bluuebunny/crossref_metadata_2025 huggingface dataset:
Biogenesis of flavor-related linalool is diverged and genetically conserved in tree peony (Paeonia × suffruticosa)
Authors: Li Shanshan , Zhang Ling , Sun Miao , Lv Mengwen , Yang Yong , Xu Wenzhong , Wang Liangsheng
Published: November 2022

Floral scent is an important and genetically complex trait in horticultural plants. Tree peony (Paeonia × suffruticosa) originates in the Pan-Himalaya and has nine wild species divided into two subsections, Delavayanae and Vaginatae. Their flowers are beloved worldwide for their sweet floral fragrance, yet the flavor-related volatiles and underlying biosynthetic pathways remain unknown. Here, we characterized the volatile blends of all wild tree peony species and found that the flavor-related volatiles were highly divergent, but linalool was a unique monoterpene in subsect. Delavayanae. Further detection of volatiles in 97 cultivars with various genetic backgrounds showed that linalool was also the characteristic aroma component in Paeonia delavayi hybrid progenies, suggesting that linalool was conserved and dominant within subsect. Delavayanae and its hybrids, instead of species and cultivars from subsect. Vaginatae. Global transcriptome analysis of all wild tree peony species and 60 cultivars revealed five candidate genes that may be involved in key steps of linalool biosynthesis; especially the expressions of three TPS genes, PdTPS1, PdTPS2, and PdTPS4, were significantly positively correlated with linalool emissions across tree peony cultivars. Further biochemical evidence demonstrated that PdTPS1 and PdTPS4 were the pivotal genes determining the species-specific and cultivar-specific emission of linalool. This study revealed a new insight into floral scent divergence in tree peony and would greatly facilitate our understanding of the phylogeny and evolution of Paeonia.
Critical assessment of transformer-based AI models for German clinical notes
Authors: Lentzen Manuel , Madan Sumit , Lage-Rupprecht Vanessa , Kühnel Lisa , Fluck Juliane , Jacobs Marc , Mittermaier Mirja , Witzenrath Martin , Brunecker Peter , Hofmann-Apitius Martin , Weber Joachim , Fröhlich Holger
Published: November 2022

Objective

Healthcare data such as clinical notes are primarily recorded in an unstructured manner. If adequately translated into structured data, they can be utilized for health economics and set the groundwork for better individualized patient care. To structure clinical notes, deep-learning methods, particularly transformer-based models like Bidirectional Encoder Representations from Transformers (BERT), have recently received much attention. Currently, biomedical applications are primarily focused on the English language. While general-purpose German-language models such as GermanBERT and GottBERT have been published, adaptations for biomedical data are unavailable. This study evaluated the suitability of existing and novel transformer-based models for the German biomedical and clinical domain.

Materials and Methods

We used 8 transformer-based models and pre-trained 3 new models on a newly generated biomedical corpus, and systematically compared them with each other. We annotated a new dataset of clinical notes and used it with 4 other corpora (BRONCO150, CLEF eHealth 2019 Task 1, GGPONC, and JSynCC) to perform named entity recognition (NER) and document classification tasks.

Results

General-purpose language models can be used effectively for biomedical and clinical natural language processing (NLP) tasks, still, our newly trained BioGottBERT model outperformed GottBERT on both clinical NER tasks. However, training new biomedical models from scratch proved ineffective.

Discussion

The domain-adaptation strategy’s potential is currently limited due to a lack of pre-training data. Since general-purpose language models are only marginally inferior to domain-specific models, both options are suitable for developing German-language biomedical applications.

Conclusion

General-purpose language models perform remarkably well on biomedical and clinical NLP tasks. If larger corpora become available in the future, domain-adapting these models may improve performances.
How do people react to AI failure? Automation bias, algorithmic aversion, and perceived controllability
Authors: Jones-Jang S Mo , Park Yong Jin
Published: November 2022

AI can make mistakes and cause unfavorable consequences. It is important to know how people react to such AI-driven negative consequences and subsequently evaluate the fairness of AI’s decisions. This study theorizes and empirically tests two psychological mechanisms that explain the process: (a) heuristic expectations of AI’s consistent performance (automation bias) and subsequent frustration of unfulfilled expectations (algorithmic aversion) and (b) heuristic perceptions of AI’s controllability over negative results. Our findings from two experimental studies reveal that these two mechanisms work in an opposite direction. First, participants tend to display more sensitive responses to AI’s inconsistent performance and thus make more punitive assessments of AI’s decision fairness, when compared to responses to human experts. Second, as participants perceive AI has less control over unfavorable outcomes than human experts, they are more tolerant in their assessments of AI.
Elekta Unity MR-linac commissioning: mechanical and dosimetry tests
Authors: Tsuneda Masato , Abe Kota , Fujita Yukio , Ikeda Yohei , Furuyama Yoshinobu , Uno Takashi
Published: November 2022

We report the commissioning results of Elekta Unity for the dosimetric performance and mechanical quality assurance (QA), and propose additional commissioning procedures. Mechanical tests included multi-leaf collimator (MLC) positional accuracy, radiation isocenter diameter at the center and off-center position, and coincidence between the magnetic resonance (MR) image center and radiation isocenter. Comparisons between the measurements and calculations of the simple irradiated field, intensity modulated radiation therapy (IMRT) commissioning, MLC output factor ratio, validation of independent dose calculation software and end-to-end testing were performed to evaluate dosimetric performance. The average values of the MLC positional accuracy for film- and imaging device-based analysis were −0.1 and 0.3 mm, respectively. The measured radiation isocenter size was 0.41 mm, and the off-center results were within 1 mm. The coincidence was −0.21, −1.19 and 0.49 mm along the x-, y- and z-axes, respectively. The calculated percent depth doses (PDD) and profiles agreed with the measurements. The results of independent dose calculation were within the action level recommended by American Associations of Physicist in Medicine. The gamma passing rate (GPR) for IMRT commissioning was 98.6 ± 0.9%, and end-to-end testing of adapted plans showed agreement within 2% between the measurement and calculation. We reported the results of mechanical and dosimetric performances of Elekta Unity, and proposed novel commissioning procedures. Our results should provide knowledge to the physics community for enhancing the QA programs.
Learning from Neighbours about a Changing State
Authors: Dasaratha Krishna , Golub Benjamin , Hak Nir
Published: November 2022

Agents learn about a changing state using private signals and their neighbours’ past estimates of the state. We present a model in which Bayesian agents in equilibrium use neighbours’ estimates simply by taking weighted sums with time-invariant weights. The dynamics thus parallel those of the tractable DeGroot model of learning in networks, but arise as an equilibrium outcome rather than a behavioural assumption. We examine whether information aggregation is nearly optimal as neighbourhoods grow large. A key condition for this is signal diversity: each individual’s neighbours have private signals that not only contain independent information, but also have sufficiently different distributions. Without signal diversity—e.g. if private signals are i.i.d.—learning is suboptimal in all networks and highly inefficient in some. Turning to social influence, we find it is much more sensitive to one’s signal quality than to one’s number of neighbours, in contrast to standard models with exogenous updating rules.
Advancing multi-level health communication research: A Delphi study on barriers and opportunities
Authors: Oh April Y , Rising Camella J , Gaysynsky Anna , Tsakraklides Sophia , Huang Grace C , Chou Wen-Ying Sylvia , Blake Kelly D , Vanderpool Robin C
Published: November 2022

Adopting a multi-level perspective that considers the many interrelated contexts influencing health could make health communication interventions more effective and equitable. However, despite increasing interest in the use of multi-level approaches, multi-level health communication (MLHC) interventions are infrequently utilized. We therefore sought to conduct a modified Delphi study to better understand how researchers conceptualize MLHC interventions and identify opportunities for advancing MLHC work. Communication and health behavior experts were invited to complete two rounds of surveys about the characteristics, benefits, pitfalls, best practices, barriers, and facilitators of MLHC interventions; the role of technology in facilitating MLHC interventions; and ways to advance MLHC intervention research (46 experts completed the first survey, 44 completed both surveys). Survey data were analyzed using a mixed-methods approach. Panelists reached consensus on two components of the proposed definition of MLHC interventions and also put forward a set of best practices for these interventions. Panelists felt that most health intervention research could benefit from a multi-level approach, and generally agreed that MLHC approaches offered certain advantages over single-level approaches. However, they also expressed concern related to the time, cost, and complexity of MLHC interventions. Although panelists felt that technology could potentially support MLHC interventions, they also recognized the potential for technology to exacerbate disparities. Finally, panelists prioritized a set of methodological advances and practical supports that would be needed to facilitate future MLHC intervention research. The results of this study point to several future directions for the field, including advancing how interactions between levels are assessed, increasing the empirical evidence base demonstrating the advantages of MLHC interventions, and identifying best practices for the use of technology. The findings also suggest that researchers may need additional support to overcome the perceived practical challenges of conducting MLHC interventions.
Fiscal state aid law as a tool against harmful tax competition in the EU: déjà vu?
Authors: Kyriazis Dimitrios
Published: November 2022

The theme of this article is the relationship between harmful tax competition measures and prohibited fiscal State aid. The aim of this article is to present a targeted examination of the use of State aid rules against national tax measures, eg tax schemes and tax rulings, following the adoption of the EU Code of Conduct for Business Taxation in 1997. The fiscal State aid decisions and judgments to be covered are divided into two parts: the first fiscal aid wave of the (early) 2000s and the second (ongoing) fiscal aid wave, which most notably includes the Apple, Fiat, Starbucks, and Amazon cases. It is argued that an important factor connecting the two fiscal State aid waves is the link they share with the EU’s fight against harmful tax competition.
High-Quality Genome Resource of Bacillus subtilis N4, a Biological Control Agent Isolated from Phoebe bournei
Authors: Long Yu , Chen Shaoru , Xu Xiaochen , Zhao Wenbao , Tang Xinghao , Zhang Lei , Zhang Qinghua
Published: November 2022

Bacillus subtilis strain N4, an endophyte isolated from the healthy leaves of Phoebe bournei, possesses an excellent biocontrol effect against stem canker of P. bournei caused by Lasiodiplodia theobromae. To understand its biocontrol mechanism, we assembled a high-quality genome of N4 using a combination of second- and third-generation sequencing methods. The N4 genome contained one circular DNA chromosome of 4,218,183 bp length with 43.5% GC content and 11 secondary metabolite biosynthesis gene clusters, including genes for subtilomycin synthesis. This high-quality genome assembly and gene annotation resource will provide better insights into the biocontrol potential of B. subtilis strain N4 against stem canker of P. bournei.
Incidence and Outcomes of Patients Receiving Chronic Kidney Replacement Therapy Admitted to Scottish ICUs Between 2009 and 2019—A National Observational Cohort Study
Authors: Lambourg Emilie , Walker Heather , Campbell Jacqueline , Watters Chrissie , O’Neil Martin , Donaldson Lorraine , Siddiqui Moneeza K. , Almond Alison , Buck Katharine , Cousland Zoe , Joss Nicola , Metcalfe Wendy , Methven Shona , Sanu Vinod , Spalding Elaine , Traynor Jamie P. , Lone Nazir I , Bell Samira ,   on behalf of the Scottish Renal Registry
Published: November 2022

OBJECTIVES:

To determine the incidence and characteristics of ICU admissions in the Scottish population of patients treated with chronic kidney replacement therapy (KRT) over an 11-year period and determine factors associated with post-ICU admission mortality.

DESIGN:

Retrospective observational cohort study.

SETTING:

We analyzed admissions to Scottish intensive care environments between January 1, 2009, and December 31, 2019.

PATIENTS:

All patients receiving chronic KRT—including maintenance dialysis and kidney transplant—in Scotland.

Intervention:

None.

MEASUREMENTS AND MAIN RESULTS:

Descriptive statistics and factors associated with mortality using logistic regression and Cox proportional hazard models. From 10,657 unique individuals registered in the Scottish Renal Registry over the 11-year study period and alive as of January 1, 2009, 1,402 adult patients were identified as being admitted to a Scottish critical care setting. Between 2009 and 2019, admissions to ICU increased in a nonlinear manner driven by increases in admissions for renal causes and elective cardiac surgery. The ICU admission rate was higher among patients on chronic dialysis than in kidney transplant recipients (59.1 vs 19.9 per 1,000 person-years), but post-ICU mortality was similar (about 24% at 30 d and 40% at 1 year). Admissions for renal reasons were most common (20.9%) in patients undergoing chronic dialysis, whereas kidney transplant recipients were most frequently admitted for pneumonia (19.3%) or sepsis (12.8%). Adjusted Cox PH models showed that receiving invasive ventilation and vasoactive drugs was associated with an increased risk of death at 30 days post-ICU admission (HR, 1.75; 95% CI, 1.28–2.39 and 1.72; 95% CI, 1.28–2.31, respectively).

CONCLUSIONS:

With a growing population of kidney transplant recipients and the improved survival of patients on chronic dialysis, the number of ICU admissions is rising in the chronic KRT population. Mortality post-ICU admission is high for these patients.
Association between influenza vaccination and SARS-CoV-2 infection and its outcomes: systematic review and meta-analysis
Authors: Jiang Binshan , Huang Qiangru , Jia Mengmeng , Xue Xinai , Wang Qing , Yang Weizhong , Feng Luzhao
Published: November 2022

Background:

World Health Organization recommends that influenza vaccines should benefit as much of the population as possible, especially where resources are limited. Corona virus disease 2019 (COVID-19) has become one of the greatest threats to health systems worldwide. The present study aimed to extend the evidence of the association between influenza vaccination and COVID-19 to promote the former.

Methods:

In this systematic review, four electronic databases, including the Cochrane Library, PubMed, Embase, and Web of Science, were searched for related studies published up to May 2022. All odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by meta-analysis.

Results:

A total of 36 studies, encompassing 55,996,841 subjects, were included in this study. The meta-analysis for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provided an OR of 0.80 (95% CI: 0.73–0.87). The statistically significant estimates for clinical outcomes were 0.83 (95% CI: 0.72–0.96) for intensive care unit admission, 0.69 (95% CI: 0.57–0.84) for ventilator support, and 0.69 (95% CI: 0.52–0.93) for fatal infection, while no effect seen in hospitalization with an OR of 0.87 (95% CI: 0.68–1.10).

Conclusion:

Influenza vaccination helps limit SARS-CoV-2 infection and severe outcomes, but further studies are needed.

Registration:

PROSPERO, CRD 42022333747.
Multi-time point imaging in 99mTc-pertechnetate scintigraphy of ectopic gastric mucosa in duplication cysts: value-added services
Authors: Khurana Aditi , Garg Sumit , Ravindra Shubha G. , Kumar Yadav Devendra , Jain Vishesh , Bajpai Minu , Agarwala Sandeep , Bal Chandrashekhar , Kumar Rakesh
Published: November 2022

Objectives

The aim of our study was to describe the scintigraphic patterns of 99mTc-pertechnetate uptake in patients who were referred to the department of nuclear medicine for evaluating and diagnosing ectopic gastric mucosa in foregut and midgut duplication cysts.

Materials and methods

This hospital-based, retrospective cum prospective research spans a period of 8 years from April 2014 to January 2022. Previous hospital medical records were analyzed and subsequently, a database was prepared which included the age, sex, clinical indication of a 99mTc-pertechnetate scan, and the planar and SPECT-computed tomography (CT) imaging findings. Postoperative histopathological reports were available for 21 patients. Dynamic and planar static imaging was performed. We included SPECT-CT in suspected duplication cysts to increase the sensitivity and specificity which is a tradeoff for a small amount of additional radiation exposure. A total of 69 patients were subjected to a 99mTc-pertechnetate scan for suspected foregut or midgut duplication cysts. All were subjected to dynamic planar and delayed static images up to 24 h or until focal uptake of radiotracer was noted which corroborated the anatomical findings, whichever was earlier. SPECT-CT was performed along with the planar study in 31 patients which confirmed the findings. Previously performed CT scans were used for anatomical correlation in the remaining ones

Results

Duplication cysts were localized in a total of 28 patients (19 foregut duplication cysts and 12 small bowel duplications – 3 patients had dual duplication cysts, both foregut, and midgut). Forty-one patients had no scintigraphic evidence of ectopic gastric mucosa. Of these 69 patients, histopathological diagnosis was available for 21 patients (22 lesions). The report was concordant with the scan findings in 15 patients (16 lesions) and 6 patients showed discordance in histopathological diagnosis and scan findings.

Conclusion

In conclusion, multi-time point imaging is the key to diagnosing ectopic gastric mucosa of various sizes and in various locations. An abnormal radiotracer uptake in dynamic sequences, even before the appearance of the stomach in the region of the small bowel is indicative of intestinal duplication, and delayed radiotracer visualization in the region of the thorax is characteristic of intrathoracic foregut duplication cyst.
An Unexpected Death Due to a Subclinical Pheochromocytoma After an Induced Abortion
Authors: Lupariello Francesco , Mirri Federica , Davico Laura , Di Vella Giancarlo
Published: November 2022

Deaths due to hypertensive crisis can be unexplained because of the impossibility to identify—before the decease—the specific cause of the crisis. In these cases, autopsy and microscopic examinations are needed. It can happen that the request to conduct these examinations can be submitted to forensic pathologists by prosecutors to ascertain medical malpractice claims. Indeed, we report the case of a 36-year-old woman who died after a minimally invasive medical procedure because of the occurrence of a severe hypertensive crisis. After death, the woman's relatives raised formal complaint for medical malpractice. For this reason, the prosecutor ordered to perform an autopsy. Examining the abdominal cavity, the forensic pathologists identified the left adrenal gland as expanded; in correspondence with organ's medulla, there was a gray and noncapsulated mass. Immunohistochemistry was performed: the microscopic samples were diffusely positive for chromogranin A, suggesting the diagnosis of a subclinical pheochromocytoma. In light of the above, medical malpractice was excluded. This case highlights that forensic pathologists should be aware that, in case of unexpected deaths due to hypertensive crisis, adrenal glands should be always accurately evaluated, performing specific immunohistochemistry study to exclude the presence of a pheochromocytoma.
Pseudoaneurysms and Orthognathic Surgery: A Systematic Review and a Proposed Algorithm of Treatment
Authors: AlMofreh AlQahtani Feras , Kuriadom Sam Thomas , Bishawi Khaled , AlAssiri Nasser
Published: November 2022

This study aimed to gather existing evidence regarding the incidence, clinical presentation, and management of pseudoaneurysms (PA) after orthognathic surgery, identify the common blood vessels involved in PA, and propose a treatment algorithm based on current evidence. The protocol for this study was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols and was registered at the International Prospective Register of Systematic Reviews under the registration number CRD42020205479. Although these are rare, oral and maxillofacial surgeons should consider PA as a possible diagnosis, specifically in the maxillary artery of patients with epistaxis, severe facial edema, and swelling following LeFort I osteotomy.
MONITORING OF PULMONARY EDEMA USING ULTRASOUND RADIOFREQUENCY SIGNAL
Authors: Kwon Hyuksool , Jo You Hwan , Lee Jae Hyuk , Hwang Ji Eun , Park Inwon , Kim Seonghye , Jang Dong-Hyun , Kim Doyun , Chang Hyunglan
Published: November 2022

Objectives: Excessive accumulation of extravascular lung water impairs respiratory gas exchange and results in respiratory distress. Real-time radiofrequency signals of ultrasound can continuously and quantitatively monitor excessive lung water. This study aims to evaluate the availability of continuous real-time quantitative pulmonary edema monitoring using ultrasound radiofrequency signals and compare it with Pao
2 (partial pressure of arterial oxygen)/Fio
2 (fraction of inspired oxygen) (PF) ratio, conventional lung ultrasound, and the Hounsfield unit of chest computed tomography. Methods: Male Yorkshire pigs (40.5 ± 0.5 kg) were anesthetized and mechanically ventilated. A balanced crystalloid was administered to induce hydrostatic pulmonary edema. Three different infusion rates of 2, 4, and 6 mL/kg per minute were tested to determine the infusion rate for the appropriate swine model. The chest computed tomography and ultrasonography with radiofrequency signals were taken every 5 min during the full inspiration. The ultrasonography scans with radiofrequency signals were measured at the intercostal space where the line crossing the two armpits and the right anterior axillary line intersected. Results: The infusion rate of fluid for the pulmonary edema model was determined to be 6 mL/kg per minute, and a total of four pigs were tested at an injection rate of 6 mL/kg. The adjusted R
2 values of regression analysis between the radiofrequency signal and computer tomography Hounsfield score were 0.990, 0.993, 0.988, and 0.993 (all P values <0.05). All radiofrequency signal changes preceded changes in PF ratio or lung ultrasound changes. The area under the receiver operating characteristic curve of the radiofrequency signal for predicting PF ratio <300 was 0.88 (95% confidence interval, 0.82–0.93). Conclusion: We evaluated ultrasound radiofrequency signals to assess pulmonary edema in a swine model that can worsen gradually and showed that quantitative ultrasound radiofrequency signal analysis could assess pulmonary edema and its progression before PF ratio or lung ultrasound changes.
Evaluating the Impact of Assessment Metrics for Simulated Central Venous Catheterization Training
Authors: Brown Dailen C. , Gonzalez-Vargas Jessica M. , Tzamaras Haroula M. , Sinz Elizabeth H. , Ng Philip K. , Yang Michael X. , Adhikary Sanjib D. , Miller Scarlett R. , Moore Jason Z.
Published: November 2022

Introduction

Performance assessment and feedback are critical factors in successful medical simulation-based training. The Dynamic Haptic Robotic Trainer (DHRT) allows residents to practice ultrasound-guided needle insertions during simulated central venous catheterization (CVC) procedures while providing detailed feedback and assessment. A study was performed to examine the effectiveness of the DHRT in training the important skills of needle tip tracking and aspiration and how these skills impact procedural complications in simulated CVC.

Methods

The DHRT data were collected for 163 residents at 2 hospitals for 6 simulated needle insertions. Users were given automated feedback on 5 performance metrics, which measure aspiration rate, arterial punctures, punctures through and through the vein, loss of access to the vein, and successful access to the vein. Aspiration rates and tip tracking rates were analyzed to determine their significance in preventing CVC complications and improving performance.

Results

Tip tracking rates higher than 40% were 2.3 times more likely to result in successful venous access than rates less than 10%. Similarly, aspiration rates higher than 80% were 2.6 times more likely to result in successful venous access than rates less than 10%. Proper tip tracking and aspiration both reduced mechanical complications. Resident performance improved for all metrics except tip tracking.

Conclusions

Proper tip tracking and aspiration both reduced complications and increased the likelihood of success. However, the skill of tip tracking was not effectively learned through practice without feedback. Therefore, ultrasound-guided needle-based procedures, including CVC, can be improved by providing specific feedback to users on their ultrasound usage to track needle insertions.
The genetic and phenotypic correlates of neonatal Complement Component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders
Authors: Borbye-Lorenzen Nis , Zhu Zhihong , Agerbo Esben , Albiñana Clara , Benros Michael E. , Bian Beilei , Børglum Anders D , Bulik Cynthia M. , Goldtsche Debost Jean-Christophe Philippe , Grove Jakob , Hougaard David M. , McRae Allan F , Mors Ole , Mortensen Preben Bo , Musliner Katherine L. , Nordentoft Merete , Petersen Liselotte V. , Privé Florian , Sidorenko Julia , Skogstrand Kristin , Werge Thomas , Wray Naomi R , Vilhjálmsson Bjarni J. , McGrath John J.
Published: November 2022

The complement system, including complement components 3 and 4 (C3, C4), traditionally has been linked to innate immunity. More recently, complement components have also been implicated in brain development and the risk of schizophrenia. Based on a large, population-based case-cohort study, we measured the blood concentrations of C3 and C4 in 68,768 neonates. We found a strong correlation between the concentrations of C3 and C4 (phenotypic correlation = 0.65,P-value < 1.0×10−100, genetic correlation = 0.38,P-value = 1.9×10−35). A genome-wide association study (GWAS) for C4 protein concentration identified 36 independent loci, 30 of which were in or near the major histocompatibility complex on chromosome 6 (which includes theC4gene), while six loci were found on six other chromosomes. A GWAS for C3 identified 15 independent loci, seven of which were located in theC3gene on chromosome 19, and eight loci on five other chromosomes. We found no association between (a) measured neonatal C3 and C4 concentrations, imputed C4 haplotypes, or predictedC4gene expression, with (b) schizophrenia (SCZ), bipolar disorder (BIP), depression (DEP), autism spectrum disorder, attention deficit hyperactivity disorder or anorexia nervosa diagnosed in later life. Mendelian randomisation (MR) suggested a small positive association between higher C4 protein concentration and an increased risk of SCZ, BIP, and DEP, but these findings did not persist in more stringent analyses. Evidence from MR supported causal relationships between C4 concentration and several autoimmune disorders: systemic lupus erythematosus (SLE, OR and 95% confidence interval, 0.37, 0.34 – 0.42); type-1 diabetes (T1D, 0.54, 0.50 - 0.58); multiple sclerosis (MS, 0.68, 0.63 - 0.74); rheumatoid arthritis (0.85, 0.80 - 0.91); and Crohn’s disease (1.26, 1.19 - 1.34). A phenome-wide association study (PheWAS) in UK Biobank confirmed that the genetic correlates of C4 concentration were associated a range of autoimmune disorders including coeliac disease, thyrotoxicosis, hypothyroidism, T1D, sarcoidosis, psoriasis, SLE and ankylosing spondylitis. We found no evidence of associations between C3 versus mental or autoimmune disorders based on either MR or PheWAS. In general, our results do not support the hypothesis that C4 is causally associated with the risk of SCZ (nor several other mental disorders). We provide new evidence to support the hypothesis that higher C4 concentration is associated with lower risks of autoimmune disorders.
Risk of SARS-CoV-2 reinfection is time- and variant-dependant, France, January 2021 to August 2022
Authors: Auvigne Vincent , Schaeffer Justine , Boudon Thibault , Tamandjou Cynthia , Figoni Julie , du Châtelet Isabelle Parent , Bernard-Stoecklin Sibylle
Published: November 2022

Since the emergence of Omicron, reinfections with SARS-CoV-2 have been rising. We estimated the risk of SARS-CoV-2 reinfection in the widely vaccinated French population, from January to August 2022. At nine weeks post-infection, the relative risk of reinfection, primary infection with pre-Delta variants being the reference group, was estimated at 0.43 [95%CI 0.40-0.47] if the primary infection was attributed to Delta, 0.21 [95%CI 0.19-0.24] with BA.1 and 0.17 [95% CI 0.15-0.18] with BA.2, and rapidly waned overtime. After a BA.1 primary infection the protection was similar against BA.2 or BA.4/5 reinfection.
Diversity and Distribution of Arrow Worms, Zooplankton Along the Mangaluru and Udupi Coast, Karnataka
Authors: Daggula Narshivudu , Ramachandra Naik A.T. , Lakshmipathi M. T , Somashekara S. R , Manjappa N , Suresh T
Published: November 2022

The present study was done to understand the abundance and species diversity of arrow worms, zooplankton in relation with hydrographical parameters and the spatial and temporal variations for a period of 16 months from October 2020 to March 2022. Monthly sampling was carried out at selected stations of coastal waters with average depth of 8m. The qualitative analyses revealed the presence of seventeen different groups of zooplankton. copepods, cladocerans are dominant group in zooplankton followed by chaetognaths, during the study period seven species of chaetognaths recorded viz,Sagitta enflata, Sagitta robusta, Sagitta bedotii, Sagitta bipunctata, Sagitta ferox, Sagitta planktonis, andSagitta elegans. Among them,Sagitta enflatawas the dominant species followed byS.bedotiiandS. robusta. The richness, evenness and diversity of chaetognaths varied in the different stations and the maximum and minimum values also varied between stations, but in the most of the stations the minimum values were observed in the post-monsoon season and the highest values ranged between January to March. On comparison of the present abundance of chaetognaths with previous study, it was observed that the density of chaetognaths decreased compared to previous studies.
Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials
Authors: Khalil Ahmadaye Ibrahim , Zhang Li , Muwonge Richard , Sauvaget Catherine , Basu Partha
Published: November 2022

Objectives

We aims to assess the efficacy and safety of therapeutic HPV vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN2/3).

Design

This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.

Data sources

PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up January 31, 2022.

Eligibility criteria

Phase II/III studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN2/3 lesions were included.

Data extraction and synthesis

Two independent reviewers extracted data, evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance.

Results

12 trials met the inclusion criteria. Out of the total 734 women receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN1 with the overall proportion of regression of 0.54 (95%CI: 0.39, 0.69) for vaccinated group. Correspondingly, 166 women receiving placebo only achieving the pooled normal/CIN1 regression of 0.27 (95%CI: 0.20, 0.34). When only including two-arm studies, the regression proportion of the vaccine group was higher than that of control group (relative risk (RR): 1.52, 95%CI: 1.14, 2.04). Six studies reported the efficacy of the therapeutic vaccines to clear high-risk human papillomavirus (hrHPV) with the pooled proportion of hrHPV clearance of 0.42 (95%CI: 0.32, 0.52) for the vaccine group and 0.17 (95%CI: 0.11, 0.26) for the control group and the RR of 2.03 (95%CI: 1.30, 3.16). Similar results were found regarding HPV16/18 clearance. No significant unsolicited adverse events have been consistently reported.

Conclusions

The efficacy of the therapeutic vaccines in the treatment of CIN2/3 was modest. Besides, the implementation issues like feasibility, acceptability, adoption, and cost-effectiveness need to be further studied.

PROSPERO registration number

CRD42020189617

Strengths and limitations

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This systematic review and meta-analysist on the clinical efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 lesions based on phase II/III trials.

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Notre recherche documentaire a impliqué une recherche approfondie d’essais cliniques, en utilisant un large éventail de termes de recherche et sans limitation de langue, de pays ou de date.

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We had to combine studies that were variable in case selection (e.g., some included CIN 2/3 lesions that were positive for HPV 16/18 only while others included lesions associated with any high-risk HPV types).

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Some of the studies did not have a control arm, which made it difficult to ascertain whether the responses observed were due to natural regression alone.
An RFX transcription factor regulated ciliogenesis in the progenitors of choanoflagellates and animals
Authors: Coyle Maxwell C. , Tajima Adia M. , Leon Fredrick , Choksi Semil P. , Yang Ally , Espinoza Sarah , Hughes Timothy R. , Reiter Jeremy F. , Booth David S. , King Nicole
Published: November 2022

Little is known about the origins of the transcriptional modules that coordinate cell-type specific functions in animals. The controlled expression of one cellular feature – the cilium – was likely critical during early animal evolution. Two key transcription factors, RFX and FoxJ1, coordinate ciliogenesis in animals but are absent from the genomes of most other ciliated eukaryotes, raising the question of how the transcriptional regulation of ciliogenesis has evolved. To reconstruct the evolution of the RFX/FoxJ1 transcriptional module and its role in the regulation of ciliogenesis, we investigated RFX and FoxJ1 function in one of the closest living relatives of animals, the choanoflagellateSalpingoeca rosetta. Targeted disruption of theS. rosettaRFX homologcRFXaresulted in delayed cell proliferation and aberrant ciliogenesis, marked by the collapse and resorption of nascent cilia. Ciliogenesis genes andfoxJ1were significantly down-regulated incRFXamutants, consistent with a pre-animal ancestry for this transcriptional module. We also found that cRFXa protein preferentially binds to a sequence motif that is enriched in the promoters ofS. rosettaciliary genes and matches the sequence motif bound by animal RFX proteins. These findings suggest that RFX coordinated ciliogenesis before the divergence of animals and choanoflagellates, and that the deployment of this module may have provided a mechanism to differentiate ciliated and non-ciliated cell types in early animal evolution.
Bispecific antibodies combine breadth, potency, and avidity of parental antibodies to neutralize sarbecoviruses
Authors: Radić Laura , Sliepen Kwinten , Yin Victor , Brinkkemper Mitch , Capella-Pujol Joan , Schriek Angela I. , Torres Jonathan L. , Bangaru Sandhya , Burger Judith A. , Poniman Meliawati , Bontjer Ilja , Bouhuijs Joey H. , Gideonse David , Eggink Dirk , Ward Andrew B. , Heck Albert J. R. , Van Gils Marit J. , Sanders Rogier W. , Schinkel Janke
Published: November 2022

SARS-CoV-2 mutational variants evade humoral immune responses elicited by vaccines and current monoclonal antibody (mAb) therapies. Novel antibody-based treatments will thus need to exhibit broad neutralization against different variants. Bispecific antibodies (bsAbs) combine the specificities of two distinct antibodies into one antibody taking advantage of the avidity, synergy and cooperativity provided by targeting two different epitopes. Here we used controlled Fab-arm exchange (cFAE), a versatile and straightforward method, to produce bsAbs that neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron and its subvariants, by combining potent SARS-CoV-2-specific neutralizing antibodies with broader but less potent antibodies that also neutralize SARS-CoV. We demonstrate that the parental IgG’s rely on avidity for their neutralizing activity by comparing their potency to bsAbs containing one irrelevant “dead” Fab arm. We used single particle mass photometry to measure formation of antibody:spike complexes, and determined that bsAbs increase binding stoichiometry compared to corresponding cocktails, without a loss of binding affinity. The heterogeneous binding pattern of bsAbs to spike (S), observed by negative-stain electron microscopy and mass photometry provided evidence for both intra- and inter-spike crosslinking. This study highlights the utility of cross-neutralizing antibodies for designing bivalent or multivalent agents to provide a robust activity against circulating variants, as well as future SARS-like coronaviruses.
Effect of Human microRNA on Dengue Virus Genome: a cross-specie approach
Authors: Deb Anwesha
Published: November 2022

Dengue virus infection being a menace worldwide particularly in West Bengal demanded investigation of a new therapeutic approach. In our work we have performed in silico analysis of target specificity of miRNA to dengue virus genome. Several human miRNAs like hsa-miR-4758-3p_MIMAT0019904, hsa-miR-6760-3p_MIMAT0027421, hsa-miR-6839-3p_MIMAT0027581, hsa-miR-6842-3p_MIMAT0027587 are found to be directly interacting with dengue virus proteins like Envelope, NS1, NS3 and 3’UTR region. The target proteins of respective dengue proteins were analysed using stringDB and Cytoscape. Analysis of the target protein interaction network revealed ACTB, AKT1, TLR4 as few of the hub genes that can be indirectly regulated by miRNA and dengue genome interaction. Thus our work focuses on finding novel miRNA that are not known to regulate dengue infection till date and proposes a novel therapeutic strategy.
Multi-group biodiversity theory and an application to multi-species maximum sustainable yield
Authors: Sadykov A. , Farnsworth K.D. , Sadykova D.
Published: November 2022

We introduce the group-based approach, use it to develop a multi-group biodiversity theory, and apply it find solutions to the multi-species maximum sustainable yield problem for a mixed species fishery. The group-based approach to community ecology is intermediate between classical species-centric and more recent trait-based (species-less) approaches. It describes ecological communities as composed of conspecific groups rather than species (as in classical models) or species-less individuals (as in trait-based models), and reconsiders community structure as results of inter-group resource competition. The approach respects species affiliation and recognises the importance of trait trade-offs at the conspecific group level. It offers an alternative to both classical and trait-based approaches and, remarkably, provides a complete analytical description of the community structure in the bench-mark case of zero-sum resource redistribution.

Highlights

We introduce a group-based approach to modelling of ecological communities and develop a multi-group biodiversity theory.

A classification of intergroup interactions is established, based on the type of contest (which is determined by the relative role of qualitative vs. quantitative factors) and the accounting of resource redistribution.

For pure resource competition, we obtain the full analytic description of multi-group and multi-species community structure and its dynamics, including the processes of fission-fusion and invasion-extinction among groups.

A principle of competitive coexistence is formulated, which explains the existence of conspecific groups as a mechanism for avoiding competitive exclusion.

We apply the theory to harvesting multi-species communities (e.g., for fisheries) and derive analytic expression for total catch and approximate solutions for multi-species maximum sustainable yield (MSY).
No evidence for schistosome parasite fitness trade-offs in the intermediate and definitive host
Authors: Le Clec’h Winka , Chevalier Frédéric D. , Jutzeler Kathrin , Anderson Timothy J.C.
Published: November 2022

Background

The trematode parasiteSchistosoma mansoniuses an aquatic snail intermediate and a vertebrate definitive host to complete its lifecycle. We previously showed that a key transmission trait – the number of cercariae larvae shed from infectedBiomphalaria spp. snails – varies significantly within and between different parasite populations and is genetically controlled by five loci. We investigated the hypothesis that the success of parasite genotypes showing high fitness in the intermediate snail host, may be offset by lower fitness in the definitive vertebrate host.

Methods

We investigated this trade-off hypothesis by selecting parasite progeny producing high or low number of larvae in the snail, and then comparing fitness parameters and virulence in the rodent host. We infected inbred BALB/c mice using twoSchistosoma mansoniparasite lines (high shedder (HS) and low shedder (LS) lines), isolated from F2 progeny generated by genetic crosses between SmLE (HS parent) and SmBRE (LS parent) parasites. We used the F3 progeny to infect two populations of inbredBiomphalaria glabratasnails. We then compared life history traits and virulence of these two selected parasite lines in the rodent host to understand pleiotropic effects of genes determining cercarial shedding in parasites infecting the definitive host.

Results

HS parasites shed high numbers of cercariae, which had a detrimental impact on snail physiology (measured by laccase-like activity and hemoglobin rate), regardless of the snail genetic background. In contrast, selected LS parasites shed fewer cercariae and had a lower impact on snail physiology. Similarly, HS worms have a higher reproductive fitness and produced more viable F3 miracidia larvae than LS parasites. This increase in transmission is correlated with an increase in virulence toward the rodent host, characterized by stronger hepato-splenomegaly and hepatic fibrosis.

Conclusions

These experiments revealed that schistosome parasite fitness was positively correlated in intermediate and definitive host (positive pleiotropy). Therefore, we rejected our trade-off hypothesis. We also show that our selected schistosome lines exhibit low and high shedding phenotype regardless of the intermediate snail host genetic background.
Single cell profiling reveals strain-specific differences in myeloid inflammatory potential in the rat liver
Authors: Pouyabahar Delaram , Chung Sai W. , Pezzutti Olivia I. , Perciani Catia T. , Wang Xinle , Ma Xue-Zhong , Jiang Chao , Camat Damra , Chung Trevor , Sekhon Manmeet , Manuel Justin , Chen Xu-Chun , McGilvray Ian D. , MacParland Sonya A. , Bader Gary D.
Published: November 2022

Liver transplantation is currently the only treatment for end-stage liver disease and acute liver failure. Liver transplant rejection is among the most lethal complications of transplantation, and therapeutic development is limited by our lack of a comprehensive understanding of the cellular landscape of the liver. The laboratory rat (Rattus norvegicus), ideal in size as a model for surgical procedures, is a strong platform to study liver biology in the context of liver transplantation. Liver allograft rejection is known to be strain-specific in the rat model, although the transplantation is accepted without rejection in some strains, it leads to acute rejection in others. To shed light on the cellular landscape of the rat liver and build a foundation for strain comparison, we present a comprehensive single-cell transcriptomics map of the healthy rat liver of Lewis and Dark Agouti strains. Using a novel computational pipeline we developed to guide the detailed annotation of our rat liver atlas, we discovered that hepatic myeloid cells have strong Lewis and Dark Agouti strain-specific differences focused on inflammatory signaling pathways. We experimentally validated these strain-specific differences in myeloid inflammatory potentialin vitrousing intracellular cytokine staining. Our work provides the first examination of the multi-strain healthy rat liver by single cell transcriptomics and uncovers key insights into strain-specific differences in this valuable model animal.

The laboratory rat (Rattus norvegicus) is a standard model animal for orthotopic liver transplantation. Transplanting a liver from a Dark agouti (DA) to a Lewis (LEW) strain rat leads to transplant rejection and the reverse procedure leads to tolerance. Understanding this strain difference may help explain the cellular drivers of liver allograft rejection post-transplant. This study uses single-cell transcriptomics to better understand the complex cellular composition of the rat liver and unravels cellular and molecular sources of inter-strain hepatic variation. We generated single-cell transcriptomic maps of the livers of healthy DA and LEW rat strains and developed a novel, factor analysis-based bioinformatics pipeline to study data covariates, such as strain and batch. Using this approach, we discovered variations within hepatocyte and myeloid populations that explain how the states of these cells differ between strains in the healthy rat, which may explain why these strains respond differently to liver transplants.