradation property through soil burial testing. This fundamental research consists of chitin extraction, CNW production, starch extraction, bioplastic production, tensile strength testing, water uptake testing and soil burial testing on the sand, humus, and compost. The use of rice bran starch and shrimp shell CNW as ingredients in the production of bioplastics are deemed potential. This bioplastic exhibited low mechanical properties such as tensile strength and water uptake but outstanding degradation in the soil burial testing.
Development and Implementation of Smart Irigation for Precision Farming
Authors: Saheed Farouq Enesi , Pebriansyah Fikri Rida , Sitorus Parlindungan , George Michael T , Turnip Arjon
Published: October 2022

The agricultural sector is one of the important sectors in people’s lives as well as an important role in Indonesia’s economic growth. However, agriculture in Indonesia is not a few who still use conventional technology, so an agricultural system that can make it easier for farmers to manage their agricultural land is needed. In this system, a smart irrigation system is developed which is implemented for precision farming, by utilizing IoT technology as a means of connection between devices as well as monitoring and controlling irrigation. Parameter values such as air humidity, air temperature, soil moisture, and soil pH measured on the sensor will be sent to the database server to be displayed on the front end of the website so that users can access them using their respective devices. In addition, the soil moisture value stored in the database will later be used by the solenoid controller component to carry out the watering process.
Extraction of Dissolved Protein of Channa striata from Tarakan, North Borneo as a Source of Fish Serum Albumin
Authors: Hutapea T P H , Suprapto  , Kurniawan F
Published: October 2022

Extraction of dissolved protein of Channa Striata from Tarakan, North Borneo, as a source of fish serum albumin has been done. Albumin is a water-soluble protein and it is applied in various fields, including health, industry, and technology. The many benefits of albumin make albumin very important. However, albumin is a protein found in the body of living things, so it is necessary to perform the separation process. One of the living things that contain relatively high albumin is snakehead fish (Channa striata). The dissolved protein was extracted from snakehead fish meat using water as a solvent at a temperature of 50 °C. The protein obtained was characterized using proximate analysis and Fourier Transform Infra Red (FTIR) Spectrophotometer. The proximate analysis showed that the water, the fat, and the protein content were 8.67%, 3%, and 64.18%, respectively. The FTIR spectrum showed an amide group at 1600-1700 cm−1 which is important in the albumin functional group. This study shows that snakehead fish in Tarakan, North Kalimantan has the potential as a source of fish serum albumin.
Performance Improvement of Grid Mapping K-Means with the Average Value at Grid Point
Authors: Ginting Salomo , Efendi Syahril , Suwilo Saib
Published: October 2022

K-Means is a method that is well-known for its ability to handle large datasets, but is often stuck in a local optima state. This issue happens because K-Means generally uses random numbers to serve as the center point (centroid) of each cluster, and places each instance based on the proximity of the distance using Euclidean Distance. Hence, the concept of density parameter was developed, which tries to determine the ideal centroid based on the determination of several grid points in each existing cluster. The concept is known as Grid Mapping. In simple terms, Grid Mapping K-Means is a method in which each cluster is divided into several grid points, and then the centroid is randomly determined from each existing grid point. Further, the grid point with the largest number of instance is used as the initial centroid of each cluster. However, this method certainly has a weakness, since there is a possibility that the initial centroid on the generated grid point is not the best initial centroid. Therefore, this study was conducted to test the determination of initial centroid by Grid Mapping K-Means.
Functional and biochemical characteristics of Oxycoccus palustris Pers. under exposure of a gas torch (Khanty-Mansi Autonomous Okrug-Yugra, Russia)
Authors: Yumagulova E R , Ivanova N A , Skorobogatova O N
Published: October 2022

The study was carried out on a sphagnum swamp exposed to thermal radiation from an associated petroleum gas (APG) combustion flare at various distances from the flare stack, which has been operating continuously for more than thirty years. The study was carried out in the period from 2018 to 2019 in the territory of the Pokachevskoye field (Khanty-Mansi Autonomous Okrug-Yugra, Nizhnevartovsk district). Some functional and biochemical characteristics of Oxycoccus palustris Pers were studied. The Oxycoccus palustris Pers. photosynthesis and respiration intensity data analysis, the pigment composition of leaves (chlorophyll and anthocyanins content), the nitrogen balance index (NBI), non-enzymatic antioxidants (flavonoids, proline and ascorbic acid content) were studied, the biochemical composition of leaves specifics (nitrogen, carbon, soluble and non-structural sugars and metals accumulation) were determined in the conditions of exposure to the flare.
Single-pixel coherent diffractive imaging based on super-pixel holography
Authors: He Yikang , Guo Yan , Hu Junyan , Li Xianye , Ma Yanyang , Sun Baoqing
Published: October 2022

Quantitative phase imaging (QPI) is a powerful approach to study dynamics associated with both thickness and refractive index fluctuations. In this work, we propose a coherent diffractive QPI scheme based on single-pixel imaging structure and coherent modulation imaging. In this scheme, digital micro-mirror device with high refresh rate is employed for structured illumination. Synchronously, a single point detector is used to perform mode selected measurement of diffraction intensity. Based on the illumination structure and point signals, phase imaging is realized using a reweighted amplitude flow phase retrieval algorithm. Non-interference modality omits the reference arm, which simplifies the apparatus and improves the system robustness. This proposed technique is demonstrated by QPI of both digital binary and grayscale objects. The three-dimensional profile measurement of a plano-convex lens shows the possibility of phase retrieval for real objects. Accordingly our technique will promote the application of single-pixel phase imaging to biomedical imaging, x-ray diffraction imaging and three-dimensional profilometry.
Effect of thermal cyclic corrosion on the microstructural degradation of platinum aluminide coatings
Authors: G Rajamurugan , Sathyajith Sanjay , Krishnasamy Prabu
Published: October 2022

The increase in fuel prices and environmental pollution has urged the need for more efficient and environment-friendly paths to operating gas turbines. One way to tackle this is by increasing the inlet temperature in the turbines. The present study is to understand the effect of thermal cycling on the microstructural degradation of Pt-Al coating on CM247 LC substrate. Pt-Al coated samples are subjected to 1000 °C for 480 cycles. Each cycle consists of 55 min of heat exposure and 5 min of cooling. The cross-section of each sample is subjected to image analysis to understand the compositional variation under cyclic conditions. The β-NiAl and RE concentration show a decreasing trend with an increase in the number of cycles, whereas γ’-Ni3Al and porosity concentration show an increasing trend with an increase in the number of cycles. 60–70 vol. % γ’-Ni3Al concentration must be present to affect adversely the coating degradation significantly.
How I Diagnose EBV-Positive B- and T-Cell Lymphoproliferative Disorders
Authors: Dojcinov Stefan D , Quintanilla-Martinez Leticia
Published: October 2022

Objectives

Epstein-Barr virus (EBV)–associated lymphoproliferative disorders (LPDs) encompass a group of well-defined entities of B-, T-, and natural killer (NK)–cell derivation. The diagnosis of these disorders is challenging because of clinical and morphologic features that may overlap with other benign and malignant EBV+ lymphoproliferations. This review describes our approach to the diagnosis of EBV-associated LPDs.

Methods

Two cases are presented that illustrate how we diagnose EBV-associated LPDs. The first case represents a systemic EBV+ T-cell lymphoma of childhood and the second case an EBV+ mucocutaneous ulcer. The clinicopathologic features that help distinguish these entities from biological and morphologic mimickers are emphasized.

Results

The accurate diagnosis of EBV-associated LPDs requires the incorporation of histologic and immunophenotypic features, the assessment of the EBV latency program, and, most important, complete clinical findings. Clonality analysis is not helpful in distinguishing benign from malignant EBV+ LPDs.

Conclusions

The better understanding of EBV-associated LPDs has resulted in the recognition of well-defined entities of B-, T-, and NK-cell derivation and consequently improvement of their treatment with curative intent. It is critical to distinguish benign from malignant EBV+ LPDs to avoid overtreatment.
Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial
Authors: Heath Paul T , Galiza Eva P , Baxter David Neil , Boffito Marta , Browne Duncan , Burns Fiona , Chadwick David R , Clark Rebecca , Cosgrove Catherine A , Galloway James , Goodman Anna L , Heer Amardeep , Higham Andrew , Iyengar Shalini , Jeanes Christopher , Kalra Philip A , Kyriakidou Christina , Bradley Judy M , Munthali Chigomezgo , Minassian Angela M , McGill Fiona , Moore Patrick , Munsoor Imrozia , Nicholls Helen , Osanlou Orod , Packham Jonathan , Pretswell Carol H , San Francisco Ramos Alberto , Saralaya Dinesh , Sheridan Ray P , Smith Richard , Soiza Roy L , Swift Pauline A , Thomson Emma C , Turner Jeremy , Viljoen Marianne Elizabeth , Fries Louis , Cho Iksung , McKnight Irene , Glenn Greg , Rivers E Joy , Robertson Andreana , Alves Katia , Smith Kathy , Toback Seth
Published: October 2022

Background

The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported.

Methods

Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.

Results

Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups.

Conclusions

A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated.

Clinical Trials Registration

EudraCT, 2020-004123-16.
Genome assembly of the Pendlebury’s roundleaf bat, Hipposideros pendleburyi, revealed the expansion of Tc1/Mariner DNA transposons in Rhinolophoidea
Authors: Nawae Wanapinun , Sonthirod Chutima , Yoocha Thippawan , Waiyamitra Pitchaporn , Soisook Pipat , Tangphatsornruang Sithichoke , Pootakham Wirulda
Published: October 2022

Bats (Chiroptera) constitute the second largest order of mammals and have several distinctive features, such as true self-powered flight and strong immunity. The Pendlebury’s roundleaf bat, Hipposideros pendleburyi, is endemic to Thailand and listed as a vulnerable species. We employed the 10× Genomics linked-read technology to obtain a genome assembly of H. pendleburyi. The assembly size was 2.17 Gb with a scaffold N50 length of 15,398,518 bases. Our phylogenetic analysis placed H. pendleburyi within the rhinolophoid clade of the suborder Yinpterochiroptera. A synteny analysis showed that H. pendleburyi shared conserved chromosome segments (up to 105 Mb) with Rhinolophus ferrumequinum and Phyllostomus discolor albeit having different chromosome numbers and belonging different families. We found positive selection signals in genes involved in inflammation, spermatogenesis and Wnt signalling. The analyses of transposable elements suggested the contraction of short interspersed nuclear elements (SINEs) and the accumulation of young mariner DNA transposons in the analysed hipposiderids. Distinct mariners were likely horizontally transferred to hipposiderid genomes over the evolution of this family. The lineage-specific profiles of SINEs and mariners might involve in the evolution of hipposiderids and be associated with the phylogenetic separations of these bats from other bat families.
Emergency transcatheter aortic valve implantation for acute heart failure due to severe aortic stenosis in critically ill patients with or without cardiogenic shock
Authors: Steffen Julius , Stocker Angelika , Scherer Clemens , Haum Magda , Fischer Julius , Doldi Philipp M , Theiss Hans , Braun Daniel , Rizas Konstantinos , Peterß Sven , Hausleiter Jörg , Massberg Steffen , Orban Martin , Deseive Simon
Published: October 2022

Aims

Severe aortic stenosis can cause acute heart failure and cardiogenic shock (CS). Transcatheter aortic valve implantation (TAVI) is the standard therapy for aortic stenosis in inoperable patients. However, its role in this setting is poorly evaluated. The study purpose was to explore clinical characteristics of these patients and to assess predictors of mortality.

Methods and results

All 2930 patients undergoing transfemoral TAVI at our centre between 2013 and 2019 were screened for critically ill patients, receiving intensive care therapy and emergency TAVI. Selected patients were subdivided into two groups, according to the presence or absence of CS. Remaining patients undergoing elective TAVI served as a comparison. Primary outcome was 90-day mortality. Out of 179 critically ill patients, 47 fulfilled criteria of CS (shock group) and 132 did not despite a severe decompensation (no shock group). Shock patients were more often male and had higher Society of Thoracic Surgeons scores [15.6, interquartile range (8.0–32.1) vs. 5.5 (3.9–8.5), P < 0.01] compared with severely decompensated patients. Ninety-day mortality was: shock group, 42.6%, vs. no shock group, 15.9%, vs. elective group, 5.3% (P < 0.01). A landmark analysis from day 90 showed similar mortality (P = 0.29). Compared with elective patients, 30-day composite endpoint device failure was higher in critically ill groups [shock group, odds ratio, 2.86 (1.43–5.36), no shock group, odds ratio, 1.74 (1.09–2.69)]. Multivariable regression revealed mechanical ventilation, haemofiltration, elevated C-reactive protein or bilirubin, and hypotension before TAVI as 90-day mortality predictors.

Conclusion

Ninety-day mortality after TAVI in critically ill patients is increased but survivors have similar outcomes as elective patients.
Prognostic implications of trabecular complexity measured by fractal analysis in left ventricular noncompaction
Authors: Azpiroz Franch M J , Casas Masnou G , Romero A , Gonzalez Del Hoyo M I , Larranaga Moreira J M , Escalona Silva R , Guala A , Limeres Freire J , Bayes Genis A , Zorio Grima E , Villacorta Arguelles E , Garcia Pavia P , Barriales Villa R , Ferreira Gonzalez I , Rodriguez Palomares J F
Published: October 2022

Introduction

Left ventricular non compaction (LVNC) is a heterogeneous entity characterized by prominent LV trabeculae. Fractal analysis, a semi-automatic method to quantify the degree of hypertrabeculation, has been described as a diagnostic criterion for LVNC. However, the prognostic implications of fractal analysis have not been investigated.

Purpose

Therefore, the aim of our study was to identify the relationship between the trabecular complexity measured by fractal analysis and the occurrence of cardiovascular events in LVNC patients.

Methods

We conducted a retrospective longitudinal multicenter cohort study of consecutive patients fulfilling LVNC criteria by cardiovascular magnetic resonance (CMR). The endpoints were heart failure (HF), ventricular arrythmias (VA), systemic embolism (SE) and all-cause mortality. Fractal analysis was performed on short-axis CMR cine images using CVI 42 software. The cohort was divided in two groups according to the maximal apical fractal dimension (FD).

Results

A total of 291 patients were included: age was 44±19 years and 56% were female. LV ejection fraction (LVEF) was 47% ± 14% and 26 patients (9%) presented late gadolinium enhancement (LGE). Mean global FD was 1.29±0.06 and maximal apical FD was 1.39±0.09. Baseline characteristics of patients with maximal apical FD 1.39 and 1.39, including functional LV parameters, were comparable (Table 1). After 3.8±2.5 years of follow-up, 37 patients (12.8%) presented HF, 30 (10.4%) had VA, SE occurred in 3 (1%) and 3 patients (1%) died. Maximal apical FD was not associated with the risk of HF or VA (both p ns), nor was mean global FD. There were no significant differences in the survival curves of both endpoints between the two groups: HR were 2.34 (95% CI 0.74–7.4, p 0.13) and 1.15 (95% CI 0.45–2.41, p 0.71) respectively for HF and VA (Image 1). LVEF and LGE remained consistent predictors of events.

Conclusions

In a large multicenter retrospective LVNC study, the degree of hypertrabeculation measured by fractal analysis was not associated with functional LV parameters and, most importantly, with the incidence of cardiovascular events. Therefore, our results suggest that diagnostic LVNC criteria should be refined to include parameters with actual prognostic implications.

Funding Acknowledgement

Type of funding sources: None.
Reason and reality—identifying barriers to patient enrolment for clinical trials in invasive candidiasis
Authors: Sprute Rosanne , Grothe Jan H , Heringer Sarah , Cornely Oliver A
Published: October 2022

Objectives

Enrolment of subjects to clinical trials investigating novel drugs for infectious diseases is an ongoing challenge. In this study, we evaluate factors associated with non-enrolment in treatment trials for invasive candidiasis.

Methods

We conducted a retrospective review of pre-screening logs of patients that were assessed for enrolment in the three clinical trials ACTIVE (NCT00413218), APX001-201 (NCT03604705) and ReSTORE (NCT03667690), investigating novel drugs for invasive candidiasis between September 2007 and August 2021 to identify reasons for study ineligibility.

Results

Two hundred and fifty-six patients with invasive candidiasis were identified for potential study participation with n = 154 for the ACTIVE trial, n = 89 for APX001-201 and n = 13 for ReSTORE. Half of the potential participants were unable or unwilling to consent. We further identified comorbid conditions such as hepatic or renal impairment [21 hepatic and renal cases (13.6%) in ACTIVE; 12 hepatic (13.5%) and 28 renal cases (31.5%) in APX], prior antifungal treatment [11 cases (7.1%) in ACTIVE; 16 (18.0%) in APX; 7 (38.5%) in ReSTORE] and the last positive culture obtained ≥96 h prior to dosing [1 case (0.6%) in ACTIVE; 7 (7.9%) in APX; 5 (38.5%) in ReSTORE] as relevant reasons for non-enrolment. We also identified criteria repetitively used in the analysed studies that did not contribute substantially to ineligibility rates. Ultimately, 254/256 patients (99.2%) were ineligible for enrolment in the respective trial.

Conclusions

This study identified barriers to enrolment in clinical trials assessing novel antifungal agents in invasive candidiasis. Identification of eligibility criteria associated with non-enrolment allows modification of future trial designs and may ultimately result in higher recruitment rates.
Spontaneous rupture and upper gastrointestinal bleeding of solid pseudopapillary neoplasm of the pancreas
Authors: Revoredo Fernando , Kometter Fritz , Núñez Juan , León Julio , Luna Juan , Valdes Jorge
Published: October 2022

The solid pseudopapillary neoplasm (SPN) of the pancreas is an uncommon, low-grade malignant tumour, mostly seen in young women. We report a rare case of a 44-year-old female who presented with spontaneous rupture and upper gastrointestinal bleeding. The emergency endoscopy revealed a 2 cm bleeding ulcer on the duodenal bulb. A computer tomography scan (CT scan) showed a 6.7 cm mass, with solid and cystic components arising in the head of the pancreas. After achieving haemostasis, she was discharged. Two months later, a new CT scan showed a persistent 6 cm mass in the head of the pancreas, now containing air and communicating with the duodenal lumen. The patient was successfully treated by pancreatoduodenectomy. Histopathological examination showed a T3N0M0 SPN with immunohistochemical expression of β-catenin, synaptophysin, vimentin and progesterone receptor, and negativity for chromogranin. The labelling index of Ki 67 was 2%. No recurrence was present after 2 years of follow-up.
The glutamate receptor-like 3.3 and 3.6 mediate systemic resistance to insect herbivores in Arabidopsis
Authors: Xue Na , Zhan Che , Song Juan , Li Yong , Zhang Jingxiong , Qi Jinfeng , Wu Jianqiang
Published: October 2022

Herbivory activates responses in local and systemic leaves, and the glutamate receptor-like genes GLR3.3 and GLR3.6 are critical in leaf-to-leaf systemic signalling. However, whether and how these genes mediate plant systemic resistance to insects remain largely unexplored. We show that a piercing-sucking insect Myzus persicae (green peach aphid, GPA) or chewing insect Spodoptera litura (cotton leafworm, CLW) feeding-induced systemic defences were attenuated in the glr3.3 glr3.6 mutants. In response to herbivory from either insect, glr3.3 glr3.6 mutants exhibited reduced accumulation of the hormone jasmonic acid (JA) and defensive metabolites glucosinolates (GSs) in systemic (but not local) leaves. Transcriptome analysis indicated that GLR3.3 and GLR3.6 play an important role in regulating the transcriptional responses to GPA and simulated CLW feeding in both local and systemic leaves, including JA- and GS-related genes. Metabolome analysis also revealed that in response to GPA or simulated CLW feeding, GLR3.3 and GLR3.6 are involved in the regulation of various metabolites locally and systemically, including amino acids, carbohydrates, and organic acids. Taken together, this study provides new insights into the function of GLR3.3 and GLR3.6 in mediating transcripts and metabolites in local and systemic leaves under insect attack, and highlights their role in regulating insect resistance in systemic leaves.
Genetic Polymorphisms
Authors: Hartl Daniel L.
Published: October 2022

Chapter 1 provides a brief introduction to genes and how they work for those without the necessary background or for review. Its emphasis is on the major types of genetic polymorphisms including single-nucleotide polymorphisms (SNPs), allele and genotype frequencies, and the utility of genetic polymorphisms in studying the history and current structure of natural populations. It examines different types of models including mathematical models, as well as their relative strength and limitations. How models are modified to be progressively more realistic is illustrated in both discrete-time and continuous-time models of exponential and logistic population growth.
Career Spillovers in Internal Labour Markets
Authors: Bianchi Nicola , Bovini Giulia , Li Jin , Paradisi Matteo , Powell Michael
Published: October 2022

This article studies career spillovers across workers, which arise in firms with limited promotion opportunities. We exploit a 2011 Italian pension reform that unexpectedly tightened eligibility criteria for the public pension, leading to sudden, substantial, and heterogeneous retirement delays. Using administrative data on Italian private-sector workers, the analysis leverages cross-firm variation to isolate the effect of retirement delays among soon-to-retire workers on the wage growth and promotions of their colleagues. We find evidence of spillover patterns consistent with older workers blocking the careers of their younger colleagues, but only in firms with limited promotion opportunities.
Is Outpatient Anterior Lumbar Fusion (ALIF) Safe? An Analysis of 30-day Outcomes
Authors: Jones Jeremy , Malik Azeem Tariq , Khan Safdar N. , Yu Elizabeth , Kim Jeffery
Published: October 2022

Study Design:

Review of publicly available database.

Objective:

To compare 30-day outcomes of single-level ALIF procedures performed in outpatient and inpatient settings.

Summary of Background Data:

Despite a growing interest in performing standalone anterior lumbar interbody fusions (ALIFs) as an outpatient procedure, no study has evaluated the safety or efficacy of this procedure outside an inpatient setting.

Methods:

The 2012–2017 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) was queried using CPT code 22558 to identify patients undergoing a single-level ALIF. Patients receiving concurrent posterior lumbar surgery/fusion/instrumentation, pelvic fixation, or surgery due to tumor, trauma and/or deformity were excluded to capture an isolated cohort of patients receiving single-level standalone ALIFs. A total of 3728 single-level standalone ALIFs were included in the study. Multivariate regression analyses were used to compare 30-day adverse events and readmissions while controlling for baseline clinical characteristics.

Results:

Out of a total of 3728 ALIFs, 149 (4.0%) were performed as outpatient procedure. Following adjustment, outpatient ALIFs versus inpatient ALIFs had lower odds of experiencing any 30-day adverse event (2.0% vs. 9.2%, OR 0.24 [95% CI 0.08–0.76]; P=0.015). No significant differences were noted with regard to severe adverse events 9p=0.261), minor adverse events 9p=0.995), and readmission rates (P=0.95).

Conclusion:

On the basis of the results of the study, it appears that ALIFs may be carried out safely in an outpatient setting in an appropriately selected patient population.
Association Between Critical Events in the PICU and Outcomes in Neighboring Patients
Authors: Arshad Ahmed , Blandon Catherine , Carey Kyle , Verhoef Philip , Jani Priti , Volchenboum Samuel , Churpek Matthew , Mayampurath Anoop
Published: October 2022

OBJECTIVE:

PICU patients who experience critical illness events, such as intubation, are at high risk for morbidity and mortality. Little is known about the impact of these events, which require significant resources, on outcomes in other patients. Therefore, we aimed to assess the association between critical events in PICU patients and the risk of similar events in neighboring patients over the next 6 hours.

DESIGN:

Retrospective observational cohort study.

SETTING:

Quaternary care PICU at the University of Chicago.

PATIENTS:

All children admitted to the PICU between 2012 and 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was a critical event defined as the initiation of invasive ventilation, initiating vasoactive medications, cardiac arrest, or death. The exposure was the occurrence of a critical event among other patients in the PICU within the preceding 6 hours. Discrete-time survival analysis using fixed 6-hour blocks beginning at the time of PICU admission was used to model the risk of experiencing a critical event in the PICU when an event occurred in the prior 6 hours. There were 13,628 admissions, of which 1,886 (14%) had a critical event. The initiation of mechanical ventilation was the most frequent event (n = 1585; 59%). In the fully adjusted analysis, there was a decreased risk of critical events (odds ratio, 0.82; 95% CI, 0.70–0.96) in the 6 hours following exposure to a critical event. This association was not present when considering longer intervals and was more pronounced in patients younger than 6 years old when compared with patients 7 years and older.

CONCLUSION:

Critical events in PICU patients are associated with decreased risk of similar events in neighboring patients. Further studies targeted toward exploring the mechanism behind this effect as well as identification of other nonpatient factors that adversely affect outcomes in children are warranted.