bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial analysis of oribatid mites provides insights into their atypical tRNA annotation, genome rearrangement and evolution
Authors: Zhan Xue-Bing , Chen Bing , Fang Yu , Dong Fang-Yuan , Fang Wei-Xi , Luo Qian , Chu Ling-Miao , Feng Rui , Wang Yan , Su Xuan , Fang Ying , Xu Jiao-Yang , Zuo Ze-Tao , Xia Xing-Quan , Yu Jie-Gen , Sun En-Tao
Published: April 2021

Background

The mitochondrial (mt) genomes of Sarcoptiformes mites typically contain 37 genes. Although the loss of genes is rare in Sarcoptiformes mite mitogenomes, two of the six previously reported oribatid mites (Acariforms: Sarcoptiformes) are reported to have lost parts of their tRNA genes. To confirm whether the tRNA genes were indeed lost and whether the loss is universal, we re-annotated the available oribatid mite sequences and sequenced the mitogenome of Oribatula sakamorii.

Methods

The mitogenome of O. sakamorii was sequenced using an Illumina HiSeq sequencer. The mt tRNA gene was annotated using multi-software combined with a manual annotation approach. Phylogenetic analyses were performed using the maximum likelihood and Bayesian inference methods with concatenated nucleotide and amino acid sequences.

Results

The mitogenomes of O. sakamorii contained 37 genes, including 22 tRNA genes. We identified all mt tRNA genes that were reported as “lost” in Steganacarus magnus and Paraleius leontonychus and revealed certain atypical tRNA annotation errors in oribatid mite sequences. Oribatid mite mitogenomes are characterized by low rates of genetic rearrangement, with six or seven gene blocks conserved between the mitogenome of all species and that of ancestral arthropods. Considering the relative order of the major genes (protein-coding genes and rRNAs), only one or two genes were rearranged with respect to their positions in the ancestral genome. We explored the phylogenetic relationships among the available oribatid mites, and the results confirmed the systematic position of Hermannia in the Crotonioidea superfamily. This was also supported by the synapomorphic gene-derived boundaries.

Conclusions

The tRNA “lost” phenomenon is not universal in oribatid mites. Rather, highly atypical secondary structure of the inferred mt tRNA genes made them unidentifiable using a single type of tRNA search program. The use of multi-software combined with a manual annotation approach can improve the accuracy of tRNA gene annotation. In addition, we identified the precise systematic position of Hermannia and validated that Astigmata is nested in Oribatida.

Graphical Abstract
Molecular detection of cattle Sarcocystis spp. in North-West Italy highlights their association with bovine eosinophilic myositis
Authors: Rubiola Selene , Civera Tiziana , Panebianco Felice , Vercellino Davide , Chiesa Francesco
Published: April 2021

Background

Cattle are intermediate hosts of six Sarcocystis species, among which Sarcocystis hominis and Sarcocystis heydorni can infect humans through the consumption of raw or undercooked meat. In addition to the zoonotic potential, there is increasing interest in these protozoa because of the evidence supporting the role of Sarcocystis spp. in the occurrence of bovine eosinophilic myositis (BEM), a specific inflammatory myopathy which leads to carcass condemnation and considerable economic losses. Actually, all the prevalence studies carried out on cattle in Italy have been based on either morphological or 18S rDNA-based molecular techniques, most likely leading to misidentification of closely related species. Therefore, there is a strong need for new data on the prevalence of the different Sarcocystis spp. in cattle in Italy and their association with bovine eosinophilic myositis.

Methods

To reach our aim, individual striated muscle samples from BEM condemned carcasses (N = 54) and diaphragm muscle samples from randomly sampled carcasses (N = 59) were obtained from Northwest Italy slaughterhouses. Genomic DNA was extracted and analyzed by multiplex-PCR targeting 18S rDNA and cox1 genes. PCR products amplified using the genus-specific primer set in absence of the specific fragment for S. hirsuta, S. cruzi, S. hominis or S. bovifelis were sequenced to achieve species identification.

Results

Sarcocystis DNA was detected in 67.8% of the samples from slaughter cattle and in 90.7% of the samples from BEM condemned carcasses. S. cruzi was identified as the most prevalent species in slaughter cattle (61%), followed by S. bovifelis (10.2%), S. hominis (8.5%) and S. hirsuta (1.7%). Notably, among the different Sarcocystis spp. detected, the presence of S. bovifelis and S. hominis was significantly higher in samples isolated from BEM condemned carcasses (46.3% and 40.7% respectively), while there was no statistically significant difference between the presence of S. cruzi or S. hirsuta in BEM condemned carcasses (42.6% and 1.8%, respectively) and randomly sampled carcasses. Furthermore, DNA sequence analysis revealed the presence of a putative new species in two carcasses.

Conclusions

Our study contributes to updating the data on the prevalence of the different Sarcocystis spp. in cattle in Italy, highlighting the presence of three Sarcocystis spp., S. cruzi, S. hominis and S. bovifelis, in BEM lesions and allowing us to speculate on the possible role of S. hominis and S. bovifelis as the major sarcosporidian species involved in bovine eosinophilic myositis.

Graphical Abstract
The effect of climate change on depression in urban areas of western Iran
Authors: Abbasi Hamed
Published: April 2021

Objective

Human is accustomed to climatic conditions of the environment where they are born and live throughout their lifetime. The aim of this study is to examine mood swings and depression caused by sudden climate changes that have not yet given the humans a chance to adapt.

Results

Our results showed that depression could be affected by climate change and as a result, the behavior of climatic elements and trends has damaged mental health in the western regions of Iran. By investigating the trends and changes of climatic time series and their relationship with the rate of depression in urban areas of western Iran, it can be said that climate change is probably a mental health challenge for urban populations. Climate change is an important and worrying issue that makes the life difficult. Rapid climate changes in western Iran including rising air temperature, changes in precipitation, its regime, changes cloudiness and the amount of sunlight have a negative effects on health. The results showed that type of increasing or decreasing trend, as well as different climatic elements in various seasons did not have the same effect on the rate of depression in the studied areas.
Intestinal thromboangiitis obliterans: a case report
Authors: Mishra Swastik Sourav , Mishra Tushar Subhadarshan , Mitra Suvradeep , Kumar Pankaj
Published: April 2021

Background

Thromboangiitis obliterans or Buerger’s disease is a form of peripheral vascular disease in young male smokers. The involvement of the intestine occurs in only about 2% of the cases, when they may present as acute abdomen due to mesenteric ischemia. The uncommonness of the condition makes it a less suspected differential diagnosis, leading to a delay in appropriate management, thereby increasing chances of morbidity or mortality. Cessation of smoking is known to stall the disease progression including visceral involvement, but may not always be the case as happened in the case being presented.

Case presentation

Our Indian Hindu male patient, a known smoker, presented with diffuse abdominal pain along with bouts of vomiting and loose motions. He had a prior history of amputation of the right foot, 4 years before. At presentation he had abdominal distension with diffuse tenderness and guarding. An omental band attached to the tip of the appendix was discovered at the initial exploration along with dilated proximal bowel loops, for which a release of the omental band along with appendectomy was done. He developed an enterocutaneous fistula on the 6th postoperative day for which he had to be reexplored, and multiple jejunal perforations were found. Segmental jejunal resection and a Roux-en-Y gastrojejunostomy with distal ileostomy were done along with a feeding jejunostomy. The patient however again had feculent discharge from the wound for which a third exploration was done. The gastrojejunostomy and feeding jejunostomy sites were leaky, both of which were repaired primarily. The patient developed septicemia which progressed to refractory septic shock, and he ultimately succumbed to his illness on the 23rd postoperative day of the index surgery.

Conclusion

Acute abdomen in a young man who is a chronic smoker and having an antecedent history of amputation of some part of an extremity for a nontraumatic cause should raise the suspicion of Buerger’s disease of the intestine. Although it is a progressive disease and the situation has already progressed by the time intestinal symptoms manifest, early detection may give some scope of salvage and decrease the morbidity and mortality.
Positive radial solutions for a noncooperative resonant nuclear reactor model with sign-changing nonlinearities
Authors: Chen Ruipeng , Liu Jiayin , Zhang Guangchen , Kong Xiangyu
Published: April 2021

This paper is concerned with the existence of positive radial solutions of the following resonant elliptic system:$$ \textstyle\begin{cases} -\Delta u=uv+f( \vert x \vert ,u), & 0< R_{1}< \vert x \vert < R_{2}, x\in \mathbb{R}^{N}, \\ -\Delta v=cg(u)-dv, & 0< R_{1}< \vert x \vert < R_{2}, x\in \mathbb{R}^{N}, \\ \frac{\partial u}{\partial \textbf{n}}=0= \frac{\partial v}{\partial \textbf{n}},& \vert x \vert =R_{1}, \vert x \vert =R_{2}, \end{cases} $${−Δu=uv+f(|x|,u),0<R1<|x|<R2,x∈RN,−Δv=cg(u)−dv,0<R1<|x|<R2,x∈RN,∂u∂n=0=∂v∂n,|x|=R1,|x|=R2,where$\mathbb{R}^{N}$RN($N\geq 1$N≥1) is the usual Euclidean space,nindicates the outward unit normal vector,$f\in C([R_{1},R_{2}]\times [0,\infty ),\mathbb{R})$f∈C([R1,R2]×[0,∞),R),$g\in C([0,\infty ),[0,\infty ))$g∈C([0,∞),[0,∞)), andcanddare positive constants. By employing the classical fixed point theory we establish several novel existence theorems. Our main findings enrich and complement those available in the literature.
Exponential synchronization and stabilization of delayed feedback hyperchaotic financial system
Authors: Rao Ruofeng , Zhu Quanxin
Published: April 2021

In a real financial market, the delayed market feedback and the delayed effect of government macrocontrol are inevitable, and both bring mathematical difficulties in studying stabilization and synchronization of the hyperchaotic financial system. However, employing the Lyapunov function method, differential mean value theorem, and suitable bounded hypotheses and pulse control technology result in globally asymptotic stabilization and synchronization criteria. It is the first paper driving the stabilization and synchronization criteria under the assumptions of double delays. Finally, numerical examples illustrate the effectiveness of the proposed methods.
Mid-trimester cesarean scar pregnancy: a case report
Authors: Fowler Mary Louise , Little Sarah , Muto Michael , Mahalingaiah Shruthi
Published: April 2021

Background

This article reports a unique case of cesarean scar pregnancy, demonstrating importance of early management and diagnosis.

Case presentation

A 30-year-old pregnant woman with prior history of two cesarean sections found to have cesarean scar pregnancy at approximately 13 weeks’ gestation and underwent a gravid hysterectomy.

Conclusions

While rare, cesarean scar pregnancies should be considered on the differential diagnosis of any pregnant patient with history of cesarean section who presents in early pregnancy with vaginal bleeding and/or cramping. Given the increased rates of cesarean sections in the times of COVID-19, one may anticipate seeing more cases of cesarean scar pregnancies.
Prognostic biomarkers and therapeutic targets in oral squamous cell carcinoma: a study based on cross-database analysis
Authors: Yang Wanli , Zhou Wei , Zhao Xinhui , Wang Xiaoqian , Duan Lili , Li Yiding , Niu Liaoran , Chen Junfeng , Zhang Yujie , Han Yu , Fan Daiming , Hong Liu
Published: April 2021

Background

Oral squamous cell carcinoma (OSCC) is a malignant cancer, the survival rate of patients is disappointing. Therefore, it is necessary to identify the driven-genes and prognostic biomarkers in OSCC.

Methods

Four Gene Expression Omnibus (GEO) datasets were integratedly analyzed using bioinformatics approaches, including identification of differentially expressed genes (DEGs), GO and KEGG analysis, construction of protein-protein interaction (PPI) network, selection of hub genes, analysis of prognostic information and genetic alterations of hub genes. ONCOMINE, The Cancer Genome Atlas (TCGA) and Human Protein Atlas databases were used to evaluate the expression and prognostic value of hub genes. Tumor immunity was assessed to investigate the functions of hub genes. Finally, Cox regression model was performed to construct a multiple-gene prognostic signature.

Results

Totally 261 genes were found to be dysregulated. 10 genes were considered to be the hub genes. The Kaplan-Meier analysis showed that upregulated SPP1, FN1, CXCL8, BIRC5, PLAUR, and AURKA were related to poor outcomes in OSCC patients. FOXM1 and TPX2 were considered as the potential immunotherapeutic targets with future clinical significance. Moreover, we constructed a nine-gene signature (TEX101, DSG2, SCG5, ADA, BOC, SCARA5, FST, SOCS1, and STC2), which can be utilized to predict prognosis of OSCC patients effectively.

Conclusion

These findings may provide new clues for exploring the molecular mechanisms and targeted therapy in OSCC. The hub genes and risk gene signature are helpful to the personalized treatment and prognostic judgement.
A review of the diversity and impact of invasive non-native species in tropical marine ecosystems
Authors: Alidoost Salimi Parisa , Creed Joel C. , Esch Melanie M. , Fenner Douglas , Jaafar Zeehan , Levesque Juan C. , Montgomery Anthony D. , Alidoost Salimi Mahsa , Edward J. K. Patterson , Raj K. Diraviya , Sweet Michael
Published: April 2021

Tropical marine ecosystems are biologically diverse and economically invaluable. However, they are severely threatened from impacts associated with climate change coupled with localized and regional stressors, such as pollution and overfishing. Non-native species (sometimes referred to as ‘alien’ species) are another major threat facing these ecosystems, although rarely discussed and overshadowed by the other stressors mentioned above. NNS can be introduced accidentally (for example via shipping activities) and/or sometimes intentionally (for aquaculture or by hobbyists). Understanding the extent of the impacts NNS have on native flora and fauna often remains challenging, along with ascertaining when the species in question actually became ‘invasive’. Here we review the status of this threat across key tropical marine ecosystems such as coral reefs, algae meadows, mangroves, and seagrass beds. We aim to provide a baseline of where invasive NNS can be found, when they are thought to have been introduced and what impact they are thought to be having on the native ecosystems they now inhabit. In the appended material we provide a comprehensive list of NNS covering key groups such as macroalgae, sponges, seagrasses and mangroves, anthozoans, bryozoans, ascidians, fishes, and crustaceans.
Cannabidiol oxidation product HU-331 is a potential anticancer cannabinoid-quinone: a narrative review
Authors: Trac Judy , Keck J. Myles , Deweese Joseph E.
Published: April 2021

Cannabidiol and related cannabinoids are under exploration for the treatment of a number of disease states. The cannabinoid-quinone HU-331 has been studied as a potential anticancer therapeutic. Previous studies provide evidence that HU-331 displays anticancer activity without some of the known adverse events associated with traditional anticancer agents. In this brief review, we will explore the literature related to the activity of HU-331 in purified systems, cancer cell lines, and animal models. For example, HU-331 displays inhibitory activity against human topoisomerase IIα, a known anticancer drug target. Further, in multiple cell model systems, the IC50 value for HU-331 was less than 10 μM. In addition, mouse model systems demonstrate the ability of HU-331 to shrink tumors without causing cardiotoxicity. In addition, we will briefly review the activity of some key analogs and derivatives of HU-331 for various disease states. Taken together, the published studies support further exploration of HU-331 for the treatment of cancer and possibly other disease states.
Role of transient elastography in the prediction of de novo recurrence of hepatocellular carcinoma after radiofrequency ablation: single-center Egyptian study
Authors: Abdelkader N. A. , Abdelaleem M. H. , El-maaty M. A. Abo , Sayed S. A. , Aly H. I.
Published: April 2021

Background

Radiofrequency is one of the curative treatment options for hepatocellular carcinoma (HCC). Despite the progressive improvements in the efficacy of radiofrequency, the survival of patients with HCC who undergo radiofrequency remains disappointing, mainly due to frequent intrahepatic recurrence of HCC after radiofrequency. We aimed to evaluate the role of transient elastography (TE) in the prediction of de novo recurrence of HCC after radiofrequency and to compare between transient elastography and the serological fibrosis indices in the prediction of de novo recurrence of HCC.

Results

Thirty HCC patients underwent baseline transient elastography for preinterventional assessment of the degree of fibrosis. Also noninvasive serum fibrosis indices were calculated from baseline data, including age platelet index (API), cirrhosis discrimination score (CDS), and FIB-4 index. Patients achieving complete response after 1 month post radiofrequency ablation were followed for further 12 months by triphasic abdominal CT scan to detect de novo lesions according to modified RECIST criteria. Baseline means of CDS, FIB4, and API were 6.03 ± 1.5, 3.98 ± 2.58, and 1.24 ± 1.08, respectively. Transient elastography revealed 28 patients with F4 and only 2 patients with F3 (mean liver stiffness 22.45 ± 10.36 Kba). There was a significant negative correlation between liver stiffness (LS) and de novo recurrence of HCC (mean of LS in patients with a complete response was 17.19 ± 3.32 while in those with de novo recurrence was 36.94 ± 5.93, with the best cut off value ≥24.65 (p value < 0.001). There was no significant correlation between CDC, FIB4, API scores, and de novo recurrence of HCC. It was found that the liver stiffness was significantly associated with the prediction of hepatic decompensation (p value <0.001). Also, liver stiffness at the cutoff value > 42.75 (p value = 0.031) was significantly associated with the prediction of 1-year mortality after radiofrequency ablation.

Conclusion

Our data suggested that liver stiffness measurement in hepatocellular carcinoma patients was a useful predictor of de novo recurrence, overall survival, and possibility of hepatic decompensation after radiofrequency ablation.
Severe acute respiratory syndrome (SARS) related coronavirus in bats
Authors: Geng Rong , Zhou Peng
Published: April 2021

Three major human coronavirus disease outbreaks, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and 2019 coronavirus disease (COVID-19), occurred in the twenty-first century and were caused by different coronaviruses (CoVs). All these viruses are considered to have originated from bats and transmitted to humans through intermediate hosts. SARS-CoV-1 and SARS-CoV-2, disease agent of COVID-19, shared around 80% genomic similarity, and thus belong to SARS-related CoVs. As a natural reservoir of viruses, bats harbor numerous other SARS-related CoVs that could potentially infect humans around the world, causing SARS or COVID-19 like outbreaks in the future. In this review, we summarized the current knowledge of CoVs on geographical distribution, genetic diversity, cross-species transmission potential and possible pathogenesis in humans, aiming for a better understanding of bat SARS-related CoVs in the context of prevention and control.
Uncertainty and interpretability analysis of encoder-decoder architecture for channel detection
Authors: Pham Nam , Fomel Sergey
Published: April 2021

We have adopted a method to understand uncertainty and interpretability of a Bayesian convolutional neural network for detecting 3D channel geobodies in seismic volumes. We measure heteroscedastic aleatoric uncertainty and epistemic uncertainty. Epistemic uncertainty captures the uncertainty of the network parameters, whereas heteroscedastic aleatoric uncertainty accounts for noise in the seismic volumes. We train a network modified from U-Net architecture on 3D synthetic seismic volumes, and then we apply it to field data. Tests on 3D field data sets from the Browse Basin, offshore Australia, and from Parihaka in New Zealand prove that uncertainty volumes are related to geologic uncertainty, model mispicks, and input noise. We analyze model interpretability on these data sets by creating saliency volumes with gradient-weighted class activation mapping. We find that the model takes a global-to-local approach to localize channel geobodies as well as the importance of different model components in overall strategy. Using channel probability, uncertainty, and saliency volumes, interpreters can accurately identify channel geobodies in 3D seismic volumes and also understand the model predictions.
The digital divide: amplifying health inequalities for people with severe mental illness in the time of COVID-19
Authors: Spanakis Panagiotis , Peckham Emily , Mathers Alice , Shiers David , Gilbody Simon
Published: April 2021

During COVID-19, health provision and information resources have been increasingly provided via digital means (e.g. websites, apps) and this will become a standard practice beyond the pandemic. People with severe mental illness face profound health inequalities (e.g. a >20-year mortality gap). Digital exclusion puts this population at risk of heightened or compounded inequalities. This has been referred to as the ‘digital divide’. For any new digital means introduced in clinical practice to augment healthcare service provision, issues of accessibility, acceptability and usability should be addressed by researchers and developers early in the design phase, and prior to full implementation, to prevent digital exclusion.
Association of Genetic Variants for Plasma LRG1 With Rapid Decline in Kidney Function in Patients With Type 2 Diabetes
Authors: Gurung Resham Lal , Dorajoo Rajkumar , M Yiamunaa , Liu Jian-Jun , Pek Sharon Li Ting , Wang Jiexun , Wang Ling , Sim Xueling , Liu Sylvia , Shao Yi-Ming , Ang Keven , Subramaniam Tavintharan , Tang Wern Ee , Sum Chee Fang , Liu Jian-Jun , Lim Su Chi
Published: April 2021

Context

Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain.

Objectives

To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D.

Design and participants

We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater.

Results

We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta P = 6.66 × 10−16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratio = 1.23, P = 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (P < 0.05).

Conclusion

We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention.
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

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 >16 years for girls and >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

Human 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

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

Chick 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

We 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

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

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

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

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

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

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

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.