bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Clinical Effectiveness of Population‐Based Atrial Fibrillation Screening Using Contemporary Modalities: A Decision‐Analytic Model
Authors: Khurshid Shaan , Chen Wanyi , Singer Daniel E. , Atlas Steven J. , Ashburner Jeffrey M. , Choi Jin G. , Hur Chin , Ellinor Patrick T. , McManus David D. , Chhatwal Jagpreet , Lubitz Steven A.
Published: September 2021

Background

Atrial fibrillation (AF) screening is endorsed by certain guidelines for individuals aged ≥65 years. Yet many AF screening strategies exist, including the use of wrist‐worn wearable devices, and their comparative effectiveness is not well‐understood.

Methods and Results

We developed a decision‐analytic model simulating 50 million individuals with an age, sex, and comorbidity profile matching the United States population aged ≥65 years (ie, with a guideline‐based AF screening indication). We modeled no screening, in addition to 45 distinct AF screening strategies (comprising different modalities and screening intervals), each initiated at a clinical encounter. The primary effectiveness measure was quality‐adjusted life‐years, with incident stroke and major bleeding as secondary measures. We defined continuous or nearly continuous modalities as those capable of monitoring beyond a single time‐point (eg, patch monitor), and discrete modalities as those capable of only instantaneous AF detection (eg, 12‐lead ECG). In total, 10 AF screening strategies were effective compared with no screening (300–1500 quality‐adjusted life‐years gained/100 000 individuals screened). Nine (90%) effective strategies involved use of a continuous or nearly continuous modality such as patch monitor or wrist‐worn wearable device, whereas 1 (10%) relied on discrete modalities alone. Effective strategies reduced stroke incidence (number needed to screen to prevent a stroke: 3087–4445) but increased major bleeding (number needed to screen to cause a major bleed: 1815–4049) and intracranial hemorrhage (number needed to screen to cause intracranial hemorrhage: 7693–16 950). The test specificity was a highly influential model parameter on screening effectiveness.

Conclusions

When modeled from a clinician‐directed perspective, the comparative effectiveness of population‐based AF screening varies substantially upon the specific strategy used. Future screening interventions and guidelines should consider the relative effectiveness of specific AF screening strategies.
Markus Barth on the Lord’s Supper
Authors: Nimmo Paul T.
Published: September 2021

This article seeks to offer the first detailed exposition and analysis of the two major writings of Markus Barth on the theme of the Lord’s Supper, highlighting matters of scriptural exegesis and considering issues of theological import as well as noting its ecumenical implications. It proceeds in three main sections. First, it sets the scene for the investigation of Markus Barth’s work on the Lord’s Supper by considering briefly the genre and the purpose of the writings in view. Second, it engages in a close reading and analysis of both writings on the Lord’s Supper. Third, and by way of conclusion, it concisely explores the wider ramifications of Barth’s teaching in relation to the work of the ecumenical movement.
Jewish-Christian Dialogue in Review
Authors: Lindsay Mark R.
Published: September 2021

Using hitherto unexplored letters and documents from the Markus Barth Papers, held at Princeton Theological Seminary, this article traces the development, and eventual end, of the friendship between Markus Barth and Emil Fackenheim. In doing so, it demonstrates Barth’s very real commitment to Jewish-Christian dialogue, but also shows how difficult this commitment was to maintain in his interpersonal relationships, in the context of differing political responses to Israeli foreign policy.
Cortinarius pseudocisticola (Agaricales, Cortinariaceae), a new species in section Calochroi from Europe
Authors: DOVANA FRANCESCO , BOCCARDO FABRIZIO , BOROVIČKA JAN , VIZZINI ALFREDO , SAAR GÜNTER , ALBERT LÁSZLÓ , MIKŠÍK MICHAL , DIMA BÁLINT
Published: September 2021

A new species of Cortinarius sect. Calochroi, C. pseudocisticola from European deciduous forests, is described on the basis of morphological and genetic features. Several collections of the species from the Czech Republic, Germany, Hungary and Italy were studied. Illustrations of fresh basidiomes in situ and of the main macro- and micromorphological features are provided. Its morphological characters are compared to those of the molecularly closest related and most similar species.
Dicliptera mercedesiae, a new species of the genus Dicliptera (Acanthaceae) from Peru
Authors: VILLANUEVA-ESPINOZA ROSA , WASSHAUSEN DIETER , FERNANDEZ-HILARIO ROBIN
Published: September 2021

Dicliptera mercedesiae (Acanthaceae: Justicieae), a new species is described and illustrated from the Junin region of Peru. The new species is similar to Dicliptera purpurascens, but differs by its subsessile flowers, smaller elliptic cymules bracts and corolla without resupination.
Touch me carefully: a step towards understanding morphological diversity in the South American spiny sunflowers (Compositae, Barnadesioideae)
Authors: FERREIRA PAOLA DE LIMA , ANTONELLI ALEXANDRE , GROPPO MILTON
Published: September 2021

The subfamily Barnadesioideae (Compositae) is endemic to South America, comprising 10 genera and 80 species of mostly spiny herbs, subshrubs, shrubs, trees, or woody vines distributed from Venezuela to Argentina. Three genera, Dasyphyllum (27 species), Chuquiraga (22 spp.) and Barnadesia (19 spp.) contain 85% of the species, while the other seven genera (Archidasyphyllum, Arnaldoa, Doniophyton, Duseniella, Fulcaldea, Huarpea, and Schlechtendalia) are represented by up to three species each. Most species are found in xeric areas in the Andean and Patagonian regions—as in the Páramos, Puna and Patagonian steppe vegetation—with a secondary center of diversity in eastern South America. Previous phylogenetic hypotheses have clarified the relationships within the subfamily, showing that there are many non-monophyletic groups in different taxonomic ranks. As a result, taxonomic changes have been proposed over recent decades in order to reflect classifications comprising only monophyletic groups. In the present study, we provide a generic synopsis of the subfamily Barnadesioideae based on the most recent generic circumscriptions, including a key, expanded morphological descriptions, information on geographical distribution and habitat, photographs and taxonomic notes for all genera.
A new synonym of the endangered new species Tigridiopalma exalata (Melastomataceae)
Authors: WANG GANG-TAO , HUANG JING
Published: September 2021

N/A
Experiences of transitioning between settings of care from the perspectives of patients with advanced illness receiving specialist palliative care and their family caregivers: A qualitative interview study
Authors: Guo Ping , Pinto Cathryn , Edwards Beth , Pask Sophie , Firth Alice , O’Brien Suzanne , Murtagh Fliss EM
Published: September 2021

Background:

Transitions between care settings (hospice, hospital and community) can be challenging for patients and family caregivers and are often an under-researched area of health care, including palliative care.

Aim:

To explore the experience of transitions between care settings for those receiving specialist palliative care.

Design:

Qualitative study using thematic analysis.

Setting/participants:

Semi-structured interviews were conducted with adult patients ( n = 15) and family caregivers ( n = 11) receiving specialist palliative care, who had undergone at least two transitions.

Results:

Four themes were identified. (1) Uncertainty about the new care setting. Most participants reported that lack of information about the new setting of care, and difficulties with access and availability of care in the new setting, added to feelings of uncertainty. (2) Biographical disruption. The transition to the new setting often resulted in changes to sense of independence and identity, and maintaining normality was a way to cope with this. (3) Importance of continuity of care. Continuity of care had an impact on feelings of safety in the new setting and influenced decisions about the transition. (4) Need for emotional and practical support. Most participants expressed a greater need for emotional and practical support, when transitioning to a new setting.

Conclusions:

Findings provide insights into how clinicians might better negotiate transitions for these patients and family caregivers, as well as improve patient outcomes. The complexity and diversity of transition experiences, particularly among patients and families from different ethnicities and cultural backgrounds, need to be further explored in future research.
Digital ventriloquism and celebrity access: Cameo and the emergence of paid puppeteering on digital platforms
Authors: Drenten Jenna , Psarras Evie
Published: September 2021

Cameo is part of a growing set of new media platforms trending toward direct routes for monetizing fame. Cameo allows fans to book personalized shout-out videos and provides celebrities—celetoids and reality stars in particular—access to new modes of income, which became increasingly important amid the pandemic. This research explores how the direct monetization of the fan-celebrity relationship is re-shaping the power dynamic of these parasocial relationships. Using digital ventriloquism as an analytical lens to study reality stars (e.g. Real Housewives) on Cameo, this study introduces the concept of paid puppeteering on digital platforms, defined as a form of digital ventriloquism in which a celebrity’s public persona is manipulated and incentivized through financial means on a paid digital platform for the illusion of close parasocial connections with fans. Paid puppeteering reinforces celebrities as gig workers as Cameo mitigates fan access to celebrities—for a fee.
Modeling of engine thermal dynamics and its application in energy management of HEVs considering engine warming-up
Authors: Chu Hongqing , Shi Haoyun , Jiang Yuyao , Shen Tielong
Published: September 2021

The process of engine warming-up leads to additional fuel consumption. Energy management strategy considering engine warming-up is expected to further improve the energy economy of hybrid electric vehicles. This study provides a simple yet practical model for engine thermal dynamics. Then, the optimization problem of energy management considering engine warming-up is formulated on the basis of the control-oriented engine thermal dynamics. Thereafter, the optimal solution is derived by using the dynamic programming algorithm. Finally, the proposed engine thermal dynamics and energy management strategy are evaluated through simulation and experiments. Results show that the established engine thermal model effectively captures the main thermal behavior, simulation results reveal a high degree of approximation to experimental results for the engine temperature and fuel consumption, and the energy management strategy with engine temperature can further improve the energy efficiency.
Educational achievement disparities between second-generation and non-immigrant students: Do school characteristics account for tracking effects?
Authors: Pomianowicz Katja
Published: September 2021

The present article investigates the relationship between the degree of tracking and inequalities in reading literacy of second-generation and non-immigrant students in 28 Western countries. The article takes into account that next to between-school tracking, there are also more subtle forms of tracking, such as tracking within schools or classes. By elaborating how the distinct mechanisms of different tracking characteristics generate achievement inequalities, I assume that any negative effects of tracking on second-generation immigrant students’ achievements are primarily driven by differences in the quality of school environments. Data from the Programme for International Student Assessment 2018 are used and multilevel regression analysis with country-fixed effects are applied. The findings reveal that a higher tracking degree is related to substantial disadvantages in reading literacy for immigrant children. Furthermore, a higher immigrant concentration in schools is associated with immigrant inequalities in reading performance as the degree of tracking increases, whereas unequal distributions of teacher and instructional quality were found to generate inequalities in countries with less tracking. Even though the results are only partly in line with the theory of tracking influences on immigrant achievement disadvantages, they suggest that the interplay between institutional tracking and school characteristics are crucial for learning inequalities.
Does Neighborhood Cohesion Moderate the Association between Cancer and Psychological Distress?
Authors: Reynolds Victoria A. , Pai Manacy
Published: September 2021

The purpose of this study is to examine (a) the association between cancer diagnosis and psychological distress and (b) the extent to which this association is moderated by perceptions of neighborhood social cohesion. Data are drawn from the 2013 wave of the National Health Interview Survey (NHIS), a nationally representative survey on broad health topics. We employ ordinary least squares (OLS) regression to examine the links between cancer, neighborhood cohesion, and distress. Findings reveal no statistically significant difference in psychological distress between women with breast and cervical cancer. However, neighborhood social cohesion does moderate the effect of cancer on distress. While perceptions of neighborhood cohesion do not affect levels of psychological distress among women with breast cancer, perceived connectedness with neighbors translates into significantly lower levels of mental distress among women diagnosed with cervical cancer.
Recent Advances in Nasoalveolar Molding Therapy Using 3D Technology
Authors: Ahsanuddin Sofia , Ahmed Mairaj , Slowikowski Leslie , Heitzler Jenna
Published: September 2021

Presurgical Nasoalveolar Molding (NAM) is an adjunctive treatment modality designed to reorient misaligned tissue structures and nasal cartilage in cleft lip and/or palate (CL/P) patients. Recent advances in NAM therapy focus on modifications to the intraoral molding plate or nasal stent intended to improve treatment outcomes, ease of use, compliance, and cost-effectiveness. Notably, 3D technological advancements have been employed to design NAM devices more efficiently and create objective, standardized means of measuring progressive morphological changes during therapy. These advances are designed to incorporate 3D technology in the treatment of cleft lip and/or palate to render it more precise, accurate, and time-efficient.
Inhibition of NADPH oxidase blocks NETosis and reduces thrombosis in heparin-induced thrombocytopenia
Authors: Leung Halina H. L. , Perdomo Jose , Ahmadi Zohra , Yan Feng , McKenzie Steven E. , Chong Beng H.
Published: September 2021

Heparin-induced thrombocytopenia (HIT) is associated with severe and potentially lethal thrombotic complications. NETosis was recently shown to be an important driver of thrombosis in HIT. We investigated the role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their contributions to thrombus development in HIT. We showed that neutrophil activation by HIT immune complexes induced ROS-dependent NETosis. Analysis of thrombi formed in a microfluidics system showed ROS production in both platelets and neutrophils, and abundant neutrophil extracellular traps (NETs) and ROS distributed throughout the clot. Neutrophil-targeted ROS inhibition was sufficient to block HIT-induced NETosis and thrombosis using human blood. Inhibition of NOX2 with diphenyleneiodonium chloride or GSK2795039 abrogated HIT-induced thrombi in vivo using FcγRIIa+/hPF4+-transgenic mice. Thrombocytopenia in mice remained unaffected by ROS inhibition. Increased ROS production in activated neutrophils was also confirmed using fresh blood from patients with active HIT. Our findings show that ROS and NOX2 play a crucial role in NETosis and thrombosis in HIT. This enhances our understanding of the processes driving thrombosis in HIT and identifies NOX2 as a potential new therapeutic target for antithrombotic treatment of HIT.
Heterogeneous modulation of Bcl-2 family members and drug efflux mediate MCL-1 inhibitor resistance in multiple myeloma
Authors: Bolomsky Arnold , Miettinen Juho J. , Malyutina Alina , Besse Andrej , Huber Julia , Fellinger Stefanie , Breid Helene , Parsons Alun , Klavins Kristaps , Hannich J. Thomas , Kubicek Stefan , Caers Jo , Hübl Wolfgang , Schreder Martin , Zojer Niklas , Driessen Christoph , Tang Jing , Besse Lenka , Heckman Caroline A. , Ludwig Heinz
Published: September 2021

Antiapoptotic Bcl-2 family members have recently (re)emerged as key drug targets in cancer, with a tissue- and tumor-specific activity profile of available BH3 mimetics. In multiple myeloma, MCL-1 has been described as a major gatekeeper of apoptosis. This discovery has led to the rapid establishment of clinical trials evaluating the impact of various MCL-1 inhibitors. However, our understanding about the clinical impact and optimal use of MCL-1 inhibitors is still limited. We therefore explored mechanisms of acquired MCL-1 inhibitor resistance and optimization strategies in myeloma. Our findings indicated heterogeneous paths to resistance involving baseline Bcl-2 family alterations of proapoptotic (BAK, BAX, and BIM) and antiapoptotic (Bcl-2 and MCL-1) proteins. These manifestations depend on the BH3 profile of parental cells that guide the enhanced formation of Bcl-2:BIM and/or the dynamic (ie, treatment-induced) formation of Bcl-xL:BIM and Bcl-xL:BAK complexes. Accordingly, an unbiased high-throughput drug-screening approach (n = 528) indicated alternative BH3 mimetics as top combination partners for MCL-1 inhibitors in sensitive and resistant cells (Bcl-xL>Bcl-2 inhibition), whereas established drug classes were mainly antagonistic (eg, antimitotic agents). We also revealed reduced activity of MCL-1 inhibitors in the presence of stromal support as a drug-class effect that was overcome by concurrent Bcl-xL or Bcl-2 inhibition. Finally, we demonstrated heterogeneous Bcl-2 family deregulation and MCL-1 inhibitor cross-resistance in carfilzomib-resistant cells, a phenomenon linked to the MDR1-driven drug efflux of MCL-1 inhibitors. The implications of our findings for clinical practice emphasize the need for patient-adapted treatment protocols, with the tracking of tumor- and/or clone-specific adaptations in response to MCL-1 inhibition.
Germline variants in DNA repair genes, including BRCA1/2, may cause familial myeloproliferative neoplasms
Authors: Elbracht Miriam , Meyer Robert , Kricheldorf Kim , Gezer Deniz , Thomas Eggermann , Betz Beate , Kurth Ingo , Teichmann Lino L. , Brümmendorf Tim H. , Germing Ulrich , Isfort Susanne , Koschmieder Steffen
Published: September 2021

The molecular causes of myeloproliferative neoplasms (MPNs) have not yet been fully elucidated. Approximately 7% to 8% of the patients carry predisposing genetic germline variants that lead to driver mutations, which enhance JAK-STAT signaling. To identify additional predisposing genetic germline variants, we performed whole-exome sequencing in 5 families, each with parent-child or sibling pairs affected by MPNs and carrying the somatic JAK2 V617F mutation. In 4 families, we detected rare germline variants in known tumor predisposition genes of the DNA repair pathway, including the highly penetrant BRCA1 and BRCA2 genes. The identification of an underlying hereditary tumor predisposition is of major relevance for the individual patients as well as for their families in the context of therapeutic options and preventive care. Two patients with essential thrombocythemia or polycythemia vera experienced progression to acute myeloid leukemia, which may suggest a high risk of leukemic transformation in these familial MPNs. Our study demonstrates the relevance of genetic germline diagnostics in elucidating the causes of MPNs and suggests novel therapeutic options (eg, PARP inhibitors) in MPNs. Furthermore, we uncover a broader tumor spectrum upon the detection of a germline mutation in genes of the DNA repair pathway.
Altered microbiota-host metabolic cross talk preceding neutropenic fever in patients with acute leukemia
Authors: Rashidi Armin , Ebadi Maryam , Rehman Tauseef Ur , Elhusseini Heba , Nalluri Harika , Kaiser Thomas , Ramamoorthy Sivapriya , Holtan Shernan G. , Khoruts Alexander , Weisdorf Daniel J. , Staley Christopher
Published: September 2021

Despite antibiotic prophylaxis, most patients with acute leukemia receiving mucotoxic chemotherapy develop neutropenic fever (NF), many cases of which remain without a documented etiology. Antibiotics disrupt the gut microbiota, with adverse clinical consequences, such as Clostridioides difficile infection. A better understanding of NF pathogenesis could inform the development of novel therapeutics without deleterious effects on the microbiota. We hypothesized that metabolites absorbed from the gut to the bloodstream modulate pyrogenic and inflammatory pathways. Longitudinal profiling of the gut microbiota in 2 cohorts of patients with acute leukemia showed that Akkermansia expansion in the gut was associated with an increased risk for NF. As a prototype mucolytic genus, Akkermansia may influence the absorption of luminal metabolites; thus, its association with NF supported our metabolomics hypothesis. Longitudinal profiling of the serum metabolome identified a signature associated with gut Akkermansia and 1 with NF. Importantly, these 2 signatures overlapped in metabolites in the γ-glutamyl cycle, suggesting oxidative stress as a mediator involved in Akkermansia-related NF. In addition, the level of gut microbial–derived indole compounds increased after Akkermansia expansion and decreased before NF, suggesting their role in mediating the anti-inflammatory effects of Akkermansia, as seen predominantly in healthy individuals. These results suggest that Akkermansia regulates microbiota-host metabolic cross talk by modulating the mucosal interface. The clinical context, including factors influencing microbiota composition, determines the type of metabolites absorbed through the gut barrier and their net effect on the host. Our findings identify novel aspects of NF pathogenesis that could be targets for precision therapeutics. This trial was registered at www.clinicaltrials.gov as #NCT03316456.
Flatness of the Meckel cave may cause primary trigeminal neuralgia: a radiomics-based study
Authors: Lin Jinzhi , Zhang Yong , Li Wuming , Yan Jianhao , Ke Yiquan
Published: September 2021

Background

Neurovascular contact (NVC) is the main cause of primary trigeminal neuralgia (PTN); however, cases of PTN without NVC are still observed. In this study, the Meckel cave (MC) morphology in PTN were analyzed by radiomics and compared to healthy controls (HCs) to explore the cause of PTN.

Methods

We studied the 3.0T MRI data of 115 patients with PTN and 46 HCs. Bilateral MC was modeled using the 3D Slicer software, and the morphological characteristics of MC were analyzed using the radiomics method.

Results

The right side incidence rate in the PTN group was higher than the left side incidence. By analyzing the flatness feature of MC, we observed that the affected side of the PTN was lower than that of the unaffected side, the right MC of the PTN and HC was lower than that of the left MC, the MC of the affected side of the left and right PTN without bilateral NVC was lower than that of the unaffected side.

Conclusions

By providing a method to analyze the morphology of the MC, we found that there is an asymmetry in the morphology of bilateral MC in the PTN and HC groups. It can be inferred that the flatness of the MC may be a cause of PTN.
Impact of an end-of-fourth-year emergency medicine bootcamp
Authors: Lewis Jason J. , Grossestreuer Anne V. , Ullman Edward A.
Published: September 2021

Background

The final months of the fourth-year of medical school are variable in educational and clinical experience, and the effect on clinical knowledge and preparedness for residency is unclear. Specialty-specific “bootcamps” are a growing trend in medical education aimed at increasing clinical knowledge, procedural skills, and confidence prior to the start of residency.

Methods

We developed a 4-week Emergency Medicine (EM) bootcamp offered during the final month of medical school. At the conclusion of the course, participants evaluated its impact. EM residency-matched participants and non-participants were asked to self-evaluate their clinical knowledge, procedural skills and confidence 1 month into the start of residency. Program directors were surveyed to assess participants and non-participants across the same domains. A Fisher’s exact test was performed to test whether responses between participants and non-participants were statistically different.

Results

From 2015 to 2018, 22 students participated in the bootcamp. The majority reported improved confidence, competence, and procedural skills upon completion of the course. Self-assessed confidence was significantly higher in EM-matched participants 1 month into residency compared to EM-matched non-participants (p = 0.009). Self-assessed clinical knowledge and procedural skill competency was higher in participants than non-participants but did not reach statistical significance. Program directors rated EM-matched participants higher in all domains but this difference was also not statistically significant.

Conclusions

Participation in an EM bootcamp increases self-confidence at the start of residency among EM-matched residents. EM bootcamps and other specialty-specific courses at the end of medical school may ease the transition from student to clinician and may improve clinical knowledge and procedural skills.
Velo-Predictor: an ensemble learning pipeline for RNA velocity prediction
Authors: Wang Xin , Zheng Jie
Published: September 2021

Background

RNA velocity is a novel and powerful concept which enables the inference of dynamical cell state changes from seemingly static single-cell RNA sequencing (scRNA-seq) data. However, accurate estimation of RNA velocity is still a challenging problem, and the underlying kinetic mechanisms of transcriptional and splicing regulations are not fully clear. Moreover, scRNA-seq data tend to be sparse compared with possible cell states, and a given dataset of estimated RNA velocities needs imputation for some cell states not yet covered.

Results

We formulate RNA velocity prediction as a supervised learning problem of classification for the first time, where a cell state space is divided into equal-sized segments by directions as classes, and the estimated RNA velocity vectors are considered as ground truth. We propose Velo-Predictor, an ensemble learning pipeline for predicting RNA velocities from scRNA-seq data. We test different models on two real datasets, Velo-Predictor exhibits good performance, especially when XGBoost was used as the base predictor. Parameter analysis and visualization also show that the method is robust and able to make biologically meaningful predictions.

Conclusion

The accurate result shows that Velo-Predictor can effectively simplify the procedure by learning a predictive model from gene expression data, which could help to construct a continous landscape and give biologists an intuitive picture about the trend of cellular dynamics.
Insights into 6S RNA in lactic acid bacteria (LAB)
Authors: Cataldo Pablo Gabriel , Klemm Paul , Thüring Marietta , Saavedra Lucila , Hebert Elvira Maria , Hartmann Roland K. , Lechner Marcus
Published: September 2021

Background

6S RNA is a regulator of cellular transcription that tunes the metabolism of cells. This small non-coding RNA is found in nearly all bacteria and among the most abundant transcripts. Lactic acid bacteria (LAB) constitute a group of microorganisms with strong biotechnological relevance, often exploited as starter cultures for industrial products through fermentation. Some strains are used as probiotics while others represent potential pathogens. Occasional reports of 6S RNA within this group already indicate striking metabolic implications. A conceivable idea is that LAB with 6S RNA defects may metabolize nutrients faster, as inferred from studies of Echerichia coli. This may accelerate fermentation processes with the potential to reduce production costs. Similarly, elevated levels of secondary metabolites might be produced. Evidence for this possibility comes from preliminary findings regarding the production of surfactin in Bacillus subtilis, which has functions similar to those of bacteriocins. The prerequisite for its potential biotechnological utility is a general characterization of 6S RNA in LAB.

Results

We provide a genomic annotation of 6S RNA throughout the Lactobacillales order. It laid the foundation for a bioinformatic characterization of common 6S RNA features. This covers secondary structures, synteny, phylogeny, and product RNA start sites. The canonical 6S RNA structure is formed by a central bulge flanked by helical arms and a template site for product RNA synthesis. 6S RNA exhibits strong syntenic conservation. It is usually flanked by the replication-associated recombination protein A and the universal stress protein A. A catabolite responsive element was identified in over a third of all 6S RNA genes. It is known to modulate gene expression based on the available carbon sources. The presence of antisense transcripts could not be verified as a general trait of LAB 6S RNAs.

Conclusions

Despite a large number of species and the heterogeneity of LAB, the stress regulator 6S RNA is well-conserved both from a structural as well as a syntenic perspective. This is the first approach to describe 6S RNAs and short 6S RNA-derived transcripts beyond a single species, spanning a large taxonomic group covering multiple families. It yields universal insights into this regulator and complements the findings derived from other bacterial model organisms.
Up-regulation of apoptotic- and cell survival-related gene pathways following exposures of western corn rootworm to B. thuringiensis crystalline pesticidal proteins in transgenic maize roots
Authors: Coates Brad S. , Deleury Emeline , Gassmann Aaron J. , Hibbard Bruce E. , Meinke Lance J. , Miller Nicholas J. , Petzold-Maxwell Jennifer , French B. Wade , Sappington Thomas W. , Siegfried Blair D. , Guillemaud Thomas
Published: September 2021

Background

Resistance of pest insect species to insecticides, including B. thuringiensis (Bt) pesticidal proteins expressed by transgenic plants, is a threat to global food security. Despite the western corn rootworm, Diabrotica virgifera virgifera, being a major pest of maize and having populations showing increasing levels of resistance to hybrids expressing Bt pesticidal proteins, the cell mechanisms leading to mortality are not fully understood.

Results

Twenty unique RNA-seq libraries from the Bt susceptible D. v. virgifera inbred line Ped12, representing all growth stages and a range of different adult and larval exposures, were assembled into a reference transcriptome. Ten-day exposures of Ped12 larvae to transgenic Bt Cry3Bb1 and Gpp34/Tpp35Ab1 maize roots showed significant differential expression of 1055 and 1374 transcripts, respectively, compared to cohorts on non-Bt maize. Among these, 696 were differentially expressed in both Cry3Bb1 and Gpp34/Tpp35Ab1 maize exposures. Differentially-expressed transcripts encoded protein domains putatively involved in detoxification, metabolism, binding, and transport, were, in part, shared among transcripts that changed significantly following exposures to the entomopathogens Heterorhabditis bacteriophora and Metarhizium anisopliae. Differentially expressed transcripts in common between Bt and entomopathogen treatments encode proteins in general stress response pathways, including putative Bt binding receptors from the ATP binding cassette transporter superfamily. Putative caspases, pro- and anti-apoptotic factors, as well as endoplasmic reticulum (ER) stress-response factors were identified among transcripts uniquely up-regulated following exposure to either Bt protein.

Conclusions

Our study suggests that the up-regulation of genes involved in ER stress management and apoptotic progression may be important in determining cell fate following exposure of susceptible D. v. virgifera larvae to Bt maize roots. This study provides novel insights into insect response to Bt intoxication, and a possible framework for future investigations of resistance mechanisms.
Genome-wide association studies for canine hip dysplasia in single and multiple populations – implications and potential novel risk loci
Authors: Wang Shizhi , Strandberg Erling , Arvelius Per , Clements Dylan N. , Wiener Pamela , Friedrich Juliane
Published: September 2021

Background

Association mapping studies of quantitative trait loci (QTL) for canine hip dysplasia (CHD) can contribute to the understanding of the genetic background of this common and debilitating disease and might contribute to its genetic improvement. The power of association studies for CHD is limited by relatively small sample numbers for CHD records within countries, suggesting potential benefits of joining data across countries. However, this is complicated due to the use of different scoring systems across countries. In this study, we incorporated routinely assessed CHD records and genotype data of German Shepherd dogs from two countries (UK and Sweden) to perform genome-wide association studies (GWAS) within populations using different variations of CHD phenotypes. As phenotypes, dogs were either classified into cases and controls based on the Fédération Cynologique Internationale (FCI) five-level grading of the worst hip or the FCI grade was treated as an ordinal trait. In a subsequent meta-analysis, we added publicly available data from a Finnish population and performed the GWAS across all populations. Genetic associations for the CHD phenotypes were evaluated in a linear mixed model using 62,089 SNPs.

Results

Multiple SNPs with genome-wide significant and suggestive associations were detected in single-population GWAS and the meta-analysis. Few of these SNPs overlapped between populations or between single-population GWAS and the meta-analysis, suggesting that many CHD-related QTL are population-specific. More significant or suggestive SNPs were identified when FCI grades were used as phenotypes in comparison to the case-control approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional candidate genes associated with hip dysplasia.

Conclusions

Our findings confirm the complex genetic nature of hip dysplasia in dogs, with multiple loci associated with the trait, most of which are population-specific. Routinely assessed CHD information collected across countries provide an opportunity to increase sample sizes and statistical power for association studies. While the lack of standardisation of CHD assessment schemes across countries poses a challenge, we showed that conversion of traits can be utilised to overcome this obstacle.
Transcriptome analysis provides genome annotation and expression profiles in the central nervous system of Lymnaea stagnalis at different ages
Authors: Rosato Martina , Hoelscher Brittany , Lin Zhenguo , Agwu Chidera , Xu Fenglian
Published: September 2021

Background

The pond snail, Lymnaea stagnalis (L. stagnalis), has served as a valuable model organism for neurobiology studies due to its simple and easily accessible central nervous system (CNS). L. stagnalis has been widely used to study neuronal networks and recently gained popularity for study of aging and neurodegenerative diseases. However, previous transcriptome studies of L. stagnalis CNS have been exclusively carried out on adult L. stagnalis only. As part of our ongoing effort studying L. stagnalis neuronal growth and connectivity at various developmental stages, we provide the first age-specific transcriptome analysis and gene annotation of young (3 months), adult (6 months), and old (18 months) L. stagnalis CNS.

Results

Using the above three age cohorts, our study generated 55–69 millions of 150 bp paired-end RNA sequencing reads using the Illumina NovaSeq 6000 platform. Of these reads, ~ 74% were successfully mapped to the reference genome of L. stagnalis. Our reference-based transcriptome assembly predicted 42,478 gene loci, of which 37,661 genes encode coding sequences (CDS) of at least 100 codons. In addition, we provide gene annotations using Blast2GO and functional annotations using Pfam for ~ 95% of these sequences, contributing to the largest number of annotated genes in L. stagnalis CNS so far. Moreover, among 242 previously cloned L. stagnalis genes, we were able to match ~ 87% of them in our transcriptome assembly, indicating a high percentage of gene coverage. The expressional differences for innexins, FMRFamide, and molluscan insulin peptide genes were validated by real-time qPCR. Lastly, our transcriptomic analyses revealed distinct, age-specific gene clusters, differentially expressed genes, and enriched pathways in young, adult, and old CNS. More specifically, our data show significant changes in expression of critical genes involved in transcription factors, metabolisms (e.g. cytochrome P450), extracellular matrix constituent, and signaling receptor and transduction (e.g. receptors for acetylcholine, N-Methyl-D-aspartic acid, and serotonin), as well as stress- and disease-related genes in young compared to either adult or old snails.

Conclusions

Together, these datasets are the largest and most updated L. stagnalis CNS transcriptomes, which will serve as a resource for future molecular studies and functional annotation of transcripts and genes in L. stagnalis.
Surveillance and care for confirmed and suspected patients with COVID-19 in general practice (CovidCare): study protocol for an observational trial
Authors: Hoffmann Mariell , Stengel Sandra , Forstner Johanna , Baldauf Annika , Laux Gunter , Aluttis Frank , Qreini Markus , Engeser Peter , Szecsenyi Joachim , Peters-Klimm Frank
Published: September 2021

Background

A SARS-CoV-2 infection can lead from asymptomatic through to critical disease in a dynamic and unpredictable course within a few days. The challenge in outpatient monitoring the highly contagious COVID-19 disease during the ongoing pandemic is to filter severe courses followed by admission to hospital with the aim of preventing an overburdening of clinics. However, little is known of the effect of risk factors on the course of the infection of outpatient patients. To support general practices in managing high risk patients, we designed a COVID-19 surveillance and care tool (CovidCare). It includes an initial assessment of yet known risk factors and symptoms and a continuous telephone monitoring of signs and symptoms. This study aims to investigate the effects of different risk factors on the course of the COVID-19 disease, utilisation of different health care services and to gain insights into the utilisation of CovidCare in general practices.

Methods

We will conduct a multi-centered prospective, longitudinal non-controlled observational trial of COVID-19 patients in general practices. Overall, 700 GPs who participate in general-practice centered care by the AOK Baden-Württemberg (large German sickness fund) are eligible and will be invited for study participation, including adult, outpatient COVID-19 patients (or urgent suspicion and ≥ 50 years) with at least one additional known risk factor, who participate in general-practice centered care. The primary outcome is hospitalisation due to COVID-19. Secondary outcomes are diagnosis of pneumonia, utilisation of palliative care, mortality rate, anxiety and identification of predictive risk factors. Quantitative data analysis will focus on valid descriptive figures and mixed regression models. The accompanying process evaluation is based on interviews and questionnaires from general practice staff and patients. The analysis of the process evaluation is descriptive and explorative.

Discussion

The use of the COVID-19 surveillance and care tool is expected to encourage the provision of structured quality of care during the ongoing pandemic. This trial will provide an understanding of the COVID-19-disease and the effect of several risk factors on the course of the disease and health care utilisation. The results can be used for a better management of the COVID-19 pandemic and its consequences.

Trial registration

German Clinical Trials Register DRKS00022054.
Clinical feature of severe fever with thrombocytopenia syndrome (SFTS)-associated encephalitis/encephalopathy: a retrospective study
Authors: Xu Ying , Shao Mingran , Liu Ning , Dong Danjiang , Tang Jian , Gu Qin
Published: September 2021

Background/objective

Severe fever with thrombocytopenia syndrome (SFTS) cause encephalitis/encephalopathy, but few reports were available. We aimed to investigate the incidence of encephalitis/encephalopathy in SFTS patients and to summarize clinical characteristics, laboratory findings and imaging features.

Methods

We conducted a retrospective review of all patients with confirmed SFTS admitted to Nanjing Drum Tower Hospital, a tertiary hospital in Nanjing City, China, between January 2016 and July 2020. The patients were divided into two groups according to whether they had encephalitis/encephalopathy: encephalitis/encephalopathy group and non- encephalitis/encephalopathy group. Clinical data, laboratory findings, imaging characteristics, treatments and outcomes of these patients were collected and analyzed.

Results

A total of 109 SFTS patients with were included, of whom 30 (27.5 %) developed encephalitis/encephalopathy. In-hospital mortality (43.3 %) was higher in encephalitis/encephalopathy group than non-encephalitis/encephalopathy group (12.7 %). Univariate logistic regression showed that cough, wheezing, dyspnoea, respiratory failure, vasopressors use, bacteremia, invasive pulmonary aspergillosis (IPA) diagnoses, PCT > 0.5 ug/L, CRP > 8 mg/L, AST > 200 U/L and serum amylase level > 80 U/L were the risk factors for the development of encephalitis/encephalopathy for SFTS patients. Multivariate logistic regression analysis identified bacteremia, PCT > 0.5 mg/L and serum amylase level > 80 U/L as independent predictors of encephalitis/ encephalopathy development for SFTS patients.

Conclusions

SFTS-associated encephalitis/encephalopathy has high morbidity and mortality. it was necessary to strengthen the screening of CSF testing and brain imaging after admission for SFTS patients who had symptoms of encephalitis/encephalopathy. SFTS patients with bacteremia, PCT > 0.5 ug/L or serum amylase level > 80 U/L should be warned to progress to encephalopathy.
Composition of the vaginal microbiota during pregnancy in women living in sub-Saharan Africa: a PRISMA-compliant review
Authors: Juliana Naomi C. A. , Peters Remco P. H. , Al-Nasiry Salwan , Budding Andries E. , Morré Servaas A. , Ambrosino Elena
Published: September 2021

Background

The vaginal microbiota (VMB) are the set of microorganisms residing in the human vagina. During pregnancy, their composition is Lactobacillus-dominant in most Caucasian women. Previous studies suggest that the VMB of women with African ancestry is more likely to be non-Lactobacillus dominant (dysbiotic) compared to other populations, and possibly relate to the high incidence of pregnancy complications, such as preterm birth. This work reviewed the literature on VMB composition in pregnant women from sub-Saharan Africa.

Methods

A search was conducted in PubMed and Embase databases following PRISMA guidelines. Observational and intervention studies analysing VMB communities from sub-Saharan African pregnant women using molecular techniques were included.

Results

Ten studies performed in seven sub-Saharan African countries were identified. They independently showed that Lactobacillus-dominant VMB (particularly L. iners or L. crispatus) or VMB containing Lactobacilli are the most prevalent, followed by a more diverse anaerobe-dominant VMB, in the studied populations. The majority of pregnant women with a sexually-transmitted infection had a Lactobacillus-dominant VMB, but with a significantly higher presence of anaerobic species.

Conclusion

In agreement with studies performed in other populations, Lactobacillus species are the most prevalent VMB species during pregnancy in sub-Saharan African women. The frequency of diverse anaerobe-dominant VMB is high in these populations. In Africa, studies on VMB in pregnancy are scant, heterogeneous in methodology, and knowledge remains limited. More insights on VMB composition and their possible sequalae among these populations is needed.
Clinical characteristics and risk factors associated with Pneumocystis jirovecii infection in patients with solid tumors: study of thirteen-year medical records of a large cancer center
Authors: Takeda Koichi , Harada Sohei , Hayama Brian , Hoashi Kosuke , Enokida Taisuke , Sasaki Toshiharu , Okamoto Koh , Nakano Kenji , Ohkushi Daisuke
Published: September 2021

Background

Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids.

Methods

We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality.

Results

Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%.

Conclusions

More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.