bluuebunny/crossref_metadata_2025 huggingface dataset:
Economics of Pass-on
Authors: Veljanovski Cento
Published: February 2021

This chapter looks at the economics of pass-on. The economics of pass-on is an aspect of the economists' theory of cost incidence. This is the study of the way a cost or tax increase is shifted and distributed between producers, consumers, and factors of production. It shows that the legal and economic incidence of a cost can differ radically and often in an unexpected way from its initial incidence. The extent of pass-on and any associated volume effect will depend on a range of factors including the nature of the overcharge; the demand and supply conditions; the market structure; and the pricing policies adopted by purchasers. The volume effect generates two losses: lost profits and the deadweight loss. Collecting all these losses together, full compensation requires that the direct purchasers as a group receive damages for the overcharge plus lost profits on the sales not made, minus the amount passed-on.
Other Treatment Standards
Authors: Salacuse Jeswald W
Published: February 2021

This chapter highlights other treatment standards. In addition to the usual treaty standards of treatment discussed in previous chapters, individual investment treaties, depending on the policies of the countries concerned and the negotiation dynamics between contracting states, may impose other obligations on host states with respect to their treatment of investments and investors. Such treatment provisions do not appear in all treaties and are subject to a variety of linguistic formulations. Moreover, although they were rarely the subject of arbitration or litigation in the early years of the bilateral investment treaty (BIT) movement, investors have increasingly alleged their violation in investor–state arbitral proceedings, beginning with the second decade of the twenty-first century. These treatment standards include treatment with respect to performance requirements; entry and residence of foreign nationals and managerial personnel; compensation for losses due to war, revolution, and civil disturbance; transparency and regulatory due process; and the subrogation obligation.
Advisory Opinions by ITLOS
Authors: Kittichaisaree Kriangsak
Published: February 2021

This chapter focuses on advisory opinions by the International Tribunal for the Law of the Sea (ITLOS). Like the International Court of Justice, ITLOS may render and has rendered advisory opinions on legal questions within its areas of competence. The 1982 United Nations Convention on the Law of the Sea (UNCLOS) expressly provides for the advisory jurisdiction of the Seabed Disputes Chamber of ITLOS, but not the full bench of ITLOS itself. According to Article 191 of UNCLOS, the Seabed Disputes Chamber shall give advisory opinions at the request of the Assembly or the Council of the International Seabed Authority on legal questions arising within the scope of their activities, and such opinions shall be given as a matter of urgency. The full bench of ITLOS has held that the substantive legal basis of the full-bench ITLOS’ advisory jurisdiction is Article 21 of its Statute stipulating that ITLOS’ jurisdiction comprises all disputes and all applications submitted to it in accordance with UNCLOS and all matters specifically provided for in any other agreement which confers jurisdiction on ITLOS. The ITLOS Rules elaborate the procedure in this respect.
Brief Resolved Unexplained Event
Authors: Claudius Ilene
Published: February 2021

The term brief resolved unexplained event (BRUE) replaced the term apparent life-threatening event (ALTE) after the publication of a 2016 American Academy of Pediatrics guideline. BRUE is defined as occurring in an infant younger than age 1 year who has experienced a brief episode of cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone; and/or altered level of responsiveness. Due to the novelty of the condition BRUE, minimal literature exists to inform incidence or risk. Although the overlap between ALTE and BRUE is not complete, historic data on ALTE can be used to fill these gaps. The American Academy of Pediatrics guideline offers recommendations for risk stratification and management. BRUE patients do not benefit from routine testing, and low-risk BRUE patients do not benefit from empiric admission for monitoring.
Neonatal Resuscitation
Authors: Hooft Anneka , Shah Seema
Published: February 2021

The majority of neonates born in the United States breathe spontaneously and do not require special assistance, but approximately 10% require some intervention, and less than 1% require extensive resuscitation measures. Although the number of infants delivered in the emergency department is unknown, out-of-hospital births have been increasing; thus, pediatric emergency physicians should be prepared for the possibility of a neonatal resuscitation in the emergency department. The acute resuscitation of the neonate should follow the Neonatal Resuscitation Program algorithm and includes assessment of heart rate, color, tone, and respiratory effort within the first minute of life. Initial treatment requires warming and gentle stimulation. Positive pressure ventilation should be initiated if the heart rate is <100 beats per minute, and chest compressions should be initiated if the heart rate is <60 beats per minute.
Pediatric Hematologic Emergencies
Authors: Baskin Jacquelyn , Nunez Jeranil
Published: February 2021

Children often present to the emergency department for evaluation of a variety of hematologic complaints ranging from pallor to bruising and bleeding. Some may require emergent evaluation and treatment, whereas others pose more of a diagnostic challenge. A detailed history and physical examination along with laboratory evaluation can aid in appropriate diagnosis and management of these patients. Hematologic emergencies include anemia, disorders of clotting, and sickle cell disease. This chapter reviews common presentations of many pediatric hematologic conditions, atypical presentations, and important diagnostic criteria. In addition, the chapter presents evidence-based treatment algorithms. Potential complications of various conditions are also discussed.
Spinal Trauma
Authors: MacNeill Emily
Published: February 2021

Spinal injury, although rare, can devastate children and their families. Clinicians must balance a conservative approach with definitive imaging of every pediatric patient after a high-velocity mechanism of trauma against the potential risk of current imaging modalities. Making thoughtful decisions about whether to image a child requires comprehension of the anatomy and physics of the developing spinal column, understanding of common injury patterns, and knowledge of the utility and limitations of current algorithms for clinical clearance. Selection of an imaging modality necessitates familiarity with the sensitivities, risks, and benefits of each type. Armed with this information, physicians can embark on shared decision-making with families to ensure the best possible care of the pediatric trauma patient.
Pediatric Otolaryngology Emergency Management
Authors: Belcher Ryan H. , Munson Patrick
Published: February 2021

Pediatric otolaryngology-related diagnoses are commonly encountered in the emergency department setting. The symptoms within the ear, nose, and throat encompass a wide variety and can often have a very high acuity, so accurate recognition and treatment are paramount. Some of the more commonly encountered pediatric otolaryngology issues in the emergency department include otitis media, otitis externa, mastoiditis, neck masses, sinusitis, epistaxis, and laryngotracheal airway obstruction. The American Academy of Otolaryngology—Head and Neck Surgery and the American Academy of Pediatrics have published several consensus guidelines on these topics, which are helpful for standardizing the care of patients and decreasing their variances in treatment.
Ophthalmologic Emergencies
Authors: Kaufman Kate
Published: February 2021

Despite sharing similar eye size and anatomy with adults, pediatric patients have unique patterns of ophthalmic infection and injury. Children, especially neonates, have a significantly less developed resistance to the systemic and central nervous system complications associated with ophthalmic infections and trauma. This chapter reviews pediatric eye conditions with a focus on practical approaches for diagnosis and treatment. Special considerations for neonatal conjunctivitis and dacryocystitis are addressed including indications for systemic treatment and criteria for admission. Guidelines are given for the treatment of household chemical exposure and for eye injuries from foreign bodies or blunt trauma. Common and atypical presentations are discussed. Treatment and selected procedures are detailed.
Male Genitourinary Emergencies
Authors: Liu Deborah R.
Published: February 2021

Male genitourinary complaints are very common in the pediatric population, although only a few entities are true emergencies. This chapter discusses the most common male genitourinary diagnoses, as well as which ones require the emergency provider to act immediately. The clinician must know how to differentiate genitourinary complaints that require emergent diagnostic or therapeutic procedures from those that require simple education and reassurance. The chapter is divided into disorders of the scrotum (testicular torsion, torsion of the testicular appendage, epididymo-orchitis, and hydrocele) and disorders of the penis (balanoposthitis, phimosis, paraphimosis, zipper injury of the penis, and tourniquet syndrome of the penis).
Gynecologic Emergencies
Authors: Agbim Chisom , Willner Emily L.
Published: February 2021

Gynecologic conditions in infants, children, and adolescents are distinct from those seen in adults, due to fluctuating hormone levels from infancy to puberty. This chapter focuses on the prepubertal child as there is significant overlap between gynecologic complaints in postpubertal adolescents and adults. The content in this chapter will enable emergency providers to distinguish normal pediatric gynecologic conditions from urgent and emergent pathology, including ovarian torsion, dysfunctional uterine bleeding and straddle injuries. Guidance for the management and treatment of these conditions is also provided in this chapter.
Emergency Pediatric Vascular Access
Authors: Pacheco Garrett S.
Published: February 2021

Vascular access is often needed for pediatric patients being treated in the emergency department. Access is often required to evaluate for acute metabolic emergencies, assess for infectious emergencies, to provide fluid resuscitation, blood product and medication administration. Obtaining vascular access can be a challenge, particularly in young children with small vessels and in critical conditions with dehydration or poor perfusion. The method, site, and size of device used to obtain vascular access primarily depend on the patient’s clinical status, the agent to be administered as well as parental preference. Anatomical differences considering the smaller vessels in pediatric patients and patient discomforts and fear of needle sticks afford challenges that are unique to this population. In addition, it is imperative that the emergency physician is cognizant and has strategies to treat both the child’s and the parent’s anxiety associated with the procedure. The emergency physician should have a level of comfort and knowledge of the various techniques and sites of access that are used for pediatric emergencies.
Care homes for older people
Authors: Dening Tom , Milne Alisoun
Published: February 2021

The care home sector has changed significantly in recent years: the vast majority of care homes are now in the independent sector, funding of care is complex, with greater reliance on self-funders to ensure profitability, and regulation has shifted to a more targeted model. In terms of the care home population, as most people are admitted at a late stage of their illness trajectory, many have comorbid conditions and multiple needs. Frailty is a dominant issue, often combined with dementia and other problems, e.g. sensory impairment and incontinence. The dimensions of a positive care home culture include a well-managed transition into the home, a commitment to person-centred care, and a well-trained and supported workforce. Over the last few years there has been a growing interest in care homes as major providers of care to some of the UK’s most vulnerable citizens; this includes welcome attention to research.
La prise en charge d’urgence du patient pédiatrique en état de mal épileptique convulsif
Authors: McKenzie Kyle C , Hahn Cecil D , Friedman Jeremy N
Published: February 2021

Les présentes lignes directrices portent sur la prise en charge d’urgence de l’état de mal épileptique convulsif chez les nourrissons âgés de plus d’un mois et les enfants. Elles remplacent un document de principes publié en 2011 et comprennent un nouvel algorithme thérapeutique, de même qu’un tableau des médicaments recommandés en fonction de nouvelles données probantes qui reflètent l’évolution de la pratique clinique des quelques dernières années. Le présent document de principes souligne l’importance d’un traitement pharmacologique rapide de l’état de mal épileptique convulsif et contient des conseils relativement à la démarche diagnostique et aux soins de soutien.
ATM controls meiotic DNA double-strand break formation and recombination and affects synaptonemal complex organization in plants
Authors: Kurzbauer Marie-Therese , Janisiw Michael Peter , Paulin Luis F , Prusén Mota Ignacio , Tomanov Konstantin , Krsicka Ondrej , von Haeseler Arndt , Schubert Veit , Schlögelhofer Peter
Published: February 2021

Meiosis is a specialized cell division that gives rise to genetically distinct gametic cells. Meiosis relies on the tightly controlled formation of DNA double-strand breaks (DSBs) and their repair via homologous recombination for correct chromosome segregation. Like all forms of DNA damage, meiotic DSBs are potentially harmful and their formation activates an elaborate response to inhibit excessive DNA break formation and ensure successful repair. Previous studies established the protein kinase ATM as a DSB sensor and meiotic regulator in several organisms. Here we show that Arabidopsis ATM acts at multiple steps during DSB formation and processing, as well as crossover (CO) formation and synaptonemal complex (SC) organization, all vital for the successful completion of meiosis. We developed a single-molecule approach to quantify meiotic breaks and determined that ATM is essential to limit the number of meiotic DSBs. Local and genome-wide recombination screens showed that ATM restricts the number of interference-insensitive COs, while super-resolution STED nanoscopy of meiotic chromosomes revealed that the kinase affects chromatin loop size and SC length and width. Our study extends our understanding of how ATM functions during plant meiosis and establishes it as an integral factor of the meiotic program.
Test-Retest Reliability and Known-Groups Validity of Trunk Muscle Tests in People With Multiple Sclerosis: A Cross-Sectional, Case-Control Study
Authors: Moreno-Navarro Pedro , Manca Andrea , Martinez Gianluca , Ventura Lucia , Barbado David , Vera-García Francisco J , Deriu Franca
Published: February 2021

Objective

Research on muscle performance testing reliability in people with multiple sclerosis (MS) has focused on limb performance while less is known about trunk strength and endurance. This work aims to 1) establish test–retest reliability of trunk flexion, lateral flexion, and extension strength tests, and plank, side bridge, and Biering-Sørensen endurance tests in people with MS and matched healthy controls (HCs); 2) analyze known-groups validity of these tests in people with MS and HCs; 3) to compare groups for side-to-side differences; and 4) to describe the relationships between trunk performance and functional mobility tests.

Methods

Fifteen people with MS (median Expanded Disability Status Scale = 3) and 15 HCs underwent 2 trunk isometric strength and endurance testing sessions. Mobility was evaluated by Timed Up-and-Go test. Intraclass correlation coefficient, SEM, and minimal detectable change (MDC) were calculated. Between-group differences in trunk performance were tested using the t test for independent measures. Between-group differences in an asymmetry index were analyzed by independent t test. Bivariate correlations between trunk tests and mobility were also examined.

Results

All trunk tests showed good-to-excellent relative reliability in both groups (intraclass correlation coefficient > 0.71). Regarding absolute reliability, strength tests were associated with low intersession variability in both groups (MDC: MS, 11.23%–36.45%; HCs, 26.60%–31.98%). Conversely, endurance tests showed higher variability scores in people with MS (MDC: MS, 69.55%–116.50%; HCs, 29.57%–54.40%). People with MS displayed significantly lower trunk performance. Likewise, the asymmetry index showed significantly higher scores in people with MS for endurance assessment but not in strength tests. Significant correlations were detected in people with MS between Timed Up-and-Go and several trunk tests (r = 0.63–0.70).

Conclusions

SEM and MDC scores revealed similar consistency and variability between groups for strength tests, whereas higher variability was observed for endurance tests in people with MS. Trunk strength tests are reliable and present discriminant validity to distinguish mildly disabled people with MS from HCs. Conversely, the high measurement error and variability of the endurance tests may hinder their application in intervention programs.

Impact

Determining the reliability and validity of the tests currently used to assess trunk function is of the greatest importance for people with MS (who show not only impaired trunk function but also wide fluctuations in performance), as it requires consistent and accurate measurements that are sensitive enough to detect minimal changes induced by rehabilitation.
Maintaining Symbiotic Homeostasis: How Do Plants Engage With Beneficial Microorganisms While at the Same Time Restricting Pathogens?
Authors: Thoms David , Liang Yan , Haney Cara H.
Published: February 2021

This article is part of the Top 10 Unanswered Questions in MPMI invited review series.

That plants recruit beneficial microbes while simultaneously restricting pathogens is critical to their survival. Plants must exclude pathogens; however, most land plants are able to form mutualistic symbioses with arbuscular mycorrhizal fungi. Plants also associate with the complex microbial communities that form the microbiome. The outcome of each symbiotic interaction—whether a specific microbe is pathogenic, commensal, or mutualistic—relies on the specific interplay of host and microbial genetics and the environment. Here, we discuss how plants use metabolites as a gate to select which microbes can be symbiotic. Once present, we discuss how plants integrate multiple inputs to initiate programs of immunity or mutualistic symbiosis and how this paradigm may be expanded to the microbiome. Finally, we discuss how environmental signals are integrated with immunity to fine-tune a thermostat that determines whether a plant engages in mutualism, resistance to pathogens, and shapes associations with the microbiome. Collectively, we propose that the plant immune thermostat is set to select for and tolerate a largely nonharmful microbiome while receptor-mediated decision making allows plants to detect and dynamically respond to the presence of potential pathogens or mutualists.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Wheat Root Protection From Cereal Cyst Nematode (Heterodera avenae) by Fluopyram Seed Treatment
Authors: Li Haolin , Liu Guang , Zhang Da-xia , Lin Xu , Liu Guangying , Xu Shuangyu , Liu Feng , Mu Wei
Published: February 2021

Cereal cyst nematode (Heterodera avenae), an important plant-parasitic nematode causing yield losses of wheat, has been found in many provinces in China. It is urgent to develop an effective method of protecting wheat from H. avenae damage. Because of its novel mode of action, fluopyram has been registered for controlling root-knot nematodes on cucumber and tomato in China. However, the bioactivity of fluopyram against H. avenae and whether this seed treatment can effectively control H. avenae on wheat remains unknown. In this study, a bioactivity assay revealed that fluopyram increased the mortality of H. avenae second-stage juveniles (J2), with lethal concentrations (LC) required to kill 50% (LC50) and 90% (LC90) of 0.92 mg⋅liter−1 and 2.92 mg⋅liter−1, respectively. Hatching tests showed that the H. avenae egg hatching percent was reduced by 35.2 to 69.2% with fluopyram at rates of 1.6 to 6.4 mg⋅liter−1, and that the egg hatching period was delayed by 3 to 9 days compared with the control. During pot and field trials, fluopyram seed treatment significantly reduced the H. avenae population density and increased wheat yield by 3.0 to 13.7%. Therefore, fluopyram seed treatment is an effective approach for the management of H. avenae on wheat in China.
Streptococcus gallolyticus subspecies pasteurianus causing early onset neonatal sepsis complicated by solitary liver abscess in a preterm infant
Authors: Geetha Odattil , Cherie Chua , Natalie Tan Woon Hui , Merchant Khurshid , Chien Chua Mei , Chandran Suresh
Published: February 2021

Streptococcus gallolyticus ssp pasteurianus (SGp) is an uncommon but increasingly recognized cause of neonatal sepsis and meningitis. Liver abscess in neonates is extremely rare. But liver abscess due to SG has never been reported in the literature. We present the first case of liver abscess due to SGp in a late preterm infant. A female infant was born at 36 weeks via normal vaginal delivery to a mother with unremarkable antenatal history. She had progressively worsening respiratory distress since birth and was intubated at 13 h of life. One dose of surfactant was delivered and ventilation continued. Parenteral crystalline Penicillin and Gentamicin were initiated and her blood culture at birth grew SGp. She had a spike of fever on day 5 of life. An ultrasound (US) scan of the abdomen was included in the septic work up. A multi-septated cystic liver abscess was noted in the right lobe of the liver. As there was inadequate response to appropriate intravenous antibiotics, needle aspiration and biopsy were performed on day 35 of life. Aspirate was sterile and histopathology confirmed a liver abscess. The patient continued to be treated with antibiotics for 8 weeks with serial US scans of the liver showing resolution of the abscess. Increasing awareness among paediatric and neonatal fraternity about these new emerging bacterial infections can facilitate early diagnosis and treatment.
Entomobacter blattae gen. nov., sp. nov., a new member of the Acetobacteraceae isolated from the gut of the cockroach Gromphadorhina portentosa
Authors: Guzman Juan , Sombolestani Atena Sadat , Poehlein Anja , Daniel Rolf , Cleenwerck Ilse , Vandamme Peter , Vilcinskas Andreas
Published: February 2021

A novel bacterium designated G55GPT and pertaining to the family

Acetobacteraceae

was isolated from the gut of the Madagascar hissing cockroach Gromphadorhina portentosa. The Gram-negative cells were rod-shaped and non-motile. The complete 16S rRNA sequence of the strain G55GPT showed the highest pairwise similarity to

Gluconacetobacter johannae

CFN-Cf-55T (95.35 %), suggesting it represents a potential new genus of the family

Acetobacteraceae

. Phylogenetic analysis based on 16S rRNA gene and 106 orthologous housekeeping protein sequences revealed that G55GPT forms a monophyletic clade with the genus

Commensalibacter

, which thus far has also been isolated exclusively from insects. The G55GPT genome size was 2.70 Mbp, and the G+C content was 45.4 mol%, which is lower than most acetic acid bacteria (51–68 mol%) but comparable to

Swingsia samuiensis

AH83T (45.1 mol%) and higher than

Commensalibacter intestini

A911T (36.8 mol%). Overall genome relatedness indices based on gene and protein sequences strongly supported the assignment of G55GPT to a new genus within the family

Acetobacteraceae

. The percentage of conserved proteins, which is a useful metric for genus differentiation, was below 54 % when comparing G55GPT to type strains of acetic acid bacteria, thus strongly supporting our hypothesis that G55GPT is a member of a yet-undescribed genus. The fatty acid composition of G55GPT differed from that of closely related acetic acid bacteria, particularly given the presence of C19 : 1
 ω9c/ω11c and the absence of C14 : 0 and C14 : 0 2-OH fatty acids. Strain G55GPT also differed in terms of metabolic features such as its ability to produce acid from d-mannitol, and its inability to produce acetic acid from ethanol or to oxidize glycerol to dihydroxyacetone. Based on the results of combined genomic, phenotypic and phylogenetic characterizations, isolate G55GPT (=LMG 31394T=DSM 111244T) is considered to represent a new species in a new genus, for which we propose the name Entomobacter blattae gen. nov., sp. nov.
Tsuneonella suprasediminis sp. nov., isolated from the Pacific Ocean
Authors: Gao Yan , Li Guangyu , Fang Chen , Shao Zongze , Wu Yue-Hong , Xu Xue-Wei
Published: February 2021

A Gram-stain-negative, rod-shaped and aerobic bacterial strain, named Ery12T, was isolated from the overlying water of the Lau Basin in the Southwest Pacific Ocean. Strain Ery12T showed high 16S rRNA gene sequences similarity to

Tsuneonella flava

MS1-4T (99.9 %),

T. mangrovi

MCCC 1K03311T (98.1 %),

Altererythrobacter ishigakiensis

NBRC 107699T (97.3 %) and exhibited ≤97.0 % sequence similarity with other type strains of species with validly published names. Growth was observed in media with 0–10.0 % NaCl (optimum 0–1.0 %, w/v), pH 5.0–9.5 (optimum 6.0–7.0) and 10–42 °C (optimum 30–37 °C). The predominant respiratory quinone was ubiquinone 10 (Q-10). The major cellular fatty acid was summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c). The major polar lipids were sphingoglycolipid, phosphatidyglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, three unidentified glycolipids, one unidentified aminoglycolipid and one unidentified lipid. The DNA G+C content was 60.8 %. The ANI and in silico DDH values between strain Ery12T and the type strains of its closely related species were 71.0- 91.8 % and 19.5- 44.6 %, respectively. According to the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain Ery12T represents a novel species of the genus

Tsuneonella

, for which the name Tsuneonella suprasediminis is proposed. The type strain is Ery12T (=CGMCC 1.16500 T=MCCC 1A04421T=KCTC 62388T). We further propose to reclassify

Altererythrobacter rhizovicinus

and

Altererythrobacter spongiae

as Pelagerythrobacter rhizovicinus comb. nov. and Altericroceibacterium spongiae comb. nov., respectively.
IgG1 pan-neurofascin antibodies identify a severe yet treatable neuropathy with a high mortality
Authors: Fehmi Janev , Davies Alexander J. , Walters R. Jon , Lavin Tim , Keh Ryan , Rossor Alexander M. , Munteanu Tudor , Delanty Norman , Roberts Rhys , B□umer Dirk , Lennox Graham , Rinaldi Simon
Published: February 2021

Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy are umbrella terms for a number of pathologically distinct diseases involving disabling, immune-mediated injury to peripheral nerves. Current treatments involve non-specific immunomodulation. Prospective identification of patients with specific disease mechanisms should increasingly inform the use of more targeted disease modifying therapies and may lead to improved outcomes. In this cohort study, we tested serum for antibodies directed against nodal/paranodal protein antigens. The clinical characteristics of antibody positive and seronegative patients were then compared. Eight patients with IgG1-subclass antibodies directed against both isoforms of the nodal/paranodal cell-adhesion molecule neurofascin were identified. All developed rapidly progressive tetraplegia. Cranial nerve deficits (100% versus 26%), autonomic dysfunction (75% versus 13%) and respiratory involvement (88% versus 14%) were more common than in seronegative patients. The response to intravenous immunoglobulin, steroids and/or plasmapheresis was poor. Four patients received the B-cell-depleting therapy rituximab. After several weeks, these patients began to show progressive functional improvements, became seronegative, and were ultimately discharged home. Four patients who did not receive rituximab did not improve and died following the development of infectious complications and/or withdrawal of intensive care support. IgG1 panneurofascin antibodies define a very severe autoimmune neuropathy. We urgently recommend trials of targeted immunotherapy for this serologically-classified patient group.
COVID-19 spread and Weather in U.S. states: a cross-correlative study on summer-autumn 2020
Authors: de Margerie Emmanuel
Published: February 2021

An effect of weather on sars-cov-2 transmission is regularly proposed as a putative cause of unexplained fluctuations of covid-19 new cases, but clear data supporting this hypothesis remains to be presented. Here I measured longitudinal time-series correlations between outdoor temperature, humidity and covid-19 reproduction number (Rt) in the 50 U.S. states (+DC). In order to mitigate the confounding influence of varying social restriction measures, the analysis spans a 5-month period during summer and autumn 2020 when restrictions were comparatively lower and more stable. I used a cross-covariance approach to account for a variable delay between infection and case report. For a delay near 11 days, most U.S. states exhibited a negative correlation between outdoor temperature and Rt, as well as between absolute humidity and Rt (mean r = −0.35). In 21 states, the correlation was strong (r < −0.5). Individual state data are presented, and associations between cold and/or dry weather episodes and short-term new case surges are proposed. After identifying potential confounding factors, I discuss 3 possible causal mechanisms that could explain a correlation between outdoor weather and indoor disease transmission: behavioral adaptations to cold weather, respiratory tract temperature, and the importing of outdoor absolute humidity to indoor spaces.
Cohort-based association study of germline genetic variants with acute and chronic health complications of childhood cancer and its treatment: Genetic risks for childhood cancer complications Switzerland (GECCOS) study protocol
Authors: Waespe Nicolas , Strebel Sven , Nava Tiago , Uppugunduri Chakradhara Rao S. , Marino Denis , Mattiello Veneranda , Otth Maria , Gumy-Pause Fabienne , von Bueren André O. , Baleydier Frederic , Mader Luzius , Spoerri Adrian , Kuehni Claudia E. , Ansari Marc
Published: February 2021

Background

Childhood cancer and its treatment may lead to many acute and chronic health complications. Related impairment in quality of life, excess in deaths, and accumulated health care costs are relevant. There is a wide inter-individual variability in the type and severity of health complications. Genetic variations are suggested to contribute to individual susceptibility. So far, only few genetic variants have been used to risk-stratify treatment and follow-up care. This study platform aims to identify germline genetic variants associated with acute and late complications of childhood cancer.

Methods

The Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study is a nationwide cohort study. It includes patients and survivors who were diagnosed with childhood cancers or Langerhans cell histiocytosis before age 21 years, were registered in the Swiss Childhood Cancer Registry (SCCR) since 1976 and have consented to the Pediatric Biobank for Research in Hematology and Oncology (BaHOP), Geneva, host of the Germline DNA Biobank Switzerland for Childhood Cancer and Blood Disorders (BISKIDS). BISKIDS is a national biobank for the collection of germline DNA in childhood cancer patients and survivors.

GECCOS uses demographic and clinical data from the SCCR and the associated Swiss Childhood Cancer Survivor Study (SCCSS), which contains health-related data of survivors. Phenotypic data consist of objective measurements, health conditions diagnosed by physicians, second primary neoplasms, self-reported and health-related information from participants. Germline genetic samples and sequencing data have been collected in BISKIDS. We will perform gene panel sequencing, whole-exome sequencing, or whole-genome sequencing depending on the research questions. We will perform association analyses to identify genetic variants associated with specified health conditions. We will use clustering and machine-learning techniques and assess multiple health conditions in different models.

Discussion

GECCOS will serve as an overarching platform to enable genotype-phenotype association analyses on complications associated with childhood cancer and its treatments. Knowledge of germline genetic variants associated with childhood cancer-associated health conditions will help to further individualize cancer treatment and follow-up care, potentially resulting in improved efficacy and reduced side effects, for personalized cancer care.

Trial registration

Clinicaltrials.gov: NCT04702321
Comparing the impact of vaccination strategies on spread of COVID-19, including a novel household-targeted vaccination strategy
Authors: Voigt André , Omholt Stig , Almaas Eivind
Published: February 2021

With limited availability of vaccines, an efficient use of the limited supply of vaccines in order to achieve herd immunity will be an important tool to combat the wide-spread prevalence of COVID-19. Here, we compare a selection of strategies for vaccine distribution, including a novel targeted vaccination approach (EHR) that provides a noticeable increase in vaccine impact on disease spread compared to age-prioritized and random selection vaccination schemes. Using high-fidelity individual-based computer simulations with Oslo, Norway as an example, we find that for a community reproductive number in a setting where the base pre-vaccination reproduction number R = 2.1 without population immunity, the EHR method reaches herd immunity at 48% of the population vaccinated with 90% efficiency, whereas the common age-prioritized approach needs 89%, and a population-wide random selection approach requires 61%. We find that age-based strategies have a substantially weaker impact on epidemic spread and struggle to achieve herd immunity under the majority of conditions. Furthermore, the vaccination of minors is essential to achieving herd immunity, even for ideal vaccines providing 100% protection.
Estimated SARS-CoV-2 Seroprevalence in Healthy Children and Those with Chronic Illnesses in The Washington Metropolitan Area as of October 2020
Authors: Bahar Burak , Simpson Joelle N. , Biddle Cara , Campbell Andrew , Dome Jeffrey S. , DeBiasi Roberta L. , Mowbray Catriona , Marguilies Stefanie , Sherman Adrienne , Reuben Jacqueline , Delaney Meghan
Published: February 2021

The estimated SARS-CoV-2 seroprevalence in children was found to be 9.46% for the Washington Metropolitan area. Hispanic/Latinx individuals were found to have higher odds of seropositivity. While chronic medical conditions were not associated with having antibodies, previous fever and body aches were predictive symptoms.
Prefrontal-motor and somatosensory-motor cortical network interactions during reactive balance are associated with distinct aspects of balance behavior in older adults
Authors: Palmer Jacqueline A. , Payne Aiden M. , Ting Lena H. , Borich Michael R.
Published: February 2021

Heightened reliance on the cerebral cortex for postural stability with aging is well-known, yet the cortical dynamics of balance control, particularly in relationship to balance function, is unclear. Here we aimed to investigate motor cortical activity in relationship to the level of balance challenge presented during reactive balance recovery, and identify circuit-specific interactions between motor cortex and prefrontal or somatosensory regions to metrics of balance function that predict fall risk. Using electroencephalography, we assessed motor cortical beta power, and beta coherence during balance reactions to perturbations in older adults. We found that individuals with greater somatosensory-motor beta coherence at baseline and lower beta power evoked over motor regions following perturbations demonstrated higher general clinical balance function. At the group-level, beta coherence between prefrontal-motor regions reduced during balance reactions. Older adults with the highest post-perturbation prefrontal-motor coherence showed greater cognitive dual-task interference and elicited stepping reactions at lower perturbation magnitudes. Our results support motor cortical beta activity as a potential biomarker for individual level of balance challenge and implicate prefrontal-and somatosensory-motor cortical networks in different aspects of balance control in older adults. Cortical network activity during balance may provide a neural target for precision-medicine efforts aimed at fall-prevention with aging.
CDSeqR: fast complete deconvolution for gene expression data from bulk tissues
Authors: Kang Kai , Huang Caizhi David , Li Yuanyuan , Umbach David M. , Li Leping
Published: February 2021

Background

Biological tissues consist of heterogenous populations of cells. Because gene expression patterns from bulk tissue samples reflect the contributions from all cells in the tissue, understanding the contribution of individual cell types to the overall gene expression in the tissue is fundamentally important. We recently developed a computational method, CDSeq, that can simultaneously estimate both sample-specific cell-type proportions and cell-type-specific gene expression profiles using only bulk RNA-Seq counts from multiple samples. Here we present an R implementation of CDSeq (CDSeqR) with significant performance improvement over the original implementation in MATLAB and an added new function to aid cell type annotation. The R package would be of interest for the broader R community.

Result

We developed a novel strategy to substantially improve computational efficiency in both speed and memory usage. In addition, we designed and implemented a new function for annotating the CDSeq estimated cell types using single-cell RNA sequencing (scRNA-seq) data. This function allows users to readily interpret and visualize the CDSeq estimated cell types. In addition, this new function further allows the users to annotate CDSeq-estimated cell types using marker genes. We carried out additional validations of the CDSeqR software using synthetic, real cell mixtures, and real bulk RNA-seq data from the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) project.

Conclusions

The existing bulk RNA-seq repositories, such as TCGA and GTEx, provide enormous resources for better understanding changes in transcriptomics and human diseases. They are also potentially useful for studying cell-cell interactions in the tissue microenvironment. Bulk level analyses neglect tissue heterogeneity, however, and hinder investigation of a cell-type-specific expression. The CDSeqR package may aidin silicodissection of bulk expression data, enabling researchers to recover cell-type-specific information.
7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome
Authors: Tomita Hideaki , Hines Kelly M. , Herron Josi M. , Li Amy , Baggett David W. , Xu Libin
Published: February 2021

Defective 3β-hydroxysterol-Δ7-reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss ofDHCR7causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis, and perturbation of neuronal localization in developing murine or human cortical neural precursors, bothin vitroandin vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss ofDHCR7or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/EBP signaling pathway in cortical neural precursors. Moreover, direct inhibition of GR activation with an antagonist or inhibition of DHCEO accumulation with antioxidants rescues the premature neurogenesis phenotype caused by the loss ofDHCR7. These results suggest that GR could be a new therapeutic target against the neurological defects observed in SLOS.
Trial-to-trial variability of spiking delay activity in prefrontal cortex constrains burst-coding models of working memory
Authors: Li Daming , Constantinidis Christos , Murray John D.
Published: February 2021

A hallmark neuronal correlate of working memory (WM) is stimulus-selective spiking activity of neurons in prefrontal cortex (PFC) during mnemonic delays. These observations have motivated an influential computational modeling framework in which WM is supported by persistent activity. Recently this framework has been challenged by arguments that observed persistent activity may be an artifact of trial-averaging, which potentially masks high variability of delay activity at the single-trial level. In an alternative scenario, WM delay activity could be encoded in bursts of selective neuronal firing which occur intermittently across trials. However, this alternative proposal has not been tested on single-neuron spike-train data. Here, we developed a framework for addressing this issue by characterizing the trial-to-trial variability of neuronal spiking quantified by Fano factor (FF). By building a doubly stochastic Poisson spiking model, we first demonstrated that the burst-coding proposal implies a significant increase in FF positively correlated with firing rate, and thus loss of stability across trials during the delay. Simulation of spiking cortical circuit WM models further confirmed that FF is a sensitive measure that can well dissociate distinct WM mechanisms. We then tested these predictions on datasets of single-neuron recordings from macaque prefrontal cortex during three WM tasks. In sharp contrast to the burst-coding model predictions, we only found a small fraction of neurons showing increased WM-dependent burstiness, and stability across trials during delay was strengthened in empirical data. Therefore, reduced trial-to-trial variability during delay provides strong constraints on the contribution of single-neuron intermittent bursting to WM maintenance.

Significance Statement

There are diverging classes of theoretical models explaining how information is maintained in working memory by cortical circuits. In an influential model class, neurons fire exhibit persistent elevated memorandum-selective firing, whereas a recently developed class of burst-coding models suggests that persistent activity is an artifact of trial-averaging, and spiking is sparse in each single trial, subserved by brief intermittent bursts. However, this alternative picture has not been characterized or tested on empirical spike-train data. Here we combine mathematical analysis, computational model simulation and experimental data analysis to test empirically theses two classes of models and show that the trial-to-trial variability of empirical spike trains is not consistent with burst coding. These findings provide constraints for theoretical models of working memory.
Pupillary aperture is a potential biomarker of movement preparation
Authors: Pandey Pragya , Ray Supriya
Published: February 2021

In response to variable light intensity, the pupils reflexively constrict or dilate to maintain a uniform retinal illumination. The pupillary light reflex (PLR) pathway receives projections from two important areas in primates’ brain that plan rapid saccadic eye-movement – frontal eye field (FEF) and superior colliculus (SC). The speed with which neurons in these areas increase firing rate to a threshold determines latency of a saccade. Micro-stimulation of FEF/SC neurons below this threshold modulates the magnitude of PLR. Nonetheless, how the saccade latency and pupil dynamics are related remains unknown. Our study shows that the appearance of a bright stimulus evokes pupil constriction at higher rate when the latency of impending saccade to the stimulus is shorter. This inverse relationship between the rate of pupil constriction and the saccade latency is robust irrespective of the reward outcome. In a homeomorphic biomechanical model of pupil, we have projected build-up signal similar to FEF and SC activity to the parasympathetic and sympathetic divisions of the PLR pathway, respectively. Model simulation mimics the observed data to indicate that the FEF and SC activity for eye movement modulates autonomic input to the pupillary muscle plant. A striking similarity between the dynamics of pupil constriction and stochastic rise in neural activity for saccade elicitation suggests that PLR is a potential proxy of movement preparation, and not mere an indicator of attentional orientation. Our study suggests a mechanism of how the retinal luminosity is timely regulated to aid perception by minimizing visual transients due to gaze orientation.
Prognosis and hematological findings in patients with COVID-19 in an Amazonian population of Peru
Authors: Iglesias-Osores Sebastian , Rafael-Heredia Arturo , Rojas-Tello Eric Ricardo , Ortiz-Uribe Washington A. , Román Leveau-Bartra Walter , Armando Leveau-Bartra Orison , Miguel Alcántara-Mimbela , Córdova-Rojas Lizbeth M. , López-López Elmer , Failoc-Rojas Virgilio E.
Published: February 2021

Objective

This study examined the laboratory results of COVID-19 patients from a hospital in the Peruvian Amazon and their clinical prognosis.

Methods

An analytical cross-sectional study was carried out whose purpose was to identify the laboratory tests of patients with COVID-19 and mortality in a hospital in Ucayali, Peru during the period from March 13 to May 9, 2020, selecting a total of 127 with Covid-19. Mean and the standard deviation was described for age, leukocytes, neutrophils, platelets, RDW-SD; median and interquartile range for the variables lymphocyte, RN / L, fibrinogen, CRP, D-dimer, DHL, hematocrit, monocytes, eosinophils.

Results

No differences were observed in this population regarding death and sex (OR: 1.31; 95% CI 0.92 to 1.87), however, it was observed that, for each one-year increase, the probability of death increased by 4% (PR: 1.04, 95% CI 1.03 to 1.05). The IRR (Incidence Risk Ratio) analysis for the numerical variables showed results strongly associated with hematological values such as Leukocytes (scaled by 2500 units) (IRR: 1.08, 95% CI 1.03 to 1.13), neutrophils (scaled by 2500 units) (IRR: 1.08; 95% CI 1.03 to 1.13), on the contrary, it is observed that the increase of 1000 units in lymphocytes, the probability of dying decreased by 48% (IRR: 0.52; 95% CI 0.38 to 071).

Conclusion

Parameters such as leukocytes and neutrophils were statistically much higher in patients who died.