bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of survival to immunotherapy and chemoimmunotherapy in non-small cell lung cancer: A meta-analysis
Authors: Di Federico Alessandro , De Giglio Andrea , Gelsomino Francesco , Sperandi Francesca , Melotti Barbara , Ardizzoni Andrea
Published: November 2022

Background

Many patients with non-small cell lung cancer (NSCLC) derive poor benefit from immunotherapy (IO). For some of them, adding chemotherapy (CT) can improve the outcomes, but the reliability of programmed death–ligand 1 (PD-L1) expression as the only biomarker to distinguish these patients is unsatisfactory. We sought to detect clinicopathological and molecular predictive factors of survival that might be added to PD-L1 expression in the selection of patients who should receive IO alone or chemoimmunotherapy (CIT).

Methods

We conducted a systematic search of randomized controlled clinical trials investigating IO, alone or with CT, vs CT alone in treatment-naïve advanced NSCLC patients. Meta-analyses and meta-regression analyses were performed to investigate IO alone vs CT, CIT vs CT, and IO alone vs CIT.

Results

A total of 14 367 patients with advanced NSCLC across 25 randomized controlled clinical trials were included. Squamous histology, male sex, current and former smoker status, PD-L1 expression of 50% or more, and high tumor mutational burden (TMB) correlated with improved survival with IO alone compared with CT. Conversely, female sex, no smoking history, negative PD-L1 expression, and low TMB correlated with unsatisfactory outcomes with IO alone vs CT but not with CIT vs CT. CIT improved survival vs IO alone in female patients, never smokers, those having a PD-L1 expression of 1% or more (but not with a PD-L1 of  ≥ 50%) or a low TMB and in patients with central nervous system metastasis.

Conclusions

These findings suggest some clinicopathological and molecular features that, added to PD-L1 expression, could help in the selection of the most appropriate first-line IO-based treatment for advanced NSCLC patients.
Planning study: prone versus supine position for stereotactic body radiotherapy in prostate by CyberKnife
Authors: Kon Mitsuhiro , Okamoto Hiroyuki , Nakamura Satoshi , Iijima Kotaro , Chiba Takahito , Takemori Mihiro , Nakayama Hiroki , Nakaichi Tetsu , Mikasa Shohei , Fujii Kyohei , Urago Yuka , Ishikawa Masayori , Sofue Toshimitsu , Katsuta Shoichi , Inaba Koji , Igaki Hiroshi , Aso Tomohiko
Published: November 2022

This study aimed to clarify the differences in radiotherapy dose characteristics and delivery efficiency between the supine and prone positions in patients with prostate cancer using the CyberKnife. The planning computed tomography (CT) and delineations of the prone position were obtained by rotating the supine CT images with delineations of 180° using image processing software. The optimization parameters for planning target volume (PTV) and organs at risk (OARs) were based on the prone position. The optimization parameters determined for the prone position were applied to the supine position for optimization and dose calculation. The dosimetric characteristics of the PTV and OARs, and delivery efficiency were compared between the two different patient positions. The plans in the prone position resulted in better PTV conformity index (nCI), rectum V90%, V80%, V75%, V50% and bladder V50%. A significant difference was observed in treatment time and depth along the central axis (dCAX) between the two plans. The mean treatment time per fraction and dCAX for the supine and prone positions were 20.9 ± 1.7 min versus 19.8 ± 1.3 min (P = 0.019) and 151.1 ± 33.6 mm versus 233.2 ± 8.8 mm (P < 0.001), respectively. In this study the prone position was found to improve dosimetric characteristics and delivery efficiency compared with the supine position during prostate cancer treatment with the CyberKnife.
STRIDES: automated uniform models for 30 quadruply imaged quasars
Authors: Schmidt T , Treu T , Birrer S , Shajib A J , Lemon C , Millon M , Sluse D , Agnello A , Anguita T , Auger-Williams M W , McMahon R G , Motta V , Schechter P , Spiniello C , Kayo I , Courbin F , Ertl S , Fassnacht C D , Frieman J A , More A , Schuldt S , Suyu S H , Aguena M , Andrade-Oliveira F , Annis J , Bacon D , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Conselice C , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Doel P , Everett S , Ferrero I , Friedel D , García-Bellido J , Gaztanaga E , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Lahav O , Menanteau F , Miquel R , Palmese A , Paz-Chinchón F , Pieres A , Plazas Malagón A A , Prat J , Rodriguez-Monroy M , Romer A K , Sanchez E , Scarpine V , Sevilla-Noarbe I , Smith M , Suchyta E , Tarle G , To C , Varga T N ,   (DES Collaboration)
Published: November 2022

Gravitational time delays provide a powerful one-step measurement of H0, independent of all other probes. One key ingredient in time-delay cosmography are high-accuracy lens models. Those are currently expensive to obtain, both, in terms of computing and investigator time (105–106 CPU hours and ∼0.5–1 yr, respectively). Major improvements in modelling speed are therefore necessary to exploit the large number of lenses that are forecast to be discovered over the current decade. In order to bypass this roadblock, we develop an automated modelling pipeline and apply it to a sample of 31 lens systems, observed by the Hubble Space Telescope in multiple bands. Our automated pipeline can derive models for 30/31 lenses with few hours of human time and <100 CPU hours of computing time for a typical system. For each lens, we provide measurements of key parameters and predictions of magnification as well as time delays for the multiple images. We characterize the cosmography-readiness of our models using the stability of differences in the Fermat potential (proportional to time delay) with respect to modelling choices. We find that for 10/30 lenses, our models are cosmography or nearly cosmography grade (<3 per cent and 3–5 per cent variations). For 6/30 lenses, the models are close to cosmography grade (5–10 per cent). These results utilize informative priors and will need to be confirmed by further analysis. However, they are also likely to improve by extending the pipeline modelling sequence and options. In conclusion, we show that uniform cosmography grade modelling of large strong lens samples is within reach.
Genomic Analyses Reveal Association of ASIP with a Recurrently evolving Adaptive Color Pattern in Frogs
Authors: Goutte Sandra , Hariyani Imtiyaz , Utzinger Kole Deroy , Bourgeois Yann , Boissinot Stéphane
Published: November 2022

Traits shared among distantly related lineages are indicators of common evolutionary constraints, at the ecological, physiological, or molecular level. Here, we show that the vertebral stripe, a cryptic color pattern, has evolved hundreds of times in the evolutionary history of anurans (frogs and toads) and is favored in terrestrial habitats. Using a genome-wide association study, we demonstrate that variation near the Agouti signaling protein gene (ASIP) is responsible for the different vertebral stripe phenotypes in the African grass frog Ptychadena robeensis. RNAseq and real-time quantitative PCR revealed that differential expression of the gene and an adjacent long non-coding RNA is linked to patterning in this species. Surprisingly, and although the stripe phenotypes are shared with closely related species, we found that the P. robeensis alleles are private to the species and unlikely to evolve under long-term balancing selection, thus indicating that the vertebral stripe phenotypes result from parallel evolution within the group. Our findings demonstrate that this cryptic color pattern evolved rapidly and recurrently in terrestrial anurans, and therefore constitutes an ideal system to study repeated evolution.
Ensembl 2023
Authors: Martin Fergal J , Amode M Ridwan , Aneja Alisha , Austine-Orimoloye Olanrewaju , Azov Andrey G , Barnes If , Becker Arne , Bennett Ruth , Berry Andrew , Bhai Jyothish , Bhurji Simarpreet Kaur , Bignell Alexandra , Boddu Sanjay , Branco Lins Paulo R , Brooks Lucy , Ramaraju Shashank Budhanuru , Charkhchi Mehrnaz , Cockburn Alexander , Da Rin Fiorretto Luca , Davidson Claire , Dodiya Kamalkumar , Donaldson Sarah , El Houdaigui Bilal , El Naboulsi Tamara , Fatima Reham , Giron Carlos Garcia , Genez Thiago , Ghattaoraya Gurpreet S , Martinez Jose Gonzalez , Guijarro Cristi , Hardy Matthew , Hollis Zoe , Hourlier Thibaut , Hunt Toby , Kay Mike , Kaykala Vinay , Le Tuan , Lemos Diana , Marques-Coelho Diego , Marugán José Carlos , Merino Gabriela Alejandra , Mirabueno Louisse Paola , Mushtaq Aleena , Hossain Syed Nakib , Ogeh Denye N , Sakthivel Manoj Pandian , Parker Anne , Perry Malcolm , Piližota Ivana , Prosovetskaia Irina , Pérez-Silva José G , Salam Ahamed Imran Abdul , Saraiva-Agostinho Nuno , Schuilenburg Helen , Sheppard Dan , Sinha Swati , Sipos Botond , Stark William , Steed Emily , Sukumaran Ranjit , Sumathipala Dulika , Suner Marie-Marthe , Surapaneni Likhitha , Sutinen Kyösti , Szpak Michal , Tricomi Francesca Floriana , Urbina-Gómez David , Veidenberg Andres , Walsh Thomas A , Walts Brandon , Wass Elizabeth , Willhoft Natalie , Allen Jamie , Alvarez-Jarreta Jorge , Chakiachvili Marc , Flint Bethany , Giorgetti Stefano , Haggerty Leanne , Ilsley Garth R , Loveland Jane E , Moore Benjamin , Mudge Jonathan M , Tate John , Thybert David , Trevanion Stephen J , Winterbottom Andrea , Frankish Adam , Hunt Sarah E , Ruffier Magali , Cunningham Fiona , Dyer Sarah , Finn Robert D , Howe Kevin L , Harrison Peter W , Yates Andrew D , Flicek Paul
Published: November 2022

Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.
SEdb 2.0: a comprehensive super-enhancer database of human and mouse
Authors: Wang Yuezhu , Song Chao , Zhao Jun , Zhang Yuexin , Zhao Xilong , Feng Chenchen , Zhang Guorui , Zhu Jiang , Wang Fan , Qian Fengcui , Zhou Liwei , Zhang Jian , Bai Xuefeng , Ai Bo , Liu Xinyu , Wang Qiuyu , Li Chunquan
Published: November 2022

Super-enhancers (SEs) are cell-specific DNA cis-regulatory elements that can supervise the transcriptional regulation processes of downstream genes. SEdb 2.0 (http://www.licpathway.net/sedb) aims to provide a comprehensive SE resource and annotate their potential roles in gene transcriptions. Compared with SEdb 1.0, we have made the following improvements: (i) Newly added the mouse SEs and expanded the scale of human SEs. SEdb 2.0 contained 1 167 518 SEs from 1739 human H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) samples and 550 226 SEs from 931 mouse H3K27ac ChIP-seq samples, which was five times that of SEdb 1.0. (ii) Newly added transcription factor binding sites (TFBSs) in SEs identified by TF motifs and TF ChIP-seq data. (iii) Added comprehensive (epi)genetic annotations of SEs, including chromatin accessibility regions, methylation sites, chromatin interaction regions and topologically associating domains (TADs). (iv) Newly embedded and updated search and analysis tools, including ‘Search SE by TF-based’, ‘Differential-Overlapping-SE analysis’ and ‘SE-based TF–Gene analysis’. (v) Newly provided quality control (QC) metrics for ChIP-seq processing. In summary, SEdb 2.0 is a comprehensive update of SEdb 1.0, which curates more SEs and annotation information than SEdb 1.0. SEdb 2.0 provides a friendly platform for researchers to more comprehensively clarify the important role of SEs in the biological process.
Twenty-five years of Genomes OnLine Database (GOLD): data updates and new features in v.9
Authors: Mukherjee Supratim , Stamatis Dimitri , Li Cindy Tianqing , Ovchinnikova Galina , Bertsch Jon , Sundaramurthi Jagadish Chandrabose , Kandimalla Mahathi , Nicolopoulos Paul A , Favognano Alessandro , Chen I-Min A , Kyrpides Nikos C , Reddy T B K
Published: November 2022

The Genomes OnLine Database (GOLD) (https://gold.jgi.doe.gov/) at the Department of Energy Joint Genome Institute (DOE-JGI) continues to maintain its role as one of the flagship genomic metadata repositories of the world. The ever-increasing number of projects and metadata are freely available to the user community world-wide. GOLD’s metadata is consumed by scientists and remains an important source for large-scale comparative genomics analysis initiatives. Encouraged by this active user engagement and growth, GOLD has continued to add new components and capabilities. The new features such as a public Application Programming Interface (API) and Ecosystem landing page as well as the growth of different entities in this current GOLD v.9 edition are described in detail in this manuscript.
ARL13B promotes angiogenesis and glioma growth by activating VEGFA-VEGFR2 signaling
Authors: Chen Limin , Xie Xinsheng , Wang Tiantian , Xu Linlin , Zhai Zhenyu , Wu Haibin , Deng Libin , Lu Quqin , Chen Zhengjun , Yang Xiao , Lu Hua , Chen Ye-Guang , Luo Shiwen
Published: November 2022

Background

Tumor angiogenesis is essential for solid tumor progression, invasion and metastasis. The aim of this study was to identify potential signaling pathways involved in tumor angiogenesis.

Methods

Genetically engineered mouse models were used to investigate the effects of endothelial ARL13B(ADP-ribosylation factor-like GTPase 13B) over-expression and deficiency on retinal and cerebral vasculature. An intracranially transplanted glioma model and a subcutaneously implanted melanoma model were employed to examine the effects of ARL13B on tumor growth and angiogenesis. Immunohistochemistry was used to measure ARL13B in glioma tissues, and scRNA-seq was used to analyze glioma and endothelial ARL13B expression. GST-fusion protein-protein interaction and co-immunoprecipitation assays were used to determine the ARL13B-VEGFR2 interaction. Immunobloting, qPCR, dual-luciferase reporter assay and functional experiments were performed to evaluate the effects of ARL13B on VEGFR2 activation.

Results

Endothelial ARL13B regulated vascular development of both the retina and brain in mice. Also, ARL13B in endothelial cells regulated the growth of intracranially transplanted glioma cells and subcutaneously implanted melanoma cells by controlling tumor angiogenesis. Interestingly, this effect was attributed to ARL13B interaction with VEGFR2, through which ARL13B regulated the membrane and ciliary localization of VEGFR2 and consequently activated its downstream signaling in endothelial cells. Consistent with its oncogenic role, ARL13B was highly expressed in human gliomas, which was well correlated with the poor prognosis of glioma patients. Remarkably, ARL13B, transcriptionally regulated by ZEB1, enhanced the expression of VEGFA by activating Hedgehog signaling in glioma cells.

Conclusions

ARL13B promotes angiogenesis and tumor growth by activating VEGFA-VEGFR2 signaling. Thus, targeting ARL13B might serve as a potential approach for developing an anti-glioma or anti-melanoma therapy.
Models for Zero-Inflated and Overdispersed Correlated Count Data: An Application to Cigarette Use
Authors: Pittman Brian , Buta Eugenia , Garrison Kathleen , Gueorguieva Ralitza
Published: November 2022

Introduction

Count outcomes in tobacco research are often analyzed with the Poisson distribution. However, they often exhibit features such as overdispersion (variance larger than expected) and zero inflation (extra zeros) that violate model assumptions. Furthermore, longitudinal studies have repeated measures that generate correlated counts. Failure to account for overdispersion, zero inflation, and correlation can yield incorrect statistical inferences. Thus, it is important to familiarize researchers with proper models for such data.

Aims and Methods

Poisson and Negative Binomial models with correlated random effects with and without zero inflation are presented. The illustrative data comes from a study comparing a mindfulness training app (Craving to Quit [C2Q], n = 60) with a control app (experience sampling-only app, n = 66) on smoking frequency at 1, 3, and 6 months. Predictors include app, time, the app-by-time interaction, and baseline smoking. Each model is evaluated in terms of accounting for zero inflation, overdispersion, and correlation in the data. Emphasis is placed on evaluating model fit, subject-specific interpretation of effects, and choosing an appropriate model.

Results

The hurdle Poisson model provided the best fit to the data. Smoking abstinence rates were 33%, 32%, and 28% at 1, 3, and 6 months, respectively, with variance larger than expected by a factor >7 at each follow-up. Individuals on C2Q were less likely to achieve abstinence across time but likely to smoke fewer cigarettes if smoking.

Conclusions

The models presented are specifically suited for analyzing correlated count outcomes and account for zero inflation and overdispersion. We provide guidance to researchers on the use of these models to better inform nicotine and tobacco research.

Implications

In tobacco research, count outcomes are often measured repeatedly on the same subject and thus correlated. Such outcomes often have many zeros and exhibit large variances relative to the mean. Analyzing such data require models specifically suited for correlated counts. The presented models and guidelines could improve the rigor of the analysis of correlated count data and thus increase the impact of studies in nicotine and tobacco research using such outcomes.
Slaves and War
Authors: Ducrey Pierre
Published: November 2022

Abstract and Keywords

War, piracy, and banditry resulted in people’s enslavement and were sources of supply for the slave workforce. Many slaves in Graeco-Roman society were the product of conflict, though uncertainties often remain about precise numbers. War was primarily the business of citizens and free men. However, it was normal for armies to include slaves as attendants. In the Greek world, in particular, slaves frequently served as rowers in the fleet; they could also sometimes be involved as combatants in land warfare, especially when conscripted in crisis situations—although it is frequently impossible to calculate numbers of slave combatants. Some slaves took more active initiatives, volunteering to fight or provide logistical support for the state in which they resided, fleeing from servitude, or assisting the enemy. Occasionally, slaves initiated and fought wars of rebellion, especially in late Republican Rome. The roles and impact of slaves in war were often significant, if incalculable.
Cluster formation in neutron-rich Be and B isotopes
Authors: Motoki Hideaki , Suzuki Yoshiki , Kawai Tsuyoshi , Kimura Masaaki
Published: November 2022

Evaluating the formation of clusters in finite and infinite nuclear systems is a fundamental problem in nuclear physics, and the variation in clustering in the isotope chain up to the neutron drip-line is one such intriguing phenomenon. Recently, experiments performed using the (p, pα) reactions have revealed a negative correlation between α-cluster formation and neutron number in Sn isotopes, showing a trend opposite to that theoretically predicted for Be and B isotopes. Although the observed charge radii of the Be and B isotopes suggest the formation of clusters as the neutron drip-line is approached, these radii themselves are not a physical quantity that can directly probe the cluster structure. Here, we directly investigate the cluster formation in Be and B isotopes to elucidate the possibility of clustering as the neutron drip-line is approached. It has been shown that the sum of the S-factors (i.e., S(α), S(6He), and S(8He)) increases as the neutron drip-line approaches, in agreement with those of previous studies. The results indicate that the excess neutrons contribute to the formation of 6He and 8He clusters as well as α clusters. Thus, S(α) is not sufficient to estimate the enhancement of clustering in Be and B isotopes.
Clinical Hypnosis for Pediatric Gastrointestinal Disorders
Authors: Chogle Ashish , Lee Amanda , Santucci Neha R. , Yeh Ann Ming , Prozialeck Joshua D. , Borlack Rachel E. , van Tilburg Miranda A.L.
Published: November 2022

Functional abdominal pain disorders (FAPDs) are common in the pediatric population and are associated with a significant reduction in quality of life. Bidirectional communication of the brain‐gut axis plays an important role in pain generation and perception in FAPDs. There is a paucity of data on the best approach to treat this group of disorders, with no Food and Drug Administration (FDA)‐approved drugs and scarce research to substantiate the use of most medications. Use of hypnosis in pediatric FAPDs is supported by evidence and has long‐term benefits of up to at least 5 years beyond completion of treatment, highlighting the importance of incorporating this therapy into the care of these patients. The mechanisms by which clinical hypnosis is beneficial in the treatment of FAPDs is not completely understood, but there is growing evidence that it impacts functioning of the brain‐gut axis, potentially through influence on central pain processing, visceral sensitivity, and motility. The lack of side effects or potential for significant harm and low cost makes it an attractive option compared to pharmacologic therapies. This review addresses current barriers to clinical hypnosis including misconceptions among patients and families, lack of trained clinicians, and questions around insurance reimbursement. The recent use of telemedicine and delivery of hypnosis via audio‐visual modalities allow more patients to benefit from this treatment. As the evidence base for hypnosis grows, acceptance and training will likely increase as well. Further research is needed to understand how hypnosis works and to develop tools that predict who is most likely to respond to hypnosis. Studies on cost‐effectiveness in comparing hypnosis to other therapies for FAPDs will increase evidence for appropriate healthcare utilization. Because hypnosis has applications beyond pain and is child‐friendly with minimal to no risk, hypnosis could be an important therapeutic tool in the wider pediatric gastrointestinal population.
Childhood deprivation and Health related quality of life and associated factors among Pediatric cancer patients at National Hospital, Tanzania
Authors: Chubi Mwanaheri , Kibusi Stephen , Chirande Lulu , Juma Shakiru
Published: November 2022

Introduction

Pediatrics cancer is one of the most important life-threatening, non-communicable diseases worldwide. However, pediatric cancer patients suffer from physical disabilities associated with cancer treatment. However, there is unclear information about level of health-related quality of life and associated factors. Aimed of this study was to assess level of Health-Related Quality of Life among pediatric cancer patients.

Methods

A hospital-based Analytical cross-sectional study design with a quantitative approach was employed among 91 conveniently sampled pediatric cancer patients with their parents/caregivers. Self-administered questionnaires were used to collect data. Data were analyzed using SPSS computer software program version 25. One-way ANOVA and linear regression were used to quantify and establish an association between Childhood Deprivation, Health-Related Quality of Life, and associated factors among Pediatric Cancer Patients at 95% CI, and a 5% level of significance.

Results

Results, the response rate was 92.3% (n = 84). The most prominent kind of pediatric cancer was Acute Lymphoblastic Leukemia 30 (35.7%) and Hodgkin lymphoma 11(13%). The mean age of pediatric cancer patients was 10.26±3.90 years while 59 (70.2%) were male. In linear regression, Childhood Deprivation (β=-1.640; P-value< 0.05) on PedsQL™ 4.0 and (β= -2.175; P-value< 0.01) on PedsQL™ 3.0. Findings imply that decreases the level of Childhood Deprivation, the chance of improving Quality of life increases.

Conclusion

The magnitude of acute lymphoblastic leukemia is higher among pediatric cancer patients. There was a significant link between pediatric cancers and childhood deprivation and thus, compromised quality of life. Innovative pediatric cancer care policies, guidelines, and or strategies may need to be advocated to address the problem accordingly.
The potential of resilience indicators to signal the risk of disease outbreaks, a systematic review and guide
Authors: Delecroix Clara , van Nes Egbert H. , van de Leemput Ingrid A. , Rotbarth Ronny , Scheffer Marten , Bosch Quirine ten
Published: November 2022

To reduce the consequences of infectious disease outbreaks, the timely implementation of public health measures is crucial. Currently used early-warning systems are highly context-dependent and require a long phase of model building. A proposed solution to anticipate the onset or termination of an outbreak is the use of so-called resilience indicators. These indicators are based on the generic theory of critical slowing down and require only incidence time series. Here we assess the potential for this approach to contribute to outbreak anticipation. We systematically reviewed studies that used resilience indicators to predict outbreaks or terminations of epidemics. We identified 37 studies meeting the inclusion criteria: 21 using simulated data and 16 real-world data. 36 out of 37 studies detected significant signs of critical slowing down before a critical transition (i.e., the onset or end of an outbreak), with a sensitivity (i.e., the proportion of true positive outbreak warnings) ranging from 0.67 to 1 and a lead time ranging from 10 days to 68 months. Challenges include low resolution and limited length of time series, a too rapid increase in cases, and strong seasonal patterns which may hamper the sensitivity of resilience indicators. Alternative types of data, such as Google searches or social media data, have the potential to improve predictions in some cases. Resilience indicators may be useful when the risk of disease outbreaks is changing gradually. This may happen, for instance, when pathogens become increasingly adapted to an environment or evolve gradually to escape immunity. High-resolution monitoring is needed to reach sufficient sensitivity. If those conditions are met, resilience indicators could help improve the current practice of prediction, facilitating timely outbreak response. We provide a step-by-step guide on the use of resilience indicators in infectious disease epidemiology, and guidance on the relevant situations to use this approach.
Long-term humoral response following simultaneous Delta and Omicron BA.1 co-infection
Authors: Saade Carla , Pozzetto Bruno , Novoa Melyssa Yaugel , Lina Bruno , Paul Stéphane , Bal Antonin , Trouillet-Assant Sophie
Published: November 2022

To provide insight into the long-term immune response following bivalent vaccines, we sampled vaccinated patients simultaneously co-infected with Delta and BA.1. We reported that simultaneous exposure to the Delta and BA.1 S protein does not confer an additional immune advantage compared to exposure to the Omicron BA.1 S protein alone.
Autism Classification using Visual and Behavioral Data
Authors: Hriti Nafisa Sadaf , Shaer Karishma , Momin Farhan M Nafis , Mahmud Hasan , Hasan Md. Kamrul
Published: November 2022

1

Currently Autism Spectrum Disorder (ASD) is diagnosed via the combination of multiple medical tools and screening tests that require extensive amounts of time and money. Autism diagnosis can be formulated as a typical machine learning classification problem between ASD patients and a control group consisting of neurotypical individuals. In order for this to yield accurate results, large datasets with different modalities are required. However, the unavailability of such robust datasets stands as a threat to this automated diagnosis. To resolve this, we propose a method of Autism Classification using Visual and Behavioral Data. The proposed technique relates datasets of two modalities (visual and behavioral) collected from similar participants by generating common attributes among the records and distributing these records into sub classes. Then records within these subclasses are combined to form an integrated dataset. Finally, decision level fusion is performed on the multimodal data. The main contribution of our work can be outlined as follows: an accuracy of 97.57% in autism classification has been obtained from the integrated data, which is higher than detection from only visual data, we have shown that combining data within sub classes based on common attributes is more accurate than combining them arbitrarily, and finally, we have introduced a novel, integrated multimodal dataset in the ASD domain.
Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents
Authors: Rudovich Anton S. , Peřina Miroslav , Krech Anastasiya V. , Novozhilova Maria Y. , Tumilovich Anastasia M , Shkel Tatyana V. , Grabovec Irina P. , Kvasnica Miroslav , Mada Lukáš , Zavialova Maria G. , Mekhtiev Arif R. , Jorda Radek , Zhabinskii Vladimir N. , Khripach Vladimir A.
Published: November 2022

Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3β-hydroxy-5-ene steroids containing an isoxazole fragment in the side chain was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used. The biological activity of the obtained compounds was studied in a number of tests, including their effects on 17α-hydroxylase and 17,20-lyase activity of human CYP17A1 and the ability of selected compounds to affect the downstream androgen receptor signaling. Three derivatives diminished the transcriptional activity of androgen receptor and displayed reasonable antiproliferative activity. The candidate compound24j, (17R)-17-((3-(2-hydroxy-propan-2-yl)isoxazol-5-yl)methyl)-androst-5-en-3β-ol, suppressed the androgen receptor signaling and decreased its protein level in two prostate cancer cell lines, LNCaP and LAPC-4. Interaction of compounds with CYP17A1 and androgen receptor was confirmed and described by molecular docking.
Internal Validation of the ForenSeq Kintelligence Kit for Application to Forensic Genetic Genealogy
Authors: Peck Michelle A. , Koeppel Alexander F. , Gorden Erin M. , Bouchet Jessica L. , Heaton Mary C. , Russell David A. , Reedy Carmen R. , Neal Christina M. , Turner Stephen D.
Published: November 2022

Forensic Genetic Genealogy (FGG) requires high density single nucleotide polymorphism (SNP) profiles to infer distant relationships. The ForenSeq Kintelligence kit is a recently developed method targeting approximately 10,000 SNPs that were selected to be compatible with genetic genealogy databases, while avoiding medically relevant SNPs. The targeted PCR method is ideal for low input and degraded samples, which are particularly challenging for microarray analysis. We made modifications to library preparation and sample pooling to further enhance the performance of low input samples. To align this FGG method with forensic laboratory standards, we performed an internal validation study in accordance with the Scientific Working Group on DNA Analysis Methods Validation Guidelines for DNA Analysis Methods. The sensitivity and precision and accuracy studies produced accurate and reliable profiles down to 0.05 ng of DNA. The mixture and contamination studies demonstrated that the method could detect the presence of a minor contributor down to 0.02 ng, while system wide contamination was negligible. Nonprobative bone, fired shell casing, and adhesive tape samples performed well with inputs ranging from 0.05 to 1.0 ng of DNA. A bone with a high degradation index and tested at 0.1 ng DNA input resulted in a call rate of 92.9% and a heterozygosity rate of 0.387. We demonstrated the importance of both call rate and heterozygosity rate to assess profile performance. Validating FGG methods is critical to ensuring the reliability and utility of SNP profiles that will be uploaded to genetic genealogy databases for the purpose of generating investigative leads.
Entomopathogen-host evolution and implications for biopesticide resistance management
Authors: Roberts Jeremy P. , Northfield Tobin D.
Published: November 2022

Insecticide resistance evolution is becoming increasingly problematic globally. With chemical insecticides, attempts to combat resistance involves developing compounds with novel modes of action, or increasing rates to overcome partial resistance. While pests can develop resistance to pathogens used as biopesticides, these “pesticides” can be subjected to evolutionary selection pressure as well and may be able to adapt countermeasures to overcome pest resistance. Here, we consider two scenarios: 1) a single trait governs an arms race between pest and parasite, and 2) an epidemiological scenario where each, pathogen transmission and virulence, are governed by host and pathogen traits. Considering the single-trait parasite attack scenario, the evolving parasite is able to overcome resistance in the pest population and effectively suppress host population abundance. In this case, overcoming biopesticide resistance may be possible from parasite evolution to resistant hosts. In contrast, when transmission and abundance are allowed to vary independently in an epidemiological model, different pathogen traits promote different types of resistance development in the host – more contagious pathogens promote pathogen-tolerant (low mortality susceptibility) hosts, while less contagious pathogens promote pathogen-resistant (low transmission susceptibility) hosts. Pathogen-tolerant hosts are particularly detrimental to control programs, because they can quickly outcompete wild types by promoting infection in wild type populations. Furthermore, because evolution of pathogen-tolerance in pests can benefit pathogens through increasing infection prevalence, we do not expect pathogen evolution to improve control. Thus, the keys to biopesticide management depend on the virulence-transmission trade-off and whether hosts evolve to better prevent or survive infection.
Self-Assembly of Tunable Intrinsically Disordered Peptide Amphiphiles
Authors: Ehm Tamara , Shinar Hila , Jacoby Guy , Meir Sagi , Koren Gil , Segal Asher Merav , Korpanty Joanna , Thompson Matthew P. , Gianneschi Nathan C. , Kozlov Michael M. , Azoulay-Ginsburg Salome Emma , Amir Roey J. , Rädler Joachim O. , Beck Roy
Published: November 2022

Intrinsically disordered peptide amphiphiles (IDPAs) present a novel class of synthetic conjugates that consist of short hydrophilic polypeptides anchored to hydrocarbon chains. These hybrid polymer-lipid block constructs spontaneously self-assemble into dispersed nanoscopic aggregates or ordered mesophases in aqueous solution due to hydrophobic interactions.

Yet, the possible sequence variations and their influence on the self-assembly structures is vast and have hardly been explored.

Here, we measure the nanoscopic self-assembled structures of four IDPA systems that differ by their amino acid sequence. We show that permutations in the charge pattern along the sequence remarkably alter the headgroup conformation and consequently alters the pH-triggered phase transitions between spherical, cylindrical micelles and hexagonal condensed phases. We demonstrate that even a single amino acid mutation is sufficient to tune structural transitions in the condensed IDPA mesophases, while peptide conformations remain unfolded and disordered. Furthermore, alteration of the peptide sequence can render IDPAs to become susceptible to enzymatic cleavage and induces enzymatically activated phase transitions.

These results hold great potential for embedding multiple functionalities into lipid nanoparticle delivery systems by incorporating IDPAs with desired properties.
SUB-OPTIMAL ENVIRONMENTAL CONDITIONS PROLONG PHAGE EPIDEMICS IN BACTERIAL POPULATIONS
Authors: Goehlich Henry , Roth Olivia , Sieber Michael , Chibani Cynthia M. , Poehlein Anja , Rajkov Jelena , Liesegang Heiko , Wendling Carolin C.
Published: November 2022

Infections by filamentous phages influence bacterial fitness in various ways. While phage-encoded accessory genes, e.g., virulence genes, can be highly beneficial, the production of viral particles is energetically costly and often reduces bacterial growth. Consequently, if costs outweigh benefits, bacteria evolve resistance which can shorten phage epidemics. Abiotic conditions are known to influence the net-fitness effect for infected bacteria. Their impact on the dynamics and trajectories of host resistance evolution, however, remains yet unknown. To address this, we experimentally evolved the bacteriumVibrio alginolyticusin the presence of a filamentous phage at three different salinity levels, i.e., (1) ambient (2) 50% reduction, and (3) fluctuations between reduced and ambient. In all three salinities, bacteria rapidly acquired resistance through super infection exclusion (SIE), whereby phage-infected cells acquired immunity at the cost of reduced growth. Over time, SIE was gradually replaced by evolutionary fitter surface receptor mutants (SRM). This replacement was significantly faster at ambient and fluctuating conditions compared to the low saline environment. Our experimentally parameterized mathematical model explains that suboptimal environmental conditions, in which bacterial growth is slower, slow down phage resistance evolution ultimately prolonging phage epidemics. Our results imply that, if filamentous phages encode virulence genes, these may persist longer in bacterial populations at sub-optimal environmental conditions, which, in times of climate change, are becoming more frequent. Thus, our future ocean may favour the emergence of phage-born pathogenic bacteria, and impose a greater risk for disease outbreaks, impacting not only marine animals but also humans.
Different biological effects of exposure to far-UVC (222 nm) and near-UVC (254 nm) irradiation
Authors: Napoleão Tavares Renata Spagolla , Adamoski Douglas , Girasole Alessandra , Lima Ellen Nogueira , Justo-Junior Amauri da Silva , Domingues Romênia , Caznok Silveira Ana Clara , Marques Rafael Elias , de Carvalho Murilo , Ambrosio Andre Luis Berteli , Paes Leme Adriana Franco , Dias Sandra Martha Gomes
Published: November 2022

Ultraviolet C (UVC) light has long been used as a sterilizing agent, primarily through devices that emit at 254 nm. Depending on the dose and duration of exposure, UV 254 nm can cause erythema and photokeratitis and potentially cause skin cancer since it directly modifies nitrogenated nucleic acid bases. Filtered KrCl excimer lamps (emitting mainly at 222 nm) have emerged as safer germicidal tools and have even been proposed as devices to sterilize surgical wounds. All the studies that showed the safety of 222 nm analyzed cell number and viability, erythema generation, epidermal thickening, the formation of genetic lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs) and cancer-inducing potential. Although nucleic acids can absorb and be modified by both UV 254 nm and UV 222 nm equally, compared to UV 254 nm, UV 222 nm is more intensely absorbed by proteins (especially aromatic side chains), causing photooxidation and cross-linking. Here, in addition to analyzing DNA lesion formation, for the first time, we evaluated changes in the proteome and cellular pathways, reactive oxygen species formation, and metalloproteinase (MMP) levels and activity in full-thicknessin vitroreconstructed human skin (RHS) exposed to UV 222 nm. We also performed the longest (40 days)in vivostudy of UV 222 nm exposure in the HRS/J mouse model at the occupational threshold limit value (TLV) for indirect exposure (25 mJ/cm2) and evaluated overall skin morphology, cellular pathological alterations, CPD and 6-4PP formation and MMP-9 activity. Our study showed that processes related to reactive oxygen species and inflammatory responses were more altered by UV 254 nm than by UV 222 nm. Our chronicin vivoexposure assay using the TLV confirmed that UV 222 nm causes minor damage to the skin. However, alterations in pathways related to skin regeneration raise concerns about direct exposure to UV 222 nm.
One-stop analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform
Authors: Yu Fengchao , Teo Guo Ci , Kong Andy T. , Li Ginny Xiaohe , Demichev Vadim , Nesvizhskii Alexey I.
Published: November 2022

Liquid chromatography (LC) coupled with data-independent acquisition (DIA) mass spectrometry (MS) has been increasingly used in quantitative proteomics studies. Here, we present a fast and sensitive approach for direct peptide identification from DIA data, MSFragger-DIA, which leverages the unmatched speed of the fragment ion indexing-based search engine MSFragger. MSFragger-DIA conducts a database search of the DIA tandem mass (MS/MS) spectra prior to spectral feature detection and peak tracing across the LC dimension. We have integrated MSFragger-DIA into the FragPipe computational platform for seamless support of peptide identification and spectral library building from DIA, data dependent acquisition (DDA), or both data types combined. We compared MSFragger-DIA with other DIA tools, such as DIA-Umpire based workflow in FragPipe, Spectronaut, andin silicolibrary-based DIA-NN and MaxDIA. We demonstrated the fast and sensitive performance of MSFragger-DIA across a variety of sample types and data acquisition schemes, including single-cell proteomics, phosphoproteomics, and large-scale tumor proteome profiling studies.
Landscape variation in defense traits along gradients of multiple resources and mammalian herbivory
Authors: Mohanbabu Neha , Veldhuis Michiel P , Jung Dana , Ritchie Mark E
Published: November 2022

Variation in defense traits likely depends on access to different resources and risk from herbivory. Plant defense theories have predicted both positive and negative associations between defense traits and access to resources, but relatively few studies have explored intraspecific variation in defense traits along multiple resource and mammalian herbivory risk gradients. We assessed relationships between herbivory intensity, multiple resources, and plant defense traits using a widely distributed tropical savanna herb,Solanum incanum. As independent measures of risk from large mammal herbivores are rare, we used a satellite-based vegetation index to predict herbivory intensity at the landscape scale. We found that the satellite-based estimate of herbivory intensity was positively associated with browser abundance and total soil P, but negatively associated with rainfall. Intraspecific defense traits too varied substantially across sites (n=43) but only variation in spine density was associated with herbivory intensity and plant resources, such that spine density was positively associated with both rainfall and soil P, but bimodally associated with herbivory intensity. Taken together, it suggests that defenses maybe favored either where resources for defense are abundant under low but still present risk (i.e, at high rainfall sites) or where resource-expensive plant tissue is at high risk (i.e, at high soil P sites). This hints at the possibility of a shift from a resource-associated (bottom-up) to an herbivory-associated (top-down) control of allocation to defenses along an environmental gradient. Additionally, the independent effect of soil P on a carbon-based defense, spine density, suggests potential for resources that are not components of defenses to also influence allocation to defense traits. Thus, our study provides evidence for the influence of multiple drivers, resources, and herbivory intensity, on anti-herbivore defenses and their shifting relative importance on allocation to defenses along an environmental gradient.
Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ears
Authors: Wang Tian , Ling Angela H. , Billings Sara E. , Hosseini Davood K. , Vaisbuch Yona , Kim Grace S. , Atkinson Patrick J. , Sayyid Zahra N. , Aaron Ksenia A. , Wagh Dhananjay , Pham Nicole , Scheibinger Mirko , Ishiyama Akira , Maria Peter Santa , Blevins Nikolas H. , Jackler Robert K. , Heller Stefan , Lopez Ivan A. , Grillet Nicolas , Jan Taha A. , Cheng Alan G.
Published: November 2022

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe previously unknown markers of 25 sensory and non-sensory cell types, with genes of hair cell and supporting cell subtypes displaying striking divergence between mice and humans. We further uncovered transcriptomes unique to hair cell precursors, which we validated to be 14-fold more robust in vestibular schwannoma utricles, representing ongoing regeneration in humans. Lastly, trajectory analysis of the supporting cell-hair cell axis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including mTOR signaling and synaptogenesis. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ears and tools to stimulate human inner ear regeneration.