bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban storm flood simulation using improved SWMM based on K‐means clustering of parameter samples
Authors: Sun Yue , Liu Chengshuai , Du Xian , Yang Fan , Yao Yichen , Soomro Shan‐e‐hyder , Hu Caihong
Published: June 2022

To address the two problems of unclear delineation of sub‐catchment and complicated and cumbersome parameter rate determination in the Storm Water Management Model (SWMM), this study proposes a rapid construction method of SWMM based on the principle of single urban functional area combined with K‐means clustering algorithm, The research area is the southern part of Jinshui District, Zhengzhou City. The Hydrological Response Unit (HRU) contains only a single urban functional area, divided by combining the natural and social attributes of the urban surface. Calibrated uncertain parameters from 76 papers were selected as samples, and the K‐means clustering algorithm was used to cluster and calculate the parameter values, to improve the SWMM model, selecting three typical rainfall runoff processes for validation application. The results show that simulated runoff is consistent with measured runoff trends, with the NSE and R2 value scores of the flow processes of the three floods above 0.86 and the, locations and numbers of flooded nodes are consistent with the actual research. This provides a new idea and technical support for the construction of urban flood models in flood prevention and mitigation. The relevant results can provide scientific decision‐making reference for urban flood forecasting and warning.
Clin‐Star corner: A new series featuring practice‐changing articles in medical, surgical, and related specialties
Authors: Mody Lona , Gill Thomas M. , Zieman Susan J.
Published: June 2022

See other related Clin‐star papers by Advani et al. and Nair et al. in this issue.
Intensive mothering in the time of coronavirus
Authors: Lutz Amy , (Crystal) Lee Sujung , Bokayev Baurzhan
Published: June 2022

We investigated experiences of mothers of school‐age children in Central New York during a time of remote education due to COVID‐19. We extend the concept of intensive mothering, characterized by the expectation that mothers are constantly available to meet their children's needs, and examine mothers’ intersectional identities related to their experience of remote education. Mothers working from home often went back and forth between work and school in what we refer to as a simultaneous shift. Essential workers were engaged in a sequential shift, engaging with children's schoolwork after work and trading off with partners. Mothers took on multiple roles during the pandemic which led to role strain. In extreme cases, multiple roles could be impossible to fill, leading to a situation of role conflict where the demands of one role made it impossible to meet the needs of another role. Mothers of children of color experienced more negative interactions with schools than White mothers. Mothers of children with disabilities spent extended time on remote schooling. A limitation of our study is that we only interviewed people in Central New York and cannot generalize the results of our research to a larger population. Another limitation to our approach was that we have little information on how fathers experienced work and overseeing children's schoolwork. Future research should examine how mothering may have changed after children returned to school.
Effects of yeast culture substituting fishmeal on growth, nonspecific immunity, intestinal, and hepatopancreatic histology of Litopenaeus vannamei
Authors: Zhang Xin , Yao Wenxiang , Sun Zhongchao , Liu Jiangying , Dang Jiangyu , Li Xiaoqin , Leng Xiangjun
Published: June 2022

This study investigated the effects of yeast culture (YC) substituting fishmeal (FM) on growth, nonspecific immunity, intestinal and hepatopancreatic histology of Litopenaeus vannamei. Based on the control diet with an FM content of 200 g/kg, YC was used to decrease dietary FM to 200, 160, 120, and 80 g/kg (FM20, FM16, FM12, FM8), respectively. Then, the four diets were fed to shrimp (2.78 ± 0.10 g) for 8 weeks. The results indicated that the FM8 group had poorer weight gain and higher feed conversion ratio than the control (p < .05), while the FM16 and FM12 groups showed no significant difference to the control (p > .05). Protein and lipid retention in the FM12 and FM8 groups were decreased (p < .05), and hepatopancreatic activities of superoxide dismutase and alkaline phosphatase were increased and malondialdehyde content was decreased in the FM12 group (p < .05). In the FM8 group, the crude protein digestibility, hepatopancreatic protease and amylase activity, the intestinal villi length and width were decreased (p < .05), and hepatic corpuscle was observed with atrophy and irregular lumen shape. In conclusion, YC can successfully replace 40 g/kg FM in a shrimp diet with FM inclusion of 200 g/kg.
Global warming responses of gut microbiota in moose (Alces alces) populations with different dispersal patterns
Authors: Chen S. , Holyoak M. , Liu H. , Bao H. , Ma Y. , Dou H. , Li G. , Roberts N. J. , Jiang G.
Published: June 2022

While dispersal is the basis of inter‐population connectivity, it is difficult to directly observe. New molecular techniques provide ways of studying the intensity and direction of dispersal among populations through quantifying gene flow. When herbivores disperse their gut microbes travel with the host, and gut microbiota is known to play an important role in host health. However, the current understanding of the driving mechanism between moose dispersal patterns and gut microbial structure is vague. Therefore, when we observe the effects of climate warming on gene flow, it is important to understand the ecological mechanisms that affect the gut microbiota. We applied integrative methods from molecular biology, nutritional ecology and microbiomics to quantify dispersal patterns of moose populations in northeast China and explore the ecological mechanisms driving gut microbe–host associations. We found that moose populations in northeast China are undergoing two dispersal patterns while retreating in a northwesterly direction. Dispersing and isolated moose populations differed in their gut microbial composition and frequency of functional types that relate to digestion and diet composition. We also found that the environmental variables related to the moose gut microbial communities also changed with different dispersal patterns. The gut microbiota of isolated moose populations was only related to ambient temperature, whereas the microbiota in dispersing moose populations was related to longitude and diet protein content. We expect that the differences in the taxonomic and functional structure of gut microbiota relating to digestion are adaptive. Consequently, this study highlights that special attention should be placed on the management of isolated moose populations, and ecological corridors or translocation of moose individuals may be needed to allow persistence in the face of global warming; doing this will likely improve the adaptability of gut microbiota.
A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation
Authors: Nomura Emi , Omote Yoshio , Takemoto Mami , Hishikawa Nozomi , Nakano Yumiko , Yunoki Taijun , Morihara Ryuta , Sasaki Tatsuya , Akagawa Hiroyuki , Abe Koji , Yamashita Toru
Published: June 2022

Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug‐resistant epilepsy and dramatic improvement after surgical resection.
The functional role of ericoid mycorrhizal plants and fungi on carbon and nitrogen dynamics in forests
Authors: Ward Elisabeth B. , Duguid Marlyse C. , Kuebbing Sara E. , Lendemer James C. , Bradford Mark A.
Published: June 2022

Ericoid mycorrhizal (ErM) shrubs commonly occur in forest understories and could therefore alter arbuscular (AM) and/or ectomycorrhizal (EcM) tree effects on soil carbon and nitrogen dynamics. Specifically, ErM fungi have extensive organic matter decay capabilities, and ErM plant and fungal tissues have high concentrations of secondary compounds that can form persistent complexes in the soil. Together, these traits could contribute to organic matter accumulation and inorganic nutrient limitation. These effects could also differ in AM‐ vs EcM‐dominated stands at multiple scales within and among forest biomes by, for instance, altering fungal guild interactions. Most work on ErM effects in forests has been conducted in boreal forests dominated by EcM trees. However, ErM plants occur in c. 96, 69 and 29% of boreal, temperate and tropical forests, respectively. Within tropical montane forests, the effects of ErM plants could be particularly pronounced because their traits are more distinct from AM than EcM trees. Because ErM fungi can function as free‐living saprotrophs, they could also be more resilient to forest disturbances than obligate symbionts. Further consideration of ErM effects within and among forest biomes could improve our understanding of how cooccurring mycorrhizal types interact to collectively affect soil carbon and nitrogen dynamics under changing conditions.
Total Hip Arthroplasty with Robotic Arm Assistance for Precise Cup Positioning: A Case‐Control Study
Authors: Guo Dong‐hui , Li Xiao‐ming , Ma Shi‐qiang , Zhao Yun‐chao , Qi Chao , Xue Yuan
Published: June 2022

Objective

To determine whether more precise cup positioning can be achieved with robot‐assisted total hip arthroplasty (THA) as compared to conventional THA.

Methods

In this study, between July 2019 and May 2021, 93 patients aged 23–75 years with osteonecrosis of the femoral head (ONFH) and adult developmental dysplasia of hip who underwent first hip surgery were included in the study. They were randomly assigned to either the robotic‐assisted THA group (n = 45) or the conventional THA group (n = 48). After the operation, all patients were given routine rapid rehabilitation guidance. The duration of operation was recorded to estimate the learning curve through cumulative summation analysis. We compared the demographics, duration of operation, cup positioning, leg length discrepancy, hip offset, and Harris Hip Score between robot‐assisted THA and manual THA. Precision in the positioning of the acetabular prosthesis using the MAKO system was also compared between the two groups.

Results

The mean duration of operation for the robot‐assisted THA group was 91.37 ± 17.34 min (range: 63 to 135 min), which was significantly higher than that for the conventional THA group. When the number of procedures was increased to 13, the duration of operation in the robot‐assisted group decreased significantly and gradually became stable. In terms of duration of operation, robot‐assisted THA was associated with a learning curve of 13 cases. The mean amount of bleeding in the robot‐assisted THA group was not significantly different from that in conventional THA group (328 ± 210 ml vs 315 ± 205 ml) (p = 0.741). There was no significant difference in the proportion of prostheses located within Lewinnek's safe zone between robot‐assisted THA group and conventional THA group (69.81% vs 64.41%). The leg length discrepancy (LLD) was significantly smaller in the robot‐assisted THA group than in the conventional THA group (p < 0.001), but both were within acceptable limits (10 mm). The inclination and anteversion angles of the acetabular prosthesis planned before operations were correlated with the actual measurement (r = 0.857 p < 0.001, r = 0.830, p < 0.001). After surgery, none of the patients experienced hip dislocation, aseptic loosening, or periprosthetic infection during the 3 months of follow‐up.

Conclusion

The proportion of acetabular prostheses in the Lewinnek's safety zone was higher and the extent of LLD was significantly lower in the robot‐assisted THA group, as compared to the same metrics in the conventional THA group. The MAKO robot improved the accuracy of implant placement in THA.
The transient expression of recombinant proteins in plant cell packs facilitates stable isotope labelling for NMR spectroscopy
Authors: Opdensteinen Patrick , Sperl Laura E. , Mohamadi Mariam , Kündgen‐Redding Nicole , Hagn Franz , Buyel Johannes Felix
Published: June 2022

Nuclear magnetic resonance (NMR) spectroscopy can be used to determine the structure, dynamics and interactions of proteins. However, protein NMR requires stable isotope labelling for signal detection. The cells used for the production of recombinant proteins must therefore be grown in medium containing isotopically labelled substrates. Stable isotope labelling is well established in Escherichia coli, but bacteria are only suitable for the production of simple proteins without post‐translational modifications. More complex proteins require eukaryotic production hosts, but their growth can be impaired by labelled media, thus reducing product yields and increasing costs. To address this limitation, we used media supplemented with isotope‐labelled substrates to cultivate the tobacco‐derived cell line BY‐2, which was then cast into plant cell packs (PCPs) for the transient expression of a labelled version of the model protein GB1. Mass spectrometry confirmed the feasibility of isotope labelling with 15N and 2H using this approach. The resulting NMR spectrum featured a signal dispersion comparable to recombinant GB1 produced in E. coli. PCPs therefore offer a rapid and cost‐efficient alternative for the production of isotope‐labelled proteins for NMR analysis, especially suitable for complex proteins that cannot be produced in microbial systems.
Strategic Choices: How Conservative Women Activists Remained Active throughout Tunisia's Democratic Transition
Authors: Youssef Maro
Published: June 2022

Gender politics scholars conclude that conservatives and religious actors curtail women's rights and political participation during a democratic transition, except in post‐conflict contexts. Yet, this was not the case in Tunisia. This article documents how Islamist women activists remained active throughout the democratic transition in Tunisia. I argue that Islamist women within Tounissiet remained politically active by making two strategic choices: (1) not challenging conservatives and (2) aligning with liberal feminists when it was in their interest. This article builds on the emerging scholarship on women's roles in a democratic transition, especially conservative women, by providing original empirical work on an Islamist women's rights organization in a democratizing Tunisia. I suggest that more needs to be understood about conservative women and new actors that democratic transitions empower and embolden.
Managing growth in medium‐sized organic businesses: Implications for local orientation and resilience building
Authors: Milestad Rebecka , von Münchhausen Susanne , Kvam Gunn‐Turid , Schermer Markus
Published: June 2022

This article explores how locally oriented organic businesses adapt to handle crises during a growth process to build resilience, how these businesses maintain the local orientation when growing and what the implications are for the relationship between territoriality and organic production. We explored four cases of organic businesses in Sweden, Norway, Germany and Austria. The cases can be described as Values‐based Territorial Food Networks. All cases experienced challenges and crises during their growth processes and sought to provide stability and flexibility in order to deal with change. The restructuration process required internalising learning into their organisations, using diversity in a strategic way and forming long‐term partnerships within their value chains. While organic certification was never at stake, the meaning of ‘local’ shifted in some of the cases.
Using VADIS to weigh competing epicentral influence
Authors: La Peruta Roberta
Published: June 2022

The present study sets out to explore the mandative subjunctive in Canadian English (CanE), vs. its potential epicentre American English (AmE), and its historical input variety British English (BrE) based on a quantitative variationist analysis of the Strathy Corpus of Canadian English (Strathy), the Corpus of Contemporary American English (COCA), and the British National Corpus (BNC). The relevance of this contribution primarily stems from the fact that no previous research has yet focused on a contrastive comparison between CanE and its alleged epicentres, namely ‘a model of English for (neighbouring?) countries’ (Hundt, 2013, p. 185), and that the new method of Variation‐Based Distance and Similarity Modeling (VADIS) has so far never been applied to research in this field. Key findings show that VADIS is indeed a valuable method in detecting epicentral constellations, and pinpoint fruitful suggestions regarding AmE's alleged transnational influence on its neighbor, as well as cross‐border and transoceanic dis/similarities concerning the subject under analysis.
Rank 2 local systems and abelian varieties II
Authors: Krishnamoorthy Raju , Pál Ambrus
Published: June 2022

Let $X/\mathbb {F}_{q}$ be a smooth, geometrically connected, quasi-projective scheme. Let $\mathcal {E}$ be a semi-simple overconvergent $F$-isocrystal on $X$. Suppose that irreducible summands $\mathcal {E}_i$ of $\mathcal {E}$ have rank 2, determinant $\bar {\mathbb {Q}}_p(-1)$, and infinite monodromy at $\infty$. Suppose further that for each closed point $x$ of $X$, the characteristic polynomial of $\mathcal {E}$ at $x$ is in $\mathbb {Q}[t]\subset \mathbb {Q}_p[t]$. Then there exists a dense open subset $U\subset X$ such that $\mathcal {E}|_U$ comes from a family of abelian varieties on $U$. As an application, let $L_1$ be an irreducible lisse $\bar {\mathbb {Q}}_l$ sheaf on $X$ that has rank 2, determinant $\bar {\mathbb {Q}}_l(-1)$, and infinite monodromy at $\infty$. Then all crystalline companions to $L_1$ exist (as predicted by Deligne's crystalline companions conjecture) if and only if there exist a dense open subset $U\subset X$ and an abelian scheme $\pi _U\colon A_U\rightarrow U$ such that $L_1|_U$ is a summand of $R^{1}(\pi _U)_*\bar {\mathbb {Q}}_l$.
Open set classification strategies for long-term environmental field recordings for bird species recognition
Authors: Morgan Mallory M. , Braasch Jonas
Published: June 2022

Deep learning is one established tool for carrying out classification tasks on complex, multi-dimensional data. Since audio recordings contain a frequency and temporal component, long-term monitoring of bioacoustics recordings is made more feasible with these computational frameworks. Unfortunately, these neural networks are rarely designed for the task of open set classification in which examples belonging to the training classes must not only be correctly classified but also crucially separated from any spurious or unknown classes. To combat this reliance on closed set classifiers which are singularly inappropriate for monitoring applications in which many non-relevant sounds are likely to be encountered, the performance of several open set classification frameworks is compared on environmental audio datasets recorded and published within this work, containing both biological and anthropogenic sounds. The inference-based open set classification techniques include prediction score thresholding, distance-based thresholding, and OpenMax. Each open set classification technique is evaluated under multi-, single-, and cross-corpus scenarios for two different types of unknown data, configured to highlight common challenges inherent to real-world classification tasks. The performance of each method is highly dependent upon the degree of similarity between the training, testing, and unknown domain.
Boundary domain genes were recruited to suppress bract growth and promote branching in maize
Authors: Xiao Yuguo , Guo Jinyan , Dong Zhaobin , Richardson Annis , Patterson Erin , Mangrum Sidney , Bybee Seth , Bertolini Edoardo , Bartlett Madelaine , Chuck George , Eveland Andrea L. , Scanlon Michael J. , Whipple Clinton
Published: June 2022

Grass inflorescence development is diverse and complex and involves sophisticated but poorly understood interactions of genes regulating branch determinacy and leaf growth. Here, we use a combination of transcript profiling and genetic and phylogenetic analyses to investigate
tasselsheath1
(
tsh1
) and
tsh4
, two maize genes that simultaneously suppress inflorescence leaf growth and promote branching. We identify a regulatory network of inflorescence leaf suppression that involves the phase change gene
tsh4
upstream of
tsh1
and the ligule identity gene
liguleless2
(
lg2
). We also find that a series of duplications in the
tsh1
gene lineage facilitated its shift from boundary domain in nongrasses to suppressed inflorescence leaves of grasses. Collectively, these results suggest that the boundary domain genes
tsh1
and
lg2
were recruited to inflorescence leaves where they suppress growth and regulate a nonautonomous signaling center that promotes inflorescence branching, an important component of yield in cereal grasses.
Semicircular canal size constrains vestibular function in miniaturized frogs
Authors: Essner Richard L. , Pereira Rudá E. E. , Blackburn David C. , Singh Amber L. , Stanley Edward L. , Moura Mauricio O. , Confetti André E. , Pie Marcio R.
Published: June 2022

Miniaturization has evolved repeatedly in frogs in the moist leaf litter environments of rainforests worldwide. Miniaturized frogs are among the world’s smallest vertebrates and exhibit an array of enigmatic features. One area where miniaturization has predictable consequences is the vestibular system, which acts as a gyroscope, providing sensory information about movement and orientation. We investigated the vestibular system of pumpkin toadlets,
Brachycephalus
(Anura: Brachycephalidae), a clade of miniaturized frogs from Brazil. The semicircular canals of miniaturized frogs are the smallest recorded for adult vertebrates, resulting in low sensitivity to angular acceleration due to insufficient displacement of endolymph. This translates into a lack of postural control during jumping in
Brachycephalus
and represents a physical constraint resulting from Poiseuille’s law, which governs movement of fluids within tubes.
HYPK promotes the activity of the
N
α
-acetyltransferase A complex to determine proteostasis of nonAc-X
2
/N-degron–containing proteins
Authors: Miklánková Pavlína , Linster Eric , Boyer Jean-Baptiste , Weidenhausen Jonas , Mueller Johannes , Armbruster Laura , Lapouge Karine , De La Torre Carolina , Bienvenut Willy , Sticht Carsten , Mann Matthias , Meinnel Thierry , Sinning Irmgard , Giglione Carmela , Hell Rüdiger , Wirtz Markus
Published: June 2022

In humans, the Huntingtin yeast partner K (HYPK) binds to the ribosome-associated
N
α
-acetyltransferase A (NatA) complex that acetylates ~40% of the proteome in humans and
Arabidopsis thaliana
. However, the relevance of
Hs
HYPK for determining the human N-acetylome is unclear. Here, we identify the
At
HYPK protein as the first in vivo regulator of NatA activity in plants
. At
HYPK physically interacts with the ribosome-anchoring subunit of NatA and promotes N
α
-terminal acetylation of diverse NatA substrates. Loss-of-
At
HYPK mutants are remarkably resistant to drought stress and strongly resemble the phenotype of NatA-depleted plants. The ectopic expression of
Hs
HYPK rescues this phenotype. Combined transcriptomics, proteomics, and N-terminomics unravel that HYPK impairs plant metabolism and development, predominantly by regulating NatA activity. We demonstrate that HYPK is a critical regulator of global proteostasis by facilitating masking of the recently identified nonAc-X
2
/N-degron. This N-degron targets many nonacetylated NatA substrates for degradation by the ubiquitin-proteasome system.
EagleC: A deep-learning framework for detecting a full range of structural variations from bulk and single-cell contact maps
Authors: Wang Xiaotao , Luan Yu , Yue Feng
Published: June 2022

The Hi-C technique has been shown to be a promising method to detect structural variations (SVs) in human genomes. However, algorithms that can use Hi-C data for a full-range SV detection have been severely lacking. Current methods can only identify interchromosomal translocations and long-range intrachromosomal SVs (>1 Mb) at less-than-optimal resolution. Therefore, we develop EagleC, a framework that combines deep-learning and ensemble-learning strategies to predict a full range of SVs at high resolution. We show that EagleC can uniquely capture a set of fusion genes that are missed by whole-genome sequencing or nanopore. Furthermore, EagleC also effectively captures SVs in other chromatin interaction platforms, such as HiChIP, Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET), and capture Hi-C. We apply EagleC in more than 100 cancer cell lines and primary tumors and identify a valuable set of high-quality SVs. Last, we demonstrate that EagleC can be applied to single-cell Hi-C and used to study the SV heterogeneity in primary tumors.
Granzyme K
+
CD8 T cells form a core population in inflamed human tissue
Authors: Jonsson A. Helena , Zhang Fan , Dunlap Garrett , Gomez-Rivas Emma , Watts Gerald F. M. , Faust Heather J. , Rupani Karishma Vijay , Mears Joseph R. , Meednu Nida , Wang Runci , Keras Gregory , Coblyn Jonathan S. , Massarotti Elena M. , Todd Derrick J. , Anolik Jennifer H. , McDavid Andrew ,   Accelerating Medicines Partnership RA/SLE Network, Wei Kevin , Rao Deepak A. , Raychaudhuri Soumya , Brenner Michael B.
Published: June 2022

T cell–derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)–γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq and flow cytometric data, we found that the vast majority of synovial tissue and synovial fluid CD8 T cells belong to an effector CD8 T cell population characterized by high expression of granzyme K (GzmK) and low expression of granzyme B (GzmB) and perforin. Functional experiments demonstrate that these GzmK
+
GzmB
+
CD8 T cells are major cytokine producers with low cytotoxic potential. Using T cell receptor repertoire data, we found that CD8 GzmK
+
GzmB
+
T cells are clonally expanded in synovial tissues and maintain their granzyme expression and overall cell state in blood, suggesting that they are enriched in tissue but also circulate. Using GzmK and GzmB signatures, we found that GzmK-expressing CD8 T cells were also the major CD8 T cell population in the gut, kidney, and coronavirus disease 2019 (COVID-19) bronchoalveolar lavage fluid, suggesting that they form a core population of tissue-associated T cells across diseases and human tissues. We term this population tissue-enriched expressing GzmK or T
teK
CD8 cells. Armed to produce cytokines in response to both antigen-dependent and antigen-independent stimuli, CD8 T
teK
cells have the potential to drive inflammation.
Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells
Authors: Icho Simoun , Rujas Edurne , Muthuraman Krithika , Tam John , Liang Huazhu , Landreth Shelby , Liao Mingmin , Falzarano Darryl , Julien Jean-Philippe , Melnyk Roman A.
Published: June 2022

An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively.
The AraC/XylS Protein MxiE and Its Coregulator IpgC Control a Negative Feedback Loop in the Transcriptional Cascade That Regulates Type III Secretion in Shigella flexneri
Authors: McKenna Joy A. , Karney Monika M. A. , Chan Daniel K. , Weatherspoon-Griffin Natasha , Becerra Larios Brianda , Pilonieta M. Carolina , Munson George P. , Wing Helen J.
Published: June 2022

The large AraC family of transcriptional regulators (AFTRs) control virulence gene expression in many bacterial pathogens. In
Shigella
species, the AraC/XylS protein MxiE and its coregulator IpgC positively regulate the expression of type III secretion system genes within the three-tiered VirF/VirB/MxiE transcriptional cascade.
Differential Effects of Small Molecule Inhibitors on the Intracellular Chlamydia Infection
Authors: Muñoz Karissa J. , Tan Ming , Sütterlin Christine
Published: June 2022

Chlamydia
is the most reported cause of bacterial, sexually transmitted infection in the United States. This bacterium infects human cells and reproduces within a cytoplasmic inclusion via an unusual developmental cycle involving two specialized chlamydial forms.
Implementation of Practical Surface SARS-CoV-2 Surveillance in School Settings
Authors: Cantú Victor J. , Belda-Ferre Pedro , Salido Rodolfo A. , Tsai Rebecca , Austin Brett , Jordan William , Asudani Menka , Walster Amanda , Magallanes Celestine G. , Valentine Holly , Manjoonian Araz , Wijaya Carrissa , Omaleki Vinton , Sanders Karenina , Aigner Stefan , Baer Nathan A. , Betty Maryann , Castro-Martínez Anelizze , Cheung Willi , Crescini Evelyn S. , De Hoff Peter , Eisner Emily , Hakim Abbas , Kapadia Bhavika , Lastrella Alma L. , Lawrence Elijah S. , Ngo Toan T. , Ostrander Tyler , Sathe Shashank , Seaver Phoebe , Smoot Elizabeth W. , Carlin Aaron F. , Yeo Gene W. , Laurent Louise C. , Manlutac Anna Liza , Fielding-Miller Rebecca , Knight Rob
Published: June 2022

The ongoing COVID-19 pandemic has claimed the lives of over 5 million people worldwide. Due to high density occupancy of indoor spaces for prolonged periods of time, schools are often of concern for transmission, leading to widespread school closings to combat pandemic spread when cases rise.
MAGNETO: An Automated Workflow for Genome-Resolved Metagenomics
Authors: Churcheward Benjamin , Millet Maxime , Bihouée Audrey , Fertin Guillaume , Chaffron Samuel
Published: June 2022

Genome-resolved metagenomics has led to the discovery of previously untapped biodiversity within the microbial world. As the development of computational methods for the recovery of genomes from metagenomes continues, existing strategies need to be evaluated and compared to eventually lead to standardized computational workflows.
The global return on investment from preventing and treating adolescent mental disorders and suicide: a modelling study
Authors: Stelmach Rachel , Kocher Erica L , Kataria Ishu , Jackson-Morris Angela Mary , Saxena Shekhar , Nugent Rachel
Published: June 2022

Introduction

Despite the high burden of mental disorders among adolescents and the potentially lifelong consequences of these conditions, access to mental health services remains insufficient for adolescents in low-income and middle-income countries. We conducted an economic modelling study to quantify the potential costs and benefits of mental health interventions to prevent or treat anxiety, depression, bipolar disorder, and suicide among adolescents.

Methods

We developed a Markov model that followed cohorts of adolescents (ages 10–19) from 36 countries to assess the impact of addressing anxiety, depression, bipolar disorder, and suicide during adolescence on health and non-health outcomes through their lives. We estimated the costs of interventions using an ingredients-based approach and modelled impacts on education and employment and the resulting economic, morbidity, and mortality benefits.

Results

Implementing the selected interventions offers a return on investment of 23.6 and a cost of $102.9 per disability adjusted life year (DALY) averted over 80 years. The high return on investment and low cost per DALY averted is observed across regions and country income levels, with the highest return on investment arising from treating mild depression with group-based cognitive behavioural therapy, prevention of suicide attempts among high-risk adolescents, and universal prevention of combined anxiety and depression in low-income and lower-middle income countries.

Conclusions

The high return on investment and low cost per DALY averted suggests the importance and value of addressing mental disorders among adolescents worldwide. Intervening to prevent and treat these mental disorders even only during adolescence can have lifelong health and economic benefits.
Recently approved treatment options for patients with metastatic triple-negative and HER2-neu-positive breast cancer
Authors: Ghafouri Sayed Reshad , Guvvala Suvarna , Jones Catherine , Philipovskiy Alexander
Published: June 2022

Breast cancer (BC) is the most common cancer affecting women worldwide. In 2021, the estimated number of new breast cancer cases was 281 550 and about 43 500 women died from metastatic breast cancer (mBC). For women aged 20–59 years, mBC remains the leading cause of cancer death and is, therefore, an important public health concern. Only 5% of women initially present with metastatic disease. Approximately 20% of patients presenting with local or locoregional disease progress to mBC despite adjuvant therapy. Inspite of all the medicosurgical advancements, the overall prognosis for patients diagnosed with mBC remains poor, with median overall survival of approximately 31 months, although this varies based on tumor biology. In recent years, there has been significant progress in developing immunotargeted therapies such as antihuman epidermal growth factor receptor 2 (anti-HER2) or check point inhibitors that confirmed to have dramatically improve the prognosis of mBC, a historically unfavorable disease subset. Even with the major progress that has been made in understanding the biology of BC, challenges such as resistance frequency to therapies, unknown efficacy, concerns for safety of drug combination and toxicities still remain high. Therefore, a new targeted and more selective treatment approaches are the need of the hour. In this review, we aim to outline the most recently approved medications in treatment of Her2-positive and triple-negative breast cancers.
Increase in serum choline levels predicts for improved progression-free survival (PFS) in patients with advanced cancers receiving pembrolizumab
Authors: Watson Geoffrey Alan , Sanz-Garcia Enrique , Zhang Wen-Jiang , Liu Zhihui Amy , Yang SY Cindy , Wang Ben , Liu Shaofeng , Kubli Shawn , Berman Hal , Pfister Thomas , Genta Sofia , Spreafico Anna , Hansen Aaron R , Bedard Philippe L , Lheureux Stephanie , Abdul Razak Albiruni , Cescon Dave , Butler Marcus O , Xu Wei , Mak Tak W , Siu Lillian L , Chen Eric
Published: June 2022

Background

Recent studies have demonstrated that T cells can induce vasodilation in a choline-acetyltransferase dependent manner, leading to an increase in T cell migration to infected tissues in response to viral infection, but its role in cancer is unclear. Choline acetyltransferase catalyzes the production of acetylcholine from choline and acetyl-CoA, however, acetylcholine is challenging to quantify due to its extremely short half-life while choline is stable. This study aims to correlate serum choline levels in patients with advanced solid tumors receiving pembrolizumab with treatment outcomes.

Methods

Blood samples were collected at baseline and at week 7 (pre-cycle 3) in patients treated with pembrolizumab in the INvestigator-initiated Phase 2 Study of Pembrolizumab Immunological Response Evaluation phase II trial (NCT02644369). Samples were analyzed for choline and circulating tumor DNA (ctDNA). Multivariable Cox models were used to assess the association between choline and overall survival (OS) and progression-free survival (PFS) when including ΔctDNAC3(the change in ctDNA from baseline to cycle 3), cohort, PD-L1 expression and tumor mutation burden (TMB). An independent validation cohort from the LIBERATE study (NCT03702309) included patients on early phase trials treated with a PD-1 inhibitor.

Results

A total of 106 pts were included in the analysis. With a median follow-up of 12.6 months, median PFS and OS were 1.9 and 13.7 months, respectively. An increase in serum choline level at week 7 compared with baseline (ΔcholineC3) in 81 pts was significantly associated with a better PFS (aHR 0.48, 95% CI 0.28 to 0.83, p=0.009), and a trend toward a better OS (aHR 0.64, 95% CI 0.37 to 1.12, p=0.119). A combination of ΔctDNAC3and ΔcholineC3was prognostic for both OS and PFS. Multivariable analyses show ΔcholineC3was a prognostic factor for PFS independent of ΔctDNAC3, cohort, PD-L1 and TMB. In the independent validation cohort (n=51), an increase in serum choline at cycle 2 was associated with a trend to improved PFS.

Conclusions

This is the first exploratory report of serum choline levels in pan-cancer patients receiving pembrolizumab. The association between improved PFS and ΔcholineC3suggests a possible role for the cholinergic system in the regulation of antitumor immunity. Further pre-clinical and clinical studies are required to validate this finding.

Trial registration number

NCT03702309.
Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
Authors: Tiu Bruce C , Zubiri Leyre , Iheke James , Pahalyants Vartan , Theodosakis Nicholas , Ugwu-Dike Pearl , Seo Jayhyun , Tang Kimberly , Sise Meghan E , Sullivan Ryan , Naidoo Jarushka , Mooradian Meghan J , Semenov Yevgeniy R , Reynolds Kerry L
Published: June 2022

Background

Immune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts.

Methods

A combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP.

Results

The attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1–7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71).

Conclusions

In a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality.
Endovascular treatment of intracranial aneurysms using the Derivo Embolization Device: a multicenter experience
Authors: Chagas Lourenço Galileu , Dantas François , Silva e Carvalho Tiago , Firmino Róberti Uili Rodrigues , Quesado Filgueiras Filho Marcelo , Tosello Renato Tavares , José Leão Cláudio , Leo Piske Ronie , Zenóbio Darwich Rogério
Published: June 2022

Background

Flow diversion is the first-line treatment for several types of intracranial aneurysms. We report on a large series of patients treated with the Derivo Embolization Device who underwent a 1-year angiographic control follow-up.

Methods

We performed a multicenter retrospective analysis of prospectively collected data, designed to evaluate the clinical and angiographic results of treatment of intracranial aneurysms with the Derivo Flow Diverter. The primary endpoint was complete occlusion of the aneurysm within 12 months, which was evaluated using DSA. The secondary endpoint was the absence of any serious adverse events. Univariate and multivariate logistic regression analyses were performed to analyze the data.

Results

The study was conducted from December 2016 to September 2019 and enrolled 127 patients with 177 intracranial aneurysms, treated at three different centers. Efficacy at 6 months was 70.1% (122/174) for total occlusion and 87.3% (152/174) for favorable occlusion and, at 12 months, it was 83.3% (145/174) for total occlusion and 97.7% (170/174) for favorable occlusion. Regarding safety concerns, 97.6% (124/127) of patients did not experience severe adverse effects during the follow-up period of 12 months, and there was no procedure-related mortality.

Conclusions

The Derivo Embolization Device, achieving a total occlusion rate of 83.3% and a favorable occlusion rate of 97.7% in a 1-year angiographic control study of 174 aneurysms with minor morbidity and no intervention-related mortality, is a safe and effective treatment for intracranial aneurysms.
Dual microcatheter and coil/balloon pressure cooker technique for transvenous embolization of cerebrospinal fluid-venous fistulas
Authors: Parizadeh Donna , Vasconcelos Antonio H C , Miller David A , Fermo Olga P , Huynh Thien J
Published: June 2022

Cerebrospinal fluid-venous fistula is increasingly recognized as a cause of spontaneous intracranial hypotension.1 Transvenous embolization is emerging as an efficacious minimally invasive treatment.2–4 The procedure aims to embolize paraspinal and foraminal veins draining the fistula; however, complete embolization may be challenging as numerous small venous tributaries at the foraminal venous plexus, including dorsal muscular branches, may serve as additional routes of cerebrospinal fluid egress.5 To ensure curative embolization, we adopted a dual microcatheter pressure cooker technique, previously used for treatment of brain arteriovenous malformations.6 This allows improved control of embolic material reflux and greater chance of complete embolization of the site of the fistula and all potential venous tributaries. Video 1 demonstrates this technique employed in a typical case using Onyx (Medtronic, Minnesota, USA) to embolize a cerebrospinal fluid-venous fistula at the left L1 neural foramen.

Video 1

Technical video demonstrating dual-microcatheter and coil/balloon pressure cooker technique.
Effect of suprainguinal fascia iliaca compartment block on postoperative opioid consumption and functional recovery in posterolateral-approached total hip arthroplasty: a single-blind randomized controlled trial
Authors: Carella Michele , Beck Florian , Piette Nicolas , Denys Sébastien , Kurth William , Lecoq Jean-Pierre , Bonhomme Vincent L
Published: June 2022

Introduction

Posterolateral-approached total hip arthroplasty (PLTHA) is followed by moderate to severe postoperative pain. Suprainguinal fascia iliaca compartment block (SFICB) has been proposed as a promising analgesia technique.

Methods

Data from 86 patients scheduled for PLTHA with spinal anesthesia were analyzed in this prospective randomized controlled trial. Patients were randomly divided into two groups of 43 patients each. As opposed to the control group (group C), ropivacaine group (group R) received additional SFICB using 40 mL of 0.375% ropivacaine. As primary endpoint, blind observers noted total morphine consumption at postoperative 48 hours. Secondary endpoints were pain at rest and mobilization on 0–10 Numeric Rating Scale (rest and dynamic NRS) at fixed time points (1 hour and 6 hours after surgery, and at day 1 and day 2 at 8:00, 13:00 and 18:00 hours), walking performance at day 1 and day 2; postoperative complications including morphine-related side effects or orthostatic intolerance symptoms such as dizziness, nausea, blurred vision or vasovagal syncope.

Results

A 48-hour morphine consumption (mg; median (IQR)) was significantly lower in group R than in group C (11 (8.5–15.5)) vs 26 (21–33.5), p<0001), as well as incidence of morphine-related side effects such as nausea at day 1 (p=0.04) and day 2 (p<0.01). Rest and dynamic NRS were globally significantly lower in group R than in group C (p<0.01). Group R showed less orthostatic intolerance at day 1 (p<0.001) and day 2 (p<0.01) and better functional walking performance at day 1 (<0.001) and day 2 (<0.001).

Discussion

In PLTHA, SFICB provides opioid sparing, improved postoperative pain control, and enhanced functional recovery.

Trial registration number

NCT04574479.
Comparison of postoperative analgesic effects of posterior quadratus lumborum block and intrathecal morphine in laparoscopic donor hepatectomy: a prospective randomized non-inferiority clinical trial
Authors: Lee Seungwon , Kang Ryung A , Kim Gaab Soo , Gwak Mi Sook , Choi Gyu-Seong , Kim Jong Man , Ko Justin Sangwook
Published: June 2022

Background

Posterior quadratus lumborum block (QLB) and intrathecal morphine are accepted analgesic strategies in laparoscopic liver resection, but their effects have not been compared after laparoscopic donor hepatectomy. This study was planned to perform this comparison.

Methods

Fifty-six donors were randomized to receive bilateral posterior (QLB2, 20 mL of 0.375% ropivacaine on each side, 150 mg total) or preoperative injection of 0.4 mg morphine sulfate intrathecally. Primary outcome was resting pain score at 24 hour postsurgery. Secondary outcomes included cumulative opioid consumption and recovery parameters. Serial plasma ropivacaine concentrations were measured in QLB group. Only the outcome assessor was properly blinded.

Results

Mean resting pain score at 24-hour postsurgery was 4.19±1.66 in QLB group (n=27) and 3.07±1.41 in intrathecal morphine group (n=27, p=0.04). Mean difference (QLB group-intrathecal morphine group) was 1.11 (95% CI 0.27 to 1.95), and the upper limit of CI was higher than prespecified non-inferiority margin (δ=1), indicating an inferior effect of QLB. Cumulative opioid consumption was significantly higher in QLB group at 24 hours and 48 hours postsurgery. QLB group exhibited lower incidence of postoperative pruritus at all time points, and there were no differences in other recovery outcomes. All measured ropivacaine concentrations were below the threshold for systemic toxicity (4.3 µg/mL).

Conclusions

Bilateral posterior QLB elicited higher resting pain scores at 24-hour after laparoscopic donor hepatectomy than intrathecal morphine and did not meet the definition of non-inferiority.

Trial registration number

KCT0005360.