bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncolytic adenoviruses expressing checkpoint inhibitors for cancer therapy
Authors: Xie Daoyuan , Tian Yaomei , Hu Die , Wang Yuanda , Yang Yuling , Zhou Bailing , Zhang Rui , Ren Zhixiang , Liu Mohan , Xu Jie , Dong Chunyan , Zhao Binyan , Yang Li 
Published: November 2023

AbstractDespite the remarkable success of immune checkpoint inhibitors (ICIs), primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment (TME). Oncolytic viruses (OVs) can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts. Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy. According to the diverse immune cell landscapes among different types of tumors, we rationally and precisely generated three recombinant oncolytic adenoviruses (OAds): OAd-SIRPα-Fc, OAd-Siglec10-Fc and OAd-TIGIT-Fc. These viruses were designed to locally deliver SIRPα-Fc, Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47, CD24 or CD155, respectively, in the TME to achieve enhanced antitumor effects. Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors, while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+ T-cell-dominated tumors. Importantly, the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory. In addition, the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME. In summary, rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.
Health benefits and harms of mammography screening in older women (75+ years)—a systematic review
Authors: Mathieu Erin , Noguchi Naomi , Li Tong , Barratt Alexandra L. , Hersch Jolyn K. , De Bock Geertruida H. , Wylie Elizabeth J. , Houssami Nehmat 
Published: November 2023

Abstract
Background
There is little evidence on the balance between potential benefits and harms of mammography screening in women 75 years and older. The aim of this systematic review was to synthesise the evidence on the outcomes of mammography screening in women aged 75 years and older.

Methods
A systematic review of mammography screening studies in women aged 75 years and over.

Results
Thirty-six studies were included in this review: 27 observational studies and 9 modelling studies. Many of the included studies used no or uninformative comparison groups resulting in a potential bias towards the benefits of screening. Despite this, there was mixed evidence about the benefits and harms of continuing mammography screening beyond the age of 75 years. Some studies showed a beneficial effect on breast cancer mortality, and other studies showed no effect on mortality. Some studies showed some harms (false positive tests and recalls) being comparable to those in younger age-groups, with other studies showing increase in false positive screens and biopsies in older age-group. Although reported in fewer studies, there was consistent evidence of increased overdiagnosis in older age-groups.

Conclusion
There is limited evidence available to make a recommendation for/against continuing breast screening beyond the age of 75 years. Future studies should use more informative comparisons and should estimate overdiagnosis given potentially substantial harm in this age-group due to competing causes of death.
This review was prospectively registered with PROSPERO (CRD42020203131).
INPP5D regulates inflammasome activation in human microglia
Authors: Chou Vicky , Pearse Richard V. , Aylward Aimee J. , Ashour Nancy , Taga Mariko , Terzioglu Gizem , Fujita Masashi , Fancher Seeley B. , Sigalov Alina , Benoit Courtney R. , Lee Hyo , Lam Matti , Seyfried Nicholas T. , Bennett David A. , De Jager Philip L. , Menon Vilas , Young-Pearse Tracy L. 
Published: November 2023

AbstractMicroglia and neuroinflammation play an important role in the development and progression of Alzheimer’s disease (AD). Inositol polyphosphate-5-phosphatase D (INPP5D/SHIP1) is a myeloid-expressed gene genetically-associated with AD. Through unbiased analyses of RNA and protein profiles in INPP5D-disrupted iPSC-derived human microglia, we find that reduction in INPP5D activity is associated with molecular profiles consistent with disrupted autophagy and inflammasome activation. These findings are validated through targeted pharmacological experiments which demonstrate that reduced INPP5D activity induces the formation of the NLRP3 inflammasome, cleavage of CASP1, and secretion of IL-1β and IL-18. Further, in-depth analyses of human brain tissue across hundreds of individuals using a multi-analytic approach provides evidence that a reduction in function of INPP5D in microglia results in inflammasome activation in AD. These findings provide insights into the molecular mechanisms underlying microglia-mediated processes in AD and highlight the inflammasome as a potential therapeutic target for modulating INPP5D-mediated vulnerability to AD.
Contribution of pks+ E. coli mutations to colorectal carcinogenesis
Authors: Chen Bingjie , Ramazzotti Daniele , Heide Timon , Spiteri Inmaculada , Fernandez-Mateos Javier , James Chela , Magnani Luca , Graham Trevor A. , Sottoriva Andrea 
Published: November 2023

AbstractThe dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from cancer patients, matched to a previous multi-omic tumour dataset. We analyse normal crypts that were distant vs adjacent to the cancer. In contrast to healthy individuals, normal crypts of colon cancer patients have a high incidence of pks + (polyketide synthases) E.coli (Escherichia coli) mutational and indel signatures, and this is confirmed by metagenomics. These signatures are compatible with many clonal driver mutations detected in the corresponding cancer samples, including in chromatin modifier genes, supporting their role in early tumourigenesis. These results provide evidence that pks + E.coli is a potential driver of carcinogenesis in the human gut.
PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma
Authors: Cappuyns Sarah , Philips Gino , Vandecaveye Vincent , Boeckx Bram , Schepers Rogier , Van Brussel Thomas , Arijs Ingrid , Mechels Aurelie , Bassez Ayse , Lodi Francesca , Jaekers Joris , Topal Halit , Topal Baki , Bricard Orian , Qian Junbin , Van Cutsem Eric , Verslype Chris , Lambrechts Diether , Dekervel Jeroen 
Published: November 2023

AbstractThe combination of atezolizumab plus bevacizumab (atezo/bev) has dramatically changed the treatment landscape of advanced HCC (aHCC), achieving durable responses in some patients. Using single-cell transcriptomics, we characterize the intra-tumoural and peripheral immune context of patients with aHCC treated with atezo/bev. Tumours from patients with durable responses are enriched for PDL1+ CXCL10+ macrophages and, based on cell–cell interaction analysis, express high levels of CXCL9/10/11 and are predicted to attract peripheral CXCR3+ CD8+ effector-memory T cells (CD8 TEM) into the tumour. Based on T cell receptor sharing and pseudotime trajectory analysis, we propose that CD8 TEM preferentially differentiate into clonally-expanded PD1- CD45RA+ effector-memory CD8+ T cells (CD8 TEMRA) with pronounced cytotoxicity. In contrast, in non-responders, CD8 TEM remain frozen in their effector-memory state. Finally, in responders, CD8 TEMRA display a high degree of T cell receptor sharing with blood, consistent with their patrolling activity. These findings may help understand the possible mechanisms underlying response to atezo/bev in aHCC.
Local adaptation and future climate vulnerability in a wild rodent
Authors: Marková Silvia , Lanier Hayley C. , Escalante Marco A. , da Cruz Marcos O. R. , Horníková Michaela , Konczal Mateusz , Weider Lawrence J. , Searle Jeremy B. , Kotlík Petr 
Published: November 2023

AbstractAs climate change continues, species pushed outside their physiological tolerance limits must adapt or face extinction. When change is rapid, adaptation will largely harness ancestral variation, making the availability and characteristics of that variation of critical importance. Here, we used whole-genome sequencing and genetic-environment association analyses to identify adaptive variation and its significance in the context of future climates in a small Palearctic mammal, the bank vole (Clethrionomys glareolus). We found that peripheral populations of bank vole in Britain are already at the extreme bounds of potential genetic adaptation and may require an influx of adaptive variation in order to respond. Analyses of adaptive loci suggest regional differences in climate variables select for variants that influence patterns of population adaptive resilience, including genes associated with antioxidant defense, and support a pattern of thermal/hypoxic cross-adaptation. Our findings indicate that understanding potential shifts in genomic composition in response to climate change may be key to predicting species’ fate under future climates.
Unlocking the mysterious polytypic features within vaterite CaCO3
Authors: San Xingyuan , Hu Junwei , Chen Mingyi , Niu Haiyang , Smeets Paul J. M. , Malliakas Christos D. , Deng Jie , Koo Kunmo , dos Reis Roberto , Dravid Vinayak P. , Hu Xiaobing 
Published: November 2023

AbstractCalcium carbonate (CaCO3), the most abundant biogenic mineral on earth, plays a crucial role in various fields such as hydrosphere, biosphere, and climate regulation. Of the four polymorphs, calcite, aragonite, vaterite, and amorphous CaCO3, vaterite is the most enigmatic one due to an ongoing debate regarding its structure that has persisted for nearly a century. In this work, based on systematic transmission electron microscopy characterizations, crystallographic analysis and machine learning aided molecular dynamics simulations with ab initio accuracy, we reveal that vaterite can be regarded as a polytypic structure. The basic phase has a monoclinic lattice possessing pseudohexagonal symmetry. Direct imaging and atomic-scale simulations provide evidence that a single grain of vaterite can contain three orientation variants. Additionally, we find that vaterite undergoes a second-order phase transition with a critical point of ~190 K. These atomic scale insights provide a comprehensive understanding of the structure of vaterite and offer advanced perspectives on the biomineralization process of calcium carbonate.
The protein interactome of the citrus Huanglongbing pathogen Candidatus Liberibacter asiaticus
Authors: Carter Erica W. , Peraza Orlene Guerra , Wang Nian 
Published: November 2023

AbstractThe bacterium Candidatus Liberibacter asiaticus (CLas) causes citrus Huanglongbing disease. Our understanding of the pathogenicity and biology of this microorganism remains limited because CLas has not yet been cultivated in artificial media. Its genome is relatively small and encodes approximately 1136 proteins, of which 415 have unknown functions. Here, we use a high-throughput yeast-two-hybrid (Y2H) screen to identify interactions between CLas proteins, thus providing insights into their potential functions. We identify 4245 interactions between 542 proteins, after screening 916 bait and 936 prey proteins. The false positive rate of the Y2H assay is estimated to be 2.9%. Pull-down assays for nine protein-protein interactions (PPIs) likely involved in flagellar function support the robustness of the Y2H results. The average number of PPIs per node in the CLas interactome is 15.6, which is higher than the numbers previously reported for interactomes of free-living bacteria, suggesting that CLas genome reduction has been accompanied by increased protein multi-functionality. We propose potential functions for 171 uncharacterized proteins, based on the PPI results, guilt-by-association analyses, and comparison with data from other bacterial species. We identify 40 hub-node proteins, including quinone oxidoreductase and LysR, which are known to protect other bacteria against oxidative stress and might be important for CLas survival in the phloem. We expect our PPI database to facilitate research on CLas biology and pathogenicity mechanisms.
Soil microbiome indicators can predict crop growth response to large-scale inoculation with arbuscular mycorrhizal fungi
Authors: Lutz Stefanie , Bodenhausen Natacha , Hess Julia , Valzano-Held Alain , Waelchli Jan , Deslandes-Hérold Gabriel , Schlaeppi Klaus , van der Heijden Marcel G. A. 
Published: November 2023

AbstractAlternative solutions to mineral fertilizers and pesticides that reduce the environmental impact of agriculture are urgently needed. Arbuscular mycorrhizal fungi (AMF) can enhance plant nutrient uptake and reduce plant stress; yet, large-scale field inoculation trials with AMF are missing, and so far, results remain unpredictable. We conducted on-farm experiments in 54 fields in Switzerland and quantified the effects on maize growth. Growth response to AMF inoculation was highly variable, ranging from −12% to +40%. With few soil parameters and mainly soil microbiome indicators, we could successfully predict 86% of the variation in plant growth response to inoculation. The abundance of pathogenic fungi, rather than nutrient availability, best predicted (33%) AMF inoculation success. Our results indicate that soil microbiome indicators offer a sustainable biotechnological perspective to predict inoculation success at the beginning of the growing season. This predictability increases the profitability of microbiome engineering as a tool for sustainable agricultural management.
Validation of machine vision and action sport cameras for 3D motion analysis model reconstruction
Authors: Johnson John David , Hales Michael , Emert Randy 
Published: November 2023

AbstractThe study investigated the feasibility of using action sport cameras for motion analysis research. Data acquired from two different marker-based motion capture systems and six different camera combinations were analyzed for motion reconstruction accuracy. Two different calibration procedures were used to determine the influence on marker position reconstruction. Static and dynamic calibration mean merit score differences between the reference and experimental camera systems were 0.4 mm and 1.3 mm, respectively. Angular displacement difference between the reference and experimental camera systems range between 0.1 and 2.0 degrees. A systematic bias (− 0.54 to 0.19 degrees) was determined between the reference and the experimental camera systems for range of motion. The mean of the multi-trial findings suggests the machine vision camera system calibrated with a dynamic procedure generated highly accurate three-dimensional reconstructed ROM data (0.5 degree) followed closely by the four action sport cameras implementing a static calibration procedure (0.5 degree). The overall findings suggest the selected machine vision and action sport camera systems produced comparable results to the reference motion analysis system. However, the combination of camera type, processing software, and calibration procedure can influence motion reconstruction accuracy.
Top-down determinants of the numerosity–time interaction
Authors: Petrizzo Irene , Pellegrino Michele , Anobile Giovanni , Doricchi Fabrizio , Arrighi Roberto 
Published: November 2023

AbstractPrevious studies have reported that larger visual stimuli are perceived as lasting longer than smaller ones. However, this effect disappears when participants provide a qualitative judgment, by stating whether two stimuli have the “same or different” duration, instead of providing an explicit quantitative judgment (which stimulus lasts longer). Here, we extended these observations to the interaction between the numerosity of visual stimuli, i.e. clouds of dots, and their duration. With “longer vs shorter” responses, participants judged larger numerosities as lasting longer than smaller ones, both when the responses were related to the order (Experiment 1) or color (Experiment 4) of stimuli. In contrast, no similar effect was found with “same vs different” responses (Experiment 2) and in a time motor reproduction task (Experiment 3). The numerosity–time interference in Experiment 1 and Experiment 4 was not due to task difficulty, as sensory precision was equivalent to that of Experiment 2. We conclude that in humans the functional interaction between numerosity and time is not guided, in the main, by a shared bottom-up mechanism of magnitude coding. Rather, high-level and top-down processes involved in decision-making and guided by the use of “magnitude-related” response codes play a crucial role in triggering interference among different magnitude domains.
Auditory attention measured by EEG in neurological populations: systematic review of literature and meta-analysis
Authors: Vanbilsen Nele , Kotz Sonja A. , Rosso Mattia , Leman Marc , Triccas Lisa Tedesco , Feys Peter , Moumdjian Lousin 
Published: November 2023

AbstractSensorimotor synchronization strategies have been frequently used for gait rehabilitation in different neurological populations. Despite these positive effects on gait, attentional processes required to dynamically attend to the auditory stimuli needs elaboration. Here, we investigate auditory attention in neurological populations compared to healthy controls quantified by EEG recordings. Literature was systematically searched in databases PubMed and Web of Science. Inclusion criteria were investigation of auditory attention quantified by EEG recordings in neurological populations in cross-sectional studies. In total, 35 studies were included, including participants with Parkinson’s disease (PD), stroke, Traumatic Brain Injury (TBI), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). A meta-analysis was performed on P3 amplitude and latency separately to look at the differences between neurological populations and healthy controls in terms of P3 amplitude and latency. Overall, neurological populations showed impairments in auditory processing in terms of magnitude and delay compared to healthy controls. Consideration of individual auditory processes and thereafter selecting and/or designing the auditory structure during sensorimotor synchronization paradigms in neurological physical rehabilitation is recommended.
Developmental transcriptomic patterns can be altered by transgenic overexpression of Uty
Authors: Rock Kylie D. , Folts Lillian M. , Zierden Hannah C. , Marx-Rattner Ruth , Leu Nicolae Adrian , Nugent Bridget M. , Bale Tracy L. 
Published: November 2023

AbstractThe genetic material encoded on X and Y chromosomes provides the foundation by which biological sex differences are established. Epigenetic regulators expressed on these sex chromosomes, including Kdm6a (Utx), Kdm5c, and Ddx3x have far-reaching impacts on transcriptional control of phenotypic sex differences. Although the functionality of UTY (Kdm6c, the Y-linked homologue of UTX), has been supported by more recent studies, its role in developmental sex differences is not understood. Here we test the hypothesis that UTY is an important transcriptional regulator during development that could contribute to sex-specific phenotypes and disease risks across the lifespan. We generated a random insertion Uty transgenic mouse (Uty-Tg) to overexpress Uty. By comparing transcriptomic profiles in developmental tissues, placenta and hypothalamus, we assessed potential UTY functional activity, comparing Uty-expressing female mice (XX + Uty) with wild-type male (XY) and female (XX) mice. To determine if Uty expression altered physiological or behavioral outcomes, adult mice were phenotypically examined. Uty expression masculinized female gene expression patterns in both the placenta and hypothalamus. Gene ontology (GO) and gene set enrichment analysis (GSEA) consistently identified pathways including immune and synaptic signaling as biological processes associated with UTY. Interestingly, adult females expressing Uty gained less weight and had a greater glucose tolerance compared to wild-type male and female mice when provided a high-fat diet. Utilizing a Uty-overexpressing transgenic mouse, our results provide novel evidence as to a functional transcriptional role for UTY in developing tissues, and a foundation to build on its prospective capacity to influence sex-specific developmental and health outcomes.
Quantifying spatial acuity of frequency resolved midair ultrasound vibrotactile stimuli
Authors: Cataldo Antonio , Frier William , Haggard Patrick 
Published: November 2023

AbstractSpatial acuity is a fundamental property of any sensory system. In the case of the somatosensory system, the two-point discrimination (2PD) test has long been used to investigate tactile spatial resolution. However, the somatosensory system comprises three main mechanoreceptive channels: the slowly adapting channel (SA) responds to steady pressure, the rapidly adapting channel (RA) responds to low-frequency vibration, and the Pacinian channel (PC) responds to high-frequency vibration. The use of mechanical stimuli in the classical 2PD test means that previous studies on tactile acuity have primarily focussed on the pressure-sensitive channel alone, while neglecting other submodalities. Here, we used a novel ultrasound stimulation to systematically investigate the spatial resolution of the two main vibrotactile channels. Contrary to the textbook view of poor spatial resolution for PC-like stimuli, across four experiments we found that high-frequency vibration produced surprisingly good spatial acuity. This effect remained after controlling for interchannel differences in stimulus detectability and perceived intensity. Laser doppler vibrometry experiments confirmed that the acuity of the PC channel was not simply an artifact of the skin’s resonance to high-frequency mechanical stimulation. Thus, PC receptors may transmit substantial spatial information, despite their sparse distribution, deep location, and large receptive fields.
The COVID-19 pandemic affects pregnancy complications and delivery outcomes in Japan: a large-scale nationwide population-based longitudinal study
Authors: Abe Yoshiko , Uchiyama Koji , Takaoka Nobuko , Yamamoto Keiko , Haruyama Yasuo , Shibata Eiji , Naruse Katsuhiko , Kobashi Gen 
Published: November 2023

AbstractThe impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes in Japan at the national level is unclear. This study aimed to assess the impact of the pandemic on pregnancy complications and delivery outcomes in Japan using nationwide population-based longitudinal data. Secondary data from the Japan Society of Obstetrics and Gynecology from 2016 to 2020 were analyzed. Obstetric information, pregnancy complications, and delivery information of pregnant women over 22 weeks of gestation were compared before and during the pandemic. The trends of hypertensive disorder of pregnancy, fetal growth restriction, and APGAR < 7 increased, whereas those of preterm birth and low birth weight decreased during the COVID-19 pandemic. Pregnancy complications and delivery outcomes have worsened during the COVID-19 pandemic in Japan. Social changes caused by unprecedented situations may have massively influenced pregnancy in several ways. Our findings suggest that even in mild lockdowns like those in Japan, the introduction of social fear during the pandemic might negatively impact pregnancy outcomes.