bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute appendicitis with associated trichobezoar of feline hair
Authors: Redden Mark , Ghadiri Marjan
Published: March 2022

A trichobezoar is an accumulation of ingested hair that forms a mass within the gastro-intestinal tract. Thrichobezoars usually consist of human hair and are known to cause obstruction and even perforation of gastrointestinal organs. There have been approximately seven reported cases of acute appendicitis with association trichobezoars found at the time of appendicectomy. We report a unique case of acute appendicitis with an associated trichobezoar of feline hair. A 15-year-old male presented with a 24-hour history of abdominal pain. A computed tomography scan demonstrated features of appendicitis with several hyperdensities within the base of the appendix. At the time of appendicectomy, the appendix was found to be perforated at the base. Faecoliths were identified containing numerous short, light-coloured hairs. Following the procedure, the family confirmed that they have a pet cat with short, light-coloured hair. The patient had an uneventful recovery.
Getting Accurate about Knowledge
Authors: Carter Sam , Goldstein Simon
Published: March 2022

There is a large literature exploring how accuracy constrains rational degrees of belief. This paper turns to the unexplored question of how accuracy constrains knowledge. We begin by introducing a simple hypothesis: increases in the accuracy of an agent’s evidence never lead to decreases in what the agent knows. We explore various precise formulations of this principle, consider arguments in its favour, and explain how it interacts with different conceptions of evidence and accuracy. As we show, the principle has some noteworthy consequences for the wider theory of knowledge. First, it implies that an agent cannot be justified in believing a set of mutually inconsistent claims. Second, it implies the existence of a kind of epistemic blindspot: it is not possible to know that one’s evidence is misleading.
The Lick Observatory Supernova Search follow-up program: photometry data release of 70 SESNe
Authors: Zheng WeiKang , Stahl Benjamin E , de Jaeger Thomas , Filippenko Alexei V , Wang Shan-Qin , Gan Wen-Pei , Brink Thomas G , Altunin Ivan , Baer-Way Raphael , Bigley Andrew , Blanchard Kyle , Blanchard Peter K , Bradley James , Cargill Samantha K , Casper Chadwick , Chapman Teagan , Chander Vidhi , Channa Sanyum , Choi Byung Yun , Choksi Nick , Chu Matthew , Clubb Kelsey I , Cohen Daniel P , Dalba Paul A , deGraw Asia , de Kouchkovsky Maxime , Ellison Michael , Falcon Edward , Fox Ori D , Fuller Kiera , Ganeshalingam Mohan , Girish Nachiket , Gould Carolina , Halevi Goni , Halle Andrew , Hayakawa Kevin T , Hardy Romain , Hestenes Julia , Hoffman Andrew M , Hyland Michael , Jeffers Benjamin T , Jennings Connor , Kandrashoff Michael T , Khodanian Anthony , Kim Minkyu , Kim Haejung , Kislak Michelle E , Krishnan Daniel , Kumar Sahana , Kumar Snehaa Ganesh , Leja Joel , Leonard Erin J , Li Gary Z , Li Weidong , Lian Ji-Shun , Liu Evelyn , Lowe Thomas B , Lu Philip , Ma Emily , Mason Michelle N , May Michael , McAllister Kyle , McGinness Emma , Modak Shaunak , Molloy Jeffrey , Murakami Yukei S , Nayak Omnarayani , Perera Derek , Pina Kenia , Punjabi Druv , Rikhter Andrew , Ross Timothy W , Sipple Jackson , Soler Costas , Stegman Samantha , Stephens Haynes , Sunseri James , Tang Kevin , Taylor Stephen , Thrasher Patrick , Van Dyk Schuyler D , Wang Xiang-Gao , Wayland Jeremy , Wilkins Andrew , Yagubyan Abel , Yuk Heechan , Yunus Sameen , Zhang Keto D
Published: March 2022

We present BVRI and unfiltered (Clear) light curves of 70 stripped-envelope supernovae (SESNe), observed between 2003 and 2020, from the Lick Observatory Supernova Search follow-up program. Our SESN sample consists of 19 spectroscopically normal SNe Ib, 2 peculiar SNe Ib, six SNe Ibn, 14 normal SNe Ic, 1 peculiar SN Ic, 10 SNe Ic-BL, 15 SNe IIb, 1 ambiguous SN IIb/Ib/c, and 2 superluminous SNe. Our follow-up photometry has (on a per-SN basis) a mean coverage of 81 photometric points (median of 58 points) and a mean cadence of 3.6 d (median of 1.2 d). From our full sample, a subset of 38 SNe have pre-maximum coverage in at least one passband, allowing for the peak brightness of each SN in this subset to be quantitatively determined. We describe our data collection and processing techniques, with emphasis toward our automated photometry pipeline, from which we derive publicly available data products to enable and encourage further study by the community. Using these data products, we derive host-galaxy extinction values through the empirical colour evolution relationship and, for the first time, produce accurate rise-time measurements for a large sample of SESNe in both optical and infrared passbands. By modelling multiband light curves, we find that SNe Ic tend to have lower ejecta masses and lower ejecta velocities than SNe Ib and IIb, but higher 56Ni masses.
Regulatory elements can be essential for maintaining broad chromatin organization and cell viability
Authors: Liu Ying , Ding Bo , Zheng Lina , Xu Ping , Liu Zhiheng , Chen Zhao , Wu Peiyao , Zhao Ying , Pan Qian , Guo Yu , Wang Wei , Wei Wensheng
Published: March 2022

Increasing evidence shows that promoters and enhancers could be related to 3D chromatin structure, thus affecting cellular functions. Except for their roles in forming canonical chromatin loops, promoters and enhancers have not been well studied regarding the maintenance of broad chromatin organization. Here, we focused on the active promoters/enhancers predicted to form many 3D contacts with other active promoters/enhancers (referred to as hotspots) and identified dozens of loci essential for cell growth and survival through CRISPR screening. We found that the deletion of an essential hotspot could lead to changes in broad chromatin organization and the expression of distal genes. We showed that the essentiality of hotspots does not result from their association with individual genes that are essential for cell viability but rather from their association with multiple dysregulated non-essential genes to synergistically impact cell fitness.
The DNA polymerase of bacteriophage YerA41 replicates its T-modified DNA in a primer-independent manner
Authors: Gomez-Raya-Vilanova Miguel V , Leskinen Katarzyna , Bhattacharjee Arnab , Virta Pasi , Rosenqvist Petja , Smith Jake L R , Bayfield Oliver W , Homberger Christina , Kerrinnes Tobias , Vogel Jörg , Pajunen Maria I , Skurnik Mikael
Published: March 2022

Yersinia phage YerA41 is morphologically similar to jumbo bacteriophages. The isolated genomic material of YerA41 could not be digested by restriction enzymes, and used as a template by conventional DNA polymerases. Nucleoside analysis of the YerA41 genomic material, carried out to find out whether this was due to modified nucleotides, revealed the presence of a ca 1 kDa substitution of thymidine with apparent oligosaccharide character. We identified and purified the phage DNA polymerase (DNAP) that could replicate the YerA41 genomic DNA even without added primers. Cryo-electron microscopy (EM) was used to characterize structural details of the phage particle. The storage capacity of the 131 nm diameter head was calculated to accommodate a significantly longer genome than that of the 145 577 bp genomic DNA of YerA41 determined here. Indeed, cryo-EM revealed, in contrast to the 25 Å in other phages, spacings of 33–36 Å between shells of the genomic material inside YerA41 heads suggesting that the heavily substituted thymidine increases significantly the spacing of the DNA packaged inside the capsid. In conclusion, YerA41 appears to be an unconventional phage that packages thymidine-modified genomic DNA into its capsids along with its own DNAP that has the ability to replicate the genome.
Trends in pneumoconiosis in Brazil, 1979–2019
Authors: Penteado Júlia Oliveira , Peres Tyele Goulart , Ramires Paula Florencio , de Lima Brum Rodrigo , da Silva Freitas Livia , Volcão Lisiane Martins , dos Santos Marina , Da Silva Júnior Flavio Manoel Rodrigues
Published: March 2022

Background

Pneumoconiosis is a lung disease related to exposure to dust in the workplace. The disease can induce irreversible damage to health, especially in lung tissue, and can cause progressive and permanent physical disabilities.

Aims

This study evaluated the temporal and spatial distribution of mortality rates (1979–2019) and hospital admissions (1995–2019) for pneumoconiosis in Brazil.

Methods

The outcomes were hospitalization and death due to pneumoconiosis: codes 500–506 according to the ICD-9 and J60–J66 according to the ICD-10. Data from this retrospective ecological study were collected from the Brazilian Ministry of Health database.

Results

Hospitalization for pneumoconiosis has decreased in all regions of Brazil. Hospitalizations occurred predominantly in men aged over 40 years. Death rates showed a temporal increase in all regions. Deaths occurred predominantly in men aged over 50 years. The highest hospitalization and death rates were in the states of the Midwest and South Regions.

Conclusions

Pneumoconiosis is a preventable occupational disease, and ongoing occurrences of hospitalizations and deaths highlight the importance of inspecting industries and controlling occupational and environmental exposures.
Functional nuclear retention of pre-mRNA involving Cajal bodies during meiotic prophase in European larch (Larix decidua)
Authors: Rudzka Magda , Wróblewska-Ankiewicz Patrycja , Majewska Karolina , Hyjek-Składanowska Malwina , Gołębiewski Marcin , Sikora Marcin , Smoliński Dariusz Jan , Kołowerzo-Lubnau Agnieszka
Published: March 2022

Gene regulation ensures that the appropriate genes are expressed at the proper time. Nuclear retention of incompletely spliced or mature mRNAs is emerging as a novel, previously underappreciated layer of posttranscriptional regulation. Studies on this phenomenon indicated that it exerts a significant influence on the regulation of gene expression by regulating export and translation delay, which allows the synthesis of specific proteins in response to a stimulus or at strictly controlled time points, for example, during cell differentiation or development. Here, we show that transcription in microsporocytes of European larch (Larix decidua) occurs in a pulsatile manner during prophase of the first meiotic division. Transcriptional activity was then silenced after each pulse. However, the transcripts synthesized were not exported immediately to the cytoplasm but were retained in the nucleoplasm and Cajal bodies (CBs). In contrast to the nucleoplasm, we did not detect mature transcripts in CBs, which only stored nonfully spliced transcripts with retained introns. Notably, the retained introns were spliced at precisely defined times, and fully mature mRNAs were released into the cytoplasm for translation. As similar processes have been observed during spermatogenesis in animals, our results illustrate an evolutionarily conserved mechanism of gene expression regulation during generative cells development in Eukaryota.
A synthetic switch based on orange carotenoid protein to control blue–green light responses in chloroplasts
Authors: Piccinini Luca , Iacopino Sergio , Cazzaniga Stefano , Ballottari Matteo , Giuntoli Beatrice , Licausi Francesco
Published: March 2022

Synthetic biology approaches to engineer light-responsive systems are widely used, but their applications in plants are still limited due to the interference with endogenous photoreceptors and the intrinsic requirement of light for photosynthesis. Cyanobacteria possess a family of soluble carotenoid-associated proteins named orange carotenoid proteins (OCPs) that, when activated by blue–green light, undergo a reversible conformational change that enables the photoprotection mechanism that occurs on the phycobilisome. Exploiting this system, we developed a chloroplast-localized synthetic photoswitch based on a protein complementation assay where two nanoluciferase fragments were fused to separate polypeptides corresponding to the OCP2 domains. Since Arabidopsis (Arabidopsis thaliana) does not possess the prosthetic group needed for the assembly of the OCP2 complex, we first implemented the carotenoid biosynthetic pathway with a bacterial β-carotene ketolase enzyme (crtW) to generate keto-carotenoid-producing plants. The photoswitch was tested and characterized in Arabidopsis protoplasts and stably transformed plants with experiments aimed to uncover its regulation by a range of light intensities, wavelengths, and its conversion dynamics. Finally, we applied the OCP-based photoswitch to control transcriptional responses in chloroplasts in response to green light illumination by fusing the two OCP fragments with the plastidial SIGMA FACTOR 2 and bacteriophage T4 anti-sigma factor AsiA. This pioneering study establishes the basis for future implementation of plastid optogenetics to regulate organelle responses upon exposure to specific light spectra.
SALT AND ABA RESPONSE ERF1 improves seed germination and salt tolerance by repressing ABA signaling in rice
Authors: Li Yuxiang , Zhou Jiahao , Li Zhe , Qiao Jinzhu , Quan Ruidang , Wang Juan , Huang Rongfeng , Qin Hua
Published: March 2022

Rice (Oryza sativa) germination and seedling establishment, particularly in increasingly saline soils, are critical to ensure successful crop yields. Seed vigor, which determines germination and seedling growth, is a complex trait affected by exogenous (environmental) and endogenous (hormonal) factors. Here, we used genetic and biochemical analyses to uncover the role of an APETALA2-type transcription factor, SALT AND ABA RESPONSE ERF1 (OsSAE1), as a positive regulator of seed germination and salt tolerance in rice by repressing the expression of ABSCISIC ACID-INSENSITIVE5 (OsABI5). ossae1 knockout lines exhibited delayed seed germination, enhanced sensitivity to abscisic acid (ABA) during germination and in early seedling growth, and reduced seedling salt tolerance. OsSAE1 overexpression lines exhibited the converse phenotype, with increased seed germination and salt tolerance. In vivo and in vitro assays indicated that OsSAE1 binds directly to the promoter of OsABI5, a major downstream component of the ABA signaling pathway and acts as a major regulator of seed germination and stress response. Genetic analyses revealed that OsABI5-mediated ABA signaling functions downstream of OsSAE1. This study provides important insights into OsSAE1 regulation of seed vigor and salt tolerance and facilitates the practical use of OsSAE1 in breeding salt-tolerant varieties suitable for direct seeding cultivation.
A maize triacylglycerol lipase inhibits sugarcane mosaic virus infection
Authors: Xu Xiao-Jie , Geng Chao , Jiang Shao-Yan , Zhu Qing , Yan Zhi-Yong , Tian Yan-Ping , Li Xiang-Dong
Published: March 2022

Triacylglycerol lipase (TGL) plays critical roles in providing energy for seed germination and plant development. However, the role of TGL in regulating plant virus infection is largely unknown. In this study, we adopted affinity purification coupled with mass spectrometry and identified that a maize (Zea mays) pathogenesis-related lipase protein Z. mays TGL (ZmTGL) interacted with helper component-proteinase (HC-Pro) of sugarcane mosaic virus (SCMV). Yeast two-hybrid, luciferase complementation imaging, and bimolecular fluorescence complementation assays confirmed that ZmTGL directly interacted with SCMV HC-Pro in vitro and in vivo. The 101–460 residues of SCMV HC-Pro were important for its interaction with ZmTGL. ZmTGL and SCMV HC-Pro co-localized at the mitochondria. Silencing of ZmTGL facilitated SCMV infection, and over-expression of ZmTGL reduced the RNA silencing suppression activity, most likely through reducing HC-Pro accumulation. Our results provided evidence that the lipase hydrolase activity of ZmTGL was associated with reducing HC-Pro accumulation, activation of salicylic acid (SA)-mediated defense response, and inhibition of SCMV infection. We show that ZmTGL inhibits SCMV infection by reducing HC-Pro accumulation and activating the SA pathway.
Complex Regional Pain Syndrome: Practical Diagnostic and Treatment Guidelines, 5th Edition
Authors: Harden R Norman , McCabe Candida S , Goebel Andreas , Massey Michael , Suvar Tolga , Grieve Sharon , Bruehl Stephen
Published: March 2022

There have been some modest recent advancements in the research of Complex Regional Pain Syndrome, yet the amount and quality of the work in this complicated multifactorial disease remains low (with some notable exceptions; e.g., the recent work on the dorsal root ganglion stimulation). The semi-systematic (though in some cases narrative) approach to review is necessary so that we might treat our patients while waiting for “better research.” This semi-systematic review was conducted by experts in the field, (deliberately) some of whom are promising young researchers supplemented by the experience of “elder statesman” researchers, who all mention the system they have used to examine the literature. What we found is generally low- to medium-quality research with small numbers of subjects; however, there are some recent exceptions to this. The primary reason for this paucity of research is the fact that this is a rare disease, and it is very difficult to acquire a sufficient sample size for statistical significance using traditional statistical approaches. Several larger trials have failed, probably due to using the broad general diagnostic criteria (the “Budapest” criteria) in a multifactorial/multi-mechanism disease. Responsive subsets can often be identified in these larger trials, but not sufficient to achieve statistically significant results in the general diagnostic grouping. This being the case the authors have necessarily included data from less compelling protocols, including trials such as case series and even in some instances case reports/empirical information. In the humanitarian spirit of treating our often desperate patients with this rare syndrome, without great evidence, we must take what data we can find (as in this work) and tailor a treatment regime for each patient.
Reshaping Global Trade: The Immediate and Long-Run Effects of Bank Failures
Authors: Xu Chenzi
Published: March 2022

I show that a disruption to the financial sector can reshape the patterns of global trade for decades. I study the first modern global banking crisis originating in London in 1866 and collect archival loan records that link multinational banks headquartered there to their lending abroad. Countries exposed to bank failures in London immediately exported significantly less and did not recover their lost growth relative to unexposed places. Their market shares within each destination also remained significantly lower for four decades. Decomposing the persistent market-share losses shows that they primarily stem from lack of extensive-margin growth, as the financing shock caused importers to source more from new trade partnerships. Exporters producing more substitutable goods, those with little access to alternative forms of credit, and those trading with more distant partners experienced more persistent losses, consistent with the existence of sunk costs and the importance of finance for intermediating trade.
Associations of the MUC5B promoter variant with timing of interstitial lung disease and rheumatoid arthritis onset
Authors: McDermott Gregory , Gill Ritu , Gagne Staci , Byrne Suzanne , Huang Weixing , Cui Jing , Prisco Lauren , Zaccardelli Alessandra , Martin Lily , Kronzer Vanessa L , Moll Matthew , Cho Michael H , Shadick Nancy , Dellaripa Paul F , Doyle Tracy , Sparks Jeffrey A
Published: March 2022

Objectives

To investigate the associations of the common MUC5B promoter variant with timing of RA-associated interstitial lung disease (RA-ILD) and RA onset.

Methods

We identified patients with RA meeting 2010 ACR/EULAR criteria and available genotype information in the Mass General Brigham Biobank, a multihospital biospecimen and clinical data collection research study. We determined RA-ILD presence by reviewing all RA patients who had CT imaging, lung biopsy or autopsy results. We determined the dates of RA and RA-ILD diagnoses by manual records review. We examined the associations of the MUC5B promoter variant (G>T at rs35705950) with RA-ILD, RA-ILD occurring before or within 2 years of RA diagnosis and RA diagnosis at age >55 years. We used multivariable logistic regression to estimate odds ratios (ORs) for each outcome by MUC5B promoter variant status, adjusting for potential confounders including genetic ancestry and smoking.

Results

We identified 1005 RA patients with available genotype data for rs35705950 (mean age 45 years, 79% female, 81% European ancestry). The MUC5B promoter variant was present in 155 (15.4%) and was associated with RA-ILD [multivariable OR 3.34 (95% CI 1.97, 5.60)], RA-ILD before or within 2 years of RA diagnosis [OR 4.01 (95% CI 1.78, 8.80)] and RA onset after age 55 years [OR 1.52 (95% CI 1.08, 2.12)].

Conclusions

The common MUC5B promoter variant was associated with RA-ILD onset earlier in the RA disease course and older age of RA onset. These findings suggest that the MUC5B promoter variant may impact RA-ILD risk early in the RA disease course, particularly in patients with older-onset RA.
How Does Human Capital Affect Investing? Evidence from University Endowments
Authors: Binfarè Matteo , Brown Gregory , Harris Robert , Lundblad Christian
Published: March 2022

We examine the links between human capital and endowment investing. Harnessing detailed information on university endowments, we find that higher asset allocations to alternative assets accompany higher levels of human capital in the endowment’s investment process. Moreover, high levels of human capital are linked to larger returns, even on a risk-adjusted basis. The improved investment outcomes arise because endowments (i) capture higher returns that can accompany alternative assets, (ii) select or have access to high performing managers, and (iii) minimize fees by accessing funds directly rather than through funds of funds. Our measures of human capital include expertise in alternatives on governing bodies, the presence of a chief investment officer, and the size of the investment staff. Finally, we conduct a novel survey of endowments and confirm that human capital is central in facilitating alternative investments.
The Bureaucratic Dissociation of Race in Policing: From State Racial Projects to Colorblind Ideologies
Authors: Gordon Daanika
Published: March 2022

Policing has long been implicated in state projects that construct race and racial inequality, yet many officers maintain that their work is colorblind. Burgeoning theories of racialized organizations offer a means of analyzing the processes that mediate such relationships between state racial projects and the ideologies of individuals. I suggest an extension of the racialized organizations framework that specifically considers the functions and forms of bureaucracies. Using a case study of policing in a segregated city, I describe a phenomenon of bureaucratic dissociation: bureaucratic arrangements facilitate racial governance, on the one hand, while obscuring the racial logics and consequences of daily work from officers, on the other. After detailing the incorporation of racial state interests into the police bureaucracy, I draw on over 500 hours of ethnographic observations of police work to explore the connections between bureaucratic structures and the racial ideologies of the police. I find widespread denial of racism in officers’ accounts of phenomena ranging from segregation to police shootings. Officers instead offer colorblind interpretations of social problems and narrate their work in relation to geographic and functional subdivisions, policies, and laws. These organizational accounts operate to legitimize police work in the face of its ongoing racial projects.
Resilience of Families Involved in Child Welfare: A Mixed-Methods Study
Authors: Helton Jesse J , Cooper-Sadlo Shannon C , House Nathaniel G , Adler Haley , Norton Lauren
Published: March 2022

Efforts to prevent child abuse and neglect have primarily focused on family deficits, including poverty and parental psychopathology. Models of resiliency, which are focused instead on family adaptation and strengths, offer an alternative to deficit-based practices. Although child-focused resilience studies are common in the field of child welfare, few focus on parents. The authors employed a mixed-methods study to understand how mothers involved in child welfare use resiliency strategies—including belief systems, organizational patterns, and open communication—to overcome adversities. Mothers (N = 129) at risk for child welfare involvement completed a quantitative survey, with 38 completing a follow-up qualitative phone interview. Both survey and interview asked a variety of questions on everyday adversities and coping. Two mothers were assessed as nonresilient. However, a majority of mothers exhibited resiliency, including consistent daily routines, peaceful homes, and family mealtimes. A strong aspirational belief system, not necessarily stemming from a faith tradition or community, provided both parents and children hope in times of trouble. Further, open communication with children about stressors was common. The authors’ results showed that resiliency strategies are being utilized by families typically defined as “at-risk,” and that child welfare professionals should consider focusing prevention efforts more on family strengths than on shortcomings.
S100 and CD34 Expressing Mesenchymal Neoplasm With Rare PLEKHH2::ALK Fusion and Response to ALK Inhibition
Authors: Coppock Joseph D. , Schneider Michael A. , Surrey Lea F. , Karakousis Giorgos C. , Maki Robert G. , Cooper Kumarasen
Published: March 2022

The PLEKHH2::ALK fusion is a rarely reported gene fusion identified predominantly in lung adenocarcinomas. Tumors with this fusion have been reported to be of durable response to ALK inhibitors. We herein present the case of a 21-year-old woman with a histomorphologically heterogenous mesenchymal neoplasm of the pelvis, expressing both s100 and CD34, with subsequently identified PLEKHH2::ALK fusion. To our knowledge, only a single mesenchymal neoplasm with this gene fusion has been previously reported. We propose that this tumor represents one with a novel ALK fusion in the emerging family of s100 and CD34 expressing mesenchymal neoplasms with oncogenic kinase alterations akin to NTRK-rearranged mesenchymal neoplasms, rather than inflammatory myofibroblastic tumor. Importantly, this tumor demonstrated a significant response to the ALK inhibitor brigatinib.
Age-Dependent Three-Dimensional Evaluation of Circummaxillary Sutures Maturation in Normal Population Using Cone-Beam Computed Tomography: Early Childhood Through Adolescence
Authors: Jahanbin Arezoo , Eslami Neda , Chamani Alireza , Zarch Hosein Hoseini , Shirazi Shirindokht , Khaniki Saeedeh Hajebi
Published: March 2022

Introduction:

Initiation time of dentofacial orthopedics is as important as the choice of treatment protocol. Morphology and degree of fusion of circummaxillary sutures differ in various populations; hence, the aim of this study was to evaluate the exact age of ossification of the most important maxillary suture using cone-beam computed tomography to find the appropriate age to start orthopedic treatment.

Methods and Materials:

This cross-sectional retrospective study was performed on 517 cone-beam computed tomography images of patients aged 6 to 18 years old. Patients with obvious pathology or fractures were excluded from the study. Two independent observers scored the radiographs. The ossification stage of the zygomatico-maxillary suture (ZMS) was classified into 5 stages and each suture was classified according to age and sex of the patients. Kendall Taub, Kruskal–Wallis, Mann–Whitney U test, and Bayesian analysis were used for statistical analysis. Statistical significance was set at P value < 0.05.

Results:

In this study, 517 samples consisting of 260 females (50.3%) and 257 males (49.7%) with a mean age of 12.03 ± 3.74 years old were examined. A significant difference did not exist between the 2 sexes regarding the stages of ZMS ossification except for in stage E. The ZMS transitional stage from B to C was found to occur at the age of 11.8 in boys and 12.6 in girls.

Conclusions:

According to the transitional age of ZMS maturation from stage B to C, it seems that orthopedic treatments of the maxilla are not much effective after the age of 12. Therefore, the authors should start orthopedic treatment of the maxilla before the age of 12 in both sexes.
Pure Prosodic Type of Primary Progressive Apraxia of Speech Mimicking Nonfluent Aphasia and Later Progressing to Corticobasal Syndrome
Authors: Kwon Miseon , Shim Woo Hyun , Jo Youngheun , Park Sohee , Lim Jae-Sung , Lee Jae-Hong
Published: March 2022

Primary progressive apraxia of speech (PPAOS), a rare neurodedegenerative disorder, can be subdivided into predominant phonetic or prosodic type. Pure prosodic type of PPAOS as an isolated disorder has been hardly found. We present 2 cases of patients with pure prosodic PPAOS who initially were misdiagnosed as nonfluent variant of primary progressive aphasia and later turned out to be corticobasal syndrome. A 65-year-old woman and a 72-year-old man were referred to our speech-language clinic under the clinical impression of nonfluent variant of primary progressive aphasia. The neurological examinations revealed no definite abnormalities except for slow and effortful speech with the production of simple sentences. However, their receptive and expressive language abilities were normal. Their brain magnetic resonance imaging was unremarkable. We initially entertained the diagnosis of pure prosodic type of PPAOS. During several years of follow up, they gradually developed extrapyramidal symptoms which are compatible with corticobasal syndrome. The characteristics of the patients and the results of neuroimaging studies are discussed.
C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)
Authors: Harit Renuka , De Sajal , Singh Piyoosh Kumar , Kashyap Deepika , Kumar Manish , Sahu Dibakar , Yadav Chander Prakash , Mohan Mradul , Singh Vineeta , Tomar Ram Singh , Pandey Kailash C , Vashisht Kapil
Published: March 2022

Background

Coronavirus disease-2019 (COVID-19) symptoms can range from asymptomatic, moderate to severe manifestations that result in an overall global case fatality rate of 2-7 %. While each variant has had it challenges, and some variants are more severe than others, risk factors of severe COVID-19 are still under investigation. In this context, the host genetic predisposition is also a crucial factor to investigate. In the present study, we investigated host genotypes of the SNP rs479200 of the host EGLN1 gene, previously implicated in high altitude pulmonary edema (HAPE), some of whose symptoms such as hypoxia profoundly overlap with severe COVID-19.

Methods

After informed consent, 158 RT-PCR confirmed COVID-19 patients (March 2020 to June 2021) were enrolled in the study. Based on their clinical manifestations, disease severity was categorized by the clinical team. Blood samples were drawn and DNA was extracted from the clot to infer different genotypes of the SNP rs479200 of the host EGLN1 gene. PCR-RFLP analysis of the SNP rs479200 (C > T) was performed with an amplicon size of 367 bp. Various genotypes (TT, TC and CC) were assigned based on the presence/absence of a restriction site (T/GTACA) for restriction enzyme BsrGI. Allele frequencies, Hardy-Weinberg Equilibrium (HWE) and multinomial logistic regression were performed using statistical tool SPSS version 23 (IBM).

Findings

We observed that the severe COVID-19 category was composed of comparatively younger patients with mean age (34.9±15.6), compared to asymptomatic and moderate categories whose mean age was 49.7±17.9 and 54.3±15.7, respectively. Preponderance of males and high heterozygosity (TC) was observed across the clinical categories. Notably, the frequency of C allele (0.664) was 2-fold higher than the T allele (0.336) in severe COVID-19 patients, whereas the allele frequencies were similar in asymptomatic and moderate category of COVID-19 patients. Multinomial logistic regression showed an association of genotypes with increasing clinical severity; odds ratio (adjusted OR-11.414 (2.564-50.812)) and (unadjusted OR-6.214 (1.84-20.99)) for the genotype CC in severe category of COVID-19. Interestingly, the TC genotype was also found to be positively associated with severe outcome (unadjusted OR-5.816 (1.489-22.709)), indicating association of C allele in imparting the risk of severe outcome.

Interpretation

The study provides strong evidence that the presence of C allele of SNP (rs479200) of the EGLN1 gene associates with severity in COVID-19 patients. Thus, the presence of C allele may be a risk factor for COVID-19 severity. This study opens new avenues towards risk assessment that include EGLN1 (rs479200) genotype testing and identifying patients with C allele who might be prioritized for critical care.
Plasma p-tau181/Aβ1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42and future cognitive decline
Authors: Fowler Christopher , Stoops Erik , Rainey-Smith Stephanie , Vanmechelen Eugeen , Vanbrabant Jeroen , Dewit Nele , Mauroo Kimberley , Maruff Paul , Rowe Christopher C. , Fripp Jurgen , Li Qiao-Xin , Bourgeat Pierrick , Collins Steven J. , Martins Ralph N. , Masters Colin L. , Doecke James D.
Published: March 2022

Background

In Alzheimer’s disease, plasma Aβ1-42and p-tau predict high amyloid status from Aβ-PET, however the extent to which combination of both plasma assays predict remains unknown.

Methods

Prototype Simoa assays were used to measure plasma samples from cognitively normal (CN) and symptomatic adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study.

Results

The p-tau181/Aβ1-42ratio showed the best prediction of Aβ-PET across all participants (AUC=0.905, 95%CI:0.86-0.95) and in CN (AUC=0.873; 0.80–0.94), and symptomatic (AUC=0.908; 0.82–1.00) adults. Plasma p-tau181/Aβ1-42ratio correlated with CSF-p-tau181 (Elecsys®, Spearman’s ρ=0.74, P<0.0001) and predicted abnormal CSF Aβ (AUC=0.816, 0.74-0.89). The p-tau181/Aβ1-42ratio also predicted future rates of cognitive decline assessed by AIBL PACC or CDR-SOB (P<0.0001).

Discussion

Plasma p-tau181/Aβ1-42ratio predicted both Aβ-PET status and cognitive decline, demonstrating potential as both a diagnostic aid and as a screening and prognostic assay for preclinical Alzheimer’s disease trials.
Planemo: a command-line toolkit for developing, deploying, and executing scientific data analyses
Authors: Bray Simon , Bernt Matthias , Soranzo Nicola , van den Beek Marius , Batut Bérénice , Rasche Helena , Čech Martin , Cock Peter , Nekrutenko Anton , Grüning Björn , Chilton John
Published: March 2022

There are thousands of well-maintained high-quality open-source software utilities for all aspects of scientific data analysis. For over a decade, the Galaxy Project has been providing computational infrastructure and a unified user interface for these tools to make them accessible to a wide range of researchers. In order to streamline the process of integrating tools and constructing workflows as much as possible, we have developed Planemo, a software development kit for tool and workflow developers and Galaxy power users. Here we outline Planemo’s implementation and describe its broad range of functionality for designing, testing and executing Galaxy tools, workflows and training material. In addition, we discuss the philosophy underlying Galaxy tool and workflow development, and how Planemo encourages the use of development best practices, such as test-driven development, by its users, including those who are not professional software developers. Planemo is a mature project widely used within the Galaxy community which has been downloaded over 80,000 times.
Connectivity in Large-Scale Resting State Brain Networks is Related to Motor Learning: a High-Density EEG Study
Authors: Titone Simon , Samogin Jessica , Peigneux Philippe , Swinnen Stephan , Mantini Dante , Albouy Genevieve
Published: March 2022

Previous research has shown that resting-state functional connectivity (rsFC) between different brain regions (seeds) is related to motor learning and motor memory consolidation. Using high-density electroencephalography (hdEEG) we addressed this question from a brain network perspective. Specifically, we examined frequency-dependent functional connectivity in resting-state networks from twenty-nine young healthy participants before and after they were trained on a motor sequence learning task. Consolidation was assessed with an overnight retest on the motor task. We showed training-related decreases in gamma band connectivity within the motor network, and between the motor and functionally distinct resting-state networks including the attentional network. Brain-behavior correlation analyses revealed that baseline beta, delta and theta rsFC was related to subsequent motor learning and memory consolidation such that lower connectivity within the motor network and between the motor and several distinct resting-state networks was correlated with better learning and overnight consolidation. Last, training-related increases in beta-band connectivity between the motor and the visual networks were related to greater consolidation. Altogether our results indicate that connectivity in large-scale resting-state brain networks is related to – and modulated by – motor learning and memory consolidation processes. These finding corroborate previous seed-based connectivity research and provide evidence that frequency-dependent functional connectivity in resting state networks is critically linked to motor learning and memory consolidation.
Loss of Stathmin-2, a hallmark of TDP-43-associated ALS, causes motor neuropathy
Authors: Krus Kelsey L. , Strickland Amy , Yamada Yurie , Devault Laura , Schmidt Robert E. , Bloom A. Joseph , Milbrandt Jeffrey , DiAntonio Aaron
Published: March 2022

TDP-43 mediates proper Stathmin-2 (STMN2) mRNA splicing, and STMN2 protein is reduced in the spinal cord of most ALS patients. To test the hypothesis that STMN2 loss contributes to ALS pathogenesis, we generated constitutive and conditional STMN2 knockout mice. Constitutive STMN2 loss results in early-onset sensory and motor neuropathy featuring impaired motor behavior and dramatic distal neuromuscular junction (NMJ) denervation of fast-fatigable motor units, which are selectively vulnerable in ALS, without axon or motoneuron degeneration. Selective excision of STMN2 in motoneurons leads to similar NMJ pathology. STMN2 KO heterozygous mice, which better model the partial loss of STMN2 protein found in ALS patients, display a slowly progressive, motor-selective neuropathy with functional deficits and NMJ denervation. Thus, our findings strongly support the hypothesis that STMN2 reduction due to TDP-43 pathology contributes to ALS pathogenesis.
Employer Requirements and COVID-19 Vaccination and Attitudes among Healthcare Personnel in the U.S.: Findings from National Immunization Survey Adult COVID Module, August – September 2021
Authors: Lee James T. , Hu S. Sean , Zhou Tianyi , Bonner Kim , Kriss Jennifer L. , Wilhelm Elisabeth , Carter Rosalind J. , Holmes Carissa , de Perio Marie A. , Lu Peng-jun , Nguyen Kimberly H. , Brewer Noel T. , Singleton James A.
Published: March 2022

Introduction

Employer vaccination requirements have been used to increase vaccination uptake among healthcare personnel (HCP). In summer 2021, HCP were the group most likely to have employer requirements for COVID-19 vaccinations as healthcare facilities led the implementation of such requirements. This study examined the association between employer requirements and HCP’s COVID-19 vaccination status and attitudes about the vaccine.

Methods

Participants were a national representative sample of United States (US) adults who completed the National Immunization Survey Adult COVID Module (NIS-ACM) during August–September 2021. Respondents were asked about COVID-19 vaccination and intent, requirements for vaccination, place of work, attitudes surrounding vaccinations, and sociodemographic variables. This analysis focused on HCP respondents. We first calculated the weighted proportion reporting COVID-19 vaccination for HCP by sociodemographic variables. Then we computed unadjusted and adjusted prevalence ratios for vaccination coverage and key indicators on vaccine attitudes, comparing HCP based on individual self-report of vaccination requirements.

Results

Of 12,875 HCP respondents, 41.5% reported COVID-19 vaccination employer requirements. Among HCP with vaccination requirements, 90.5% had been vaccinated against COVID-19, as compared to 73.3% of HCP without vaccination requirements—a pattern consistent across sociodemographic groups. Notably, the greatest differences in uptake between HCP with and without employee requirements were seen in sociodemographic subgroups with the lowest vaccination uptake, e.g., HCP aged 18–29 years, HCP with high school or less education, HCP living below poverty, and uninsured HCP. In every sociodemographic subgroup examined, vaccine uptake was more equitable among HCP with vaccination requirements than in HCP without. Finally, HCP with vaccination requirements were also more likely to express confidence in the vaccine’s safety (68.3% vs. 60.1%) and importance (89.6% vs 79.6%).

Conclusion

In a large national US sample, employer requirements were associated with higher and more equitable HCP vaccination uptake across all sociodemographic groups examined. Our findings suggest that employer requirements can contribute to improving COVID-19 vaccination coverage, similar to patterns seen for other vaccines.
CDC (Cindy and David’s Conversations) Game: Advising President to Survive Pandemic
Authors: Ma Zhanshan (Sam) , Yang Liexun
Published: March 2022

Abstract

Ongoing debates on anti-COVID19 policies have been focused on coexistencevs. zero-out strategies, which can be simplified as “always open (AO)”vs. “always closed (AC).” We postulate that, the middle ground between the two extremes, dubbed LOHC (low-risk open and high-risk closed), is likely more favorable, precluding obviously irrational HOLC (high-open-low-closed). From a meta-strategy perspective, these four policies cover the full spectrum of anti-pandemic policies. We argue that, among numerous factors influencing strategic policy-making, the competence of advisory body such as CDC chief-scientist (say, Cindy) and politics in decision-making body such as president (David), and their cooperation/communication can be critical. Here we investigate anti-pandemic policy-making by harnessing the power of evolutionary game theory in modeling competition/cooperation/communication (three critical processes underlying biological and social evolutions). Specifically, we apply the Sir Philip Sydney (SPS) game, a 4×4 signaler-responder evolutionary game with 16 strategic interactions, which was devised to investigate the reliability of communication that can modulate competition and cooperation, to capture rich idiosyncrasies surrounding today’s anti-pandemic policies. By emulating the reality of anti-pandemic policies today, the study aims to identify possible cognitive gaps and traps. The extended SPS, dubbed CDC (Cindy and David’s Conversations) game, offers a powerful cognitive model for investigating the coexistence/zero-out dichotomy and possible alternatives. The rigorous analytic solutions and extensive simulations suggest a take-home message—keep it persistently simple and rational: while apparently preferred middle-ground LOHC seems to be small-probability (∼0.05) event counter-intuitively, the AO and AC policies appears to be large-probability (∼0.41-0.53) events.

LaySummary

Ongoing debates on anti-COVID19 policies have been focused on coexistence-withvs. zero-out (virus) strategies, which can be simplified as “always open (AO)”vs. “always closed (AC).” We postulate that middle ground, dubbed LOHC (low-risk-open and high-risk-closed), is likely more favorable, precluding obviously irrational HOLC (high-risk-open and low-risk-closed). From a meta-strategy perspective, these four policies cover the full spectrum of anti-pandemic policies. By emulating the reality of anti-pandemic policies today, the study aims to identify possible cognitive gaps and traps by harnessing the power of evolutionary game-theoretic analysis and simulations, which suggest that (i) AO and AC seems to be “high-probability” events (∼0.41-0.53); (ii) counter-intuitively, the middle ground—LOHC—seems to be small-probability event (∼0.05), possibly due to its unduly complexity, mirroring its wide-range failures in practice.
Hypoxia-inducible factor 1 signaling drives placental aging and can provoke preterm labor
Authors: Ciampa Erin J. , Flahardy Padraich , Srinivasan Harini , Jacobs Christopher , Tsai Linus , Karumanchi S. Ananth , Parikh Samir M.
Published: March 2022

Most cases of preterm labor have unknown cause, and the burden of preterm birth is immense. Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. We report findings stemming from unbiased transcriptomic analysis of mouse placenta, which revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysregulation and cellular senescence; we detected similar effects in aging human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma cells, we modeled HIF-1 induction and demonstrated resultant mitochondrial dysfunction and cellular senescence. Transcriptomic analysis revealed that HIF-1 stabilization recapitulated gene signatures observed in aged placenta. Further, conditioned media from trophoblasts following HIF-1 induction promoted contractility in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may drive the transition from uterine quiescence to contractility at the onset of labor. Finally, pharmacological induction of HIF-1 via intraperitoneal administration of dimethyloxalyl glycine (DMOG) to pregnant mice caused preterm labor. These results provide clear evidence for placental aging in normal pregnancy, and demonstrate how HIF-1 signaling in late gestation may be a causal determinant of the mitochondrial dysfunction and senescence observed within the trophoblast as well as a trigger for uterine contraction.
Mutational footprint of platinum chemotherapy in a secondary thyroid cancer
Authors: Schiantarelli Julia , Pappa Theodora , Conway Jake , Crowdis Jett , Reardon Brendan , Dietlein Felix , Huang Julian , Stanizzi Darren , Carey Evan , Bosma-Moody Alice , Imamovic Alma , Han Seunghun , Camp Sabrina , Kofman Eric , Shannon Erin , Barletta Justine A. , He Meng Xiao , Liu David , Park Jihye , Lorch Jochen H. , Van Allen Eliezer M.
Published: March 2022

Although papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor with a generally excellent prognosis, a patient developed a clinically aggressive PTC eleven years after receiving platinum chemotherapy for ovarian endometrioid adenocarcinoma. Germline and somatic analyses of multi-temporal and multi-regional molecular profiles indicated that ovarian and thyroid tumors did not share common genetic alterations. PTC tumors had driver events associated with aggressive PTC behavior, an RBPMS-NTRK3 fusion and a TERT promoter mutation. Spatial and temporal genomic heterogeneity analysis indicated a close link between anatomical locations and molecular patterns of PTC. Mutational signature analyses demonstrated a molecular footprint of platinum exposure, and that aggressive molecular drivers of PTC were linked to prior platinum-associated mutagenesis. This case provides a direct association between platinum chemotherapy exposure and secondary solid tumor evolution, in specific aggressive thyroid carcinoma, and suggests that uniform clinical assessments for secondary PTC after platinum chemotherapy may warrant further evaluation.