bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of Pubertal Onset in Girls and Boys With Constitutional Delay
Authors: Jonsdottir-Lewis Elfa , Feld Amalia , Ciarlo Ryan , Denhoff Erica , Feldman Henry A , Chan Yee-Ming 
Published: April 2021

Abstract

Context
The decision whether to treat a child with delayed puberty with sex steroids is primarily based on patient, family, and provider preference. Knowing when children with constitutional delay eventually enter puberty would inform this decision.

Objective, Design, Setting, Participants, and Outcome Measures
To estimate and compare rates of pubertal entry, we conducted a retrospective cohort study by reviewing medical records of children evaluated for delayed puberty at a large academic medical center between 2000 and 2015, extracting data on pubertal status for all clinical visits, then conducting time-to-event analyses.

Results
Of 392 girls and 683 boys with delayed puberty, constitutional delay was the most common cause, found in 32% of girls and 70% of boys. In a subcohort of 97 girls and 243 boys who were prepubertal at one or more visits, we observed a broad age range for pubertal entry, up to &gt;16 years for girls and &gt;17 years for boys. The probability of entering puberty within the next year for 12- to 15.5-year-old girls and 13.5- to 16.5-year-old boys with delayed puberty ranged between 38% and 74%. No differences in the rates of pubertal entry were seen between girls and boys after data harmonization.

Conclusion
The broad range of ages at pubertal entry for children with constitutional delay challenges the concept that constitutional delay is merely an extreme of normal variation. Discussions with patients and families about management should consider the possibility that some children may need to wait years after presentation until puberty starts.
The Prevalence of Difficult Airway in Children With Beckwith-Wiedemann Syndrome: A Retrospective Cohort Study
Authors: Sequera-Ramos Luis , Duffy Kelly A. , Fiadjoe John E. , Garcia-Marcinkiewicz Annery G. , Zhang Bingqing , Perate Alison , Kalish Jennifer M. 
Published: April 2021

BACKGROUND:
Beckwith-Wiedemann syndrome (BWS) is the most common congenital overgrowth disorder with an incidence of approximately 1 in 10,000 live births. The condition is characterized by lateralized overgrowth, abdominal wall defects, macroglossia, and predisposition to malignancy. Historically, children with BWS have been presumed to have difficult airways; however, most of the evidence to support this has been anecdotal and derived from case reports. Our study aimed to determine the prevalence of difficult airway in patients with BWS. We hypothesized that most patients with BWS would not have difficult airways.

METHODS:
We retrospectively reviewed the electronic medical records of patients enrolled in our institution’s BWS registry. Patients with a molecular diagnosis of BWS who were anesthetized between January 2012 and July 2019 were included for analysis. The primary outcome was the presence of difficult airway, defined as difficult facemask ventilation, difficult intubation, or both. We defined difficult intubation as the need for 3 or more tracheal intubation attempts and the need for advanced airway techniques (nondirect laryngoscopy) to perform tracheal intubation or a Cormack and Lehane grade ≥3 during direct laryngoscopy. Secondary objectives were to define predictors of difficult intubation and difficult facemask ventilation, and the prevalence of adverse airway events. Generalized linear mixed-effect models were used to account for multiple anesthesia events per patient.

RESULTS:
Of 201 BWS patients enrolled in the registry, 60% (n = 122) had one or more documented anesthetics, for a total of 310 anesthetics. A preexisting airway was present in 22 anesthetics. The prevalence of difficult airway was 5.3% (95% confidence interval [CI], 3.0-9.3; 18 of 288) of the cases. The prevalence of difficult intubation was 5.2% (95% CI, 2.9-9.4; 12 of 226). The prevalence of difficult facemask ventilation was 2.9% (95% CI, 1.4-6.2; 12 of 277), and facemask ventilation was not attempted in 42 anesthetics. Age <1 year, macroglossia, lower weight, endocrine comorbidities, plastics/craniofacial surgery, tongue reduction surgery, and obstructive sleep apnea were associated with difficult airways in cases without a preexisting airway. About 83.8% (95% CI, 77.6-88.5) of the cases were intubated with a single attempt. Hypoxemia was the most common adverse event.

CONCLUSIONS:
The prevalence of difficult tracheal intubation and difficult facemask ventilation in children with BWS was 5.2% and 2.9%, respectively. We identified factors associated with difficult airway, which included age <1 year, macroglossia, endocrine abnormalities, plastics/craniofacial surgery, tongue reduction surgery, and obstructive sleep apnea. Clinicians should anticipate difficult airways in patients with these factors.
Anesthetic Complications Associated With Severe Acute Respiratory Syndrome Coronavirus 2 in Pediatric Patients
Authors: Saynhalath Rita , Alex Gijo , Efune Proshad N. , Szmuk Peter , Zhu Hong , Sanford Ethan L. 
Published: April 2021

BACKGROUND:
Coronavirus disease 2019 (COVID-19) is associated with high perioperative morbidity and mortality among adults. The incidence and severity of anesthetic complications in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We hypothesized that there would be an increased incidence of intra- and postoperative complications in children with SARS-CoV-2 infection as compared to those with negative testing.

METHODS:
We conducted a retrospective cohort study analyzing complications for children <18 years of age who underwent anesthesia between April 28 and September 30, 2020 at a large, academic pediatric hospital. Each child with a positive SARS-CoV-2 test within the prior 10 days was matched to a patient with a negative SARS-CoV-2 test based on American Society of Anesthesiologists (ASA) physical status, age, gender, and procedure. Children who were intubated before the procedure, underwent organ transplant surgery, or had severe COVID-19 were excluded. The primary outcome was the risk difference of a composite of intra- or postoperative respiratory complications in children positive for SARS-CoV-2 compared to those with negative testing. Secondarily, we used logistic regression to determine the odds ratio for respiratory complications before and after adjustment using propensity scores weighting to adjust for possible confounders. Other secondary outcomes included neurologic, cardiovascular, hematologic, and renal complications, unanticipated postoperative admission to the intensive care unit, length of hospital stay, and mortality.

RESULTS:
During the study period, 9812 general anesthetics that had a preoperative SARS-CoV-2 test were identified. Sixty encounters occurred in patients who had positive SARS-CoV-2 testing preoperatively and 51 were included for analysis. The matched controls cohort included 99 encounters. A positive SARS-CoV-2 test was associated with a higher incidence of respiratory complications (11.8% vs 1.0%; risk difference 10.8%, 95% confidence interval [CI], 1.6–19.8; P = .003). After adjustment, the odds ratio for respiratory complications was 14.37 (95% CI, 1.59–130.39; P = .02) for SARS-CoV-2–positive children as compared to controls. There was no occurrence of acute respiratory distress syndrome, postoperative pneumonia, or perioperative mortality in either group.

CONCLUSIONS:
Pediatric patients with nonsevere SARS-CoV-2 infection had higher rates of perianesthetic respiratory complications than matched controls with negative testing. However, severe morbidity was rare and there were no mortalities. The incidence of complications was similar to previously published rates of perianesthetic complications in the setting of an upper respiratory tract infection. This risk persisted after adjustment for preoperative upper respiratory symptoms, suggesting an increased risk in symptomatic or asymptomatic SARS-CoV-2 infection.
High-resolution autoradiographic localization of DNA-containing sites and RNA synthesis in developing nucleoli of human preimplantation embryos: a new concept of embryonic nucleologenesis
Authors: Tesarik Jan , Kopečný Vaclav , Plachot Michelle , Mandelbaum Jacqueline 
Published: April 2021

ABSTRACTHuman embryos from the 2-cell to the morula stage, obtained by in vitro fertilization, were incubated with [3H]thymidine or [3H]uridine so as to achieve labelling of all replicating nuclear DNA and the newly synthesized RNA, respectively. The label was localized in different structural components of developing nucleoli using electron microscopic autoradiography. Careful study of the relationship between the structural pattern and nucleic acid distribution made it possible to define four stages of embryonic nucleologenesis. Homogeneous nucleolar precursors (i) consist of nucleolar matrix elements appearing as filaments of 3 nm thickness, (ii) do not contain recently replicated DNA and (iii) lack RNA synthetic activity. Penetration of DNA into these bodies is a key event leading to their transformation into heterogeneous nucleolar precursors. In addition to the 3nm matrix filaments, two types of 5 nm fibrillar components can be recognized in them. The denser type contains DNA and is the site of nucleolar RNA synthesis, while the more loosely arranged 5 nm fibrils are not labelled with [3H]thymidine and apparently represent the newly produced pre-rRNA detached from the transcribing rDNA filament. Compact fibrillogranular nucleoli are characterized by the first appearance of the granular component and reduction of the nontranscribing part of the fibrillar component, both indicating the activation of the machinery for rRNA processing. Finally, the granular component is most evident in reticulated nucleoli, occupying mostly the inner parts of their nucleolonema, while the transcription sites tend to be located at the nucleolar periphery. Our findings advocate a unique concept of embryonic nucleologenesis, different from any other nucleolar event during the cell cycle of differentiated cells. This developmental pattern is characterized by a gradual activation of rRNA synthesis and processing, mediated by progressive association of rDNA and, later on, the newly formed pre-rRNA with pre-existing nucleolar matrix elements that are originally topically separated from nucleolar organizer regions. This model may have a general validity in early animal embryos despite some interspecies variability in the timing of individual steps and resulting structural peculiarities.
Highly efficient β globin transcription in the absence of both a viral enhancer and erythroid factors
Authors: Walmsley Maggie E. , Patient Roger K. 
Published: April 2021

ABSTRACT
We have studied the transcription of the Xenopus major adult β globin gene in microinjected Xenopus oocytes at various levels of injected template, with or without the SV40 enhancer. We find that enhancerindependent transcription is highly efficient, being only two orders of magnitude below the calculated in vivo rate. Linkage to the SV40 enhancer has very little stimulatory effect. We have also tested the effect of replication on transcription in the oocyte system where replication was induced by progesterone treatment followed by prick activation. We found that the presence of replicated templates did not stimulate expression of the Xenopus /J globin gene either in the presence or absence of the SV40 enhancer. In addition, we found that specificity of transcription, in terms of initiation at the cap site versus initiation at cryptic promoters upstream of the cap site, was dramatically improved by the injection of higher numbers of β globin templates, by oocyte maturation and activation or by the presence of the SV40 enhancer.
pp60c-srcexpression in transdifferentiating cultures of embryonic chick neural retina cells
Authors: Ellis D. K. , Carr A. , Pomerai D. I. de 
Published: April 2021

ABSTRACTChick embryo neural retinal cells transdifferentiate extensively into lens cells when cultured in Eagle’s MEM containing horse and fetal calf sera (FHMEM). Such cultures express elevated levels of pp60c-src-associated tyrosine kinase activity relative to parallel cultures prevented from transdifferentiating by the addition of supplementary glucose (FHGMEM) or replacement of MEM by medium 199 (F199). Northern blotting and in vitro translation studies suggest that c-src mRNA levels are only slightly higher in late transdifferentiating (FHMEM) cultures as compared to parallel blocked (FHGMEM or F199) cultures. By immunocytochemical staining, we show that pp60c-src protein is largely localized in cell groups undergoing conversion into lens (i.e. expressing δ crystallin) in late FHMEM cultures. Initial studies of pp60c-sre in chick lens tissues during development indicate that higher kinase activity is found in the epithelial cells relative to mature lens fibres. Thus pp60c-src may be expressed both during the differentiation of lens cells in vivo and during the transdifferentiation of neural retina cells into lens in vitro.
The development of an assay to detect mRNAs that affect early development
Authors: Woodland H. R. , Jones E. A. 
Published: April 2021

ABSTRACTWe have constructed an assay to identify developmental effects of injected RNA molecules. The RNA is injected into the animal pole region of a 2- to 8-cell embryo. At the blastula stage, the animal cap is removed and its development in isolation tested. In controls, only epidermis is produced, but several of the injected RNA preparations, though not all, also form dorsal and ventral mesoderm and nervous tissue. This assay should be suitable for selecting cDNA clones complementary to mRNAs that direct development.
Telomeres of the human X and Y chromosomes
Authors: Cooke Howard J. 
Published: April 2021

ABSTRACT
Analysis of the nature of the DNA sequences at the telomeres of the short arms of the human sex chromosomes suggests parallels with the structures found at telomeres of a number of lower eukaryotes. The exact nature of the end of the DNA has not yet been established but it is clear that there are multiple levels of variability both between and within individuals in this region of the genome.
The role of the mammalian Y chromosome in spermatogenesis
Authors: Burgoyne Paul S. 
Published: April 2021

ABSTRACT
All aspects of the mammalian male phenotype are due either directly or indirectly to Y-chromosome activity. This review summarizes what is known of the role of the Y in male germ cell differentiation in the mouse.
The initial diversion of germ cells to the male pathway in fetal life (that is the formation of amitotic T1-prospermatogonia rather than meiotic oocytes) is an indirect effect of the Y: the Y-chromosomal testisdetermining gene (Tdy) acts to create a testis and the testicular environment causes the germ cells to follow the male pathway. XX and XO germ cells can therefore form T1-prospermatogonia, but the extra X of XX prospermatogonia in some way causes their death perinatally.
The first direct effect of the Y in the germ line occurs at the initiation of the spermatogenic cycles (approx. 1 week after birth) when a Y-chromosomal gene (Spy) is needed for normal spermatogonial survival and progression to meiosis. Spy is present in the Y-derived Sxr fragment so XOSxr germ cells enter meiosis normally. An Sxr derivative, Sxr’, which has lost the capacity to produce H-Y antigen, has also lost the Spy function, raising the possibility that H-Y antigen is the mediator of Spy activity.
The Y is next required in the male germ line during meiotic prophase, when it provides a pairing partner for the X chromosome. If the X (or, indeed, the Y when present) remains unpaired, there are severe spermatogenic losses and the second meiotic division is frequently omitted, leading to the formation of diploid spermatids. Spermatogenesis in XOSxr males is affected in this way and the few sperm produced are morphologically abnormal. These sperm abnormalities could also be a consequence of the X univalence, but there is some evidence suggesting that there is another gene on the Y, lacking in Sxr, which is involved in sperm morphogenesis.
Sex determination in mice: Y and chromosome 17 interactions
Authors: Erickson Robert P. , Durbin Edward J. , Tres Laura L. 
Published: April 2021

ABSTRACT
Mice provide material for studies of Y-chromosomal and autosomal sequences involved in sex determination. Eicher and coworkers have identified four subregions in the mouse Y chromosome, one of which corresponds to the Sxr fragment. This fragment demonstrates that only a small portion of the Y is necessary for male sex determination. The mouse Y chromosome also shows variants: the BALB/cWt Y chromosome, which causes nondisjunction of the Y in some germ cells leading to XO and XYY cells and resulting in many infertile true hermaphrodites; the YDom, a wild-type chromosome which can result in sex reversal on a C57BL/6J background; and Y-chromosomal variants detected with Y-derived genomic DNA clones among inbred strains. Two different autosomal loci affecting sex differentiation have been identified in the mouse by Eicher and coworkers. The first of these has not been mapped to a particular chromosome and has been designated Tda-1 (Testis-determining autosomal-1). This is the locus in C57BL/6J mice at which animals must be homozygous in order to develop as true hermaphrodites or sex-reversed animals in the presence of YDom. The other locus has been identified on proximal chromosome 17. This locus also caused hermaphrodites on the C57BL/6J background and it is most easily interpreted as a locus deleted in 7hp. It is located in a region on chromosome 17 containing other genes or DNA sequences that may be related to sex determination. These include both the Hye (histocompatibility Y expression) locus that affects the amount of male-specific antigen detected by serological and cell-mediated assays and a concentration of Bkm sequences. Despite the Y and chromosomal 17 localizations of Bkm sequences, there is no evidence that transcripts from these are involved in sex determination: RNA hybridizing to sense and anti-sense Bkm clones can be detected in day-14 fetal gonads of both sexes.
Structure of repeated sequences in the centromeric region of the human Y chromosome
Authors: Tyler-Smith Chris 
Published: April 2021

ABSTRACT
Alphoid satellite DNA is a family of sequences with an approximately 170 bp periodicity which is found near the centromere of all human chromosomes. The structure of the human Y-chromosome alphoid DNA has been studied in two somatic cell hybrids, 3E7 and 853 (Tyler-Smith & Brown, 1987). The 170 bp alphoid subunits are tandemly repeated and are organized into units approximately 5-7 kb long. A few variant units on the 3E7 Y chromosome contain two extra 170 bp subunits and are approximately 6-0 kb long; the variant units are present in two clusters at least 90 kb apart on the chromosome. On each Y chromosome there is a single major block of alphoid DNA: on the 3E7 Y chromosome it is approximately 440 kb long and on the 853 Y chromosome it is approximately 540 kb long. A long-range restriction map of the 853 block has been constructed covering approximately 1-1 mb of DNA. The distribution of restriction sites suggests that the sequences on one side of the alphoid block may be typical euchromatic DNA, while the sequences on the other side may be another satellite sequence.
Detection of nerve growth factor mRNA in the developing chicken embryo
Authors: Ebendal Ted , Persson Håkan 
Published: April 2021

Abstract
Nerve growth factor (βNGF) is a protein supporting sympathetic and sensory innervation in the peripheral tissues as well as cholinergic innervation in the brain. A DNA probe derived from a genomic clone coding for chicken NGF was used to study NGF mRNA levels during development. NGF mRNA was detected in the chicken embryo as early as day 3·5 of incubation. The level of NGF mRNA in total embryo increased four-fold until day 8, remained high until day 12, and subsequently decreased. No corresponding peak in NGF mRNA expression was found in heart and brain measured separately. Instead these organs showed increased NGF mRNA levels after hatching. The highest levels of NGF mRNA in the day-8 embryo were found in skin and eye (in particular cornea, but also iris, sclera-choroid and neural retina) suggesting a correlation between sensory innervation and this early peak of NGF expression.
Studies of SI/Sl
d ↔ + /+ mouse aggregation chimaeras : I. Different distribution patterns between melanocytes and mast cells in the skin
Authors: Nakayama Hiroki , Kuroda Hideya , Fujita Jun , Kitamura Yukihiko 
Published: April 2021

Abstract
In spite of their different origin, both melanocytes and mast cells are deficient in the skin of mutant mice of the Sl/Sld genotype. Since the neural crest and the liver of Sl/Std embryos contain normal precursors of melanocytes and mast cells, respectively, the deficiency is attributed to a defect in tissue environment necessary for migration and/or differentiation of precursor cells. We investigated whether the tissue environment used for differentiation of melanocytes and mast cells was identical by producing aggregation chimaeras from Sl/Sld and +/ + embryos. Chimaeric mice with apparent pigmented and nonpigmented stripes were obtained. In the nonpigmented stripes of these Sl/Sld ↔ + / + chimaeras, melanocytes were not detectable in hair follicles but were detectable in the dermis. In contrast, melanocytes were detectable neither in hair follicles nor in the dermis of non-chimaeric Sl/Sl mice. Concentrations of mast cells were comparable in the pigmented and nonpigmented stripes of Sl/Sld ↔ + / + chimaeras, but the average concentration of mast cells significantly varied in the chimaeras (from 8 % to 74 % of the value observed in control +/+ mice). The present result suggests that mesodermal cells that support the migration and differentiation of both melanocyte precursors and mast-cell precursors mix homogeneously in the dermis and that ectodermal cells that influence the invasion of differentiating melanocytes into hair follicles make discrete patches.
Differentiation of embryonic haemopoietic stem cells from mouse blastocysts grown in vitro
Authors: Hollands P. 
Published: April 2021

Abstract
Embryonic haemopoietic stem cells can differentiate from mouse blastocysts grown in vitro. Mouse blastocysts were cultured for 3 or 4 days and the resultant cells were injected intravenously into lethally X-irradiated or genetically anaemic recipient mice. Blastocysts grown in vitro did not maintain normal embryonic morphology. The presence of donor haemoglobin and donor lymphocytic glucose phos-phate isomerase in grafted recipients, demonstrates the presence of embryonic haemopoietic stem cells. Recipients of embryonic haemopoietic stem cells, obtained from growth in vitro, were haematologically stable with no evidence of neoplasia.
Pluripotent embryonic cells, maintained on fibroblast feeder layers, were unable to colonize X-ir-radiated or genetically anaemic mice. Recipients of pluripotent cells died at the same time as salineinjected controls.