bluuebunny/crossref_metadata_2025 huggingface dataset:
Calibration experiments for radon in drinking water measurements using portable-type electrostatic-collection radon monitors
Authors: Hosoda Masahiro , Omori Yasutaka , Hashimoto Hiroki , Matsumoto Maho , Yasuoka Yumi , Sanada Tetsuya , Oda Yuki , Kiso Mizuki , Sampei Aoi , Kranrod Chutima , Tazoe Hirofumi , Akata Naofumi , Taira Yasuyuki , Tamakuma Yuki , Yamada Ryohei , Kudo Hiromi , Shimizu Mayumi , Tokonami Shinji
Published: November 2023

Portable-type electrostatic-collection radon monitors (RAD7) are often used for in-situ measurements of radon in water. In this study, we evaluated the calibration factors and their uncertainties for two RAD7 monitors based on comparative measurements with the liquid scintillation counting method. In the first experiment, we found that both RAD7 monitors had relatively large uncertainties due to leakage of radon gas that bubbled from the gaps between the lids of the desiccant container and the glass vial. Therefore, for the second experiment, these gaps were closed as much as possible using parafilm and clay, respectively. As a result, the relative uncertainties for both RAD7 monitors were significantly decreased. Furthermore, we collected spring water samples to confirm the reliability of radon concentrations. After closing the leakage point, the uncertainty of radon concentrations in spring water we measured using the typical protocol of the RAD7 were significantly lower, which improves the measurement.
True and spurious anomalies in ambient dose rate monitoring
Authors: Bossew Peter , Kuča Petr , Helebrant Jan
Published: November 2023

Ambient dose rate surveys reveal zones of an elevated dose rate. As the observation results from two physical processes—the ‘true’ process in nature that one wants to assess and the observation process that consists of measuring under certain conditions—an observed anomaly can have its cause in either process. Anomalous effects rooted in the observation process are called spurious. Distinction between true and spurious anomalies may not be straightforward in many cases. As an example, dose rate surveying using a specific instrument is discussed, whose analysis shows the presence of both types of anomalies. Examples of both types are shown. The physical cause of a true anomaly can often be identified by inspecting the environment or by more sophisticated investigation, e.g. by gamma spectrometry. Identification of spurious anomalies is more difficult and requires investigation of count time series.
Development of calculation tool for iodine 131 biodistribution depending on the aerosol particle distribution
Authors: Iwaoka Kazuki , Enriquez Eliza B , Tamakuma Yuki , Hosoda Masahiro , Tokonami Shinji , Feliciano Chitho P , Kanda Reiko
Published: November 2023

Radiation damage to tissues depends on radiation exposure levels. Therefore, we have studied accurate estimations of radiation exposure levels so far. Recently, we developed a tool that can calculate the respiratory tract deposition of radionuclides based on polydisperse particle size distribution. As a next step, there is a need for a new calculation tool for the biodistribution of radionuclides because a fraction of the radionuclides deposited in the respiratory tract is absorbed into the body. In this study, a calculation tool for iodine 131 biodistribution depending on aerosol size distribution was developed. The developed tool in this study is used with the former tool.
Critical Role of miR-130b-5p in Cardiomyocyte Proliferation and Cardiac Repair in Mice After Myocardial Infarction
Authors: Feng Ke , Wu Yukang , Li Jianguo , Sun Qiaoyi , Ye Zihui , Li Xuan , Guo Xudong , Kang Jiuhong
Published: November 2023

Poor proliferative capacity of adult cardiomyocytes is the primary cause of heart failure after myocardial infarction (MI), thus exploring the molecules and mechanisms that promote the proliferation of adult cardiomyocytes is crucially useful for cardiac repair after MI. Here, we found that miR-130b-5p was highly expressed in mouse embryonic and neonatal hearts and able to promote cardiomyocyte proliferation both in vitro and in vivo. Mechanistic studies revealed that miR-130b-5p mainly promoted the cardiomyocyte proliferation through the MAPK-ERK signaling pathway, and the dual-specific phosphatase 6 (Dusp6), a negative regulator of the MAPK-ERK signaling, was the direct target of miR-130b-5p. Moreover, we found that overexpression of miR-130b-5p could promote the proliferation of cardiomyocytes and improve cardiac function in mice after MI. These studies thus revealed the critical role of miR-130b-5p and its targeted MAPK-ERK signaling in the cardiomyocyte proliferation of adult hearts and proved that miR-130b-5p could be a potential target for cardiac repair after MI.
Establishment of Biocontrol Agents and Their Impact on Rhizosphere Microbiome and Induced Grapevine Defenses Are Highly Soil-Dependent
Authors: Leal Catarina , Eichmeier Ales , Štůsková Kateřina , Armengol Josep , Bujanda Rebeca , Fontaine Florence , Trotel-Aziz Patricia , Gramaje David
Published: November 2023

With a reduction in available chemical treatments, there is an increased interest in biological control of grapevine trunk diseases. Few studies have investigated the impact of introducing beneficial microorganisms in the rhizosphere on the existing indigenous soil microbiome. In this study, we explored the effect of two biocontrol agents (BCAs), Trichoderma atroviride SC1 (Ta SC1) (Vintec; Certis Belchim) and Bacillus subtilis PTA-271 (Bs PTA-271), on the grapevine rhizosphere bacterial and fungal microbiome as well as plant defense expression using high-throughput amplicon sequencing and quantitative real-time polymerase chain reaction (PCR), respectively. Additionally, we quantified both Ta SC1 and Bs PTA-271 in the rhizosphere over time using droplet digital PCR. The fungal microbiome was more affected by factors such as soil type, BCA treatment, and sampling time compared with the bacterial microbiome. Specifically, Ta SC1 application produced negative impacts on fungal diversity, whereas application of BCAs did not affect bacterial diversity. Interestingly, the survival and establishment of both BCAs showed opposite trends depending on the soil type, indicating that the physicochemical properties of soils have a role in BCA establishment. Fungal co-occurrence networks were less complex than bacterial networks but highly impacted by Ta SC1 application. Soils treated with Ta SC1 presented more complex and stable co-occurrence networks, with a higher number of positive correlations. Induced grapevine defenses also differed according to the soil, being more affected by BCA inoculation on sandy soil. The findings of this research emphasize the complex relationships among microorganisms in the rhizosphere and highlight the significance of taking into account various factors, such as soil type, sampling time, and BCA treatment, and their influence on the structure and dynamics of microbial communities.
The Role of Fatty Acids from Plant Surfaces in the Infectivity of Colletotrichum fioriniae
Authors: Waller Timothy J. , Häggblom Max M. , Oudemans Peter V.
Published: November 2023

Aqueous extracts derived from flowers stimulate germination, secondary conidiation, and appressorial formation of various latent fruit rotting fungi. Even raindrops passing over flowers accumulate sufficient activity to influence the infectivity of fruit rotting fungi. Using a spore germination bioassay, high levels of bioactivity were found in chloroform extracts from plant tissues, implicating the nonpolar components of the cuticle. The fatty acid (FA) and fatty acid methyl ester (FAME) composition (C9-C20) of blueberry and cranberry tissues as well as aqueous flower extracts were characterized using a gas chromatography-mass spectrometry (GC-MS) method. The FAs and FAMEs found in the plant extracts were then tested for bioactivity using a spore germination bioassay. The C16:0 and C18:2 FAs and FAMEs, as well as the C18:0 FAME and the C20:0 FA, all stimulated appressorial formation while the C10:0 FA stimulated secondary conidiation. The C10:0 and C16:0 FAs were the only two bioactive components also identified from the aqueous floral extracts of both blueberry and cranberry and are therefore considered as contributors to the bioactivity observed in these extracts. The aqueous extracts from surfaces other than flowers showed little or no activity, and it is speculated that the movement of FAs may be related to the level of polymerization and cutin polyester development in flowers versus other plant organs. This study highlights the importance of the bloom period for infection and that the apparent effects on host susceptibility may therefore depend on the availability of specific FAs or combinations thereof.
POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer
Authors: Chen Hualin , Ma Lin , Yang Wenjie , Li Yingjie , Ji Zhigang
Published: November 2023

RNA Polymerase III Subunit G (POLR3G) promotes tumorigenesis, metastasis, cancer stemness, and chemoresistance of breast cancer and lung cancer; however, its biological function in bladder cancer (BLCA) remains unclear. Through bioinformatic analyses, we found that POLR3G expression was significantly elevated in BLCA tumor tissues and was associated with decreased survival. Multivariate Cox analysis indicated that POLR3G could serve as an independent prognostic risk factor. Our functional investigations revealed that POLR3G deficiency resulted in reduced migration and invasion of BLCA cells both in vitro and in vivo. Additionally, the expressions of EMT‐related mesenchymal markers were also downregulated in POLR3G knockdown cells. Mechanistically, we showed that POLR3G could activate the PI3K/AKT signaling pathway. Inhibition of this pathway with LY294002 reduced the enhanced migration and invasion of BLCA cells induced by POLR3G overexpression, whereas the activation of this pathway using 740Y‐P restored the abilities that were inhibited by POLR3G knockdown. Taken together, our findings suggested that POLR3G is a prognostic predictor for BLCA and promotes EMT of BLCA through activation of the PI3K/AKT signaling pathway.
CE: Suicide Prevention: Protecting the Future of Nurses
Authors: Hofstetter Tifphany , Mayer Noralynn L.
Published: November 2023

Nurse suicide is an alarming issue that remains largely underexplored and underaddressed. Moreover, rates of suicide among nurses, which are higher than those in the general population, may increase due to additional stressors caused by the COVID-19 pandemic. There is a decided lack of data regarding nurse suicide or the efficacy of evidence-based prevention programs. This article examines the state of nurse suicide and explores the latest statistics on nurse suicide rates; contributing factors to nurse suicide; and current suicide prevention programs, such as the Critical Incident Stress Management and Healer Education Assessment and Referral programs.
Reference suture of gluteus minimus muscle: a modification of the lateral approach in total hip arthroplasty
Authors: García López José María , Gómez Alcaraz Jorge , García de la Blanca Juan Carlos , Iliadis Alexis D.
Published: November 2023

The lateral approach is one of the most frequently used surgical procedures in total hip arthroplasty, being its main disadvantage the postsurgical abductor muscle weakness that many patients present, which may lead to Trendelenburg gait in a high percent of cases. For this reason we propose a surgical variation which consists in using a suture reference for the gluteus minimus just before its tenotomy, that allows a better repair of the abductor musculature during the closure. It also facilities muscles mobilization during the dissection, reducing the risk of neurovascular damage if we place an additional retractor, and also protects the gluteus minimus and gluteus medium during the insertion of the prosthetic components. With these advantages, we aim to reduce the most frequent complication of the lateral approach as it is the abductor muscle weakness. This modification only consists in a new suture, so it does not implies additional complications in contrast with the classical approach. However, in some patients can be difficult to place the suture if they have a tendinous deterioration of the gluteus minimus or a chronic break.
Clinical consequences of weight gain during treatment for HIV infection
Authors: Hill Andrew , Venter Willem Daniel Francois
Published: November 2023

Purpose of review

The introduction of dolutegravir, an oral integrase inhibitor, within public health HIV programs has been a success, with excellent sustained viral load suppression, persistence, and safety. Initial concerns around integrase-inhibitors being implicated in safety concerns around immune reconstitution inflammatory syndromes (IRIS), neural tube defects, and weight gain, have been largely laid to rest, but new concerns about cardiovascular risk have arisen, including a link between hypertension and this antiretroviral class.

Recent findings

We review the pertinent studies here, and while we find both observational and randomized controlled study associations in some but not all studies, these are often confounded by associated weight gain and aging. In addition, definitions of hypertension, as well as measurement within the studies (such as cuff size), were not consistent within studies.

Careful analysis will be needed, as with the weight-gain signal, before assigning causation, especially as plausible physiological mechanisms for this rise in blood pressure are unclear.
Deep Learning Based Prediction of Myopia Control Effect in Children Treated With Overnight Orthokeratology
Authors: Cao Jingwen , Sun Xiaoming , Sun Lu , Song Hongxin , Niu Kai , He Zhiqiang
Published: November 2023

Objectives:

To develop and validate a deep learning–based model for predicting 12-month axial length (AL) elongation using baseline factors and early corneal topographic changes in children treated with orthokeratology (Ortho-K) and to investigate the association between these factors and myopia control impact.

Methods:

A total of 115 patients with Ortho-K were enrolled. Influential baseline factors that have a statistically significant correlation with 12-month AL from medical records were selected using Pearson correlation coefficients. Simultaneously, the height, area, and volume of the defocus region were directly calculated from the corneal topography. Then, the prediction model was developed by combining multiple linear regression and deep neural network and evaluated in an independent group (83 patients for developing the algorithm and 32 patients for evaluation).

Results:

Age (r=−0.30, P<0.001), spherical equivalent refractive (SE; r=0.20, P=0.032), and sex (r=0.19, P=0.032) were significantly correlated with the AL elongation while pupil diameter, flat k, steep k, horizontal corneal diameter (white to white), anterior chamber depth, and cell density were not (P>0.1). The prediction model was developed using age, SE, and corneal topographic variation, and the validation of the model demonstrated its effectiveness in predicting AL elongation.

Conclusions:

The AL elongation was accurately predicted by the deep learning model, which effectively incorporated both baseline factors and corneal topographic variation.
Immunosuppression minimization is safe and associated with good long-term success in pediatric recipients of liver transplant
Authors: Chapin Catherine A. , Whitehead Bridget , Shakhin Victoria , Taylor Sarah A. , Kriegermeier Alyssa , Mohammad Saeed , Alonso Estella M.
Published: November 2023

Immunosuppression reduction after liver transplant is an important strategy to mitigate long-term medication side effects. We describe our center’s experience with immunosuppression minimization to once-daily calcineurin inhibitor dosing. Success was defined as continuing daily calcineurin inhibitor monotherapy with normal transaminases and no rejection. We performed a retrospective review of eligible children who received a liver transplant between 2009 and 2016, had a surveillance biopsy, and were on twice-daily calcineurin inhibitor monotherapy. Twenty-eight of 51 eligible patients were minimized to daily calcineurin inhibitor with goal 12-hour trough detectable. Nineteen patients (68%) had 1-year success, and 17 (61%) had long-term success at a median follow-up of 5.0 years (interquartile range (IQR): 2.9–6.6). Minimization failure occurred at a median of 0.6 years (IQR: 0.3–1.0) after dose reduction. Patients with long-term success had lower aspartate aminotransferase levels prior to minimization compared to those who failed with a median of 28.0 IU/L (IQR: 20.5–32.0) versus 32.0 IU/L (IQR: 30.0–37.0), p = 0.047. The long-term success group demonstrated a trend toward greater recipients of liver transplant from living donors (53% vs. 18%, p = 0.07). At the time of the last follow-up at a median of 5.0 years (IQR: 2.9–6.1) after surveillance biopsy, most (73%) patients who failed had returned to twice-daily calcineurin inhibitor monotherapy, all had liver enzymes <2 times the upper limit of normal, and there were no patient deaths or graft losses. In conclusion, immunosuppression minimization is safe in pediatric recipients of liver transplant and should be considered to reduce long-term medication side effects and improve patient quality of life. Future studies are necessary to follow long-term outcomes and develop biomarkers to predict minimization success.
Role of microRNA in colorectal carcinoma (CRC): a narrative review
Authors: Sado Abdulmaleek Idanesimhe , Batool Wajiha , Ahmed Amna , Zafar Summiya , Patel Siddharth K. , Mohan Anmol , Zia Umar , Aminpoor Hasibullah , Kumar Vikash , Tejwaney Usha
Published: November 2023

MicroRNAs (miRNAs) are short non-coding RNAs that play a critical role in regulating gene expression by binding to target messenger RNAs (mRNAs). They were first discovered around 8 years after the identification of the first miRNA in 1993, and since then, there has been a significant increase in miRNA-related research and discoveries. MiRNAs have been implicated in various biological processes, including cancer, particularly in colorectal cancer (CRC). In CRC, miRNAs act as either oncogenes or tumor suppressors, influencing essential cellular functions such as cell proliferation, apoptosis, angiogenesis, and metastasis. The dysregulation of miRNAs in CRC can arise from different factors, leading to abnormal expression levels of their target mRNAs and subsequently affecting protein production. Consequently, miRNAs may directly target oncogenes or tumor suppressor genes, thereby contributing to cancer initiation and progression. Notably, tumors often exhibit reduced expression of mature miRNAs. In CRC research, miRNAs offer potential as diagnostic biomarkers and therapeutic targets. Specific miRNA profiles could serve as non-invasive tools for early CRC detection and risk assessment. Additionally, miRNA-based therapies present a promising approach for targeted cancer treatment by modulating miRNA expression. However, challenges related to delivery systems and long-term safety must be addressed to fully harness their therapeutic potential.
Predictive performance of 1H-NMR metabolomics derived biomarkers of bacterial vaginosis
Authors: Challa Apoorva , Sharma Uma , Tyagi Ritu , Kumar Pawan , Sood Seema , Kachhawa Garima , Jagannathan Naranamangalam R. , Gupta Somesh
Published: November 2023

1H-NMR metabolomics-derived biomarkers maltose, acetate, formate and lactate have excellent potential as predictive biomarkers for BV with an AUC of 0.97 (95%CI = 0.88-1.00), sensitivity of 0.90 and specificity of 0.95.
Is Postoperative Helmet Molding Therapy Necessary for Craniectomy for Sagittal Suture Synostosis?
Authors: Uno Kayoko , Sakamoto Yoshiaki , Miwa Tomoru
Published: November 2023

Endoscopic strip craniectomy followed by postoperative remodeling helmet therapy for scaphocephaly is widely accepted, but the requirement of several helmets might burden patients or their families. This study examined whether craniectomy via a bicoronal approach without molding helmet therapy is worth considering. The authors retrospectively reviewed patients with nonsyndromic sagittal suture synostosis who underwent the modified Renier H technique between 2016 and 2021. We collected data on preoperative and postoperative cephalic index (CI), operative time, estimated blood loss, and blood transfusion rates. The authors also examined all related literature in English describing endoscopic craniectomy with postoperative helmet molding therapy for sagittal suture craniosynostosis. Among 17 patients, the average operative time was 92.2±15.6 minutes, the mean estimated blood loss was 35.8±22.4 mL, and a blood transfusion was needed for 9 patients (52.9%). The mean preoperative and postoperative CIs were 69.1±2.6 and 78.4±2.2, respectively. A comparison of the literature review with the authors’ results showed that their procedures required a slightly longer operative time and a higher frequency of blood transfusions. There are no significant differences in blood loss or preoperative and postoperative CIs reported in the literature. The open procedure required a higher operative time than endoscopic suturectomy. However, dealing with bleeding is more challenging with endoscopic suturectomy. The cost of the helmets and the duration patients have to wear them, which might be burdensome for the patients or their families when determining the optimal minimally invasive treatment, should also be considered.
Improving the reliability of fMRI-based predictions of intelligence via semi-blind machine learning
Authors: Lohmann Gabriele , Heczko Samuel , Mahler Lucas , Wang Qi , Steiglechner Julius , Kumar Vinod J. , Roost Michelle , Jost Jürgen , Scheffler Klaus
Published: November 2023

Predicting neuromarkers for cognitive abilities using fMRI has been a major focus of research in the past few years. However, it has recently been reported that many thousands of participants are required to obtain reproducible results (Marek et al (2022)). This appears to be a major impediment to obtaining neuromarkers from fMRI because large sample sizes are typically not available in neuroimaging studies. Here we show that the out-of-sample prediction accuracy can be dramatically improved by supplementing fMRI with readily available non-imaging information so that reliable predictive modeling becomes feasible even for small sample sizes. Specifically, we introduce a novel machine learning method that predicts intelligence from resting-state fMRI data, leveraging educational level as supplementary information. We refer to our approach as “semi-blind machine learning (SML)” because it operates under the assumption that supplementary information, such as educational level, is available for subjects in both the training and test sets. This setup closely mirrors real-world scenarios, especially in clinical contexts, where patient background information typically exists and can be utilized to boost prediction accuracy. However, guarding against bias is crucial. Subjects should not be categorized as more intelligent simply based on their higher education levels. Therefore, our approach contains a component explicitly designed for bias control. We have applied our method to three different data collections and observed marked improvements in prediction accuracies across a wide range of sample sizes. We anticipate that semi-blind machine learning provides a promising approach to fMRI-based predictive modelling with the potential for a wide range of future applications.
Large-scale alternative polyadenylation (APA)-wide association studies to identify putative susceptibility genes in human common cancers
Authors: Guo Xingyi , Ping Jie , Yang Yaohua , Su Xinwan , Shu Xiao-ou , Wen Wanqing , Chen Zhishan , Zhang Yunjing , Tao Ran , Jia Guochong , He Jingni , Cai Qiuyin , Zhang Qingrun , Giles Graham G , Pearlman Rachel , Rennert Gad , Vodicka Pavel , Phipps Amanda , Gruber Stephen B , Casey Graham , Peters Ulrike , Long Jirong , Lin Weiqiang , Zheng Wei
Published: November 2023

Alternative polyadenylation (APA) modulates mRNA processing in the 3’ untranslated regions (3’UTR), which affect mRNA stability and translation efficiency. Here, we build genetic models to predict APA levels in multiple tissues using sequencing data of 1,337 samples from the Genotype-Tissue Expression, and apply these models to assess associations between genetically predicted APA levels and cancer risk with data from large genome-wide association studies of six common cancers, including breast, ovary, prostate, colorectum, lung, and pancreas among European-ancestry populations. At a Bonferroni-correctedP□<□0.05, we identify 58 risk genes, including seven in newly identified loci. Using luciferase reporter assays, we demonstrate that risk alleles of 3’UTR variants, rs324015 (STAT6), rs2280503 (DIP2B), rs1128450 (FBXO38) and rs145220637 (LDAH), could significantly increase post-transcriptional activities of their target genes compared to reference alleles. Further gene knockdown experiments confirm their oncogenic roles. Our study provides additional insight into the genetic susceptibility of these common cancers.
In vivosilencing of regulatory elements using a single AAV-CRISPRi vector
Authors: Laurette P , Cao C , Ramanujam D , Schwaderer M , Lueneburg T , Kuss S , Weiss L , Dilshat R , Furlong EEM , Rezende F , Engelhardt S , Gilsbach R
Published: November 2023

CRISPR-Cas9 based transcriptional repressors (CRISPRi) have emerged as specific and robust tools for functional epigenetic silencing of regulatory elements. Adeno-associated viruses (AAVs) are promising CRISPRi delivery vectors for cardiovascular research and therapy. However, compact vectors enabling codelivery of all CRISPRi components by a single AAV are needed for an enhanced and consistent performance.

We engineered a 4.7kb all-in-one CRISPRi construct compatible with AAV-mediated delivery and produced cardiotropic AAVi 6 and 9 particles for invitroand invivoapplication, respectively.

AAVi vectors targeting theNppapromoter (AAViNppa) reduced gene expression in cultivated cardiomyocytes (HL-1 cells) in a dose-dependent manner. The maximum effect was a >95% reduction as measured by qPCR and RNA-seq. This effect was orchestrated by loss of chromatin accessibility (ATAC-seq) and establishment of heterochromatin (H3K9me3 ChIP-seq) specifically at the target promoter region. We confirmed the broad applicability of AAVi to different cardiomyocyte cell culture systems by silencing several genes in primary neonatal rat ventricular cardiomyocytes (NRVMs), human iPSC-derived cardioids and iPSC-CMs.

To demonstrate the efficacy of AAVi invivowe injected 8-week-old C57Bl/6 WT mice with a single dose of AAViNppaand implanted osmotic minipumps releasing Phenylephrine (50 mg/kg/d) and Angiotensin II (0.45 mg/kg/d) to induceNppatranscription. AAViNppasilencedNppatranscription as revealed by qPCR and single nuclei RNA-seq even under stress conditions. On the epigenome layer AAViNppainduced closed chromatin at theNppapromoter site comparable to the invitroeffect. Here, we present an efficient AAV-based method for CRISPRi-mediated epigenetic silencing of gene expression in cardiac myocytesin vivoandin vitro. This functional epigenetic approach provides an efficient way to modulate gene expression in the heart and could become a standard method for cardiovascular disease modelling and translational research.
A paradoxical population structure ofvarDBLα types in Africa
Authors: Tan Mun Hua , Tiedje Kathryn E. , Feng Qian , Zhan Qi , Pascual Mercedes , Shim Heejung , Chan Yao-ban , Day Karen P.
Published: November 2023

Thevarmultigene family encodes theP. falciparumerythrocyte membrane protein 1 (PfEMP1), which is important in host-parasite interaction as a virulence factor and major surface antigen of the blood stages of the parasite, responsible for maintaining chronic infection. Whilst important in the biology ofP. falciparum, these genes (50 to 60 genes per parasite genome) are routinely excluded from whole genome analyses due to their hyper-diversity, achieved primarily through recombination. The PfEMP1 head structure almost always consists of a DBLα-CIDR tandem. Categorised into different groups (upsA, upsB, upsC), different head structures have been associated with different ligand-binding affinities and disease severities. We study how conserved individual DBLα types are at the country, regional, and local scales in Sub-Saharan Africa. Using publicly-available sequence datasets and a novel ups classification algorithm,cUps, we performed anin silicoexploration of DBLα conservation through time and space in Africa. In all three ups groups, the population structure of DBLα types in Africa consists of variants occurring at rare, low, moderate, and high frequencies. Non-rare variants were found to be temporally stable in a local area in endemic Ghana. When inspected across different geographical scales, we report different levels of conservation; while some DBLα types were consistently found in high frequencies in multiple African countries, others were conserved only locally, signifying local preservation of specific types. Underlying this population pattern is the composition of DBLα types within each isolate DBLα repertoire, revealed to also consist of a mix of types found at rare, low, moderate, and high frequencies in the population. We further discuss the adaptive forces and balancing selection, including host genetic factors, potentially shaping the evolution and diversity of DBLα types in Africa.
Chemokine Receptor 2 Is A Theranostic Biomarker for Abdominal Aortic Aneurysms
Authors: Elizondo-Benedetto Santiago , Sastriques-Dunlop Sergio , Detering Lisa , Arif Batool , Heo Gyu Seong , Sultan Deborah , Luehmann Hannah , Zhang Xiaohui , Gao Xuefeng , Harrison Kitty , Thies Dakkota , McDonald Laura , Combadière Christophe , Lin Chieh-Yu , Kang Yeona , Zheng Jie , Ippolito Joseph , Laforest Richard , Gropler Robert J. , English Sean J. , Zayed Mohamed A. , Liu Yongjian
Published: November 2023

Abdominal aortic aneurysm (AAA) is a degenerative vascular disease impacting aging populations with a high mortality upon rupture. There are no effective medical therapies to prevent AAA expansion and rupture. We previously demonstrated the role of the monocyte chemoattractant protein-1 (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis in rodent AAA pathogenesis via positron emission tomography/computed tomography (PET/CT) using CCR2 targeted radiotracer64Cu-DOTA-ECL1i. We have since translated this radiotracer into patients with AAA. CCR2 PET showed intense radiotracer uptake along the AAA wall in patients while little signal was observed in healthy volunteers. AAA tissues collected from individuals scanned with64Cu-DOTA-ECL1i and underwent open-repair later demonstrated more abundant CCR2+ cells compared to non-diseased aortas. We then used a CCR2 inhibitor (CCR2i) as targeted therapy in our established male and female rat AAA rupture models. We observed that CCR2i completely prevented AAA rupture in male rats and significantly decreased rupture rate in female AAA rats. PET/CT revealed substantial reduction of64Cu-DOTA-ECL1i uptake following CCR2i treatment in both rat models. Characterization of AAA tissues demonstrated decreased expression of CCR2+ cells and improved histopathological features. Taken together, our results indicate the potential of CCR2 as a theranostic biomarker for AAA management.

Graphical Abstract
“Urban-Satellite” estimates in the ABCD Study: Linking Neuroimaging and Mental Health to Satellite Imagery Measurements of Macro Environmental Factors
Authors: Goldblatt Ran , Holz Nathalie , Tate Garrett , Sherman Kari , Ghebremicael Selamawit , Bhuyan Soumitra S , Al-Ajlouni Yazan , Santillanes Sara , Araya Ghermay , Abad Shermaine , Herting Megan M. , Thompson Wesley , Thapaliya Bishal , Sapkota Ram , Xu Jiayuan , Liu Jingyu ,   the environMENTAL consortium, Schumann Gunter , Calhoun Vince D.
Published: November 2023

While numerous studies over the last decade have highlighted the important influence of environmental factors on mental health, globally applicable data on physical surroundings are still limited. Access to such data and the possibility to link them to epidemiological studies is critical to unlocking the relationship of environment, brain and behaviour and promoting positive future mental health outcomes. The Adolescent Brain Cognitive Development (ABCD) Study is the largest ongoing longitudinal and observational study exploring brain development and child health among children from 21 sites across the United States. Here we describe the linking of the ABCD study data with satellite-based “Urban-Satellite” (UrbanSat) variables consisting of 11 satellite-data derived environmental indicators associated with each subject’s residential address at their baseline visit, including land cover and land use, nighttime lights, and population characteristics. We present these UrbanSat variables and provide a review of the current literature that links environmental indicators with mental health, as well as key aspects that must be considered when using satellite data for mental health research. We also highlight and discuss significant links of the satellite data variables to the default mode network clustering coefficient and cognition. This comprehensive dataset provides the foundation for large-scale environmental epidemiology research.
KUL@SMM4H’23: Text Augmentations with R-drop for Classification of Tweets Self Reporting Covid-19
Authors: Francis Sumam , Moens Marie-Francine
Published: November 2023

This paper presents models created for the Social Media Mining for Health 2023 shared task. Our team addressed the first task, classifying tweets that self-report Covid-19 diagnosis. Our approach involves a classification model that incorporates diverse textual augmentations and utilizes R-drop to augment data and mitigate overfitting, boosting model efficacy. Our leading model, enhanced with R-drop and augmentations like synonym substitution, reserved words, and back translations, outperforms the task mean and median scores. Our system achieves an impressive F1 score of 0.877 on the test set.
Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice
Authors: Oliveira Thais Cristina de Souza , Viegas Katia Aparecida da Silva , Lima Rariane Silva de , Alba-Loureiro Tatiana C. , Lima Cintia Taniguti , Campos Luciene Cristina Gastalho , Barauna Valerio Garrone , Curi Rui , Irigoyen Maria Claudia , Lacchini Silvia
Published: November 2023

To verify if a low dose of angiotensin II (Ang II) can induce an inflammatory response in cardiac arteries, even though blood pressure remains at normal values. Were used C57Bl/6J male mice treated with a low dose of Ang II (30ng/kg IP) and AT1R blockers. Blood pressure was recorded after 10, 30, 60min, 2 and 6hours after Saline or Ang II injection. Time curve (30 and 60min, 2, 6, 12, 24, and 48hours after treatment) for expression of inflammatory markers was evaluated in cardiac arteries (TGF-β, IL-1β, IL-6, TNF-α and ICAM-1) by immunohistochemistry and western blot. Serum TNF-α and IL-6 were analyzed by ELISA. Although Ang II did not alter blood pressure, local TGF-α and IL-6 presented an early increase in cardiac arteries. IL-1β and ICAM-1 participated in a late response to Ang II (12 hours). Ang II group showed a systemic increase of IL-6 30 to 60 minutes after treatment. AT1 and AT2 receptor blockers (losartan, 20mg/kg, and PD123.319, 15mg/kg) were given alone or concomitant to Ang II. This combination showed that Ang II increases TGF-β and IL-6 by acting on the AT1 receptor in a fast response. IL-1β regulation by Ang II seems to be mediated by both AT1 and AT2 receptors. The results suggest that, independently of hemodynamic influences, Ang II, acting on AT1R, leads to the expression of inflammatory markers in cardiac vessels. AT2 receptor seems to be involved in the counterbalance of AT1R during modulation of IL-1β production in cardiac arteries.
BIOMAPP::CHIP: Large-Scale Motif Analysis
Authors: Caldonazzo Garbelini Jader M. , Sanches Danilo S. , Ramirez Pozo Aurora T.
Published: November 2023

Background

Discovery biological motifs plays a fundamental role in understanding regulatory mechanisms. Computationally, they can be efficiently represented askmers, making the counting of these elEMents a critical aspect for ensuring not only the accuracy but also the efficiency of the analytical process. This is particularly useful in scenarios involving large data volumes, such as those generated by theChIP-seqprotocol. Against this backdrop, we introducebiomapp ::chip, a tool specifically designed to optimize the discovery of biological motifs in large data volumes.

Results

We conducted a comprehensive set of comparative tests with state-of-the-art algorithms. Our analyses revealed thatbiomapp ::chipoutperforms existing approaches in various metrics, excelling both in terms of performance and accuracy. The tests demonstrated a higher detection rate of significant motifs and also greater agility in the execution of the algorithm. Furthermore, thesmtcomponent played a vital role in the system’s efficiency, proving to be both agile and accurate inkmercounting, which in turn improved the overall efficacy of our tool.

Conclusion

biomapp ::chiprepresent real advancements in the discovery of biological motifs, particularly in large data volume scenarios, offering a relevant alternative for the analysis ofChIP-seqdata and have the potential to boost future research in the field. This software can be found at the following address:https://github.com/jadermcg/BIOMAPP-CHIP.
Cutaneous T cell lymphoma atlas reveals malignant Th2 cells supported by a B cell-rich microenvironment
Authors: Li Ruoyan , Strobl Johanna , Poyner Elizabeth F.M. , Torabi Fereshteh , Mazin Pasha , Chipampe Nana-Jane , Stephenson Emily , Gardner Louis , Olabi Bayanne , Coulthard Rowen , Botting Rachel A. , Zila Nina , Prigmore Elena , Gopee Nusayhah , Engelbert Justin , Goh Issac , Chan Hon Man , Johnson Harriet , Ellis Jasmine , Rowe Victoria , Tun Win , Reynolds Gary , Foster April Rose , Gambardella Laure , Winheim Elena , Admane Chloe , Rumney Benjamin , Steele Lloyd , Jardine Laura , Nenonen Julia , Pickard Keir , Lumley Jennifer , Hampton Philip , Hu Simeng , Liu Fengjie , Liu Xiangjun , Horsfall David , Basurto-Lozada Daniela , Grimble Louise , Bacon Chris M. , Weatherhead Sophie , Brauner Hanna , Wang Yang , Bai Fan , Reynolds Nick J. , Allen Judith E. , Jonak Constanze , Brunner Patrick M. , Teichmann Sarah A. , Haniffa Muzlifah
Published: November 2023

Cutaneous T-cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides (MF), can be difficult to diagnose resulting in treatment delay. The pathogenesis of CTCL is not fully understood due to limited data from patient studies. We performed single-cell RNA sequencing and spatial transcriptomics profiling of skin from patients with MF-type CTCL, and an integrated comparative analysis with human skin cell atlas datasets from healthy skin, atopic dermatitis and psoriasis. We reveal the co-optation of Th2-immune gene programmes by malignant CTCL cells and modelling of the tumour microenvironment to support their survival. We identify MHC-II+fibroblast subsets reminiscent of lymph node T-zone reticular cells and monocyte-derived dendritic cells that can maintain Th2-like tumour cells. CTCL Th2-like tumour cells are spatially associated with B cells, forming aggregates reminiscent of tertiary lymphoid structures which are more prominent with progressive disease. Finally, we validated the enrichment of B cells in CTCL skin infiltrates and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.
Nucleocapsid condensation drives Ebola viral factory maturation and dispersion
Authors: Vallbracht Melina , Bodmer Bianca S. , Fischer Konstantin , Makroczyova Jana , Winter Sophie L. , Wendt Lisa , Wachsmuth-Melm Moritz , Hoenen Thomas , Chlanda Petr
Published: November 2023

Replication and genome encapsidation of many negative-sense RNA viruses take place in virus-induced membrane-less organelles termed viral factories (VFs). While liquid properties of VFs are believed to control the transition from genome replication to encapsidation, the nucleocapsid assembly, VF maturation and interactions with the cellular environment remain elusive. Here we applyin situcryo-correlative light and electron tomography to follow nucleocapsid assembly and changes in VF morphology and their liquid properties during Ebola virus infection. We show that Ebola viral nucleocapsids transition from loosely packed helical assemblies in early VFs to condensed cylinders that arrange into highly organized parallel bundles later in infection. Early VFs associate with intermediate filaments and are devoid of other host material, but become progressively accessible to cellular components. Our data suggest that this process is coupled to VF solidification and dispersion, and that changes in liquid properties of VFs promote nucleocapsid transport to budding sites.

Highlights

- Cryo-ET reveals the molecular architecture of Ebola virus replication compartments

- Loosely coiled nucleocapsids transition to condensed cylinders forming bundles

- Nucleocapsid condensation drives dispersion of viral factories promoting viral egress

- Intermediate filaments associate with and are critical for virus factory formation
One infusion of engineered long-lasting and multifunctional T cells cures asthma in mice
Authors: Jin Gang , Liu Yanyan , He Zihao , Wang Lixia , Zhao Xiaocui , Li Zhuoyang , Yin Na , Peng Min
Published: November 2023

The majority of common chronic human diseases are incurable, which affect a large portion of population and require life-long treatments that impose huge disease, economic and social burden. For example, asthma is the most common respiratory disease affecting over 300 million people and accounts for > 250,000 death annually, for which there is no cure. Unlike traditional therapyies, engineered T cells, such as chimeric antigen receptor CAR T (CAR-T) cells, function as living drugs and can cure some hematological malignancies, but whether engineered T cells can cure common diseases beyond cancer remains elusive. Here, we develop a curative therapy for asthma based on enginerred T cell. With IL-5 as the targeting domain and depletion of BCOR and ZC3H12A, we produce long-lasting CAR-T cells eradicating IL-5Rα+eosinophils, termedImmortal-like andFunctional IL-5 CAR-T cells (5TIF) cells. We further enginerred 5TIFcells to secrete an IL-4 mutein that blocks the singaling of both IL-4 and IL-13, two driver inflammatory cytokines in asthma, named as 5TIF4 cells. In multiple models of asthma, one infusion of 5TIF4 cells in fully immunocompetent mice, in the absence of any conditioning regimen, confers long-term depletion of pathological eosinophils and blockade of IL-4/IL-13 actions, resulting in sustained repression of type 2 inflammation and asthmatic symptoms. Furthurmore, 5TIF4 cells can also be induced in human T cells in NSG mice. Our data demonstrate that asthma, a common noncancerous disease, can be cured by a single infusion of engineered long-lasting and multifunctional T cells, which paves the way for curing common chronic diseases by engineered long-lived T cells.
Differential quantification of alternative splicing events on spliced pangenome graphs
Authors: Ciccolella Simone , Cozzi Davide , Vedova Gianluca Della , Kuria Stephen Njuguna , Bonizzoni Paola , Denti Luca
Published: November 2023

Pangenomes are becoming a powerful framework to perform many bioinformatics analyses taking into account the genetic variability of a population, thus reducing the bias introduced by a single reference genome. With the wider diffusion of pangenomes, integrating genetic variability with transcriptome diversity is becoming a natural extension that demands specific methods for its exploration. In this work, we extend the notion of spliced pangenomes to that ofannotated spliced pangenomes; this allows us to introduce a formal definition of Alternative Splicing (AS) events on a graph structure.

To investigate the usage of graph pangenomes for the quantification of AS events across conditions, we developedpantas, the first pangenomic method for the detection and differential analysis of AS events from short RNA-Seq reads. A comparison with state-of-the-art linear reference-based approaches proves thatpantasachieves competitive accuracy, making spliced pangenomes effective for conducting AS events quantification and opening future directions for the analysis of population-based transcriptomes.pantasis open-source and freely available atgithub.com/algolab/pantas.

Author summary

The ever increasing availability of complete genomes is advancing our comprehension of many biological mechanisms and is enhancing the knowledge we can extract from sequencing data. Pange3PM ESTnome graphs are a convenient way to represent multiple genomes and the genetic variability within a population. Integrating genetic variability with transcriptome diversity can improve our understanding of alternative splicing, a regulation mechanism which allows a single gene to code for multiple proteins. However, many unanswered questions are limiting our comprehension of the relationship between genetic and trancriptomic variations. With this work, we start to fill this gap by introducingpantas, the first approach based on pangenome graphs for the detection and differential quantification of alternative splicing events. A comparison with state-of-the-art approaches based on linear genome prove that pangenome graphs can be effectively used to perform such an analysis. By integrating genetic and transcriptome variability in a single structure,pantascan pave the way to next generation bioinformatic approaches for the accurate analysis of the relations between genetic variations and alternative splicing aberrations.