bluuebunny/crossref_metadata_2025 huggingface dataset:
Rehabilitation of the water supply network of Timişoara City from Timiş County in Romania
Authors: Stanciu Alina , Pavel Vasile Lucian , Toma Daniel , Toma Cristina Mihaela Vîrlan
Published: January 2023

In such an urban centre like Timisoara (the largest one from the West of Romania), the problem of water treatment for drinking, respectively wastewater collection and treatment, have always been issues of strategic importance to the community. The policies of the European Union to support the financing of the member states in the field of environmental engineering and protection represented the basic pillar in the development of the water supply network also in this case. In light of the increasing and pressing need to efficiently manage scarce water resources, there has been renewed interest by water distribution network owners to develop and implement water management strategies and tools that would assist in the integrated and automated management of those networks. The modernizations made at the treatment plants can be summarized in a few basic ideas: the automatic control of processes, lower costs, and higher safety. The most commonly used rehabilitation techniques for reducing both types of water losses are pressure management and pipeline rehabilitation. In Timişoara City, this modernization, and the rehabilitation of the water supply network led to a significant reduction of the environmental pollution (water, soil, air), and to a better protection of human health. Investments in modern technologies for water treatment, which allow an automatic monitoring of the process, translate into more safety in exploitation, and, implicitly, a better-quality control. The main objectives pursued in this study aim at: improving the quality of drinking water supplied to the population, ensuring continuous supply of drinking water, compliance with the regulations in force, both Romanian and European, and ensuring the access for the majority of the population at this system. There were followed the rehabilitation systems for street drinking water supply networks, also those for street sewerage networks, with modern constructive solutions.
PVA and PMMA nano-composites: a review on strategies, applications and future prospects
Authors: Palanichamy Kalyani , Anandan Muthupandeeswari , Sridhar Jayavel , Natarajan Varagunapandiyan , Dhandapani Aravind
Published: January 2023

Nanotechnology has facilitated unique ways of developing novel nano-composites. In that sense, polymer-based nano-composites are being extensively researched for their outstanding properties as a result of incorporating nano-fillers in the polymer matrix. They have activated enormous research interests owing to their potential in addressing environmental issues, packaging, optics, electronics, battery electrolytes, pneumatic actuation, molecular separations, sensors, biomedical applications, etc Hence, the authors intend to consolidate reported information about these polymer matrices, diverse inorganic nanofillers, and nano-filled polymer composites for improvement in properties and future advanced applications. The review exhaustively covers 15 years of literature on theoretical, experimental, and application aspects of PVA & PMMA-based nano-composites, mainly focusing on inorganic oxide-based fillers. It also summarizes the structure-property correlations that govern their performance. Hence this review is hoped to provide the readers with stimulating insights on strategies, noteworthy challenges, and future opportunities/prospects in developing polymer nano-composites that may cater to the need of our society and scientific industries as well.
The structure group for quasi-linear equations via universal enveloping algebras
Authors: Linares Pablo , Otto Felix , Tempelmayr Markus
Published: January 2023

We replace trees by multi-indices as an index set of the abstract model space to tackle quasi-linear singular stochastic partial differential equations. We show that this approach is consistent with the postulates of regularity structures when it comes to the structure group, which arises from a Hopf algebra and a comodule.

Our approach, where the dual of the abstract model space naturally embeds into a formal power series algebra, allows to interpret the structure group as a Lie group arising from a Lie algebra consisting of derivations on this power series algebra. These derivations in turn are the infinitesimal generators of two actions on the space of pairs (non-linearities, functions of space-time mod constants).

We also argue that there exist pre-Lie algebra and Hopf algebra morphisms between our structure and the tree-based one in the cases of branched rough paths (Grossman-Larson, Connes-Kreimer) and of the stochastic heat equation.
On Singular Vortex Patches, I: Well-posedness Issues
Authors: Elgindi Tarek , Jeong In-Jee
Published: January 2023

The purpose of this work is to discuss the well-posedness theory of singular vortex patches. Our main results are of two types: well-posedness and ill-posedness. On the well-posedness side, we show that globallymm-fold symmetric vortex patches with corners emanating from the origin are globally well-posed in natural regularity classes as long asm≥3.m\geq 3.In this case, all of the angles involved solve aclosedODE system which dictates the global-in-time dynamics of the corners and only depends on the initial locations and sizes of the corners. Along the way we obtain a global well-posedness result for a class of symmetric patches with boundary singular at the origin, which includes logarithmic spirals. On the ill-posedness side, we show thatanyother type of corner singularity in a vortex patch cannot evolve continuously in time except possibly when all corners involved have precisely the angleπ2\frac {\pi }{2}for all time. Even in the case of vortex patches with corners of angleπ2\frac {\pi }{2}or with corners which are only locallymm-fold symmetric, we prove that they are generically ill-posed. We expect that in these cases of ill-posedness, the vortex patches actually cusp immediately in a self-similar way and we derive some asymptotic models which may be useful in giving a more precise description of the dynamics. In a companion work from 2020 on singular vortex patches, we discuss the long-time behavior of symmetric vortex patches with corners and use them to construct patches onR2\mathbb {R}^2with interesting dynamical behavior such as cusping and spiral formation in infinite time.
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

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.
Barbara Bromage
Authors: Ward-Thompson Derek
Published: January 2023

Derek Ward-Thompson remembers a solar physicist, researcher, lecturer and occasional shepherd
Bacillus Calmette–Guérin-induced lupus vulgaris in a patient with Mendelian susceptibility to mycobacterial disease caused by a novel STAT1 variation
Authors: Shionoya Aika , Yoto Yuko , Hida Tokimasa , Ishikawa Aki , Hasegawa Tadashi , Tsugawa Takeshi , Uhara Hisashi
Published: January 2023

We reported a case of BCG vaccination-induced lupus vulgaris in an 11-year-old girl with Mendelian susceptibility to mycobacterial disease (MSMD) due to a novel STAT1 gene variation. The dermatologists should suspect MSMD in patients with cutaneous tuberculosis after BCG vaccination. It prevents both the patients and the family members with inborn errors of immunity from receiving inadequate vaccines.
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

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.
Biologic tapering for patients with psoriasis with low disease activity: data from the French PsoBioTeq Registry
Authors: Aubert Helene , Arlegui Hugo , De Rycke Yann , Bachelez Herve , Beylot-Barry Marie , Dupuy Alain , Joly Pascal , Jullien Denis , Mahé Emmanuel , Paul Carle , Richard Marie-Aleth , Sbidian Emilie , Viguier Manuelle , Chosidow Olivier , Tubach Florence , Bénéton Nathalie ,   for the PsoBioTeq Study Group
Published: January 2023

Dose tapering strategies with biologics in psoriasis may lower the treatment burden over time, while enabling high therapeutic response maintenance in patients benefiting from them. Our results should contribute to developing clinical guidelines to fill the current gap in knowledge on this promising therapeutic approach
Prevalence of rosacea in transgender and gender-diverse populations: a retrospective cohort study
Authors: Sanz Jessika , Gao Julia L , King Dana S , Modest Anna M , Dommasch Erica D
Published: January 2023

Hormones have been shown to affect the pathophysiology of rosacea, however, the prevalence of rosacea in transgender and gender diverse (TGD) patients on gender affirming hormone therapy (GAHT) has never been studied. Our retrospective cohort study showed a significantly decreased prevalence TGD patients on feminizing GAHT compared to cisgender men, women, and TGD not on GAHT. Our results suggest that estrogen and/or anti-androgenetic agents may play a protective role in the development or course of rosacea.
No association between physical activity and primary melanoma thickness in a cohort of Norwegian women
Authors: Perrier Flavie , Robsahm Trude E , Ghiasvand Reza , Borch Kristin B , Braaten Tonje , Weiderpass Elisabete , Rueegg Corina S , Green Adele C , Veierød Marit B
Published: January 2023

‘In a cohort of Norwegian woman aged 30–75 years at recruitment, we investigated the association between physical activity and melanoma thickness at diagnosis, the most important prognostic factor for localized primary melanoma survival. We concluded that physical activity is unlikely to be associated with melanoma thickness.’
Inguinal patch in mpox (monkeypox) virus infection and eccrine syringometaplasia: report of two cases with in situ hybridization and electron microscopy findings
Authors: Roy Simon F , Sarhan Joseph , Liu Xinran , Murphy Michael J , Bunick Christopher G , Choate Keith A , Damsky William B , McNiff Jennifer M
Published: January 2023

We report two cases of cutaneous mpox virus infection (formerly known as monkeypox), one of which presented with unusual clinical findings, and demonstrate their histopathological, RNA in situ hybridization (ISH) and ultrastructural characteristics. We observed in two patients with polymerase chain reaction-confirmed mpox virus infection squamous syringometaplasia of the eccrine ducts, a finding that can aid in recognizing this disease and is explained by the demonstration of viral mRNA within eccrine epithelium by ISH.
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

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 < 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’.
Iso–Kikuchi syndrome: report of a Chinese case
Authors: Zheng Bingjie , Chen Jia , Qian Qiufang , Lin Xiao
Published: January 2023

We report a case of Iso-Kikuchi syndrome (congenital onychodysplasia of the index finger), a rare condition that has never been reported in the Chinese population. To our knowledge, this is therefore the first case reported in China.
Löfgren syndrome associated with scleroedema adultorum of Buschke
Authors: Gambichler Thilo , Susok Laura , Doerler Martin , Dickel Heinrich , Chatzipantazi Maria
Published: January 2023

A case of systemic sarcoidosis (Löfgren syndrome) associated with scleroedema adultorum of Buschke is reported. Sarcoidosis should be included in the spectrum of the underlying conditions of scleroedema adultorum of Buschke, and clinicians should be aware of this very rare association.
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

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.
Monkeypox: is topical cidofovir a good idea?
Authors: Rubio-Muniz Carmen Alejandra , Montero-Menárguez Julia , López-Valle Alba , Agud-Dios Manuel , Arroyo-Andrés Jorge , Rodriguez-Peralto José Luis , Palencia-Pérez Sara Isabel , Tarín-Vicente Eloy José
Published: January 2023

We report the use of topical cidofovir to treat patients with human monkeypox. We found that lesions on the trunk and limbs responded better than facial lesions, while anogenital lesions were affected by local irritation, leading to eventual discontinuation of treatment.
Actinic lichen planopilaris: a new variant of lichen planopilaris triggered by ultraviolet radiation
Authors: Lalagianni Nikolina , McSweeney Sheila M , Christou Evangelos A A , Rayinda Tuntas , Ferguson John , Stefanato Catherine M , McGrath John A , Tziotzios Christos
Published: January 2023

We present the case of a Sri Lankan woman with a novel clinical entity, actinic lichen planopilaris. Treatment with high-potency topical corticosteroids and adherence to strict photoprotection was successful in treating the disorder.
Combination dermoscopy for initiation and monitoring of systemic antifungal therapy for paediatric tinea faciei with invasion of vellus hair owing to Microsporum canis
Authors: Zhi Hui-Lin , Xia Xiu-Jiao , Liu Ze-Hu
Published: January 2023

Combination dermoscopy is a simple, noninvasive and accurate technique for the rapid diagnosis, initiation and monitoring of systemic antifungal therapy for tinea faciei caused by Microsporum canis, especially in settings where fungal testing is not available.
Checkpoint inhibitor therapy and psoriasis: a case series
Authors: Hussain Khawar , Kanji Alpa , Zaheri Shirin , Malek Dalila , Terlizzo Monica , Weir Justin , Turajlic Samra , Fearfield Louise
Published: January 2023

Checkpoint inhibitor therapy (CPI) has significantly improved overall survival in several cancers, including metastatic melanoma and in the adjuvant setting. Cutaneous immune-related adverse events secondary to CPI are commonly observed; however, the development of psoriasis or exacerbation of existing psoriasis has not been widely reported and management can be challenging.
Too much of a good thing? Iatrogenic Cushing syndrome secondary to excessive topical steroid use in lichen sclerosus
Authors: Psomadakis Cristina , Tweddell Rebecca , Lewis Fiona
Published: January 2023

We report a patient using excessive quantities of topical steroid treatment for lichen sclerosus without supervision who developed Cushing syndrome. These treatments are very safe when used appropriately and this highlights the importance of good follow-up and patient education.
A novel KRT14 null mutation leads to autosomal recessive epidermolysis bullosa simplex
Authors: Banner Lauren , Cohen Alexa , McGrath Lauren , Nikbakht Neda , South Andrew P
Published: January 2023

We describe a novel homozygous KRT14 (also known as K14) mutation detected in a patient with a relatively mild form of epidermolysis bullosa simplex (EBS). Our patient harbours loss of function of both alleles of the KRT14 gene. This is the 16th reported mutation of recessive EBS in KRT14.
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

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 < 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

Let $L$ be an $n$-component link ($n>1$) 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

Metastases 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

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

Differential 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

Generating 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

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

Drought 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 < 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

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.
Emerged donor limb growth morbidity and malalignment after combined ipsilateral tibial and fibular cortical harvest graft in children. Early follow-up report
Authors: Deo Nitish Bikram , Agarwal Anil
Published: January 2023

The quantity of bone grafts required in certain pediatric conditions is sometimes substantial. This retrospective study details the radiological changes occurring in the donor leg and ankle following the simultaneous harvest of large diaphyseal cortical grafts from the tibia and fibula in 14 children (16 legs). The following preoperative and follow-up radiological parameters were measured and compared for donor legs: the longitudinal continuous regeneration of fibula, distal fibular station, medial proximal tibial angle, lateral distal tibial angle, posterior proximal tibial angle (PPTA), anterior distal tibial angle and interphyseal angle (tibia diaphyseal angulation) in both coronal and sagittal planes. Additionally, the impact of fibular regeneration in combined harvests was separately analyzed. Children were operated at the mean age of 52 months. Mean follow-up of 25.2 months was available. At follow-up, the donor tibia healed completely in all legs whereas fibular regeneration was complete only in 10 legs (62.5%). At follow-up, ankle valgus was present in 6 out of 16 legs (37%) and tibia valga increased in all legs except one (94%). Procurvatum was present in 7 legs. The fibular nonregeneration group was prone to ankle valgus deformity (P = 0.014), valgus angulation of tibial diaphysis (P = 0.0076) and lower mean PPTA (P = 0.026) when compared to the regenerate group. There was a complication of stress fracture in one donor tibia. Combined tibial and fibular harvest is a major surgical undertaking in children. The donor limbs have their share of complications postharvest, more so when the fibula remains nonregenerated. Serial monitoring of donor sites is emphasized.
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.
Effects of CFTR modulators on serum biomarkers of liver fibrosis in children with cystic fibrosis
Authors: Levitte Steven , Fuchs Yonathan , Wise Russell , Sellers Zachary M.
Published: January 2023

The cystic fibrosis (CF) transmembrane conductance regulator corrector/potentiator combinations lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor improve sweat chloride, pulmonary function, and nutrition. Yet it is unclear whether they may also impact the progression of liver fibrosis, which is a substantial source of morbidity and mortality for patients with CF. We conducted a retrospective, single-center analysis of children and adolescents with CF treated with lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor therapy, focusing on alterations in liver function tests and fibrosis indices using previously-established thresholds that corresponded with increased liver elastography. In pairwise comparisons of before and during treatment timepoints, we found that those with CF-associated liver involvement experienced significant decreases in gamma-glutamyl transferase, aspartate aminotransferase-to-platelet index, and gamma-glutamyl transferase-to-platelet ratio while on lumacaftor/ivacaftor. These differences were not observed in patients treated with elexacaftor/tezacaftor/ivacaftor, nor were they observed in patients without underlying CF-associated liver disease. These results provide the first evidence that lumacaftor/ivacaftor may improve liver fibrosis in children and adolescents with CF and suggest it may be beneficial in the treatment of CF-associated liver disease.
Injectable Long-Acting Cabotegravir–Rilpivirine Therapy for People Living With HIV/AIDS: Addressing Implementation Barriers From the Start
Authors: Pinto Rogério M. , Hall Evan , Tomlin Ryan
Published: January 2023

Injectable cabotegravir and rilpivirine (CAB/RPV), administered bimonthly by a medical provider, is convenient and improves privacy and medication management. One year after approval, myriad implementation barriers threaten the access and sustainability of this life-saving innovation: (1) eligibility issues (viral suppression, drug resistance, and failed oral regimens); (2) injection requires medical provider and transportation to facility; (3) strict medication adherence; (4) life challenges—mental health, homelessness, joblessness; and (5) lack of insurance and high cost. Universal implementation of CAB/RPV calls for social, human, and health organizations to partner and provide HIV continuum of care and prevention services to facilitate CAB/RPV access and maintenance and for transparent health insurance billing practices to abate uncertainty concerning CAB/RPV's classification as a pharmaceutical or medical benefit and related cost implications.
Three-year results of renal function in liver transplant recipients on low-dose sirolimus and tacrolimus: a multicenter randomized, controlled trial
Authors: Mulder M.B. , van Hoek B. , van den Berg A.P. , Polak W.G. , Alwayn I.P.J. , de Jong K.P. , de Winter B.C.M. , Verhey-Hart E. , Erler N.S. , den Hoed C.M. , Metselaar H.J.
Published: January 2023

The aim of this study was to investigate whether the combination of low-dose sirolimus (SRL) and low-dose extended-release tacrolimus (TAC) compared to normal-dose extended-release TAC results in a difference in the renal function and comparable rates of rejection, graft and patient survival at 36 months after transplantation. This study was an open-label, multicenter randomized, controlled trial. Patients were randomized to once daily normal-dose extended-release TAC (control group) or once daily combination therapy of SRL and low-dose extended-release TAC (interventional group). The primary endpoint was the cumulative incidence of chronic kidney disease (CKD) defined as grade ≥3 (eGFR <60 mL/min/1.73 m2) at 36 months after transplantation. In total, 196 patients were included. CKD at 36 months was not different between the control and interventional group (50.8%, 95% confidence interval (CI) 39.7% – 59.9%) vs. 43.7%, 95% CI: 32.8% - 52.8%). Only at six months after transplantation, the eGFR was higher in the interventional group compared to the control group (mean eGFR 73.1±15 vs. 67.6±16 mL/min/1.73 m2, P=0.02) in the intention to treat population. No differences in the secondary endpoints and the number of serious adverse events were found between the groups. Once-daily low-dose SRL combined with low-dose extended-release TAC does ultimately not provide less CKD grade ≥3 at 36 months compared to normal-dose extended-release TAC.
Low-carbohydrate diets in type 1 diabetes: balancing benefits and risks
Authors: Hancock Michael , Burns Kharis , Gan Seng Khee , Chew Gerard T.
Published: January 2023

Purpose of review

Interest in the use of calorie restriction with low-carbohydrate diets for patients with type 1 diabetes appears to be increasing despite physicians’ discomfort about its longer term outcomes. A divergence in opinion regarding the balance of benefits and safety may lead to patient disengagement from conventional medical supervision. This review describes the current evidence regarding the benefits and risks of these diets and suggests a way forward to addressing this potential misalignment between the aims of patients and their physicians.

Recent findings

Benefits on glycaemia are observed in many studies, with improved HbA1c, time within target range and reduced glycaemic variability. A characteristic lipid profile with high LDL cholesterol is observed in many patients, but association with future cardiovascular events is undefined. A negative impact on growth has been identified in the paediatric population, and impact on mental health and disordered eating is of theoretical concern, without measurement in clinical studies.

Patients will continue to trial and, with immediate glycaemic benefits, potentially remain on lower carbohydrate diets irrespective of concern by treating physicians about potential longer term risks. A supportive multidisciplinary approach with greater nutritional supervision and more research is required, to allow these patients to achieve their desired glycaemic outcomes without compromising longer term safety.
The Local and Systemic Exposure to Oxygen in Children With Severe Bronchiolitis on Invasive Mechanical Ventilation: A Retrospective Cohort Study
Authors: Lilien Thijs A. , de Sonnaville Eleonore S. V. , van Woensel Job B. M. , Bem Reinout A.
Published: January 2023

OBJECTIVES:

Oxygen supplementation is a cornerstone treatment in critically ill children with bronchiolitis in the PICU. However, potential deleterious effects of high-dose oxygen are well-known. In this study, we aim to describe the pulmonary (local) and arterial (systemic) oxygen exposure over the duration of invasive mechanical ventilation (IMV) in children with severe bronchiolitis. Our secondary aim was to estimate potentially avoidable exposure to high-dose oxygen in these patients.

DESIGN:

Retrospective cohort study.

SETTING:

Single-center, tertiary-care PICU.

PATIENTS:

Children younger than 2 years old admitted to the PICU for severe bronchiolitis receiving IMV.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Hourly measurements of Fio
2 and peripheral oxygen saturation (Spo
2), and arterial blood gas data were collected up to day 10 of IMV. A total of 24,451 hours of IMV were observed in 176 patients (median age of 1.0 mo [interquartile range (IQR), 1.0–2.3 mo]). The pulmonary exposure to oxygen was highest during the first day of IMV (median time-weighted average [TWA]–Fio
2 0.46 [IQR, 0.39–0.53]), which significantly decreased over subsequent days. The systemic exposure to oxygen was relatively low, as severe hyperoxemia (TWA–Pao
2 > 248 Torr [> 33 kPa]) was not observed. However, overuse of oxygen was common with 52.3% of patients (n = 92) having at least 1 day of possible excessive oxygen exposure and 14.8% (n = 26) with severe exposure. Furthermore, higher oxygen dosages correlated with increasing overuse of oxygen (rrepeated measures, 0.59; 95% CI, 0.54–0.63). Additionally, caregivers were likely to keep Fio
2 greater than or equal to 0.50 when Spo
2 greater than or equal to 97%.

CONCLUSIONS:

Moderate to high-dose pulmonary oxygen exposure and potential overuse of oxygen were common in this cohort of severe bronchiolitis patients requiring IMV; however, this was not accompanied by a high systemic oxygen burden. Further studies are needed to determine optimal oxygenation targets to prevent overzealous use of oxygen in this vulnerable population.