bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of a chimeric ACE-2/Fc-silent fusion protein with ultrahigh affinity and neutralizing capacity for SARS-CoV-2 variants
Authors: Bodie Neil M , Hashimoto Rina , Connolly David , Chu Jennifer , Takayama Kazuo , Uhal Bruce D 
Published: January 2023

Abstract

Background
As SARS-CoV-2 continues to mutate into Variants of Concern (VOC), there is growing and urgent need to develop effective antivirals to combat COVID-19. Monoclonal antibodies developed earlier are no longer capable of effectively neutralizing currently active VOCs. This report describes the design of variant-agnostic chimeric molecules consisting of an Angiotensin-Converting Enzyme 2 (ACE-2) domain mutated to retain ultrahigh affinity binding to a wide variety of SARS-CoV-2 variants, coupled to an Fc-silent immunoglobulin domain that eliminates antibody-dependent enhancement and extends biological half-life.

Methods
Molecular modeling, Surrogate Viral Neutralization tests (sVNTs) and infection studies of human airway organoid cultures were performed with synthetic chimeras, SARS-CoV-2 spike protein mimics and SARS-CoV-2 Omicron variants B.1.1.214, BA.1, BA.2 and BA.5.

Results
ACE-2 mutations L27, V34 and E90 resulted in ultrahigh affinity binding of the LVE-ACE-2 domain to the widest variety of VOCs, with KDs of 93 pM and 73 pM for binding to the Alpha B1.1.7 and Omicron B.1.1.529 variants, and notably, 78fM, 133fM and 1.81pM affinities to the Omicron BA.2, BA2.75 and BQ.1.1 subvariants, respectively. sVNT assays revealed titers of ≥4.9 ng/ml, for neutralization of recombinant viral proteins corresponding to the Alpha, Delta and Omicron variants. The values above were obtained with LVE-ACE-2/mAB chimeras containing the FcRn-binding Y-T-E sequence which extends biological half-life 3–4-fold.

Conclusions
The ACE-2-mutant/Fc silent fusion proteins described have ultrahigh affinity to a wide variety of SARS-CoV-2 variants including Omicron. It is proposed that these chimeric ACE-2/mABs will constitute variant-agnostic and cost-effective prophylactics against SARS-CoV-2, particularly when administered nasally.
Deficient mismatch repair is detected in large-to-giant congenital melanocytic naevi: providing new insight into aetiology and diagnosis
Authors: Wei Boxuan , Gu Jieyu , Gao Bowen , Bao Yongyang , Duan Ran , Li Qingfeng , Xie Feng 
Published: January 2023

Abstract

Background
The aetiologies of large-to-giant congenital melanocytic naevi (LGCMN) remain ambiguous. A previous study discovered signatures associated with deficient mismatch repair (dMMR) in patients with LGCMN. However, a screening diagnostic immunohistochemistry (IHC) panel of dMMR in patients with LGCMN has not been performed to date.

Objectives
To identify the MMR status and aetiologies of LGCMN.

Methods
A total of 110 patients with CMN, including 30 giant CMN, 30 large CMN, 30 medium CMN and 20 small CMN, underwent diagnostic IHC (for MSH6, MSH2, PMS2 and MLH1) screening of dMMR. The control group comprised normal skin samples from 20 healthy people. MMR proteins with little effect (MSH3 and PMS1) on the MMR system were stained in all samples. The surgical procedures conducted on each patient were noted because they might alter the behaviour of CMN and confound the results. Binary logistic regression analyses were performed between the phenotypic data and MMR status to identify associations. Whole-exome sequencing was performed on the main naevi, satellite naevi and normal skin tissues of four patients to detect variants. Mutational signature analyses were conducted to explore the aetiologies of LGCMN.

Results
dMMR was detected in 37% (11 of 30) of giant, 23% (7 of 30) of large and 7% (2 of 30) of medium CMNs, but were not identified in small CMNs or normal skin tissues. Moreover, multiple LGCMNs had a much higher dMMR rate than did single LGCMNs. The regression analyses showed that MMR status was significantly associated with CMN size and the presence of satellites, but was not correlated with age, sex, location, satellite diversity or tissue expansion. Notably, the pattern of protein loss in LGCMN mainly consisted of PMS2 loss. Mutational signature analyses detected dMMR-related signatures in patients with LGCMN. Additionally, rare deleterious germline mutations in DNA repair genes were detected in LGCMN, mainly in MSH6, ATM, RAD50, BRCA1 and ERCC8. These germline mutations were single-patient variants with unknown significance.

Conclusions
dMMR is one of the aetiologies underlying LGCMN, particularly in patients with giant main lesions and multiple satellite lesions. Further studies are necessary to investigate the role of the DNA repair system, particularly MMR, in LGCMN.
Migraine among adults with atopic dermatitis: a cross-sectional study in the All of Us research programme
Authors: Fan Ryan , Leasure Audrey C , Damsky William , Cohen Jeffrey M 
Published: January 2023

Abstract
Atopic dermatitis (AD) has been previously associated with migraine headaches in paediatric and adolescent populations, though there is less evidence for this relationship among adults. In this cross-sectional study, we investigated the association between AD and migraine among a cohort of US adults in the All of Us research programme. After controlling for common comorbidities, we found that adults with AD were 89% more likely to have a diagnosis of migraine (OR = 1·89, P &lt; 0·001).
Comment on ‘Eosinophilic pustular folliculitis developing at the site of COVID-19 vaccination’
Authors: Martora Fabrizio , Battista Teresa , Fabbrocini Gabriella , Potestio Luca 
Published: January 2023

Several cutaneous adverse reactions have been reported following Covid-19 vaccination.
Herein, we want to comment the article by Rikitake et al. entitled ‘Eosinophilic pustular folliculitis developing at site of Covid-19 vaccination’.
Cross-sectional study to estimate the prevalence and risk factors of nonalcoholic fatty liver disease in children and adolescents with psoriasis
Authors: Panjiyar Rohit , Mahajan Rahul , Bhatia Anmol , Narang Tarun , Dogra Sunil 
Published: January 2023

Abstract

Background
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent comorbidity in adult patients with psoriasis, but there is a paucity of data on NAFLD in paediatric patients with psoriasis.

Aim
To estimate the prevalence of NAFLD in children and adolescents with psoriasis compared with age- and sex-matched healthy controls (HCs) and to evaluate risk factors for NAFLD in paediatric psoriasis.

Methods
This was a cross-sectional study performed from July 2019 to December 2020 in a single tertiary care centre, which enrolled 52 children/adolescents aged 2–18 years diagnosed with psoriasis at least 6 months previously, and 52 HCs matched for age and sex. Anthropometric, metabolic and radiological assessment was performed for all participants. NAFLD prevalence was determined by liver enzyme (serum glutamic pyruvic transferase) levels, ultrasonography, shear wave elastography and aspartate aminotransferase/platelet index. Multivariate analysis was performed to determine the independent risk factors for NAFLD.

Results
The frequency of NAFLD was found to be 28·8% in patients with paediatric psoriasis compared with 3·8% in HCs. Logistic regression showed that greater disease severity (Psoriasis Area and Severity Index ≥ 10), obesity and decreased high-density lipoprotein cholesterol (HDL-C) level were independently associated with NAFLD, and thus can be considered risk factors for NAFLD.

Conclusion
Patients with paediatric psoriasis have a higher prevalence of NAFLD compared with HCs. Children who are obese or have moderate to severe psoriasis or decreased HDL-C levels are at a higher risk of developing NAFLD.
Global diversity in individualized cortical network topography
Authors: Yang Guoyuan , Bozek Jelena , Noble Stephanie , Han Meizhen , Wu Xinyu , Xue Mufan , Kang Jujiao , Jia Tianye , Fu Jilian , Ge Jianqiao , Cui Zaixu , Li Xuesong , Feng Jianfeng , Gao Jia-Hong 
Published: January 2023

Abstract
Individualized cortical network topography (ICNT) varies between people and exhibits great variability in the association networks in the human brain. However, these findings were mainly discovered in Western populations. It remains unclear whether and how ICNT is shaped by the non-Western populations. Here, we leveraged a multisession hierarchical Bayesian model to define individualized functional networks in White American and Han Chinese populations with data from both US and Chinese Human Connectome Projects. We found that both the size and spatial topography of individualized functional networks differed between White American and Han Chinese groups, especially in the heteromodal association cortex (including the ventral attention, control, language, dorsal attention, and default mode networks). Employing a support vector machine, we then demonstrated that ethnicity-related ICNT diversity can be used to identify an individual’s ethnicity with high accuracy (74%, pperm &lt; 0.0001), with heteromodal networks contributing most to the classification. This finding was further validated through mass-univariate analyses with generalized additive models. Moreover, we reveal that the spatial heterogeneity of ethnic diversity in ICNT correlated with fundamental properties of cortical organization, including evolutionary cortical expansion, brain myelination, and cerebral blood flow. Altogether, this case study highlights a need for more globally diverse and publicly available neuroimaging datasets.
The effect of link Dehn surgery on the Thurston norm
Authors: Miller Maggie 
Published: January 2023

Abstract
Let $L$ be an $n$-component link ($n&gt;1$) with pairwise nonzero linking numbers in a rational homology $3$-sphere $Y$. Assume the complement $X:=Y\setminus \nu (L)$ has nondegenerate Thurston norm. We study when a Thurston norm-minimizing surface $S$ properly embedded in $X$ remains norm-minimizing after Dehn filling all boundary components of $X$ according to $\partial S$ and capping off $\partial S$ by disks. In particular, for $n=2$ the capped-off surface is norm-minimizing when $[S]$ lies outside of a finite set of rays in $H_2(X,\partial X;{\mathbb {R}})$, answering a conjecture of Gabai. When $Y$ is an integer homology sphere this gives an upper bound on the number of surgeries on $L$ which may yield $S^1\times S^2$. The main techniques come from Gabai’s proof of the Property R conjecture and related work.
A Spectrum of Metastases to the Breast: Radiologic-Pathologic Correlation
Authors: Huayanay Espinoza Jorge L , Mego Ramírez Fiorela N , Guerra Miller Henry , Huayanay Santos Jorge L , Guelfguat Mark 
Published: January 2023

AbstractMetastases to the breast from non-mammary origin are rare. The majority of these lesions appear as secondary manifestations of melanoma and lymphoma, followed by lung carcinomas, gynecological carcinomas, and sarcomas. There has been a steady trend of an increase in diagnosis of intramammary metastases owing to the current advances in imaging technology. Imaging features depend on the type of primary neoplasm and route of dissemination, some of which resemble primary breast cancer and benign breast entities. There are certain imaging features that raise the level of suspicion for metastases in the correct clinical context. However, imaging manifestations of intramammary metastases do not always comply with the known classic patterns. The aim of this review is to clarify these features, emphasizing radiologic-pathologic correlation and a multidisciplinary approach, since most cases are found in patients with advanced disease.
A bio-orthogonal linear ubiquitin probe identifies STAT3 as a direct substrate of OTULIN in glioblastoma
Authors: Du Xianli , Pang Jing , Gu Bin , Si Tian , Chang Yan , Li Tianqi , Wu Min , Wang Zicheng , Wang Yuxia , Feng Jiannan , Wu Ning , Man Jianghong , Li Huiyan , Li Ailing , Zhang Tong , Wang Bo , Duan Xiaotao 
Published: January 2023

Abstract
While linear ubiquitin plays critical roles in multiple cell signaling pathways, few substrates have been identified. Global profiling of linear ubiquitin substrates represents a significant challenge because of the low endogenous level of linear ubiquitination and the background interference arising from highly abundant ubiquitin linkages (e.g. K48- and K63-) and from the non-specific attachment of interfering proteins to the linear polyubiquitin chain. We developed a bio-orthogonal linear ubiquitin probe by site-specific encoding of a norbornene amino acid on ubiquitin (NAEK-Ub). This probe facilitates covalent labeling of linear ubiquitin substrates in live cells and enables selective enrichment and identification of linear ubiquitin-modified proteins. Given the fact that the frequent overexpression of the linear linkage-specific deubiquitinase OTULIN correlates with poor prognosis in glioblastoma, we demonstrated the feasibility of the NAEK-Ub strategy by identifying and validating substrates of linear ubiquitination in patient-derived glioblastoma stem-like cells (GSCs). We identified STAT3 as a bona fide substrate of linear ubiquitin, and showed that linear ubiquitination negatively regulates STAT3 activity by recruitment of the phosphatase TC-PTP to STAT3. Furthermore, we demonstrated that preferential expression of OTULIN in GSCs restricts linear ubiquitination on STAT3 and drives persistent STAT3 signaling, and thereby maintains the stemness and self-renewal of GSCs.
Pairwise ratio-based differential abundance analysis of infant microbiome 16S sequencing data
Authors: Mildau Kevin , te Beest Dennis E , Engel Bas , Gort Gerrit , Lambert Jolanda , Swinkels Sophie H N , van Eeuwijk Fred A 
Published: January 2023

AbstractDifferential abundance analysis of infant 16S microbial sequencing data is complicated by challenging data properties, including high sparsity, extreme dispersion and the relative nature of the information contained within the data. In this study, we propose a pairwise ratio analysis that uses the compositional data analysis principle of subcompositional coherence and merges it with a beta-binomial regression model. The resulting method provides a flexible and easily interpretable approach to infant 16S sequencing data differential abundance analysis that does not require zero imputation. We evaluate the proposed method using infant 16S data from clinical trials and demonstrate that the proposed method has the power to detect differences, and demonstrate how its results can be used to gain insights. We further evaluate the method using data-inspired simulations and compare its power against related methods. Our results indicate that power is high for pairwise differential abundance analysis of taxon pairs that have a large abundance. In contrast, results for sparse taxon pairs show a decrease in power and substantial variability in method performance. While our method shows promising performance on well-measured subcompositions, we advise strong filtering steps in order to avoid excessive numbers of underpowered comparisons in practical applications.
BLEND: a fast, memory-efficient and accurate mechanism to find fuzzy seed matches in genome analysis
Authors: Firtina Can , Park Jisung , Alser Mohammed , Kim Jeremie S , Cali Damla Senol , Shahroodi Taha , Ghiasi Nika Mansouri , Singh Gagandeep , Kanellopoulos Konstantinos , Alkan Can , Mutlu Onur 
Published: January 2023

AbstractGenerating the hash values of short subsequences, called seeds, enables quickly identifying similarities between genomic sequences by matching seeds with a single lookup of their hash values. However, these hash values can be used only for finding exact-matching seeds as the conventional hashing methods assign distinct hash values for different seeds, including highly similar seeds. Finding only exact-matching seeds causes either (i) increasing the use of the costly sequence alignment or (ii) limited sensitivity. We introduce BLEND, the first efficient and accurate mechanism that can identify both exact-matching and highly similar seeds with a single lookup of their hash values, called fuzzy seed matches. BLEND (i) utilizes a technique called SimHash, that can generate the same hash value for similar sets, and (ii) provides the proper mechanisms for using seeds as sets with the SimHash technique to find fuzzy seed matches efficiently. We show the benefits of BLEND when used in read overlapping and read mapping. For read overlapping, BLEND is faster by 2.4×–83.9× (on average 19.3×), has a lower memory footprint by 0.9×–14.1× (on average 3.8×), and finds higher quality overlaps leading to accurate de novo assemblies than the state-of-the-art tool, minimap2. For read mapping, BLEND is faster by 0.8×–4.1× (on average 1.7×) than minimap2. Source code is available at https://github.com/CMU-SAFARI/BLEND.
Massive nasopharyngeal rhabdomyosarcoma in an adult patient: a rare case report
Authors: Seifen Christopher , Matthias Christoph , O'Brien Karoline 
Published: January 2023

ABSTRACT
Rhabdomyosarcoma (RMS) is a highly invasive malignant soft tissue sarcoma that rarely affects adults. The head and neck region accounts for most adult RMSs. Here, we report a case of a 24-year-old Caucasian woman who was diagnosed with persistent hoarseness and a painless left-sided neck mass. Physical examination and image studies showed a massive tumor of the nasopharynx, extending from the left-sided skull base to supraglottic structures. Histopathologic evaluation revealed the diagnosis of a poorly differentiated RMS. Due to the primary tumor size and involvement of crucial structures, extensive surgical excision was not amenable. Thus, the patient was treated with radiotherapy and chemotherapy. Although very rare, nasopharyngeal RMSs should be considered in the differential diagnosis of neck masses in adult patients. This case report illustrates the difficulty in the diagnosis and treatment of rare head and neck malignancies and encourages its reporting.
Melatonin-priming enhances maize seedling drought tolerance by regulating the antioxidant defense system
Authors: Muhammad Ihsan , Yang Li , Ahmad Shakeel , Farooq Saqib , Khan Ahmad , Muhammad Nisar , Ullah Saif , Adnan Muhammad , Ali Shamsher , Liang Qing Ping , Zhou Xun Bo 
Published: January 2023

AbstractDrought stress (DS) challenges sustainable agriculture production by limiting crop growth and development. The objective of the study was to evaluate the effect of melatonin-priming on enzymatic and non-enzymatic antioxidant defense mechanisms and its relation with leaf ultrastructure and stomatal traits in maize (Zea mays L) seedlings under DS (PEG-6000). DS drastically decreased seed germination, plant growth, and leaf chlorophyll content due to excessive reactive oxygen species (ROS) production. Melatonin-priming significantly (P &lt; 0.05) increased seed germination, root length, shoot length, fresh seedling weight, proline content, total soluble protein content, sugar content, chlorophyll content, and stomatal aperture size by 101%, 30%, 133%, 51%, 22%, 59%, 54%, 20%, and 424%, compared to no priming (NP) under DS, respectively. Similarly, priming improved leaf ultrastructure and reduced the amount of chlorophyll loss and oxidative damage in maize seedlings. Melatonin seed priming with 500 µM melatonin (M2) greatly increased superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione, and ascorbate (AsA) activity, by 65%, 63%, 94%, 41%, and 55% compared to NP under DS and by 0.26%, 8%, 33%, 42%, and 15% under no-stress (NS), respectively. Melatonin-priming also reduced malondialdehyde content, electrolyte leakage, hydrogen peroxide (H2O2) content, and superoxide anion (O2−) content by 26%, 31%, 31%, and 33% compared to NP under DS and by 8%, 18%, 10%, and 11% under NS, respectively. In response to DS, melatonin-priming also stabilized the chloroplast structure, sustained cell expansion, protected cell walls, and greatly improved stomatal traits, including stomatal number, length, and width. Our results suggest that melatonin-priming improves drought tolerance in maize seedlings by alleviating the negative effect of ROS.
Ferroptosis: challenges and opportunities for nanomaterials in cancer therapy
Authors: Liu Qiaolin , Zhao Yuliang , Zhou Huige , Chen Chunying 
Published: January 2023

Abstract
Ferroptosis, a completely new form of regulated cell death, is mainly caused by an imbalance between oxidative damage and reductive protection and has shown great anti-cancer potential. However, existing small-molecule ferroptosis inducers have various limitations, such as poor water solubility, drug resistance and low targeting ability, hindering their clinical applications. Nanotechnology provides new opportunities for ferroptosis-driven tumor therapy. Especially, stimuli-responsive nanomaterials stand out among others and have been widely researched because of their unique spatiotemporal control advantages. Therefore, it’s necessary to summarize the application of those stimuli-responsive nanomaterials in ferroptosis. Here, we describe the physiological feature of ferroptosis and illustrate the current challenges to induce ferroptosis for cancer therapy. Then, nanomaterials that induce ferroptosis are classified and elaborated according to the external and internal stimuli. Finally, the future perspectives in the field are proposed. We hope this review facilitates paving the way for the design of intelligent nano-ferroptosis inducers.
Mortality As a Measure of Treatment Effect in Clinical Trials Recruiting Critically Ill Patients*
Authors: Friedrich Jan O. , Harhay Michael O. , Angus Derek C. , Burns Karen E. A. , Cook Deborah J. , Fergusson Dean A. , Finfer Simon , Hébert Paul , Rowan Kathy , Rubenfeld Gordon , Marshall John C. ,   in collaboration with the International Forum for Acute Care Trialists (InFACT)
Published: January 2023

OBJECTIVES:
All-cause mortality is a common measure of treatment effect in ICU-based randomized clinical trials (RCTs). We sought to understand the performance characteristics of a mortality endpoint by evaluating its temporal course, responsiveness to differential treatment effects, and impact when used as an outcome measure in trials of acute illness.

DATA SOURCES:
We searched OVID Medline for RCTs published from 1990 to 2018.

STUDY SELECTION:
We reviewed RCTs that had randomized greater than or equal to 100 patients, were published in one of five high-impact general medical or eight critical care journals, and reported mortality at two or more distinct time points. We excluded trials recruiting pediatric or neonatal patients and cluster RCTs.

DATA EXTRACTION:
Mortality by randomization group was recorded from the article or estimated from survival curves. Trial impact was assessed by inclusion of results in clinical practice guidelines.

DATA SYNTHESIS:
From 2,592 potentially eligible trials, we included 343 RCTs (228,784 adult patients). While one third of all deaths by 180 days had occurred by day 7, the risk difference between study arms continued to increase until day 60 (p = 0.01) and possibly day 90 (p = 0.07) and remained stable thereafter. The number of deaths at ICU discharge approximated those at 28–30 days (95% [interquartile range [IQR], 86–106%]), and deaths at hospital discharge approximated those at 60 days (99% [IQR, 94–104%]). Only 13 of 43 interventions (30.2%) showing a mortality benefit have been adopted into widespread clinical practice.

CONCLUSIONS:
Our findings provide a conceptual framework for choosing a time horizon and interpreting mortality outcome in trials of acute illness. Differential mortality effects persist for 60 to 90 days following recruitment. Location-based measures approximate time-based measures for trials conducted outside the United States. The documentation of a mortality reduction has had a modest impact on practice.