bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful transvenous implantable cardioverter-defibrillator implantation supported by preceding 3D electro-anatomical mapping for a ventricular fibrillation survivor with surgically repaired congenitally corrected transposition of the great arteries: a case report
Authors: Mitama Tadayuki , Kabutoya Tomoyuki , Kashihara Kana Kubota , Kario Kazuomi
Published: September 2022

Background

The atrial sites suitable for lead placement are limited after complex surgical atrial procedures, and lead placement can be challenging in patients with congenitally corrected transposition of the great arteries (ccTGA) after intracardiac repair.

Case summary

A 34-year-old man with ccTGA, who had undergone a double-switch operation with combined Senning and Jatene operations at the age of 14 was transferred to us. He experienced faintness and suffered cardiopulmonary arrest, and electrocardiography revealed ventricular fibrillation. After conversion to sinus rhythm by urgent external defibrillation, sinus bradycardia was revealed. Electrophysiological study was done using a three-dimensional (3D) mapping system (Ensite®) to evaluate the electrical condition of atria and to decide whether atrial lead can be transvenously placed. The electrical potential of the functional right atrium was good in the lateral or posterior wall, but the threshold was high. By contrast, the roof of the functional right atrium beyond cavoatrial junction was characterized by low voltage, but in a limited region of the roof of right atrium, the threshold was satisfactory and the electrical potential was normal. Thus, 3 weeks later, we implanted a transvenous implantable cardioverter-defibrillator (ICD). We used a 3D mapping system to place the atrial lead in the limited region of the roof of the right atrium mentioned above, the threshold was 0.7 V.

Discussion

Electrophysiological examination using a 3D mapping system before implantation of a dual-chamber ICD is useful because atrial sites suitable for lead placement are limited in patients.
Electromechanical factors associated with favourable outcome in cardiac resynchronization therapy
Authors: Maffessanti Francesco , Jadczyk Tomasz , Wilczek Jacek , Conte Giulio , Caputo Maria Luce , Gołba Krzysztof S , Biernat Jolanta , Cybulska Magdalena , Caluori Guido , Regoli François , Krause Rolf , Wojakowski Wojciech , Prinzen Frits W , Auricchio Angelo
Published: September 2022

Aims

Electromechanical coupling in patients receiving cardiac resynchronization therapy (CRT) is not fully understood. Our aim was to determine the best combination of electrical and mechanical substrates associated with effective CRT.

Methods and results

Sixty-two patients were prospectively enrolled from two centres. Patients underwent 12-lead electrocardiogram (ECG), cardiovascular magnetic resonance (CMR), echocardiography, and anatomo-electromechanical mapping (AEMM). Remodelling was measured as the end-systolic volume (ΔESV) decrease at 6 months. CRT was defined effective with ΔESV ≤ −15%. QRS duration (QRSd) was measured from ECG. Area strain was obtained from AEMM and used to derive systolic stretch index (SSI) and total left-ventricular mechanical time. Total left-ventricular activation time (TLVAT) and transeptal time (TST) were derived from AEMM and ECG. Scar was measured from CMR. Significant correlations were observed between ΔESV and TST [rho = 0.42; responder: 50 (20–58) vs. non-responder: 33 (8–44) ms], TLVAT [−0.68; 81 (73–97) vs. 112 (96–127) ms], scar [−0.27; 0.0 (0.0–1.2) vs. 8.7 (0.0–19.1)%], and SSI [0.41; 10.7 (7.1–16.8) vs. 4.2 (2.9–5.5)], but not QRSd [−0.13; 155 (140–176) vs. 167 (155–177) ms]. TLVAT and SSI were highly accurate in identifying CRT response [area under the curve (AUC) > 0.80], followed by scar (AUC > 0.70). Total left-ventricular activation time (odds ratio = 0.91), scar (0.94), and SSI (1.29) were independent factors associated with effective CRT. Subjects with SSI >7.9% and TLVAT <91 ms all responded to CRT with a median ΔESV ≈ −50%, while low SSI and prolonged TLVAT were more common in non-responders (ΔESV ≈ −5%).

Conclusion

Electromechanical measurements are better associated with CRT response than conventional ECG variables. The absence of scar combined with high SSI and low TLVAT ensures effectiveness of CRT.
Carbon footprint of atrial fibrillation catheter ablation
Authors: Ditac Geoffroy , Cottinet Pierre-Jean , Quyen Le Minh , Grinberg Daniel , Duchateau Josselin , Gardey Kévin , Dulac Arnaud , Delinière Antoine , Haddad Christelle , Boussuge-Roze Julie , Sacher Frédéric , Jaïs Pierre , Chevalier Philippe , Bessière Francis
Published: September 2022

Aims

Climate change represents the biggest global health threat of the 21st century. Health care system is itself a large contributor to greenhouse gas (GHG) emissions. In cardiology, atrial fibrillation (AF) catheter ablation is an increasing activity using numerous non-reusable materials that could contribute to GHG emission. Determining a detailed carbon footprint analysis of an AF catheter ablation procedure allows the identification of the main polluting sources that give opportunities for reduction of environmental impact. To assess the carbon footprint of AF catheter ablation procedure. To determine priority actions to decrease pollution.

Methods and results

An eco-audit method used to predict the GHG emission of an AF catheter ablation procedure was investigated. Two workstations were considered including surgery and anaesthesia. In the operating room, every waste produced by single-use medical devices, pharmaceutical drugs, and energy consumption during intervention were evaluated. All analyses were limited to the operating room. Thirty procedures were analysed over a period of 8 weeks: 18 pulmonary veins isolation RF ablations, 7 complex RF procedures including PVI, roof and mitral isthmus lines, ethanol infusion of the Marshall vein and cavo tricuspid isthmus line, and 5 pulmonary vein isolation with cryoballoon. The mean emission during AF catheter ablation procedures was 76.9 kg of carbon dioxide equivalent (CO2-e). The operating field accounted for 75.4% of the carbon footprint, while only 24.6% for the anaesthesia workstation. On one hand, material production and manufacturing were the most polluting phases of product life cycle which, respectively, represented 71.3% (54.8 kg of CO2-e) and 17.0% (13.1 kg of CO2-e) of total pollution. On the other hand, transport contributed in 10.6% (8.1 kg of CO2-e), while product use resulted in 1.1% (0.9 kg of CO2-e) of GHG production. Electrophysiology catheters were demonstrated to be the main contributors of environmental impact with 29.9 kg of CO2-e (i.e. 38.8%). Three dimensional mapping system and electrocardiogram patches were accounting for 6.8 kg of CO2-e (i.e. 8.8% of total).

Conclusion

AF catheter ablation involves a mean of 76.9 kg of CO2-e. With an estimated 600 000 annual worldwide procedures, the environmental impact of AF catheter ablation activity is estimated equal to 125 tons of CO2 emission each day. It represents an equivalent of 700 000 km of car ride every day. Electrophysiology catheters and patches are the main contributors of the carbon footprint. The focus must be on reducing, reusing, and recycling these items to limit the impact of AF ablation on the environment. A road map of steps to implement in different time frames is proposed.
Extended LH administration as a strategy to increase the pool of recruitable antral follicles in hypothalamic amenorrhea: evidence from a case series
Authors: La Marca Antonio , Longo Maria
Published: September 2022

New evidence is indicating a growing role of LH in promoting ovarian follicular growth and maturation, even at the early stages. LH seems to enhance the transition of follicles to the antral stage hence leading to an increase in the so-called functional ovarian reserve (recruitable antral follicles). Hypogonadotropic hypogonadism is characterized by low, and sometimes undetectable, serum LH and FSH levels, which may indeed explain the low anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) found in patients affected by this condition. We report here the cases of two young women affected by hypothalamic amenorrhea (HA) that presented for fertility treatment with very low functional ovarian reserve. The two patients were treated with exogenous LH for 1 and 2 months (extended LH administration: ELHA) at the dose of 187.5 IU LH every day and 150 IU LH every other day, respectively. In both the cases there was an increase in serum AMH levels and in the AFC. In one patient, the AMH and AFC increased from a baseline 1.3 ng/ml and 8 to 2.3 ng/ml and 14 at end of treatment, respectively. In the second case, serum AMH and AFC increased from 0.4 ng/ml and 6 to 1.6 ng/ml and 13, respectively. One patient underwent ovarian stimulation before and after ELHA, showing an increase in the number of mature oocytes recruited (3 versus 8 metaphase II (MII) oocytes before and after, respectively). The second patient underwent an IVF cycle after ELHA resulting in the retrieval of six MII oocytes and an ongoing pregnancy following transfer of a single blastocyst. Women with HA are characterized by chronic, low levels of gonadotrophins, which may impact not only on the cyclic recruitment of follicles but also the progression of small growing follicles through the first stages of folliculogenesis. Some women with HA may in fact show very low serum AMH and AFC. Our case series shows that the administration of LH at a dose of at least 150–187.5 IU every day or every other day may contribute to a clinically evident increase in the functional ovarian reserve (AFC), and probably accounts for a positive effect of LH on the progression of follicles throughout the early stages of folliculogenesis.
Slow Waning of Antibodies Following BNT162b2 as a Third Dose in Adults Who Had Previously Received 2 Doses of Inactivated Vaccine
Authors: Cowling Benjamin J , Cheng Samuel M S , Martín-Sánchez Mario , Au Niki Y M , Chan Karl C K , Li John K C , Fung Lison W C , Luk Leo L H , Tsang Leo C H , Ip Dennis K M , Poon Leo L M , Leung Gabriel M , Peiris J S Malik , Leung Nancy H L
Published: September 2022

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1 month and 6 months, and found robust antibody responses to the ancestral strain at 6 months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by 6 months.
A comprehensive review of traditional uses, phytochemistry and pharmacology of Reynoutria genus
Authors: Zhang Zi-Long , Li Yu-Ze , Wu Guo-Qing , Zhang Dong-Dong , Deng Chong , Wang Zhi-Min , Song Xiao-Mei , Wang Wei
Published: September 2022

Objectives

The genus Reynoutria belonging to the family Polygonaceae is widely distributed in the north temperate zone and used in folk medicine. It is administered as a sedative, tonic and digestive, also as a treatment for canities and alopecia. Herein, we reported a review on traditional uses, phytochemistry and pharmacology reported from 1985 up to early 2022. All the information and studies concerning Reynoutria plants were summarized from the library and digital databases (e.g. ScienceDirect, SciFinder, Medline PubMed, Google Scholar, and CNKI).

Key findings

A total of 185 articles on the genus Reynoutria have been collected. The phytochemical investigations of Reynoutria species revealed the presence of more than 277 chemical components, including stilbenoids, quinones, flavonoids, phenylpropanoids, phospholipids, lactones, phenolics and phenolic acids. Moreover, the compounds isolated from the genus Reynoutria possess a wide spectrum of pharmacology such as anti-atherosclerosis, anti-inflammatory, antioxidative, anticancer, neuroprotective, anti-virus and heart protection.

In this paper, the traditional uses, phytochemistry and pharmacology of genus Reynoutria were reviewed. As a source of traditional folk medicine, the Reynoutria genus have high medicinal value and they are widely used in medicine. Therefore, we hope our review can help genus Reynoutria get better development and utilization.
The transcription factors DcHB30 and DcWRKY75 antagonistically regulate ethylene-induced petal senescence in carnation (Dianthus caryophyllus)
Authors: Xu Han , Wang Siqi , Larkin Robert M , Zhang Fan
Published: September 2022

Although numerous transcription factors with antagonistic activities have been shown to contribute to growth and development, whether and how they regulate senescence in plants is largely unknown. In this study, we investigated the role of antagonistic transcription factors in petal senescence in carnation (Dianthus caryophyllus), one of the most common types of ethylene-sensitive cut flowers produced worldwide. We identified DcHB30 that encodes a ZF-HD transcription factor that is down-regulated in ethylene-treated petal transcriptomes. We found that silencing DcHB30 accelerated ethylene-induced petal senescence and that DcHB30 physically interacts with DcWRKY75, a positive regulator of ethylene-induced petal senescence. Phenotypic characterization and molecular evidence indicated that DcHB30 and DcWRKY75 competitively regulate the expression of their co-targeted genes DcACS1, DcACO1, DcSAG12, and DcSAG29 by reciprocally inhibiting the DNA-binding activity of each other on the gene promoters. This transcriptional regulation mechanism demonstrates that these transcription factors serve as positive and negative regulators in ethylene-induced petal senescence in carnation. Thus, our study provides insights into how antagonizing transcription factors regulate plant senescence.
Contributing Factors to Israeli Soldiers’ Adaptation to Military Noncombat Positions
Authors: Yakobi Michal , Dekel Rachel , Yavnai Nirit , Ben Yehuda Ariel , Shelef Leah
Published: September 2022

Objective

Adjusting to a military environment is a complex process, with unique demands and various stressors placed on conscripts. In this study, we examined the unique and combined contribution of the independent variables that constitute an individual soldier’s personal resources—the meaningfulness of the military role and the match between expectations and the job itself; cognitive flexibility; social support; and seeking help from a mental health officer (MHO)—to the adaptation (dependent variable) of noncombat soldiers to military service.

Method

The study group comprised 200 Israel Defense Forces noncombat soldiers aged 18-23 years (Meanage = 20.046 years, SD = 0.951). Of them, 107 (53.3%) had consulted a MHO. The remaining soldiers who had not consulted an MHO (n = 93, 46.5%) served as the comparison group. Research tools included the work and meaning questionnaire, the Cognitive Flexibility Scale, the Medical Outcomes Study (social support) questionnaire, and adaptation to the army questionnaire.

Results

Adaptation to service was found to relate positively to the meaningfulness of the military role, cognitive flexibility, and social support. Social support partially mediated the relation between cognitive flexibility and adaptation to service. Additionally, soldiers who had consulted an MHO had lower levels of cognitive flexibility and social support, and they adapted less well to service compared to the comparison group.

Conclusions

The study indicates that soldiers who seek help have lower resources. Additional personal and environmental variables that contribute to the adjustment of soldiers in noncombat positions were also identified.
Measurement of AGN dust extinction based on the near-infrared flux variability of WISE data
Authors: Mizukoshi Shoichiro , Minezaki Takeo , Tsunetsugu Shoichi , Yoshida Atsuhiro , Sameshima Hiroaki , Kokubo Mitsuru , Noda Hirofumi
Published: September 2022

We present the measurement of the line-of-sight extinction of the dusty torus for a large number of obscured active galactic nuclei (AGNs) based on the reddening of the colour of the variable flux component in near-infrared (NIR) wavelengths. We collected long-term monitoring data by Wide-field Infrared Survey Explorer (WISE) for 513 local AGNs catalogued by the Swift/BAT AGN Spectroscopic Survey (BASS) and found that the multi-epoch NIR flux data in two different bands (WISE W1 and W2) are tightly correlated for more than 90 per cent of the targets. The flux variation gradient (FVG) in the W1 and W2 bands was derived by applying linear regression analysis, and we reported that those for unobscured AGNs fall in a relatively narrow range, whereas those for obscured AGNs are distributed in a redder and broader range. The AGN’s line-of-sight dust extinction (AV) is calculated using the amount of the reddening in the FVG and is compared with the neutral hydrogen column density (NH) of the BASS catalogue. We found that the NH/AV ratios of obscured AGNs are greater than those of the Galactic diffuse interstellar medium (ISM) and are distributed with a large scatter by at most two orders of magnitude. Furthermore, we found that the lower envelope of the NH/AV of obscured AGNs is comparable to the Galactic diffuse ISM. These properties of the NH/AV can be explained by increase in the NH attributed to the dust-free gas clouds covering the line of sight in the broad-line region.
A Bayesian calibration framework for EDGES
Authors: Murray Steven G , Bowman Judd D , Sims Peter H , Mahesh Nivedita , Rogers Alan E E , Monsalve Raul A , Samson Titu , Vydula Akshatha Konakondula
Published: September 2022

We develop a Bayesian model that jointly constrains receiver calibration, foregrounds, and cosmic 21 cm signal for the EDGES global 21 cm experiment. This model simultaneously describes calibration data taken in the lab along with sky-data taken with the EDGES low-band antenna. We apply our model to the same data (both sky and calibration) used to report evidence for the first star formation in 2018. We find that receiver calibration does not contribute a significant uncertainty to the inferred cosmic signal ($\lt 1{{\ \rm per\ cent}}$), though our joint model is able to more robustly estimate the cosmic signal for foreground models that are otherwise too inflexible to describe the sky data. We identify the presence of a significant systematic in the calibration data, which is largely avoided in our analysis, but must be examined more closely in future work. Our likelihood provides a foundation for future analyses in which other instrumental systematics, such as beam corrections and reflection parameters, may be added in a modular manner.
Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities
Authors: Dannenberg Rachel L , Cardina Joseph A , Pytko Kara G , Hedglin Mark
Published: September 2022

During DNA replication, DNA lesions in lagging strand templates are initially encountered by DNA polymerase δ (pol δ) holoenzymes comprised of pol δ and the PCNA processivity sliding clamp. These encounters are thought to stall replication of an afflicted template before the lesion, activating DNA damage tolerance (DDT) pathways that replicate the lesion and adjacent DNA sequence, allowing pol δ to resume. However, qualitative studies observed that human pol δ can replicate various DNA lesions, albeit with unknown proficiencies, which raises issues regarding the role of DDT in replicating DNA lesions. To address these issues, we re-constituted human lagging strand replication to quantitatively characterize initial encounters of pol δ holoenzymes with DNA lesions. The results indicate pol δ holoenzymes support dNTP incorporation opposite and beyond multiple lesions and the extent of these activities depends on the lesion and pol δ proofreading. Furthermore, after encountering a given DNA lesion, subsequent dissociation of pol δ is distributed around the lesion and a portion does not dissociate. The distributions of these events are dependent on the lesion and pol δ proofreading. Collectively, these results reveal complexity and heterogeneity in the replication of lagging strand DNA lesions, significantly advancing our understanding of human DDT.
Plant mitochondrial RNA editing factors can perform targeted C-to-U editing of nuclear transcripts in human cells
Authors: Lesch Elena , Schilling Maximilian T , Brenner Sarah , Yang Yingying , Gruss Oliver J , Knoop Volker , Schallenberg-Rüdinger Mareike
Published: September 2022

RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.
Widespread autogenous mRNA–protein interactions detected by CLIP-seq
Authors: Kapral Thomas H , Farnhammer Fiona , Zhao Weihao , Lu Zhi J , Zagrovic Bojan
Published: September 2022

Autogenous interactions between mRNAs and the proteins they encode are implicated in cellular feedback-loop regulation, but their extent and mechanistic foundation are unclear. It was recently hypothesized that such interactions may be common, reflecting the role of intrinsic nucleobase–amino acid affinities in shaping the genetic code's structure. Here we analyze a comprehensive set of CLIP-seq experiments involving multiple protocols and report on widespread autogenous interactions across different organisms. Specifically, 230 of 341 (67%) studied RNA-binding proteins (RBPs) interact with their own mRNAs, with a heavy enrichment among high-confidence hits and a preference for coding sequence binding. We account for different confounding variables, including physical (overexpression and proximity during translation), methodological (difference in CLIP protocols, peak callers and cell types) and statistical (treatment of null backgrounds). In particular, we demonstrate a high statistical significance of autogenous interactions by sampling null distributions of fixed-margin interaction matrices. Furthermore, we study the dependence of autogenous binding on the presence of RNA-binding motifs and structured domains in RBPs. Finally, we show that intrinsic nucleobase–amino acid affinities favor co-aligned binding between mRNA coding regions and the proteins they encode. Our results suggest a central role for autogenous interactions in RBP regulation and support the possibility of a fundamental connection between coding and binding.
Human Thg1 displays tRNA-inducible GTPase activity
Authors: Antika Titi Rindi , Nazilah Kun Rohmatan , Lee Yi-Hsueh , Lo Ya-Ting , Yeh Chung-Shu , Yeh Fu-Lung , Chang Tien-Hsien , Wang Tzu-Ling , Wang Chien-Chia
Published: September 2022

tRNAHis guanylyltransferase (Thg1) catalyzes the 3′-5′ incorporation of guanosine into position -1 (G-1) of tRNAHis. G-1 is unique to tRNAHis and is crucial for recognition by histidyl-tRNA synthetase (HisRS). Yeast Thg1 requires ATP for G-1 addition to tRNAHis opposite A73, whereas archaeal Thg1 requires either ATP or GTP for G-1 addition to tRNAHis opposite C73. Paradoxically, human Thg1 (HsThg1) can add G-1 to tRNAsHis with A73 (cytoplasmic) and C73 (mitochondrial). As N73 is immediately followed by a CCA end (positions 74–76), how HsThg1 prevents successive 3′-5′ incorporation of G-1/G-2/G-3 into mitochondrial tRNAHis (tRNAmHis) through a template-dependent mechanism remains a puzzle. We showed herein that mature native human tRNAmHis indeed contains only G-1. ATP was absolutely required for G-1 addition to tRNAmHis by HsThg1. Although HsThg1 could incorporate more than one GTP into tRNAmHisin vitro, a single-GTP incorporation prevailed when the relative GTP level was low. Surprisingly, HsThg1 possessed a tRNA-inducible GTPase activity, which could be inhibited by ATP. Similar activity was found in other high-eukaryotic dual-functional Thg1 enzymes, but not in yeast Thg1. This study suggests that HsThg1 may downregulate the level of GTP through its GTPase activity to prevent multiple-GTP incorporation into tRNAmHis.
EventPointer 3.0: flexible and accurate splicing analysis that includes studying the differential usage of protein-domains
Authors: Ferrer-Bonsoms Juan A , Gimeno Marian , Olaverri Danel , Sacristan Pablo , Lobato César , Castilla Carlos , Carazo Fernando , Rubio Angel
Published: September 2022

Alternative splicing (AS) plays a key role in cancer: all its hallmarks have been associated with different mechanisms of abnormal AS. The improvement of the human transcriptome annotation and the availability of fast and accurate software to estimate isoform concentrations has boosted the analysis of transcriptome profiling from RNA-seq. The statistical analysis of AS is a challenging problem not yet fully solved. We have included in EventPointer (EP), a Bioconductor package, a novel statistical method that can use the bootstrap of the pseudoaligners. We compared it with other state-of-the-art algorithms to analyze AS. Its performance is outstanding for shallow sequencing conditions. The statistical framework is very flexible since it is based on design and contrast matrices. EP now includes a convenient tool to find the primers to validate the discoveries using PCR. We also added a statistical module to study alteration in protein domain related to AS. Applying it to 9514 patients from TCGA and TARGET in 19 different tumor types resulted in two conclusions: i) aberrant alternative splicing alters the relative presence of Protein domains and, ii) the number of enriched domains is strongly correlated with the age of the patients.
SPROUT: spectral sparsification helps restore the spatial structure at single-cell resolution
Authors: Wang Jingwan , Li Shiying , Chen Lingxi , Li Shuai Cheng
Published: September 2022

Single-cell RNA sequencing thoroughly quantifies the individual cell transcriptomes but renounces the spatial structure. Conversely, recently emerged spatial transcriptomics technologies capture the cellular spatial structure but skimp cell or gene resolutions. Ligand-receptor interactions reveal the potential of cell proximity since they are spatially constrained. Cell–cell affinity values estimated by ligand–receptor interaction can partially represent the structure of cells but falsely include the pseudo affinities between distant or indirectly interacting cells. Here, we develop a software package, SPROUT, to reconstruct the single-cell resolution spatial structure from the transcriptomics data through diminished pseudo ligand–receptor affinities. For spatial data, SPROUT first curates the representative single-cell profiles for each spatial spot from a candidate library, then reduces the pseudo affinities in the intercellular affinity matrix by partial correlation, spectral graph sparsification, and spatial coordinates refinement. SPROUT embeds the estimated interactions into a low-dimensional space with the cross-entropy objective to restore the intercellular structures, which facilitates the discovery of dominant ligand–receptor pairs between neighboring cells at single-cell resolution. SPROUT reconstructed structures achieved shape Pearson correlations ranging from 0.91 to 0.97 on the mouse hippocampus and human organ tumor microenvironment datasets. Furthermore, SPROUT can solely de novo reconstruct the structures at single-cell resolution, i.e., reaching the cell-type proximity correlations of 0.68 and 0.89 between reconstructed and immunohistochemistry-informed spatial structures on a human developing heart dataset and a tumor microenvironment dataset, respectively.
Computational identification of signals predictive for nuclear RNA exosome degradation pathway targeting
Authors: Wu Mengjun , Schmid Manfred , Jensen Torben Heick , Sandelin Albin
Published: September 2022

The RNA exosome degrades transcripts in the nucleoplasm of mammalian cells. Its substrate specificity is mediated by two adaptors: the ‘nuclear exosome targeting (NEXT)’ complex and the ‘poly(A) exosome targeting (PAXT)’ connection. Previous studies have revealed some DNA/RNA elements that differ between the two pathways, but how informative these features are for distinguishing pathway targeting, or whether additional genomic features that are informative for such classifications exist, is unknown. Here, we leverage the wealth of available genomic data and develop machine learning models that predict exosome targets and subsequently rank the features the models use by their predictive power. As expected, features around transcript end sites were most predictive; specifically, the lack of canonical 3′ end processing was highly predictive of NEXT targets. Other associated features, such as promoter-proximal G/C content and 5′ splice sites, were informative, but only for distinguishing NEXT and not PAXT targets. Finally, we discovered predictive features not previously associated with exosome targeting, in particular RNA helicase DDX3X binding sites. Overall, our results demonstrate that nucleoplasmic exosome targeting is to a large degree predictable, and our approach can assess the predictive power of previously known and new features in an unbiased way.
Harmonizing Surveillance Methodologies for Group A Streptococcal Diseases
Authors: Moore Hannah C , Miller Kate M , Carapetis Jonathan R , Van Beneden Chris A
Published: September 2022

Group A Streptococcus (Strep A) is responsible for a significant global health and economic burden. The recent prioritization of Strep A vaccine development by the World Health Organization has prompted global research activities and collaborations. To progress this prioritization, establishment of robust surveillance for Strep A to generate updated regional disease burden estimates and to establish platforms for future impact evaluation is essential. Through the activities of the Strep A Vaccine Global Consortium (SAVAC), we have refined and harmonized surveillance protocols for 7 Strep A disease endpoints with a view that these will form part of surveillance standards for ongoing research and public health activities.
Standardization of Epidemiological Surveillance of Acute Rheumatic Fever
Authors: Scheel Amy , Beaton Andrea Z , Katzenellenbogen Judith , Parks Tom , Miller Kate M , Cherian Thomas , Van Beneden Chris A , Cannon Jeffrey W , Moore Hannah C , Bowen Asha C , Carapetis Jonathan R
Published: September 2022

Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body’s autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis.

We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed.
Standardization of Epidemiological Surveillance of Group A Streptococcal Cellulitis
Authors: Miller Kate M , Lamagni Theresa , Hay Roderick , Cannon Jeffrey W , Marks Michael , Bowen Asha C , Kaslow David C , Cherian Thomas , Seale Anna C , Pickering Janessa , Daw Jessica N , Moore Hannah C , Van Beneden Chris , Carapetis Jonathan R , Manning Laurens
Published: September 2022

Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue usually found complicating a wound, ulcer, or dermatosis. This article provides guidelines for the surveillance of cellulitis. The primary objectives of cellulitis surveillance are to (1) monitor trends in rates of infection, (2) describe the demographic and clinical characteristics of patients with cellulitis, (3) estimate the frequency of complications, and (4) describe the risk factors associated with primary and recurrent cellulitis. This article includes case definitions for clinical cellulitis and group A streptococcal cellulitis, based on clinical and laboratory evidence, and case classifications for an initial and recurrent case. It is expected that surveillance for cellulitis will be for all-cause cellulitis, rather than specifically for Strep A cellulitis. Considerations of the type of surveillance are also presented, including identification of data sources and surveillance type. Minimal surveillance necessary for cellulitis is facility-based, passive surveillance. Prospective, active, facility-based surveillance is recommended for estimates of pathogen-specific cellulitis burden. Participant eligibility, surveillance population, and additional surveillance considerations such as active follow-up of cases, the use of International Classification of Disease diagnosis codes, and microbiological sampling of cases are discussed. Finally, the core data elements to be collected on case report forms are presented.
Standardization of Epidemiological Surveillance of Invasive Group A Streptococcal Infections
Authors: Miller Kate M , Lamagni Theresa , Cherian Thomas , Cannon Jeffrey W , Parks Tom , Adegbola Richard A , Pickering Janessa , Barnett Tim , Engel Mark E , Manning Laurens , Bowen Asha C , Carapetis Jonathan R , Moore Hannah C , Barth Dylan D , Kaslow David C , Van Beneden Chris A
Published: September 2022

Invasive group A streptococcal (Strep A) infections occur when Streptococcus pyogenes, also known as beta-hemolytic group A Streptococcus, invades a normally sterile site in the body. This article provides guidelines for establishing surveillance for invasive Strep A infections. The primary objective of invasive Strep A surveillance is to monitor trends in rates of infection and determine the demographic and clinical characteristics of patients with laboratory-confirmed invasive Strep A infection, the age- and sex-specific incidence in the population of a defined geographic area, trends in risk factors, and the mortality rates and rates of nonfatal sequelae caused by invasive Strep A infections.

This article includes clinical descriptions followed by case definitions, based on clinical and laboratory evidence, and case classifications (confirmed or probable, if applicable) for invasive Strep A infections and for 3 Strep A syndromes: streptococcal toxic shock syndrome, necrotizing fasciitis, and pregnancy-associated Strep A infection.

Considerations of the type of surveillance are also presented, noting that most people who have invasive Strep A infections will present to hospital and that invasive Strep A is a notifiable disease in some countries. Minimal surveillance necessary for invasive Strep A infection is facility-based, passive surveillance. A resource-intensive but more informative approach is active case finding of laboratory-confirmed Strep A invasive infections among a large (eg, state-wide) and well defined population.

Participant eligibility, surveillance population, and additional surveillance components such as the use of International Classification of Disease diagnosis codes, follow-up, period of surveillance, seasonality, and sample size are discussed. Finally, the core data elements to be collected on case report forms are presented.
Polymicrobial Foot Infection Patterns Are Common and Associated With Treatment Failure
Authors: Barshes Neal R , Clark Nicholas J , Bidare Deeksha , Dudenhoeffer J H , Mindru Cezarina , Rodriguez-Barradas Maria C
Published: September 2022

Background

That foot infections are predominately polymicrobial has long been recognized, but it is not clear if the various species co-occur randomly or in patterns. We sought nonrandom species co-occurrence patterns that might help better predict prognosis or guide antimicrobial selection.

Methods

We analyzed tissue (bone, skin, and other soft tissue), fluid, and swab specimens collected from initial foot infection episodes during a 10-year period using a hospital registry. Nonrandom co-occurrence of microbial species was identified using simple pairwise co-occurrence rates adjusted for multiple comparisons, Markov and conditional random fields, and factor analysis. A historical cohort was used to validate pattern occurrence and identify clinical significance.

Results

In total, 156 unique species were identified among the 727 specimens obtained from initial foot infection episodes in 694 patients. Multiple analyses suggested that Staphylococcus aureus is negatively associated with other staphylococci. Another pattern noted was the co-occurrence of alpha-hemolytic Streptococcus, Enterococcus fecalis, Klebsiella, Proteus, Enterobacter, or Escherichia coli, and absence of both Bacteroides and Corynebacterium. Patients in a historical cohort with this latter pattern had significantly higher risk-adjusted rates of treatment failure.

Conclusions

Several nonrandom microbial co-occurrence patterns are frequently seen in foot infection specimens. One particular pattern with many Proteobacteria species may denote a higher risk for treatment failure. Staphylococcus aureus rarely co-occurs with other staphylococci.
Improving refugee resettlement: insights from market design
Authors: Hadad Justin , Teytelboym Alexander
Published: September 2022

The current refugee resettlement system is inefficient because there are too few resettlement places and because refugees are resettled to locations where they might not thrive. We outline how ideas from market design can lead to better resettlement practices. In particular, we discuss how market design can incentivize participation of countries in resettlement and improve the matching of refugees at international and local levels; some of these insights have already put into practice. Finally, we highlight several further applications of market design in refugee resettlement, including cardinal preference submission and matching with transfers.
Born Again but Not Evangelical?
Authors: Margolis Michele F
Published: September 2022

Public opinion research often identifies evangelical Christians based on a double-barreled, yes-or-no, question asking respondents whether they are an evangelical or born-again Christian. This paper uses a survey experiment to demonstrate the implications of this measurement strategy. Among White Americans, more than one-third of those whom researchers classify as evangelical using the standard double-barreled question actually eschew the evangelical label; the same is true for just under two-thirds of African Americans. Additionally, these born-again non-evangelical Christians hold less conservative political outlooks compared to the self-identified evangelicals with whom they are grouped, and, in fact, oftentimes more closely resemble those who reject both the evangelical and born-again labels. Despite this, the double-barreled identification question produces a White “evangelical or born-again” group that looks politically similar to a composite “evangelical” or “born-again” group based on two questions asking about each identity separately. Finally, important differences appear across race, suggesting that religious and political histories affect how people interpret and respond to double-barreled questions.
Prejudice Toward People With Mental Illness, Schizophrenia, and Depression: Measurement, Structure, and Antecedents
Authors: Bizumic Boris , Gunningham Beth
Published: September 2022

Objectives

Many existing measures of prejudiced attitudes toward people with mental illness have conceptual, theoretical, and psychometric problems. The recently created Prejudice toward People with Mental Illness (PPMI) scale has addressed many of these limitations, but prejudice toward people with different mental disorders may be unique and require further exploration. This study aimed to facilitate this exploration by adapting the PPMI to focus on schizophrenia and depression, and investigate the structure, distinctiveness, and the nomological network of prejudice toward people with these mental disorders.

Study Design

We adapted the original 28-item PPMI scale to create the Prejudice toward People with Schizophrenia (PPS) and Prejudice toward People with Depression (PPD) scales. There were 406 participants from the general population, who completed these scales and related measures.

Study Results

The original 4-factor structure (fear/avoidance, unpredictability, authoritarianism, and malevolence) was supported for each scale. Participants expressed the highest levels of prejudice toward people with schizophrenia, followed by prejudice toward people with mental illness, and lastly by prejudice toward people with depression. Analyses supported the proposed nomological network of prejudice, which involves theoretical antecedents of social dominance orientation, right-wing authoritarianism, empathy, personality traits, disgust sensitivity, and prior contact.

Conclusions

This research provides evidence for the validity and psychometric properties of the PPMI, PPS, and PPD scales, expanding our understanding of antecedents to prejudice toward people with different mental disorders. This research also shows that we gain more insight into prejudice when we use measures targeting specific disorders rather than mental illness in general.
Relationships between neighborhood social stressors and sleep among Jackson Heart Study participants: mediation through physical activity and psychosocial stressors
Authors: Tamura Kosuke , Johnson Dayna A , Neally Sam J , Sims Mario , Powell-Wiley Tiffany M
Published: September 2022

Study Objectives

To examine associations between perceived neighborhood social environment (PNSE) and sleep, mediated by physical activity (PA) and psychosocial stressors.

Methods

A sample (n = 4705) of African Americans (mean age 55.0 years; 63.4% female) enrolled in the 2000–2004 Jackson Heart Study (JHS). Four self-reported sleep outcomes were analyzed: sleep duration (minutes/night), sleep quality (high/low), short sleep (short ≤ 6 h vs recommended = 7–8 h), and long sleep (long ≥ 9 h vs recommended). PNSE factors included violence (e.g. robbery), problems (trash/litter), and social cohesion (trusting neighbors). PA and psychosocial stressors (lifetime and everyday discrimination, perceived stress, and depressive symptoms) were tested as mediators. With bootstrap-generated 95% bias-corrected confidence intervals (BC CIs), linear regression was used to test for mediation adjusting for covariates.

Results

Neighborhood violence and problems were associated with sleep duration, mediated through PA (B = −1.97, 95%BC CI = −3.76, −0.60; B = −1.23, 95%BC CI = −2.55, −0.27, respectively), lifetime discrimination (B = 2.61, 95%BC CI = 0.93, 4.80; B = 2.25, 95%BC CI = 0.93, 3.94), perceived stress (B = −3.08, 95%BC CI = −6.20, −0.41; B = −2.17, 95%BC CI = −4.33, −0.28), and depressive symptoms (B = −2.22, 95%BC CI = −5.09, −0.25; B = −1.94, 95%BC CI = −4.10, −0.35). Social cohesion was positively associated with sleep duration, mediated through PA, lifetime discrimination, and perceived stress. Similar patterns were demonstrated for binary outcomes. Yet, effect sizes were relatively small. PNSE was neither directly nor indirectly associated with sleep outcomes by everyday discrimination.

Conclusions

Each PNSE factor was associated with sleep outcomes, mediated by PA and psychosocial stressors. Further research should emphasize effective community efforts to decrease adverse neighborhood conditions and psychosocial factors and increase PA; thereby reducing CVD events for African Americans.
Women’s Political Participation through Social Movements and Nongovernmental Organizations: The Case of Compromiso Ciudadano in Medellín, Colombia
Authors: González-Malabet María
Published: September 2022

This article demonstrates how female participation in social movements and nongovernmental organizations (NGOs) influences the political participation of women activists. It highlights how women from the social movement Compromiso Ciudadano successfully led progressive bottom-up programs for the democratic transformation of Medellín, Colombia. This study draws upon the first-hand experiences of women who participated in a focus group and in interviews. The findings reveal that engaging in social movements and NGO activities strengthens women’s agency in political participation, individually and collectively. This kind of grassroots participation increases women’s inclusion in formal politics, and it creates bridges between local governments and female grassroots leaders and movements.
Perfluorooctane Sulfonic Acid Disrupts Protective Tight Junction Proteins via Protein Kinase D in Airway Epithelial Cells
Authors: Lucas Joseph H , Wang Qixin , Rahman Irfan
Published: September 2022

Perfluorooctane sulfonic acid (PFOS) is a long chain per- and polyfluoroalklyl substance (PFAS) that has been used in aqueous film-forming foams. Emerging epidemiological evidence indicates that PFOS may be associated with chronic lung diseases such as asthma and analysis of human tissues demonstrates that the lungs carry a significant body burden of PFOS. Deficits in barrier function are a major risk factor for asthma. Thus, we hypothesized that PFOS exposure will lead to impaired epithelial barrier function through dysregulated tight junctions. Hence, we assessed the impact of PFOS on epithelial barrier integrity. Bronchial epithelial cells (16HBE) were grown on collagen-coated transwells and treated to 5–25 μM PFOS, and assessed for changes in barrier function and tight junction proteins. Rescue experiments were performed using the protein kinase D (PKD) inhibitor, CID755673. PFOS treatment reduced transepithelial electrical resistance (TEER) and increased 4 kDa FITC-dextran flux. Additionally, PFOS significantly decreased protein levels and the tight junction organization rate of occludin and zonula occludens 1. Increased phosphorylation (Ser744/Ser748) of PKD was observed 3 h following PFOS treatment. Pretreatment with the PKD inhibitor attenuated PFOS-mediated changes in TEER and FITC-dextran flux and restored occludin protein levels. In conclusion, PFOS causes loss of airway barrier integrity and the disruption of tight junctions in bronchial epithelial cells, which was partly attenuated through the inhibition of PKD. These findings demonstrate that PFOS is capable of disrupting airway barrier function, a potentially driving factor underlying associations between PFOS and respiratory diseases such as asthma.