bluuebunny/crossref_metadata_2025 huggingface dataset:
Scaffold-Scaffold Interaction Facilitates Cell Polarity Development in Caulobacter crescentus
Authors: Lu Ning , Duvall Samuel W. , Zhao Guohong , Kowallis Kimberley A. , Zhang Chao , Tan Wei , Sun Jingxian , Petitjean Haley N. , Tomares Dylan T. , Zhao Guo-Ping , Childers W. Seth , Zhao Wei
Published: March 2023

Caulobacter crescentus
is a well-established bacterial model to study asymmetric cell division for decades. During cell development, the polarization of scaffold protein PopZ from monopolar to bipolar plays a central role in
C. crescentus
asymmetric cell division.
Whole Genome Sequencing of Brucella melitensis Isolated from Patients in Hohhot, China
Authors: Chen Shana , Fu Quan , Mandlaa Mandlaa , Wang Qingchun , Sheng De , Saijilahu Saijilahu , Tana Tana , Yang Dezhi
Published: March 2023

Brucellosis is a class B infectious disease that is spreading rapidly in Inner Mongolia, China. Investigating the genetics of this disease might provide insights into the mechanism by which the bacteria adapt to their hosts. Here, we report the genome sequence of
Brucella melitensis
strain BM6144, which was isolated from a human patient.
Complete Genome Sequences of Two Pasteurella multocida Isolates from Seabirds
Authors: Hashish Amro , Johnson Timothy J. , Chundru Dhiraj , Williams Michele L. , Sato Yuko , Macedo Nubia R. , Clessin Augustin , Gantelet Hubert , Bost Caroline , Tornos Jérémy , Gamble Amandine , LeCount Karen J. , Ghanem Mostafa , Boulinier Thierry , El-Gazzar Mohamed
Published: March 2023

Pasteurella multocida
is one of the major causes of mass mortalities in wild birds. Here, we report the complete genome sequences of two
P. multocida
isolates from wild populations of two endangered seabird species, the Indian yellow-nosed albatrosses (
Thalassarche carteri
) and the northern rockhopper penguins (
Eudyptes moseleyi
).
Survival of Bordetella bronchiseptica in Acanthamoeba castellanii
Authors: Nugraha Dendi Krisna , Nishida Takashi , Tamaki Yuki , Hiramatsu Yukihiro , Yamaguchi Hiroyuki , Horiguchi Yasuhiko
Published: March 2023

The pathogenic bacterium
Bordetella bronchiseptica
, which causes respiratory diseases in various mammals, exhibits distinct Bvg
+
and Bvg
−
phenotypes. The former represents the virulent phase, in which the bacteria express a set of virulence factors, while the role of the latter in the bacterial life cycle remains to be understood.
Rational Use of Microbiological Tests in the Diagnosis of Central Nervous System Infections Using Restrictive Criteria: a Retrospective Study
Authors: Ngo Nsoga M. T. , Pérez-Rodriguez F. J. , Mamin A. , L’Huillier A. G. , Cherkaoui A. , Kaiser L. , Schibler M.
Published: March 2023

Microbiological testing in general and in the setting of central nervous system (CNS) infection in particular are often excessive, leading to superfluous laboratory work and costs. In this regard, restrictive criteria, named Reller criteria, have been developed to reduce unnecessary CSF herpes simplex virus 1 (HSV-1) PCR testing when suspecting encephalitis.
Development and validation of a nomogram for predicting in-hospital mortality of elderly patients with persistent sepsis-associated acute kidney injury in intensive care units: a retrospective cohort study using the MIMIC-IV database
Authors: Jiang Wei , Zhang Chuanqing , Yu Jiangquan , Shao Jun , Zheng Ruiqiang
Published: March 2023

Objectives

To identify the clinical risk factors that influence in-hospital mortality in elderly patients with persistent sepsis-associated acute kidney injury (S-AKI) and to establish and validate a nomogram to predict in-hospital mortality.

Design

Retrospective cohort analysis.

Setting

Data from critically ill patients at a US centre between 2008 and 2021 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database (V.1.0).

Participants

Data from 1519 patients with persistent S-AKI were extracted from the MIMIC-IV database.

Primary outcome

All-cause in-hospital death from persistent S-AKI.

Results

Multiple logistic regression revealed that gender (OR 0.63, 95% CI 0.45–0.88), cancer (2.5, 1.69–3.71), respiratory rate (1.06, 1.01–1.12), AKI stage (2.01, 1.24–3.24), blood urea nitrogen (1.01, 1.01–1.02), Glasgow Coma Scale score (0.75, 0.70–0.81), mechanical ventilation (1.57, 1.01–2.46) and continuous renal replacement therapy within 48 hours (9.97, 3.39–33.9) were independent risk factors for mortality from persistent S-AKI. The consistency indices of the prediction and the validation cohorts were 0.780 (95% CI: 0.75–0.82) and 0.80 (95% CI: 0.75–0.85), respectively. The model’s calibration plot suggested excellent consistency between the predicted and actual probabilities.

Conclusions

This study’s prediction model demonstrated good discrimination and calibration abilities to predict in-hospital mortality of elderly patients with persistent S-AKI, although it warrants further external validation to verify its accuracy and applicability.
Successful quality improvement project to increase hydroxyurea prescriptions for children with sickle cell anaemia
Authors: Alvarez Ofelia A , Rodriguez-Cortes Hector , Clay E Leila Jerome , Echenique Sandra , Kanter Julie , Strouse John J , Buitrago-Mogollon Talia , Courtlandt Cheryl , Noonan Laura , Osunkwo Ifeyinwa
Published: March 2023

Hydroxyurea (HU) is an effective but underused disease-modifying therapy for patients with sickle cell anaemia (SCA). EMBRACE SCD, a sickle cell disease treatment demonstration project, aimed to improve access to HU by increasing prescription (Rx) rates by at least 10% from baseline in children with SCA.

The Model for Improvement was used as the quality improvement framework. HU Rx was assessed from clinical databases in three paediatric haematology centres. Children aged 9 months–18 years with SCA not on chronic transfusions were eligible for HU treatment. The health belief model was the conceptual framework to discuss with patients and promote HU acceptance. A visual aid showing erythrocytes under the effect of HU and the American Society of Hematology HU brochure were used as educational tools. At least 6 months after offering HU, a Barrier Assessment Questionnaire was given to assess reasons for HU acceptance and refusals. If HU was declined, the providers discussed with family again. We conducted chart audits to find missed opportunities to prescribe HU as one plan–do–study–act cycle.

At initial measurement, 50.2% of 524 eligible patients had HU prescribed. During the testing and initial implementation phase, the mean performance after 10 data points was 53%. After 2 years, the mean performance was 59%, achieving an 11% increase in mean performance and a 29% increase from initial to the last measurement (64.8% HU Rx). During a 15-month period, 32.1% (N=168) of the eligible patients who were offered HU completed the barrier questionnaire with 19% (N=32) refusing HU, mostly based on not perceiving enough severity of their children’s SCA or fearing side effects.

Reviewing patient charts for missed opportunity of offering HU with feedback and evaluating the reasons of declining HU via a questionnaire were key components in increasing HU Rx in our population.
Military occupation and testicular germ cell tumour risk among US Air Force servicemen
Authors: Denic-Roberts Hristina , McGlynn Katherine , Rhee Jongeun , Byrne Celia , Lang Michael , Vu Paul , Purdue Mark , Rusiecki Jennifer
Published: March 2023

Objectives

Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy among active duty US military servicemen. Occupational risk factors may play a role in TGCT aetiology, although the evidence is inconclusive. The objective of our study was to investigate associations between military occupations and TGCT risk among US Air Force (USAF) servicemen.

Methods

This nested case–control study among active duty USAF servicemen obtained information on military occupations for 530 histologically confirmed TGCT cases diagnosed during 1990–2018 and 530 individually matched controls. We determined military occupations using Air Force Specialty Codes ascertained at two time points: at case diagnosis and at a time point on average 6 years earlier. We computed adjusted ORs and 95% CIs from conditional logistic regression models to evaluate associations between occupations and TGCT risk.

Results

The mean age at TGCT diagnosis was 30 years. Increased TGCT risk was observed for pilots (OR=2.84, 95% CI: 1.20–6.74) and servicemen with aircraft maintenance jobs (OR=1.85, 95% CI: 1.03–3.31) who held those jobs at both time points. Fighter pilots (n=18) and servicemen with firefighting jobs (n=18) at the time of case diagnosis had suggestively elevated TGCT odds (OR=2.73, 95% CI: 0.96–7.72 and OR=1.94, 95% CI: 0.72–5.20, respectively).

Conclusions

In this matched, nested case–control study of young active duty USAF servicemen, we found that pilots and men with aircraft maintenance jobs had elevated TGCT risk. Further research is needed to elucidate specific occupational exposures underlying these associations.
Simulation of cemented paste backfill (CPB) deposition through column experiments: comparisons of field measurements, laboratory measurements, and analytical solutions
Authors: Shahsavari Mohammad , Jafari Mohammadamin , Grabinsky Murray
Published: March 2023

Estimating the as-placed properties of mine backfill is fundamental to optimizing the safety and productivity of underground mines. For cemented paste backfill (CPB), an important consideration is the extent to which self-weight consolidation during deposition may reduce the void ratio and enhance the binder’s effectiveness. Field monitoring and sampling campaigns can help investigate this phenomenon but they are expensive and logistically difficult. Therefore, mesoscale column experiments are performed in the controlled laboratory environment to better understand the coupling between self-weight consolidation and cement hydration. In this paper, columns are backfilled with uncemented paste tailings and with CPB and the pore water pressure, electrical conductivity, and volume changes are monitored during and after backfilling. The pore water pressure profiles at the end of backfilling are compared with an available analytical solution and restrictions on the solution’s validity are identified. Void ratios of samples taken from columns are compared with the ones obtained from field samples and the similarity indicates the filling conditions simulated in the laboratory are representative of field conditions. The changes in void ratio after curing were small compared to the initial void ratio of fresh CPB. The tests’ results help explain why self-weight consolidation during backfilling is not significant at the studied mine, which may be the case for many other mining operations as well.
Representation of s-process abundances for comparison to data from bulk meteorites
Authors: Lugaro Maria , Ek Mattias , Pető Mária , Pignatari Marco , Makhatadze Georgy V. , Onyett Isaac J. , Schönbächler Maria
Published: March 2023

Analysis of bulk meteorite compositions has revealed small isotopic variations due to the presence of material (e.g., stardust) that preserved the signature of nuclear reactions occurring in specific stellar sites. The interpretation of such anomalies provides evidence for the environment of the birth of the Sun, its accretion process, the evolution of the solar proto-planetary disk, and the formation of the planets. A crucial element of such interpretation is the comparison of the observed anomalies to predictions from models of stellar nucleosynthesis. To date, however, this comparison has been limited to a handful of model predictions. This is mostly because the calculated stellar abundances need to be transformed into a specific representation, which nuclear astrophysicists and stellar nucleosynthesis researchers are not familiar with. Here, we show in detail that this representation is needed to account for mass fractionation effects in meteorite data that can be generated both in nature and during instrumental analysis. We explain the required internal normalisation to a selected isotopic ratio, describe the motivations behind such representation more widely, and provide the tools to perform the calculations. Then, we present some examples considering two elements produced by the slow neutron-capture (s) process: Sr and Mo. We show which specific representations for the Sr isotopic composition calculated by s-process models better disentangle the nucleosynthetic signatures from stars of different metallicity. For Mo, the comparison between data and models is improved due to a recent re-analysis of the $$^{95}$$

95

Mo neutron-capture cross section.
Multiscalar-torsion cosmology: exact and analytic solutions from noether symmetries
Authors: Dialektopoulos K. , Leon G. , Paliathanasis A.
Published: March 2023

The Noether symmetry analysis is applied in a multiscalar field cosmological model in teleparallel gravity. In particular, we consider two scalar fields with interaction in scalar-torsion theory. The field equations have a minisuperspace description, and the evolution of the physical variables depends on the potential function that drives the scalar fields’ dynamics. With the requirement for the field equations to admit non-trivial Noether point symmetries and the use of the first theorem of Noether, we constrain all the functional forms for the potential. Finally, we apply symmetry vectors and the corresponding conservation laws to determine exact and analytic solutions in multiscalar-torsion cosmology.
Diagrammatic analysis of hidden- and open-charm tetraquark production in B decays
Authors: Qin Qin , Qiu Jing-Liang , Yu Fu-Sheng
Published: March 2023

Discoveries of tetraquarks not only enrich the hadronic spectrum but also provide more platforms to understand quantum chromodynamics. We study the production processes of hidden-charm and open-charm tetraquarks in B decays by analyzing their topological amplitudes. Relations between different channels are found, which confront tests by experiments to probe the nature of the tetraquarks. Furthermore, promising channels to find more tetraquarks are proposed.
Dyon production from near-extremal Kerr–Newman–(anti-)de Sitter black holes
Authors: Chen Chiang-Mei , Kim Sang Pyo
Published: March 2023

Using the enhanced symmetry in the near-horizon region of the near-extremal dyonic Kerr–Newman (KN) black hole in the (A)dS space, we find the exact solutions for dyonic charged scalar field in terms of the hypergeometric function and explicitly compute the Schwinger effect for the emission of electric and/or magnetic charges. The emission formula confirms a universal factorization of the Schwinger formula in the AdS$$_2$$

2

and another Schwinger formula in the two-dimensional Rindler space determined by the effective temperature and the Hawking temperature with the chemical potentials of electric and/or magnetic charges and the angular momentum. The emission of the same species of charges from the KN black hole is enhanced in the AdS boundary while it is suppressed in the dS boundary. In addition, the dragging of particles in the KN black hole diminishes the emission of charges in both AdS and dS spaces. The AdS geometry of near-horizon gives the Breitenloher–Freedman (BF) bound, within which the stability of dyonic KN black holes is guaranteed against both the emission of charges and Hawking radiation.
Anisotropic charged stellar models with modified Van der Waals EoS in f(Q) gravity
Authors: Ditta Allah , Tiecheng Xia , Errehymy Abdelghani , Mustafa G. , Maurya S. K.
Published: March 2023

This paper is based on the study of compact stars in the context of electric fields and the nonmetricity effects of gravity. Due to this, we are motivated to build stellar models based on spherically symmetric space-time in f(Q) gravity. The space-time solution is obtained by Durgapal and Bannerji (Phys Rev D 27:328–331,1983) potential along with modified Van der Waals equation of state (EoS) $$p_r=\eta \rho ^2+ \frac{\beta \rho }{\gamma \rho +1}$$

p
r

=
η

ρ
2

+

β
ρ

γ
ρ
+
1

by introducing a specific form of electric charge function $$q(r)=kr^3$$

q

(
r
)

=
k

r
3

. In order to validate our charge model, we used observational data from the literature for celestial objects like Her X-1, 4U 1538-52, SAX J1808.4-3658, and SMC X-1. Furthermore, we have also retrieved the uncharged effects of gravity for the model SMC X-1 by taking $$k=0$$

k
=
0

. Our present physical analysis shows that all the obtained features for the present solution are in excellent agreement with the viable model as far as observational data is concerned.
Experimental evaluation of baselines for forecasting social media timeseries
Authors: Ng Kin Wai , Mubang Frederick , Hall Lawrence O. , Skvoretz John , Iamnitchi Adriana
Published: March 2023

Forecasting social media activity can be of practical use in many scenarios, from understanding trends, such as which topics are likely to engage more users in the coming week, to identifying unusual behavior, such as coordinated information operations or currency manipulation efforts. To evaluate a new approach to forecasting, it is important to have baselines against which to assess performance gains. We experimentally evaluate the performance of four baselines for forecasting activity in several social media datasets that record discussions related to three different geo-political contexts synchronously taking place on two different platforms, Twitter and YouTube. Experiments are done over hourly time periods. Our evaluation identifies the baselines which are most accurate for particular metrics and thus provides guidance for future work in social media modeling.
Multiple convected conditions in Williamson nanofluidic flow with variable thermal conductivity: Revised bioconvection model
Authors: Gangadhar Kotha , Rupa Lavanya M. , Chamkha Ali J.
Published: March 2023

The importance of bioconvection into the application of nanoparticles has had a significant impact on fundamental technological and industrial functions in recent years. These discussions are being carried forward by the bioconvection appearance on that flow by attracting nanoparticles into additional features on thermal radiation and activation energy. The investigation had been proposed on the appealing features of the mass and thermal convective boundary constraints. The high desirable subclass on rate-type fluid, especially Williamson fluid, was used to anticipate the absolute rheological parameters. The designated partial differential system was modified along with nonlinear ordinary differential equations applying enhance being related conversion, the designated partial differential system was modified along nonlinear ordinary differential equations. The governing equations are interpreted into ordinary differential equations, and in the following, shooting process was obeyed to build up the mathematical classification on the convert dimensionless flow problem. This value of physical restraint was displayed on the table and plots tests. This noted theoretical imitation could be highly successful in improving the solar energy systems and thermal extrusion processes. The outcomes reported that the rise in Weissenberg number and Hartmann number decreased the nanoparticles velocity distribution. The progressing temperature distribution was observed to develop radiation parameter and thermal conductivity parameter. That was further noted to modify bioconvection Lewis number and Peclet number that were reduced into motile microorganism distribution effectively.
Occurrence of
Tannuolina
in the early Cambrian siltstones of the Hazara Basin, North Pakistan, and its biostratigraphical significance
Authors: Pan Bing , Khan Malik Muhammad Saud Sajid , Li Guoxiang , Ahmed Shehryar , Qasim Muhammad , Yin Zongjun , Jadoon Ishtiaq A. K. , Zhu Maoyan
Published: March 2023

The tommotiids are an important group of Cambrian small shelly fossils, primarily retrieved from carbonate rock by acid dissolution. In this study, abundant isolated sclerites of
Tannuolina
are recovered from the siltstone-dominated upper part of the Hazira Formation in the eastern Hazara Basin, North Pakistan. This discovery of tommotiids preserved in the siltstones not only suggests their occurrence in a variety of sedimentary lithofacies, but also provides the opportunity to look for the sclerites or scleritomes (or even soft tissue) of tommotiids in much wider taphonomic windows. The sclerites include two morphs (i.e. mitral and sellate types). Through morphological comparison, they can be identified as
Tannuolina zhangwentangi
Qian and Bengtson, 1989. The large mitral and sellate sclerites (about 1 cm) illustrated in the present study manifest a relatively consistent morphology during size increase. The sellate sclerites may contain two sub-types, a larger sellate sclerite with sella on the sellate side and a smaller convex triangular sclerite without sella on either side. In the original scleritome, the two sub-types of sellate sclerites probably combine as a composite with the duplicatural side of the smaller one attached on the sella area of the large one. For the first time,
T. zhangwentangi
, previously unknown outside South China, has been recovered from the Indian subcontinent. The middle and upper part of the Hazira Formation exclusively bearing
T. zhangwentangi
can directly invite correlation with the
S. flabelliformis
–
T. zhangwentangi
Assemblage Zone of South China representing the uppermost Cambrian Stage 2. This new find not only signifies the utility of
T. zhangwentangi
for intercontinental biostratigraphical correlation, but also suggests that the Terreneuvian small shelly fossil (SSF) biostratigraphy between the Indian subcontinent and South China is consistent, comprising three (at least two) correlative SSF Assemblage Zones (Zone I, possibly Zone III, and Zone IV of South China). Additionally, our result may also support a relatively close palaeogeographical linkage between these two regions in the early Cambrian.

Thematic collection:
This article is part of the Advances in the Cambrian Explosion collection available at:
https://www.lyellcollection.org/topic/collections/advances-in-the-cambrian-explosion
Inculcating Context for Emoji Powered Bengali Hate Speech Detection using Extended Fuzzy SVM and Text Embedding Models
Authors: Ghosal Sayani , Jain Amita , Tayal Devendra Kumar , Menon Varun G. , Kumar Akshi
Published: March 2023

The massive growth of social webs offer opportunities to communicate with diverse languages, unstructured text, informal posts, misspelled contents and emojis. Social media users feel comfortable to express their emotions specially emotions with high intensity (hate speech) in their mother tongue. Hate speech in any form targets groups and individuals that may trigger antisocial activities, hate crimes, and terrorist acts. Bengali social media users use Bengali for posting implicit or indirect hate text. Existing Bengali hate speech detection research considers explicit hate speech detection but in actual hate is expressed more in implicit way. In order to detect both implicit and explicit hate speech from low resource content, social webs need highly efficient automated tools. Researchers applied discriminative learning approaches (i.e. SVM, MLP, CNN) to distinguish hate text with only clear-cut outcomes in detecting direct hate speech. The proposed novel Bengali hate speech detection model considers two parallel approaches: (i) It applies extended fuzzy SVM classifier for class imbalanced dataset (FSVMCIL) and multilingual BERT (mBERT) text embedding model to detect first hate label; (ii) Morphological analysis method to detect implicit and explicit hate content with the hate similarity (HS) scheme for second hate label. Linking both labeling methods, this research extracts contextual Bengali hate speech from informal text. This novel HS method considers Word2Vec word embedding model and Bengali hate lexicon. It also considers emoji to text conversion for efficient contextual analysis. This study also conducts extensive experiments for various categories with the Bengali hate speech dataset. It also evaluates the proposed model performance considering weighted F1 score, precision, recall and accuracy parameters. Results reveal significant improvement in Bengali hate speech detection with 2.35% increase in F1- score and 9.11 % increase in accuracy.
Concept Drift in Software Defect Prediction: A Method for Detecting and Handling the Drift
Authors: Gangwar Arvind Kumar , Kumar Sandeep
Published: March 2023

Software Defect Prediction (SDP) is crucial towards software quality assurance in software engineering. SDP analyzes the software metrics data for timely prediction of defect prone software modules. Prediction process is automated by constructing defect prediction classification models using machine learning techniques. These models are trained using metrics data from historical projects of similar types. Based on the learned experience, models are used to predict defect prone modules in currently tested software. These models perform well if the concept is stationary in a dynamic software development environment. But their performance degrades unexpectedly in the presence of change in concept (Concept Drift). Therefore, concept drift (CD) detection is an important activity for improving the overall accuracy of the prediction model. Previous studies on SDP have shown that CD may occur in software defect data and the used defect prediction model may require to be updated to deal with CD. This phenomenon of handling the CD is known as CD adaptation. It is observed that still efforts need to be done in this direction in the SDP domain. In this article, we have proposed a pair of paired learners (PoPL) approach for handling CD in SDP. We combined the drift detection capabilities of two independent paired learners and used the paired learner (PL) with the best performance in recent time for next prediction. We experimented on various publicly available software defect datasets garnered from public data repositories. Experimentation results showed that our proposed approach performed better than the existing similar works and the base PL model based on various performance measures.
Engineering Nutritionally Improved Edible Plant Oils
Authors: Zhou Xue-Rong , Liu Qing , Singh Surinder
Published: March 2023

In contrast to traditional breeding, which relies on the identification of mutants, metabolic engineering provides a new platform to modify the oil composition in oil crops for improved nutrition. By altering endogenous genes involved in the biosynthesis pathways, it is possible to modify edible plant oils to increase the content of desired components or reduce the content of undesirable components. However, introduction of novel nutritional components such as omega-3 long-chain polyunsaturated fatty acids needs transgenic expression of novel genes in crops. Despite formidable challenges, significant progress in engineering nutritionally improved edible plant oils has recently been achieved, with some commercial products now on the market.
Nondigestible Functional Oligosaccharides: Enzymatic Production and Food Applications for Intestinal Health
Authors: Yang Shaoqing , Wu Chenxuan , Yan Qiaojuan , Li Xiuting , Jiang Zhengqiang
Published: March 2023

Nondigestible functional oligosaccharides are of particular interest in recent years because of their unique prebiotic activities, technological characteristics, and physiological effects. Among different types of strategies for the production of nondigestible functional oligosaccharides, enzymatic methods are preferred owing to the predictability and controllability of the structure and composition of the reaction products. Nondigestible functional oligosaccharides have been proved to show excellent prebiotic effects as well as other benefits to intestinal health. They have exhibited great application potential as functional food ingredients for various food products with improved quality and physicochemical characteristics. This article reviews the research progress on the enzymatic production of several typical nondigestible functional oligosaccharides in the food industry, including galacto-oligosaccharides, xylo-oligosaccharides, manno-oligosaccharides, chito-oligosaccharides, and human milk oligosaccharides. Moreover, their physicochemical properties and prebiotic activities are discussed as well as their contributions to intestinal health and applications in foods.
Effects of Oral Inflammatory Diseases and Oral Hygiene on Atrial Fibrillation: A Systematic Review
Authors: Zhang Zhanxin , Chen Fei , Gao Xueying , Xiao Bing , Liu Fan , Lu Jingchao
Published: March 2023

Objective. Research evidence suggests a link between periodontitis (PD) and atrial fibrillation, but the nature of this link is unclear. This study aimed to systematically review and evaluate the association between PD, other oral diseases, and atrial fibrillation and the role of oral hygiene in preventing atrial fibrillation. Methods. We searched the Medline, Embase, Cochrane Library, and Web of Science databases for the clinical study of oral health and atrial fibrillation from inception to November 2022. Oral health conditions included PD and other oral inflammatory diseases, regular oral hygiene, and tooth brushing. The primary outcomes were the risk of new-onset atrial fibrillation in patients with oral disease, the effect of regular oral care on preventing atrial fibrillation, the effect of frequent tooth brushing on preventing atrial fibrillation, and the incidence of atrial fibrillation in PD patients. Results. Eight clinical trials with a total of 4,328,355 patients were included. The result of the research showed that PD and other impaired oral health may be associated with new-onset atrial fibrillation, and its severity was dose-responsive to the risk of atrial fibrillation. The incidence of atrial fibrillation in patients with severe PD was about 16.3%. Moreover, PD may increase the risk of long-term arrhythmia in patients with atrial fibrillation. Regular oral care and frequent tooth brushing can reduce the incidence of atrial fibrillation. Conclusion. Regular and moderate oral hygiene, frequent tooth brushing, and prevention of PD and other oral inflammatory diseases could reduce the occurrence of atrial fibrillation. It is recommended to strengthen the popularization of oral health knowledge in the publicity related to atrial fibrillation.
Mildly Elevated Pulmonary Artery Systolic Pressure is Associated with Extracorporeal Membrane Oxygenation Support after Heart Transplantation
Authors: Yuan Li , Ma Wenrui , Cui Jie , Liu Junjiang , Yang Zhaohua , Yang Shouguo , Zhang Hongqiang , Wang Fanshun , Liu Huan , Wang Chunsheng , Sun Xiaoning
Published: March 2023

Background. Pulmonary hypertension is a well-known risk factor for hemodynamic instability after heart transplantation. However, it remains unclear whether a mild elevation of pulmonary artery systolic pressure (PASP) is associated with higher risks of graft dysfunction and resultant extracorporeal membrane oxygenation (ECMO) support. Methods. From 2016 to 2021, 102 adult recipients undergoing orthotopic heart transplantation at our institution were investigated (mean age, 48.5 ± 13.2 years; 22.5% female). This study cohort was stratified into 3 groups based on the PASP measured by right heart catheterization before surgery: >50 mmHg, 35–50 mmHg, and <35 mmHg. The primary end point was ECMO support after procedure. Results. ECMO was implemented in 24 (23.5%) patients due to difficult weaning from cardiopulmonary bypass or cardiac low output in the intensive care unit, which was likely to be associated with higher mortality (

P
=
0.053

). Age, gender, comorbidities, preoperative medications, and graft ischemia time were comparable across the 3 groups. The use of ECMO was significantly more common in patients with baseline PASP >50 mmHg (11/36, 30.6%) and 35–50 mmHg (12/38, 31.6%), while only 1 (3.6%) patient with baseline PASP <35 mmHg required ECMO support after transplant (

P
=
0.007

). Multivariate logistic models demonstrated that PASP (odds ratio = 2.34;

P
=
0.028

) and cardiopulmonary bypass time (odds ratio = 1.01;

P
<
0.001

) were independent risk factors for postoperative ECMO. Conclusions. A mild elevation of pretransplant PASP (e.g., 35–50 mmHg) is related to low cardiac output and subsequent ECMO after heart transplantation, for which prompt administration of vasodilators before transplant may be protective.
Comparison of Antimicrobial Activity against Porphyromonas gingivalis between Advanced Platelet-Rich Fibrin and Injectable Platelet-Rich Fibrin
Authors: Pham Thuy Anh Vu
Published: March 2023

Platelet-rich fibrin (PRF) obtained via low-speed centrifugation has antimicrobial properties. This study was conducted to evaluate the effectiveness of advanced platelet-rich fibrin plus (A-PRF+) and injectable platelet-rich fibrin (I-PRF), obtained from patients with different periodontal states, against Porphyromonas gingivalis. A-PRF+ and I-PRF samples were obtained from venous blood of 60 subjects divided equally into three groups: periodontitis, gingivitis, and healthy gingiva groups. The antibacterial experiments evaluated biofilm inhibition, mature biofilm impact, and time-kill kinetics. The percent reduction in biofilm-growing and mature biofilm bacteria ranged from 39% to 49% and 3% to 7%, respectively. In the time-kill kinetics assay, PRF from the periodontitis group was more effective as an antimicrobial than that from the gingivitis and healthy gingiva group (

p
<
0.001

); I-PRF was more effective than A-PRF+ (

p
<
0.05

) and both of them showed peak antibacterial activity after 12 h of exposure. Both A-PRF+ and I-PRF exhibited antibacterial properties against P. gingivalis, but I-PRF appeared to be more effective. The PRF obtained from the different groups appeared to have different degrees of antimicrobial efficacy.
Trends in Bacterial Pathogens of Bats: Global Distribution and Knowledge Gaps
Authors: Szentivanyi Tamara , McKee Clifton , Jones Gareth , Foster Jeffrey T.
Published: March 2023

Bats have received considerable recent attention for infectious disease research because of their potential to host and transmit viruses, including Ebola, Hendra, Nipah, and multiple coronaviruses. These pathogens are occasionally transmitted from bats to wildlife, livestock, and to humans, directly or through other bridging (intermediate) hosts. Due to their public health relevance, zoonotic viruses are a primary focus of research attention. In contrast, other emerging pathogens of bats, such as bacteria, are vastly understudied despite their ubiquity and diversity. Here, we describe the currently known host ranges and geographic distributional patterns of potentially zoonotic bacterial genera in bats, using published presence-absence data of pathogen occurrence. We identify apparent gaps in our understanding of the distribution of these pathogens on a global scale. The most frequently detected bacterial genera in bats are Bartonella, Leptospira, and Mycoplasma. However, a wide variety of other potentially zoonotic bacterial genera are also occasionally found in bats, such as Anaplasma, Brucella, Borrelia, Coxiella, Ehrlichia, Francisella, Neorickettsia, and Rickettsia. The bat families Phyllostomidae, Vespertilionidae, and Pteropodidae are most frequently reported as hosts of bacterial pathogens; however, the presence of at least one bacterial genus was confirmed in all 15 bat families tested. On a spatial scale, molecular diagnostics of samples from 58 countries and four overseas departments and island states (French Guiana, Mayotte, New Caledonia, and Réunion Island) reported testing for at least one bacterial pathogen in bats. We also identified geographical areas that have been mostly neglected during bacterial pathogen research in bats, such as the Afrotropical region and Southern Asia. Current knowledge on the distribution of potentially zoonotic bacterial genera in bats is strongly biased by research effort towards certain taxonomic groups and geographic regions. Identifying these biases can guide future surveillance efforts, contributing to a better understanding of the ecoepidemiology of zoonotic pathogens in bats.
Extrachromosomal Amplification of Human Papillomavirus Episomes Is a Mechanism of Cervical Carcinogenesis
Authors: Rossi Nicole M. , Dai Jieqiong , Xie Yi , Wangsa Darawalee , Heselmeyer-Haddad Kerstin , Lou Hong , Boland Joseph F. , Yeager Meredith , Orozco Roberto , Freites Enrique Alvirez , Mirabello Lisa , Gharzouzi Eduardo , Dean Michael
Published: March 2023

HPV16 is the most oncogenic type of human papillomaviruses (HPV). Integration of HPV into the human genome is an important mechanism of carcinogenesis but is absent in at least 30% of HPV16+ tumors. We applied long-read whole-genome sequencing (WGS) to cervical cancer cell lines and tumors to characterize HPV16 carcinogenesis in the absence of integration. Large tandem arrays of full-length and unique truncated viral genomes integrated into multiple chromosomes were identified in two HPV16+ cell lines. The dispersion of characteristic viral variants to multiple integration sites indicates that viral deletions formed as extrachromosomal DNA (a phenomenon we term HPV superspreading). In addition, we identified an HPV16+ cell line with unintegrated (episomal) DNA that has tandem arrays of full-length, truncated, and rearranged HPV16 genomes (multimer episomes). Cytogenetic analysis of this cell line shows intense extrachromosomal HPV staining, including structures resembling double-minute chromosomes. WGS of HPV16+ cervical tumor samples from Latin America revealed that 11 of 20 tumors with only episomal HPV (EP) had intact monomer episomes. The remaining nine EP tumors had multimer and rearranged HPV genomes. The majority (80%) of HPV rearrangements and deletions disrupted the E1 and E2 genes, and EP tumors overexpressed the E6 and E7 viral oncogenes, a similar profile to tumors with HPV integration. Tumors with putative multimer HPV integrations display HPV multimers and concatemers of human and viral sequences. Our data uncovered a novel mechanism for HPV16 to cause cancer without integration through aberrant episomal replication, forming rearranged, mutated, and multimer episomes.

Significance:

Multimers of the HPV genome are generated in cervical tumors replicating as extrachromosomal episomes, which is associated with deletion and rearrangement of the HPV genome and provides a mechanism for oncogenesis without integration.
Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in PDGFRA D842V-Mutant Gastrointestinal Stromal Tumor
Authors: Rossi Ferdinand , Liu Mengyuan , Tieniber Andrew , Etherington Mark S. , Hanna Andrew , Vitiello Gerardo A. , Param Nesteene J. , Do Kevin , Wang Laura , Antonescu Cristina R. , Zeng Shan , Zhang Jennifer Q. , DeMatteo Ronald P.
Published: March 2023

Purpose:

To create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy.

Experimental Design:

We created a patient-derived xenograft (PDX) of PDGFRA D842V-mutant GIST and tested the effects of imatinib, avapritinib, and ML-7, an inhibitor of myosin light-chain kinase (MYLK). Bulk tumor RNA sequencing and oncogenic signaling were evaluated. Apoptosis, survival, and actin cytoskeleton were evaluated in GIST T1 cells and isolated PDX cells in vitro. Human GIST specimens were analyzed for MYLK expression.

Results:

The PDX was minimally responsive to imatinib but sensitive to avapritinib. Avapritinib therapy increased tumor expression of genes related to the actin cytoskeleton, including MYLK. ML-7 induced apoptosis and disrupted actin filaments in short-term cultures of PDX cells and decreased survival in GIST T1 cells in combination with imatinib or avapritinib. Combined therapy with ML-7 improved the antitumor effects of low-dose avapritinib in vivo. Furthermore, MYLK was expressed in human GIST specimens.

Conclusions:

MYLK upregulation is a novel mechanism of tumor persistence after tyrosine kinase inhibition. Concomitant MYLK inhibition may enable the use of a lower dose of avapritinib, which is associated with dose-dependent cognitive side effects.
Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: March 2023

Multiple studies have identified metabolic changes within the tumor and its microenvironment during carcinogenesis. Yet, the mechanisms by which tumors affect the host metabolism are unclear. We find that systemic inflammation induced by cancer leads to liver infiltration of myeloid cells at early extrahepatic carcinogenesis. The infiltrating immune cells via IL6–pSTAT3 immune–hepatocyte cross-talk cause the depletion of a master metabolic regulator, HNF4α, consequently leading to systemic metabolic changes that promote breast and pancreatic cancer proliferation and a worse outcome. Preserving HNF4α levels maintains liver metabolism and restricts carcinogenesis. Standard liver biochemical tests can identify early metabolic changes and predict patients’ outcomes and weight loss. Thus, the tumor induces early metabolic changes in its macroenvironment with diagnostic and potentially therapeutic implications for the host.

Significance:

Cancer growth requires a permanent nutrient supply starting from early disease stages. We find that the tumor extends its effect to the host's liver to obtain nutrients and rewires the systemic and tissue-specific metabolism early during carcinogenesis. Preserving liver metabolism restricts tumor growth and improves cancer outcomes.

This article is highlighted in the In This Issue feature, p. 1501
Depression Risk in Post-Stroke Aphasia Patients: A Nationwide Population-Based Cohort Study
Authors: Lin Hui-Lin , Sung Fung-Chang , Muo Chih-Hsin , Chen Pei-Chun
Published: March 2023

Introduction: Depression and aphasia impair the quality of life after a stroke. Studies linking depression risk to post-stroke aphasia (PSA) lacked confirmation using a large database. Methods: Using Taiwan’s National Health Insurance claims data, we identified ≥18-year-old patients hospitalized for stroke from 2005 to 2009, and those diagnosed with aphasia during hospitalization or within 3 months after discharge were selected to form the aphasic group. We estimated depression incidence by December 31, 2018, and used the Cox proportional hazards model to estimate aphasia group to non-aphasia group hazard ratios (HRs). Results: With a median follow-up period of 7.91 and 8.62 years for aphasia (n = 26,754) and non-aphasia groups (n = 139,102), respectively, the incidence of depression was higher in the aphasia group than in the non-aphasia group (9.02 vs. 8.13 per 1,000 person-years), with an adjusted HR (95% confidence intervals [CI]) of 1.21 (1.15–1.29) for depression. The adjusted HRs (95% CI) of depression were homogenous for females, 1.26 (1.15–1.37); for males, 1.18 (1.09–1.27); for hemorrhagic stroke, 1.22 (1.09–1.37); and for ischemic stroke, 1.21 (1.13–1.30). Results in analyzing 25,939 propensity score-matched pairs demonstrated an equivalent effect. Conclusion: Patients with PSA are at an increased risk of developing depression, regardless of sex or stroke type.
Primary Human Herpes Virus-6 Causing Recalcitrant Pyrexia after Pilocytic Astrocytoma Resection
Authors: Chan Julie L. , Nisson Peyton , Danielpour Moise , Green Jack
Published: March 2023

Introduction: Human herpes virus-6 (HHV-6) is a ubiquitous virus but can lead to deleterious clinical manifestations due to its predilection for the pediatric central nervous system. Despite significant literature describing its common clinical course, it is rarely considered as a causative agent in CSF pleocytosis in the setting of craniotomy and external ventricular drainage device. Identification of a primary HHV-6 infection allowed for timely treatment with an antiviral agent along with earlier discontinuation of antibiotic regimen and expedited placement of a ventriculoperitoneal shunt. Case Presentation: A two-year-old girl presented with 3 months of progressive gait disturbance and intranuclear ophthalmoplegia. Following craniotomy for removal of 4th ventricular pilocytic astrocytoma and decompression of hydrocephalus, she suffered a prolonged clinical course due to persistent fevers and worsening CSF leukocytosis despite multiple antibiotic regimens. The patient was admitted to the hospital during the COVID-19 pandemic and isolated with her parents in the intensive care unit with strict infection control measures. FilmArray Meningitis/Encephalitis (FAME) panel ultimately detected HHV-6. Clinical confirmation of HHV-6-induced meningitis was proposed given improvement in CSF leukocytosis and fever reduction following the initiation of antiviral medications. Pathologic analysis of brain tumor tissue failed to show HHV-6 genome positivity, suggesting a primary peripheral etiology of infection. Conclusion: Here, we present the first known case of HHV-6 infection detected by FAME following intracranial tumor resection. We propose a modified algorithm for persistent fever of unknown origin which may decrease symptomatic sequelae, minimize additional procedures, and shorten length of ICU stay.
Corticosteroid Therapy in Immunoglobulin A Nephropathy: A Friend or Foe?
Authors: Kim Dana , Wong Muh Geot
Published: March 2023

Background: The administration of corticosteroids in addition to supportive care to delay progressive immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis worldwide, remains controversial. This is partly due to the paucity of well-designed randomized controlled trials and well-known corticosteroid-related side effects. As a result, clinical equipoise in corticosteroid therapy exists depending on geographical regions and the clinician’s preference. Summary: Better understanding around the pathogenesis of IgAN has prompted several clinical trials exploring the effects of immunosuppressive agents including corticosteroids. Earlier studies of corticosteroids were limited by suboptimal study designs, inadequate implementation of standard of care, and inconsistent adverse event data collection. Two well-designed, adequately powered, multi-centre randomized controlled trials, the STOP-IgAN and TESTING studies, have reported contrasting kidney outcomes that have further fuelled the clinical conundrum regarding the efficacy of corticosteroids. Both studies independently reported greater adverse events with corticosteroids. A novel targeted release formulation of budesonide, which has been hypothesized to reduce the adverse events associated with systemic corticosteroids, has shown promising results in the Phase 3 NefigaRD trial. Studies of treatments targeting B cells and the complement cascade are currently underway, and early data appear encouraging. This review provides an overview of the current literature around the understanding of the pathomechanisms and benefits and harm of corticosteroid use in IgAN. Key Messages: Recent evidence suggests the use of corticosteroids in a selected cohort of people with IgAN at high risk of disease progression can improve kidney outcomes but comes with an associated risk of treatment-related adverse events, particularly with higher doses. Management decisions should therefore follow an informed patient-clinician discussion.