bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brominated flame retardants and organochlorine pesticides and incidence of uterine leiomyomata
Authors: Orta Olivia R. , Wesselink Amelia K. , Bethea Traci N. , Claus Henn Birgit , Weuve Jennifer , Fruh Victoria , McClean Michael D. , Sjodin Andreas , Baird Donna D. , Wise Lauren A. 
Published: January 2021

Background:
Uterine leiomyomata (UL) are hormone-responsive benign neoplasms. Brominated flame retardants and organochlorine pesticides (OCPs) can disrupt hormones involved in UL etiology.

Methods:
The Study of Environmental, Lifestyle, and Fibroids is a Detroit-area prospective cohort of 1693 Black women 23–35 years of age. At baseline and approximately every 20 months for 5 years, women completed questionnaires and underwent transvaginal ultrasounds. Using a case-cohort study design, we selected 729 UL-free participants at baseline and analyzed baseline plasma samples for polybrominated diphenyl ethers (PBDEs), a polybrominated biphenyl ether (PBB-153), and OCPs. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:
Compared with total PBDE plasma concentrations <50th percentile, adjusted HRs for the 50th–74th, 75th–89th, and ≥90th percentiles were 1.00 (95% CI = 0.68, 1.47), 1.04 (95% CI = 0.63, 1.68), and 0.85 (95% CI = 0.48, 1.50), respectively. HRs for PBB-153 plasma concentrations were generally similar to total PBDE plasma concentrations. Compared with total OCP plasma concentrations <50th percentile, HRs for the 50th–74th, 75th–89th, and ≥90th percentiles were 0.86 (95% CI = 0.57, 1.29), 0.73 (95% CI = 0.43, 1.22), and 0.58 (95% CI = 0.32, 1.04), respectively. HRs for individual PBDEs and OCPs were similar to their respective totals.

Conclusion:
We found little support for an association between brominated flame retardant plasma concentrations and UL incidence, and some evidence of lower UL incidence with the highest OCP plasma concentrations.
DANON DISEASE: A MODEL OF PHOTORECEPTOR DEGENERATION SECONDARY TO PRIMARY RETINAL PIGMENT EPITHELIUM DISEASE
Authors: O'Neil Erin C. , Uyhazi Katherine E. , O'Connor Keli , Aleman Isabella A. , Pulido Jose S. , Rossano Joseph W. , Aleman Tomas S. 
Published: January 2021

Purpose:
To describe in detail the retinal phenotype of LAMP2-associated Danon disease.

Methods:
Three LAMP2-positive patients from two unrelated families were studied with spectral-domain optical coherence tomography and with short-wavelength and near-infrared fundus autofluorescence (FAF) imaging. Visual function was measured with full-field electroretinography and chromatic perimetry. A patient with choroideremia was also studied for comparison.

Results:
A 45-year-old LAMP2-heterozygous woman, her 21-year-old hemizygous son, and an unrelated heterozygous 60-year-old woman had normal visual acuities. Central spectral-domain optical coherence tomographies were grossly normal in the younger two patients (mother and son). The oldest patient showed a tenuous interdigitation signal, interruptions of the inner segment ellipsoid zone band, and parafoveal outer nuclear layer thinning. Quantitatively, all patients had shorter than normal ellipsoid zone to retinal pigment epithelium distance in pericentral retina, normal at the foveola. A speckled hypoautofluorescence pattern on short-wavelength FAF contrasted with grossly abnormal near-infrared FAF in the heterozygous carriers. The oldest patient had reduced full-field electroretinography amplitudes (to ∼50% of normal) for rod- and cone-mediated responses and her perimetry showed severe rod dysfunction but substantial cone function. A disproportionate loss of the near-infrared FAF compared with the short-wavelength FAF, predominantly outer segment changes, and severe rod dysfunction with preserved cone function was similarly documented in a 9-year-old choroideremia hemizygous patient.

Conclusion:
A disproportionate loss of the near-infrared FAF signal compared with the short-wavelength FAF signal, outer segment abnormalities, and severe rod dysfunction but relatively preserved cone vision suggests a stereotypical pattern of primary retinal pigment epithelial or parallel retinal pigment epithelial + photoreceptor disease in Danon disease.
MULTIMODAL IMAGING OF MULTIFOCAL CHOROIDITIS WITH ADAPTIVE OPTICS OPHTHALMOSCOPY
Authors: Amarasekera Sohani , Williams Andrew M. , Freund K. Bailey , Rossi Ethan A. , Dansingani Kunal K. 
Published: January 2021

Purpose:
To describe longitudinal, anatomical, and functional alterations caused by inflammatory and neovascular lesions of idiopathic multifocal choroiditis/punctate inner choroidopathy using adaptive optics imaging and microperimetry.

Methods:
Longitudinal case study using multiple imaging modalities, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, flood illumination adaptive optics, and microperimetry.

Results:
A 21-year-old myopic Asian man presented with blurred vision in the right eye. Clinical examination was notable for an isolated hypopigmented, perifoveal lesion in each eye. Multimodal imaging showed inflammatory lesions in the outer retina, retina pigment epithelium, and inner choroid lesions of both eyes. The right eye additionally exhibited active Type-2 macular neovascularization with loss of cone mosaic regularity that was associated with reduced sensitivity on microperimetry. The clinical picture was consistent with multifocal choroiditis/punctate inner choroidopathy. The patient was treated with oral steroids and three injections of intravitreal bevacizumab in the right eye. After therapy, imaging showed reestablishment of the cone mosaic on flood illumination adaptive optics and improvement in sensitivity on microperimetry.

Conclusion:
Adaptive optics imaging and microperimetry may detect biomarkers that help to characterize the nature and activity of multifocal choroiditis lesions and to help monitor response to therapy. With timely intervention, structural abnormalities in the outer retina and choroid can be treated, and anatomical improvements precede improvements in visual function.
Infertility management in women with polycystic ovary syndrome: a review
Authors: Cunha Anita , Póvoa Ana Margarida 
Published: January 2021

Abstract
Polycystic ovary syndrome is the most common endocrine disorder in women and a major cause of anovulatory infertility. Various medical options are used, alone or in combination, to treat subfertility associated with polycystic ovary syndrome. This narrative review was conducted to provide an update and summarize the available evidence on the management of polycystic ovary syndrome related infertility. A wide literature search was performed and preferably randomized controlled trials and systematic reviews were included. Management is often centered on lifestyle changes. Pharmacological ovulation induction is the next step, with recommended use of letrozole, clomiphene citrate or gonadotropins. When it fails, assisted reproductive technologies or laparoscopic ovarian drilling are frequently advised. Combination treatment with metformin is often recommended. More recent alternative and adjunctive treatments have been suggested, like inositol, vitamin D, bariatric surgery and acupuncture, but further research is needed for recommendation.
Companilactobacillus pabuli sp. nov., a lactic acid bacterium isolated from animal feed
Authors: Jung Ji Young , Kang Hye Kyeong , Jin Hyun Mi , Han Sang-Soo , Kwon Young Chul , Eun Jong Jun , Kim Sang Cheol , Seo Min Jeong , Ryu Byung-Gon , Chung Eu Jin 
Published: January 2021

A Gram-positive, facultative anaerobic, catalase-negative, non-motile, non-spore-forming and rod-shaped lactic acid bacterium strain, denoted as NFFJ11T and isolated from total mixed fermentation feed in the Republic of Korea, was characterized through polyphasic approaches, including sequence analyses of the 16S rRNA gene and housekeeping genes (rpoA and pheS), determination of average nucleotide identity and in silico DNA–DNA hybridization, fatty acid methyl ester analysis, and phenotypic characterization. Phylogenetic analyses based on 16S rRNA, rpoA and pheS gene sequences revealed that strain NFFJ11T belonged to the genus

Companilactobacillus

. The 16S rRNA gene sequence of strain NFFJ11T exhibited high similarity to

Companilactobacillus formosensis

S215T (99.66 %),

Companilactobacillus farciminis

Rv4 naT (99.53 %),

Companilactobacillus crustorum

LMG 23699T (99.19 %),

Companilactobacillus futsaii

YM 0097T (99.06 %),

Companilactobacillus zhachilii

HBUAS52074T (98.86 %) and Companilactobacillus heilongiiangensis S4-3T (98.66 %). However, average nucleotide identity and in silico DNA–DNA hybridization values for these type strains were in the range of 79.90–92.93 % and 23.80–49.30 %, respectively, which offer evidence that strain NFFJ11T belongs to a novel species of the genus

Companilactobacillus

. The cell-wall peptidoglycan type was A4α (l-Lys–d-Asp) and the G+C content of the genomic DNA was 35.7 mol%. The main fatty acids of strain NFFJ11T were C18 : 1
ω9c (43.3 %), C16 : 0 (20.1 %) and summed feature 7 (18.3 %; comprising any combination of C19 : 1
ω7c, C19 : 1
ω6c and C19 : 0 cyclo ω10c). Through polyphasic taxonomic analysis, it was observed that strain NFFJ11T represents a novel species belonging to the genus

Companilactobacillus

, for which the name Companilactobacillus pabuli sp. nov. is proposed. The type strain is NFFJ11T (= KACC 21771T= JCM 34088T).
Embryonic development in the acoelHofstenia miamia
Authors: Kimura Julian O. , Ricci Lorenzo , Srivastava Mansi 
Published: January 2021

AbstractAcoels are marine worms that belong to the phylum Xenacoelomorpha. The phylogenetic placement of this group as a deep-diverging lineage makes acoel embryos an attractive system to study the evolution of major bilaterian traits. Thus far, acoel development has not been described in detail at the morphological and transcriptomic levels in a species where functional genetic studies are possible. Here, we present a set of developmental landmarks for embryogenesis in the highly regenerative acoelHofstenia miamia. We generated a developmental staging atlas from zygote to hatched worm based on gross morphology, with accompanying bulk transcriptome data for each of the stages.Hofsteniaembryos undergo a stereotyped cleavage program known as duet cleavage, which results in two large ‘macromeres’ at the vegetal pole and numerous small ‘micromeres’ at the animal pole. The macromeres become internalized as micromere progeny proliferate and move vegetally, enveloping the larger blastomeres. We also noted a second, previously undescribed cell internalization event at the animal pole, following which we detected tissues corresponding to all three germ layers. Our work onHofsteniaembryos provides a resource for future investigations of acoel development, which will yield insights into the evolution of development and regeneration.Summary StatementComprehensive characterization of embryonic development in the acoel wormHofstenia miamiawith accompanying transcriptome data.
Nickel-Sulfonate Mode of Substrate Binding for Forward and Reverse Reactions of Methyl-SCoM Reductase Suggest a Radical Mechanism Involving Long Range Electron Transfer
Authors: Patwardhan Anjali , Sarangi Ritimukta , Ginovska Bojana , Raugei Simone , Ragsdale Stephen W. 
Published: January 2021

ABSTRACTMethyl-coenzyme M reductase (MCR) catalyzes both synthesis and anaerobic oxidation of methane (AOM). Its catalytic site contains Ni at the core of Cofactor F430. The Ni ion, in its low-valent Ni(I) state lights the fuse leading to homolysis of the C-S bond of methyl-coenzyme M (methyl-SCoM) to generate a methyl radical, which abstracts a hydrogen atom from Coenzyme B (HSCoB) to generate methane and the mixed disulfide CoMSSCoB. Direct reversal of this reaction activates methane to initiate anaerobic methane oxidation. Based on crystal structures, which reveal a Ni-thiol interaction between Ni(II)-MCR and inhibitor CoMSH, a Ni(I)-thioether complex with substrate methyl-SCoM has been transposed to canonical MCR mechanisms. Similarly, a Ni(I)-disulfide with CoMSSCoB is proposed for the reverse reaction. However, this Ni(I)-sulfur interaction poses a conundrum for the proposed hydrogen atom abstraction reaction because the >6 Å distance between the thiol group of SCoB and the thiol of SCoM observed in the structures appears too long for such a reaction. Spectroscopic, kinetic, structural and computational studies described here establish that both methyl-SCoM and CoMSSCoB bind to the active Ni(I) state of MCR through their sulfonate groups, forming a hexacoordinate Ni(I)-N/O complex, not Ni(I)-S. These studies rule out direct Ni(I)-sulfur interactions in both substrate-bound states. As a solution to the mechanistic conundrum, we propose that both forward and reverse MCR reactions emanate through long-range electron transfer from Ni(I)-sulfonate complexes with methyl-SCoM or CoMSSCoB, respectively.
Structural and immunological identification and antiviral infection experiment of the dominant cytotoxic T lymphocyte epitopes of the oncogenic Marek’s disease virus
Authors: Sun Beibei , Wang Yawen , Wang Zhenbao , Lu Shuangshuang , Xia Chun 
Published: January 2021

AbstractMarek’s disease (MD) is a serious cancer caused by MDV in chickens, and it is also the first tumor disease that could be controlled by an attenuated vaccine in the world. However, the attenuated vaccine is able to inhibit only the formation of tumors but cannot prevent the infection of oncogenic viruses; instead, it leads to mutations and the emergence of a number of virulent strains. In this paper, the crystal structures of chicken MHC class I (pBF2*1501) molecules bound with 8-mer and 9-mer MDV peptides were solved. The results showed that the conformations of the 8-mer and 9-mer peptides in the antigen-binding groove (ABG) of pBF2*1501 are different; the ABG-8-mer is flat, and the ABG-9-mer has the “featured” M-type epitope morphology. Based on these results, multiple MDV epitopes were confirmed using the tetramer technique, and the immunoprotective effect of dominant epitope was confirmed using the protein adjuvant HSP108-N333 in BF2*1501-expressing chickens. The results showed that the two epitopes have obvious protective effects after a standard immunization program. After challenge, the mortality rate was only 20%, and the protective index (PI) reached 33% in the epitope group. The results verified that a single epitope could induce extremely strong specific antitumor T lymphocyte immunity. The results show that three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant cytotoxic T lymphocyte (CTL) epitopes, efficient protein adjuvant and MHC matching. Meanwhile, the results also provided obvious advantages for the development of multiple epitope vaccines for tumor diseases.ImportanceMarek’s disease (MD) is the first tumor disease that can be controlled by an attenuated vaccine. However, the attenuated vaccine cannot prevent the infection of the oncogenic virus and instead leads to the emergence of a number of mutated virulent strains. First, the mechanism of the chicken BF2*1501 preferentially presents 9-mer peptide was clarified. Based on this result, multiple MDV epitopes were confirmed, and the dominant epitopes were identified. Subsequently, two epitope groups showed obvious protective effects after a standard immunization program, and the protective index (PI) of one of the epitope groups reached over 30%. The results showed that a single epitope could induce strong and efficient antitumor CTL immunity. Overall, three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant epitopes, efficient protein adjuvant and MHC matching. Our results provide an obvious strategy for the development of multiple epitope vaccines in tumor diseases.
PERIPHERAL INOTROPES IN CRITICALLY ILL CHILDREN - IS IT SAFE?
Authors: Mooli Ravi K , Sadasivam K 
Published: January 2021

ABSTRACTMany children needing paediatric intensive care units care require inotropes, which are started peripherally prior to securing a central venous access. However, many hospitals in low- and middle-income countries may not have access to central lines and the vasoactive medications are frequently given through a peripheral venous access.AimThe aim of our study was to estimate the safety of peripheral vasoactive inotropes in children.MethodsChildren requiring peripheral vasoactive medications were included in this study. We retrospectively collected data at two time points on use and complications of peripheral vasoactive medications.ResultsEighty-four children (51 pre-COVID era and 33 COVID pandemic) received peripheral vasoactive medications. Only 3% of children (3/84) developed extravasation injury, all of whom recovered completely.ConclusionsResults from our study suggest that extravasation injury due to peripheral inotrope infusion is very low (3%) and it can be safely administered in children at a diluted concentration.
Impact of COVID-19 on education, health and lifestyle behaviour of Brazilian urology residents
Authors: Prezotti Jose Antonio , Henriques João Victor T. , Favorito Luciano A. , Canalini Alfredo F. , Machado Marcos G. , Brandão Thulio B. V. , Barbosa Akemi M. V. , Moromizato Julyana K.M. , Anzolch Karin M. J. , de C. Fernandes Roni , Rodrigues Fransber R. A. , Bellucci Carlos H. S. , Silva Caroline S. , Pompeo Antonio Carlos L. , de Bessa Jose , Gomes Cristiano M. 
Published: January 2021

ABSTRACTObjectivesTo evaluate the impact of COVID-19 on clinical and surgical practice, educational activities, health and lifestyle behavior of Brazilian urology residents.Materials and MethodsA web-based survey was sent to 468 Brazilian urology residents from postgraduate years (PGY) 3 to 5 to collect data on clinical practice and training after 4 months of COVID-19. We also assessed health-related and behavior changes, rate of infection by SARS-CoV-2, deployment to the front line of COVID-19, residents’ concerns, and access to personal protective equipment (PPE).ResultsMassive reductions in elective and emergency patient consultations, diagnostic procedures and surgeries were reported across the country, affecting PGY 3 to 5 alike. Most in-person educational activities were abolished. The median damage to the urological training expected for 2020 was 6.0 [3.4 -7.7], on a scale from 0 to 10, with senior residents estimating a greater damage (P< 0.001). Educational interventions developed included online case-based discussions, subspeciality conferences and lectures, and grand rounds. Most senior residents favored extending residency to compensate for training loss and most younger residents favored no additional training (p< 0.001). Modifications in health and lifestyle included weight gain (43.8%), reduced physical activity (68.6%), increased alcoholic intake (44.9%) and cigarette consumption (53.6%), worsening of sexual life (25.2%) and feelings of sadness or depression (48,2%). Almost half were summoned to work on the COVID-19 front-line and 24.4% had COVID-19. Most residents had inadequate training to deal with COVID-19 patients and most reported a shortage of PPE. Residents’ concerns included the risk of contaminating family members, being away from residency program, developing severe COVID-19 and overloading colleagues.ConclusionsCOVID-19 had a massive impact in Brazilian urology residents’ training, health and lifestyle behavior, which may reflect what happened in other medical specialties. Studies should confirm these findings to help developing strategies to mitigate residents’ losses.
Role of tonsillar chronic inflammation and commensal bacteria in the pathogenesis of pediatric OSA
Authors: Varón Lindybeth Sarmiento , De Rosa Javier , Rodriguez Raquel , Fernández Pablo M. , Billordo L. Ariel , Baz Plácida , Beccaglia Gladys , Spada Nicolás , Mendoza F. Tatiana , Barberis Claudia M. , Vay Carlos , Arabolaza M. Elena , Paoli Bibiana , Arana Eloísa I. 
Published: January 2021

AbstractImmune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We uncovered a crucial role of pro-inflammatory tonsillar B and T cells in sustaining hypertrophy and hyperplasia by producing TNF and IL17, respectively. We detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. By combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work shed light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization.
Local adaptation and archaic introgression shape global diversity at human structural variant loci
Authors: Yan Stephanie M. , Sherman Rachel M. , Taylor Dylan J. , Nair Divya R. , Bortvin Andrew N. , Schatz Michael C. , McCoy Rajiv C. 
Published: January 2021

AbstractLarge genomic insertions, deletions, and inversions are a potent source of functional and fitness-altering variation, but are challenging to resolve with short-read DNA sequencing alone. While recent long-read sequencing technologies have greatly expanded the catalog of structural variants (SVs), their costs have so far precluded their application at population scales. Given these limitations, the role of SVs in human adaptation remains poorly characterized. Here, we used a graph-based approach to genotype 107,866 long-read-discovered SVs in short-read sequencing data from diverse human populations. We then applied an admixture-aware method to scan these SVs for patterns of population-specific frequency differentiation—a signature of local adaptation. We identified 220 SVs exhibiting extreme frequency differentiation, including several SVs that were among the lead variants at their corresponding loci. The top two signatures traced to separate insertion and deletion polymorphisms at the immunoglobulin heavy chain locus, together tagging a 325 Kbp haplotype that swept to high frequency and was subsequently fragmented by recombination. Alleles defining this haplotype are nearly fixed (60-95%) in certain Southeast Asian populations, but are rare or absent from other global populations composing the 1000 Genomes Project. Further investigation revealed that the haplotype closely matches with sequences observed in two of three high-coverage Neanderthal genomes, providing strong evidence of a Neanderthal-introgressed origin. This extraordinary episode of positive selection, which we infer to have occurred between 1700 and 8400 years ago, corroborates the role of immune-related genes as prominent targets of adaptive archaic introgression. Our study demonstrates how combining recent advances in genome sequencing, genotyping algorithms, and population genetic methods can reveal signatures of key evolutionary events that remained hidden within poorly resolved regions of the genome.