bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of COVID-19 Control Measures on the Concentration and Composition of PM2.5-Bound Polycyclic Aromatic Hydrocarbons in Shanghai
Authors: Feng Jialiang , Fan Fan , Feng Yi , Hu Ming , Chen Jia , Shen Yutong , Fu Qingyan , Wang Shunyao
Published: January 2023

In order to explore the effects of COVID-19 control measures on the concentration and composition of PM2.5-bound polycyclic aromatic hydrocarbons (PAHs), and to better understand the sources of PM2.5-bound PAHs, PM2.5, samples were collected at two sites in urban and suburban areas of Shanghai before the lockdown, during the lockdown, after the lockdown in 2020, and during the same periods in 2019. The mass concentrations of 21 individual PAHs were determined via GC-MS analysis. While the COVID-19 control measures significantly reduced the absolute concentration of PM2.5-bound PAHs, they had no significant effect on their relative abundances, indicating that the significantly reduced traffic emission may not originally be the major source of PAHs in Shanghai. The differences in the composition of PM2.5-bound PAHs at three different lockdown-related periods may be caused by the gas-particle distribution of semi-volatile PAHs. The similarity in the composition of PM2.5-bound PAHs in different functional areas and different periods brings more uncertainties to the identification of PAH sources using the diagnostic ratios. During the lockdown period, the toxic equivalent concentration of PM2.5-bound PAHs in Shanghai was estimated to decrease by about 1/4, which still exhibits substantial carcinogenic risk upon exposure via inhalation.
The Use of Multilayer Perceptrons to Model PM2.5 Concentrations at Air Monitoring Stations in Poland
Authors: Hoffman Szymon , Jasiński Rafał
Published: January 2023

The biggest problem facing air protection in Poland is the high levels of suspended particular matter concentrations. Air monitoring reports show that air quality standards, related to PM10 and PM2.5 concentrations, are exceeded every year in many Polish cities. The PM2.5 aerosol fraction is particularly dangerous to human and animal health. Therefore, monitoring the level of PM2.5 concentration should be considered particularly important. Unfortunately, most monitoring stations in Poland do not measure this dust fraction. However, almost all stations are equipped with analyzers measuring PM10 concentrations. PM2.5 is a fine fraction of PM10, and there is a strong correlation between the concentrations of these two types of suspended dust. This relationship can be used to determine the concentration of PM2.5. The main purpose of this analysis was to assess the accuracy of PM2.5 concentration prediction using PM10 concentrations. The analysis was carried out on the basis of long-term hourly data recorded at several monitoring stations in Poland. Artificial neural networks in the form of a multilayer perceptron were used to model PM2.5 concentrations.
Wildland Fires in the Subtropical Hill Forests of Southeastern Bangladesh
Authors: Farukh Murad , Islam Md. , Hayasaka Hiroshi
Published: January 2023

The first ever comprehensive study on wildland fires in Bangladesh is carried out to develop a fire prevention and prediction method. The major causes of huge wildland fires (88%) in the subtropical Chittagong Hill forest (43% of total) of southern Bangladesh are reported as shifting cultivation, grazing and unauthorized settlement. We used satellite hotspot (HS) data from 2003 to 2021 (a total of 54,669 HSs) to clarify the spatio-temporal structure of wildland fires. Fire weather conditions were analyzed using various weather data and synoptic-scale weather maps at different air levels. Fires concentrated from March through April or a transitional period from the dry season, caused by the Asian winter monsoon, to the wet season, due to the Asian summer monsoon. Fire occurrence depended on dry conditions and pre-monsoon showers and their timing. The difference in 925 hPa heights of high and low pressure systems may be attributed to the different types of the Asian winter and summer monsoons. The average maximum air temperature and incident shortwave solar energy in April were the highest and strongest, contributing fire-prone weather conditions. Based on the analysis, a fire prevention and prediction method will be developed, and this report may also facilitate the establishment of future CO2 reduction measures for Bangladesh.
Seasonal Lifting Condensation Level Trends: Implications of Warming and Reforestation in Appalachia’s Deciduous Forest
Authors: Kutta Evan , Hubbart Jason A.
Published: January 2023

Lifting condensation level (LCL) has long been used to estimate cloud base heights. However, spatial and temporal patterns of cloud bases embedded within atmospheric currents flowing over mountainous terrain still need to be more adequately described. To advance understanding, hourly observations of barometric pressure and ambient and dew point temperatures from 1948 to 2017 were acquired for seven airports located at 40.21° N (average) and crossing the Allegheny Mountains of the northeastern United States. Daily LCL trends were quantified, and large positive (2.3 m yr−1) and negative (−1.3 m yr−1) LCL trends were found to be greatest near seasonal transition dates (17 April and 9 November 2022). Cool season LCLs (795 m) increased significantly (p < 0.007) at five sites resulting in an average LCL increase of 81 m and implying a deeper and drier sub-cloud layer. Average warm season LCLs (773 m) decreased by 23 m, suggesting a deeper convective cloud layer and less sub-cloud evaporation that may facilitate higher hydrometeor growth and precipitation rates. Collective results indicate divergent seasonally averaged LCLs characterized by more rapid seasonal transitions, warmer and less cloudy cool seasons, and cloudier and more humid warm seasons that may be partly attributable to aggressive reforestation and contribute to more significant rainfall events and higher flood risks.
Exploitation of the Timing Capabilities of Metallic Magnetic Calorimeters for a Coincidence Measurement Scheme
Authors: Pfäfflein Philip , Weber Günter , Allgeier Steffen , Bernitt Sonja , Fleischmann Andreas , Friedrich Marvin , Hahn Christoph , Hengstler Daniel , Herdrich Marc Oliver , Kalinin Anton , Kröger Felix Martin , Kuntz Patricia , Lestinsky Michael , Löher Bastian , Menz Esther Babette , Spillmann Uwe , Zhu Binghui , Enss Christian , Stöhlker Thomas
Published: January 2023

In this report, we compare two filter algorithms for extracting timing information using novel metallic magnetic calorimeter detectors, applied to the precision X-ray spectroscopy of highly charged ions in a storage ring. Accurate timing information is crucial when exploiting coincidence conditions for background suppression to obtain clean spectra. For X-rays emitted by charge-changing interactions between ions and a target, this is a well-established technique when relying on conventional semiconductor detectors that offer a good temporal resolution. However, until recently, such a coincidence scheme had never been realized with metallic magnetic calorimeters, which typically feature much longer signal rise times. In this report, we present optimized timing filter algorithms for this type of detector. Their application to experimental data recently obtained at the electron cooler of CRYRING@ESR at GSI, Darmstadt is discussed.
Preliminary Results for Observation of Radiative Double-Electron Capture by F9+,8+ on Graphene
Authors: La Mantia D. S. , Kayani A. , Bhatt K. , Tanis J. A.
Published: January 2023

Radiative double-electron capture, which can be considered the inverse of double photoionization, has been investigated for 2.11 MeV/u F9+ and F8+ projectiles colliding with the two-dimensional target single-layer graphene. Preliminary results for the cross sections are obtained and presented and compared with our previous measurements for the one-dimensional gas targets N2 and Ne, with the three-dimensional target thin-foil C, and with the most accurate theoretical results that currently exist. The graphene results reported here are reasonable when compared with the F9++N2, Ne results given the thicknesses of the respective targets, being larger by about a factor of four.
Electronic Structure Calculations with the Exact Pseudopotential and Interpolating Wavelet Basis
Authors: Höynälänmaa Tommi , Rantala Tapio T.
Published: January 2023

Electronic structure calculations are mostly carried out with Coulomb potential singularity adapted basis sets such as STO or contracted GTO. With another basis or for heavy elements, the pseudopotentials may appear as a practical alternative. Here, we introduce the exact pseudopotential (EPP) to remove the Coulomb singularity and test it for orbitals of small atoms with the interpolating wavelet basis set. We apply EPP to the Galerkin method with a basis set consisting of Deslauriers–Dubuc scaling functions on the half-infinite real interval. We demonstrate the EPP–Galerkin method by computing the hydrogen atom 1s, 2s, and 2p orbitals and helium atom configurations He1s2, He1s2s1S, and He1s2s3S. We compare the method to the ordinary interpolating wavelet Galerkin method (OIW–Galerkin), handling the singularity at the nucleus by excluding the scaling function located at the origin from the basis. We also compare the performance of our approach to that of finite-difference approach, which is another practical method for spherical atoms. We find the accuracy of the EPP–Galerkin method to be better than both of the above-mentioned methods.
A Protocol to Investigate Deep Brain Stimulation for Refractory Tinnitus: From Rat Model to the Set-Up of a Human Pilot Study
Authors: van Zwieten Gusta , Devos Jana V. P. , Kotz Sonja A. , Ackermans Linda , Brinkmann Pia , Dauven Lobke , George Erwin L. J. , Janssen A. Miranda L. , Kremer Bernd , Leue Carsten , Schwartze Michael , Temel Yasin , Smit Jasper V. , Janssen Marcus L. F.
Published: January 2023

Background: Chronic tinnitus can have an immense impact on quality of life. Despite recent treatment advances, many tinnitus patients remain refractory to them. Preclinical and clinical evidence suggests that deep brain stimulation (DBS) is a promising treatment to suppress tinnitus. In rats, it has been shown in multiple regions of the auditory pathway that DBS can have an alleviating effect on tinnitus. The thalamic medial geniculate body (MGB) takes a key position in the tinnitus network, shows pathophysiological hallmarks of tinnitus, and is readily accessible using stereotaxy. Here, a protocol is described to evaluate the safety and test the therapeutic effects of DBS in the MGB in severe tinnitus sufferers. Methods: Bilateral DBS of the MGB will be applied in a future study in six patients with severe and refractory tinnitus. A double-blinded, randomized 2 × 2 crossover design (stimulation ON and OFF) will be applied, followed by a period of six months of open-label follow-up. The primary focus is to assess safety and feasibility (acceptability). Secondary outcomes assess a potential treatment effect and include tinnitus severity measured by the Tinnitus Functional Index (TFI), tinnitus loudness and distress, hearing, cognitive and psychological functions, quality of life, and neurophysiological characteristics. Discussion: This protocol carefully balances risks and benefits and takes ethical considerations into account. This study will explore the safety and feasibility of DBS in severe refractory tinnitus, through extensive assessment of clinical and neurophysiological outcome measures. Additionally, important insights into the underlying mechanism of tinnitus and hearing function might be revealed. Trial registration: ClinicalTrials.gov NCT03976908 (6 June 2019).
Improved Multidimensional Quality of Life Index Based on Outranking Relations
Authors: De Vicente Oliva María Auxiliadora , Romero-Ania Alberto
Published: January 2023

The aim of this research is to propose an improved multidimensional quality of life index, which could replace the current methodology designed by Eurostat and applied by the national statistical institutes of the European Union member states. The novelty of the proposed index is that it is based on a non-compensatory multicriteria decision method (ELECTRE III). All other quality of life indices propose compensatory aggregation methods at some stage in the construction of the index. The data used in this study are openly available on the website of the INE, which is the Spanish National Statistics Institute, and were obtained by INE from population surveys. The data were entered by the authors in the Diviz software to conduct an ELECTRE III method. Three innovative versions for the multidimensional quality of life index are proposed in this study, which are called Basic ELECTRE, Full ELECTRE, and Full Fuzzy ELECTRE. The comparison of the results obtained by INE with the results provided by our proposals shows that it is possible to construct an improved multidimensional quality of life index to be applied by the member states of the European Union.
Interval-Valued General Residuated Lattice-Ordered Groupoids and Expanded Triangle Algebras
Authors: Zhang Xiaohong , Liang Rong
Published: January 2023

As an extension of interval-valued pseudo t-norms, interval-valued pseudo-overlap functions (IPOFs) play a vital role in solving interval-valued multi-attribute decision making problems. However, their corresponding interval-valued algebraic structure has not been studied yet. On the other hand, with the development of non-commutative (non-associative) fuzzy logic, the study of residuated lattice theory is gradually deepening. Due to the conditions of operators being weakened, the algebraic structures are gradually expanding. Therefore, on the basis of interval-valued residuated lattice theory, we generalize and research the related contents of interval-valued general, residuated, lattice-ordered groupoids. In this paper, the concept of interval-valued, general, residuated, lattice-ordered groupoids is given, and some examples are presented to illustrate the relevance of IPOFs to them. Then, in order to further study them, we propose the notions of expanded, interval-valued, general, residuated lattice-ordered groupoids and expanded triangle algebras, and explain that there is one-to-one correspondence between them through a specific proposition. Some of their properties are also analyzed. Lastly, we show the definitions of the filters on the expanded triangle algebras, and investigate the congruence and quotient structure through them.
A Sound Definitional Interpreter for a Simply Typed Functional Language
Authors: Ekici Burak
Published: January 2023

In this paper, we develop, in the proof assistant Coq, a definitional interpreter and a type-checker for a simply typed functional language, and formally prove that the mentioned type-checker is sound with respect to the definitional interpreter via progress and preservation. To represent binders, we embark on the choice of “concrete syntax” in which parameters are just names (or strings).
Stability for Weakly Coupled Wave Equations with a General Internal Control of Diffusive Type
Authors: Beniani Abderrahmane , Bahri Noureddine , Alharbi Rabab , Bouhali Keltoum , Zennir Khaled
Published: January 2023

The present paper deals with well-posedness and asymptotic stability for weakly coupled wave equations with a more general internal control of diffusive type. Owing to the semigroup theory of linear operator, the well-posedness of system is proved. Furthermore, we show a general decay rate result. The method is based on the frequency domain approach combined with multiplier technique.
Organoid Cultures In Silico: Tools or Toys?
Authors: Thalheim Torsten , Aust Gabriela , Galle Joerg
Published: January 2023

The implementation of stem-cell-based organoid culture more than ten years ago started a development that created new avenues for diagnostic analyses and regenerative medicine. In parallel, computational modelling groups realized the potential of this culture system to support their theoretical approaches to study tissues in silico. These groups developed computational organoid models (COMs) that enabled testing consistency between cell biological data and developing theories of tissue self-organization. The models supported a mechanistic understanding of organoid growth and maturation and helped linking cell mechanics and tissue shape in general. What comes next? Can we use COMs as tools to complement the equipment of our biological and medical research? While these models already support experimental design, can they also quantitatively predict tissue behavior? Here, we review the current state of the art of COMs and discuss perspectives for their application.
Applications of Extracellular Vesicles in Nervous System Disorders: An Overview of Recent Advances
Authors: Khan Safir Ullah , Khan Muhammad Imran , Khan Munir Ullah , Khan Noor Muhammad , Bungau Simona , Hassan Syed Shams ul
Published: January 2023

Diseases affecting the brain and spinal cord fall under the umbrella term “central nervous system disease”. Most medications used to treat or prevent chronic diseases of the central nervous system cannot cross the blood–brain barrier (BBB) and hence cannot reach their intended target. Exosomes facilitate cellular material movement and signal transmission. Exosomes can pass the blood–brain barrier because of their tiny size, high delivery efficiency, minimal immunogenicity, and good biocompatibility. They enter brain endothelial cells via normal endocytosis and reverse endocytosis. Exosome bioengineering may be a method to produce consistent and repeatable isolation for clinical usage. Because of their tiny size, stable composition, non-immunogenicity, non-toxicity, and capacity to carry a wide range of substances, exosomes are indispensable transporters for targeted drug administration. Bioengineering has the potential to improve these aspects of exosomes significantly. Future research into exosome vectors must focus on redesigning the membrane to produce vesicles with targeting abilities to increase exosome targeting. To better understand exosomes and their potential as therapeutic vectors for central nervous system diseases, this article explores their basic biological properties, engineering modifications, and promising applications.
Measurement of Force and Intramuscular Pressure Changes Related to Thrust Spinal Manipulation in an In Vivo Animal Model
Authors: Reed William R. , Lima Carla R. , Liebschner Michael A. K. , Hurt Christopher P. , Li Peng , Gudavalli Maruti R.
Published: January 2023

Current knowledge regarding biomechanical in vivo deep tissue measures related to spinal manipulation remain somewhat limited. More in vivo animal studies are needed to better understand the effects viscoelastic tissue properties (i.e., dampening) have on applied spinal manipulation forces. This new knowledge may eventually help to determine whether positive clinical outcomes are associated with particular force thresholds reaching superficial and/or deep spinal tissues. A computer-controlled feedback motor and a modified Activator V device with a dynamic load cell attached were used to deliver thrust spinal manipulations at various magnitudes to the L7 spinous process in deeply anesthetized animals. Miniature pressure catheters (Millar SPR-1000) were inserted unilaterally into superficial and deep multifidi muscles. Measurements of applied mechanical forces and superficial/deep multifidi intramuscular pressure changes were recorded during spinal manipulations delivered in vivo. Manipulative forces and net changes in intramuscular pressures reaching deep spinal tissues are greatly diminished by viscoelastic properties of in vivo tissues, which could have possible clinical safety and/or mechanistic implications.
Pathophysiology and Clinical Meaning of Ventilation-Perfusion Mismatch in the Acute Respiratory Distress Syndrome
Authors: Slobod Douglas , Damia Anna , Leali Marco , Spinelli Elena , Mauri Tommaso
Published: January 2023

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35–45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient’s pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.
Evaluation of Epigenetic Age Acceleration Scores and Their Associations with CVD-Related Phenotypes in a Population Cohort
Authors: Chervova Olga , Chernysheva  Elizabeth , Panteleeva  Kseniia , Widayati  Tyas Arum , Hrbkova Natalie , Schneider  Jadesada , Maximov  Vladimir , Ryabikov  Andrew , Tillmann  Taavi , Pikhart Hynek , Bobak  Martin , Voloshin  Vitaly , Malyutina  Sofia , Beck  Stephan
Published: January 2023

We evaluated associations between nine epigenetic age acceleration (EAA) scores and 18 cardiometabolic phenotypes using an Eastern European ageing population cohort richly annotated for a diverse set of phenotypes (subsample, n = 306; aged 45–69 years). This was implemented by splitting the data into groups with positive and negative EAAs. We observed strong association between all EAA scores and sex, suggesting that any analysis of EAAs should be adjusted by sex. We found that some sex-adjusted EAA scores were significantly associated with several phenotypes such as blood levels of gamma-glutamyl transferase and low-density lipoprotein, smoking status, annual alcohol consumption, multiple carotid plaques, and incident coronary heart disease status (not necessarily the same phenotypes for different EAAs). We demonstrated that even after adjusting EAAs for sex, EAA–phenotype associations remain sex-specific, which should be taken into account in any downstream analysis involving EAAs. The obtained results suggest that in some EAA–phenotype associations, negative EAA scores (i.e., epigenetic age below chronological age) indicated more harmful phenotype values, which is counterintuitive. Among all considered epigenetic clocks, GrimAge was significantly associated with more phenotypes than any other EA scores in this Russian sample.
M.tb-Rv2462c of Mycobacterium tuberculosis Shows Chaperone-like Activity and Plays a Role in Stress Adaptation and Immunomodulation
Authors: Khawary Masuma , Rakshit Roopshali , Bahl Aayush , Juneja Pallavi , Kant Sashi , Pandey Saurabh , Tripathi Deeksha
Published: January 2023

Mycobacterium tuberculosis (M.tb)-encoded factors protect it against host-generated stresses and support its survival in the hostile host environment. M.tb possesses two peptidyl-prolyl cis-trans isomerases and a probable trigger factor encoded by Rv2462c which has an FKBP-like PPIase domain. PPIases are known to assist the folding of peptidyl-prolyl bonds and are involved in various cellular processes important for bacterial survival in host-generated stresses. In this study, we aim to functionally characterize Rv2462c of M.tb. Our data suggest that the trigger factor of M.tb exhibits chaperone activity both in vitro and in vivo. Heterologous expression of M.tb-Rv2462c locus into Mycobacterium smegmatis enhanced its survival within macrophages, adaptation to oxidative stress and biofilm formation. M.tb-trigger factor has strong immunomodulatory potential and modifies the cytokine profile of the host towards the proinflammatory axis.
Decline of Sperm Quality over the Last Two Decades in the South of Europe: A Retrospective Study in Infertile Patients
Authors: Garcia-Grau Emma , Lleberia Judith , Costa Laura , Guitart Miriam , Yeste Marc , Benet Jordi , Amengual María José , Ribas-Maynou Jordi
Published: January 2023

Semen quality has a direct relation to male fertility. Whether sperm variables in humans have decreased over the last years is still uncertain, with some studies showing a decline and others reporting no changes. In this regard, previous research has suggested that lifestyle and environmental conditions may contribute to this variability, calling for regional studies. The present work is a retrospective, unicentric study that includes semen samples analyzed between 1997 and 2017 at the Parc Taulí Hospital (Barcelona metropolitan area). First, a multivariate analysis including the age as a confounding factor showed a statistically significant decrease in semen volume, pH, progressive motility, morphology and total motile sperm over time. Contrarily, no significant variation in sperm count or concentration was observed. Mean reductions per year were −0.02 mL for volume, −0.57% for progressively motile sperm and −0.72% for sperm with normal morphology. Interestingly, the average annual temperature registered by the Spanish Meteorology Agency negatively correlated to sperm morphology and sperm count (Rs = −0.642; p = 0.002 and Rs = −0.435; p = 0.049, respectively). In conclusion, the present study based on infertile patients from the Barcelona area found a decline in sperm motility and morphology, without effects on sperm count. Changes in temperature appeared to be associated to this decline, but further studies are needed to address the mechanisms linked to the observed variations.
A Novel Method to Screen Strong Constitutive Promoters in Escherichia coli and Serratia marcescens for Industrial Applications
Authors: Pan Xuewei , Tang Mi , You Jiajia , Hao Yanan , Zhang Xian , Yang Taowei , Rao Zhiming
Published: January 2023

Promoters serve as the switch of gene transcription, playing an important role in regulating gene expression and metabolites production. However, the approach to screening strong constitutive promoters in microorganisms is still limited. In this study, a novel method was designed to identify strong constitutive promoters in E. coli and S. marcescens based on random genomic interruption and fluorescence-activated cell sorting (FACS) technology. First, genomes of E. coli, Bacillus subtilis, and Corynebacterium glutamicum were randomly interrupted and inserted into the upstream of reporter gene gfp to construct three promoter libraries, and a potential strong constitutive promoter (PBS) suitable for E. coli was screened via FACS technology. Second, the core promoter sequence (PBS76) of the screened promoter was identified by sequence truncation. Third, a promoter library of PBS76 was constructed by installing degenerate bases via chemical synthesis for further improving its strength, and the intensity of the produced promoter PBS76-100 was 59.56 times higher than that of the promoter PBBa_J23118. Subsequently, promoters PBBa_J23118, PBS76, PBS76-50, PBS76-75, PBS76-85, and PBS76-100 with different strengths were applied to enhance the metabolic flux of L-valine synthesis, and the L-valine yield was significantly improved. Finally, a strong constitutive promoter suitable for S. marcescens was screened by a similar method and applied to enhance prodigiosin production by 34.81%. Taken together, the construction of a promoter library based on random genomic interruption was effective to screen the strong constitutive promoters for fine-tuning gene expression and reprogramming metabolic flux in various microorganisms.
New Bacillus subtilis Strains Isolated from Prosopis glandulosa Rhizosphere for Suppressing Fusarium Spp. and Enhancing Growth of Gossypium hirsutum L.
Authors: Abdelmoteleb Ali , Moreno-Ramírez Lizbeth , Valdez-Salas Benjamín , Seleiman Mahmoud F. , El-Hendawy Salah , Aldhuwaib Khalid J. , Alotaibi Majed , González-Mendoza Daniel
Published: January 2023

Rhizobacteria from desert plants can alleviate biotic stress and suppress plant diseases, and consequently can enhance plant growth. Therefore, the current study was performed to isolate and identify Prosopis glandulosa-associating rhizobacteria based on their antagonistic activity against Fusarium species and plant growth-promoting properties. Three bacterial isolates were identified as Bacillus subtilis: LDA-1, LDA-2, and LDA-3. The molecular analysis suggests the biosynthesis of the bacteriocins subtilisin and subtilosin, as well as the lipopeptide iturin, by these strains. In addition, the antagonistic study by dual-culture assay showed a high efficacy of all B. subtilis strains against phytopathogenic fungi (Fusarium nygamai, F. equisseti, F. solani, F. solani ICADL1, and F. oxysporum ICADL2) with inhibition percentages ranging from 43.3 to 83.5% in comparison to the control. Moreover, atomic force microscopy (AFM) analysis showed significant differences in the cell wall topography of the F. solani ICADL1 among the treated mycelia and untreated control. As a result, these three B. subtilis strains were used as bioinoculants for cotton seedlings infected by F. solani ICADL1 in pot trials, and the results revealed that the bacterial inoculations as an individual or combined with F. solani ICADL1 significantly improved cotton root and stem length, lateral roots, indole acetic acid (IAA), and gibberellic acid (GA3) contents, as well as increased antioxidants, flavonoids, and phenols in comparison to those obtained from healthy and infected control plants. In conclusion, the three bacterial strains of B. subtilis (i.e., LDA-1, LDA-2, and LDA-3) are considered promising tools as biocontrol agents for F. solani and cotton growth promoters, and consequently can be used as bio-ertilizer in sustainable agriculture systems.
Overlap and Segregation among Multiple 3D Home Ranges: A Non-Pairwise Metric with Demonstrative Application to the Lesser Kestrel Falco naumanni
Authors: Ferrarini Alessandro , Giglio Giuseppe , Pellegrino Stefania Caterina , Gustin Marco
Published: January 2023

In this study we solved the issue of measuring the degree of overlap/segregation among an arbitrarily large number (n ≥ 2) of 3D volumetric home ranges (i.e., x, y, and hg; where hg is height above ground level) for the first time. For this purpose, we introduced the novel non-pairwise index MVOI (Multiple Volumetric Overlap Index) and its complement to 100 MVSI (Multiple Volumetric Segregation Index). Regardless of the number of 3D volumetric home ranges, the MVOI and MVSI generate a single score of overlap/segregation between 0 and 100, making ecological interpretation much easier and more meaningful when compared to n × n pairwise overlap indices. As a case study, we applied the MVOI and MVSI to 12,081 GPS points of five lesser kestrels (Falco naumanni) during the nesting period at Santeramo in Colle (Apulia region; Italy) in an area with the most elevated density of lesser kestrels in urban colonies worldwide. The 3D volumetric home ranges ranged between 1.79 km3 and 8.19 km3. We found that the tracked birds had different vertical profiles, possibly to limit intraspecific competition, resulting in a 3D home range overlap that was only 61.1% of the 2D overlap and 52.8% of the probabilistic one.
Integration of scRNA-Seq and Bulk RNA-Seq Reveals Molecular Characterization of the Immune Microenvironment in Acute Pancreatitis
Authors: Fang Zhen , Li Jie , Cao Feng , Li Fei
Published: January 2023

Acute pancreatitis (AP) is an acute inflammatory disease of the exocrine pancreas. The pathogenesis of AP is still unclear, and there is currently no specific treatment. A variety of immune cells infiltrate in AP, which may play an important role in the progression of the disease. In this study, for the first time, scRNA-Seq and Bulk RNA-Seq data were used to show the characteristics of immune cell infiltration in AP, and to explore the specific molecular markers of different cell types. The present study also investigated cell-to-cell communication networks using the CellChat package, and AP-specific gene signatures (Clic1, Sat1, Serpina3n, Atf3, Lcn2, Osmr, Ccl9, Hspb1, Anxa2, Krt8, Cd44, Cd9, Hsp90aa1, Tmsb10, Hmox1, Fxyd5, Plin2, Pnp) were identified through integrative analysis of multiple sequencing datasets. We also defined disease-specific associated genes in different cell types, revealing dynamic changes through cell trajectory and pseudo-time analysis using the Monocle2 package. The results showed that macrophages were significantly increased in acute pancreatitis, and the number of interactions and interaction weight/strength of the macrophages in AP were significantly higher than those in the controls. The activities of various signaling pathways were abnormally regulated such as apoptosis, oxidative stress, lysosome, autophagy, ferroptosis, and inflammatory responses signaling pathways. In conclusion, this study comprehensively depicted the immune microenvironment of AP, explored the interaction network between different cell types, and defined AP-specific gene signatures, providing many new directions for basic research in AP.
Plasma Levels of sFas-sFasL and FASL Gene Expression Are Associated with Tuberculosis
Authors: Souza Iury de Paula , Amoras Ednelza da Silva Graça , Sousa Francisca Dayse Martins de , Sousa Paulo Victor Negrão Raiol de , Lima Sandra Souza , Cayres-Vallinoto Izaura Maria Vieira , Ishak Ricardo , Vallinoto Antonio Carlos Rosário , Queiroz Maria Alice Freitas
Published: January 2023

Apoptosis of macrophages infected by Mycobacterium tuberculosis via Fas-FasL is an important immune mechanism against infection. This study investigated the association of tuberculosis (TB) with the presence of the polymorphisms FAS -670A/G and FASL -124A/G, the levels of sFas and sFasL, and the gene expression of FASL and cytokines. Samples of 200 individuals diagnosed with TB and 200 healthy controls were evaluated. Real-time PCR (genotyping and gene expression) and ELISA (dosages of sFas, sFasL, IFN-γ, and IL-10) tests were performed. There was no association of FAS -670A/G and FASL -124A/G polymorphisms with TB. The TB group exhibited high plasma levels of sFas and reduced plasma levels of sFasL (p < 0.05). The correlation analysis between these markers revealed a positive correlation between the levels of sFas and sFasL, sFasL and FASL expression, and between sFas and FASL expression (p < 0.05). In the TB group, there was a positive correlation between FASL expression and IFN-γ levels and higher levels of IL-10 compared to IFN-γ (p < 0.05). High levels of sFas and reduced levels of sFasL and FASL expression may contribute to the inhibition of apoptosis in infected cells and represent a possible bacterial resistance resource to maintain the infection.
DNA Repair and Immune Response: Editorial
Authors: Oksenych Valentyn
Published: January 2023

Developing B and T lymphocytes requires programmed DNA double-strand breaks followed by the activation of the DNA damage response (DDR) pathway and DNA repair [...]
Cysteine Biosynthesis in Campylobacter jejuni: Substrate Specificity of CysM and the Dualism of Sulfide
Authors: Hitchcock Noah , Kelly David J. , Hitchcock Andrew , Taylor Aidan J.
Published: January 2023

Campylobacter jejuni is a highly successful enteric pathogen with a small, host-adapted genome (1.64 Mbp, ~1650 coding genes). As a result, C. jejuni has limited capacity in numerous metabolic pathways, including sulfur metabolism. Unable to utilise ionic sulfur, C. jejuni relies on the uptake of exogenous cysteine and its derivatives for its supply of this essential amino acid. Cysteine can also be synthesized de novo by the sole cysteine synthase, CysM. In this study, we explored the substrate specificity of purified C. jejuni CysM and define it as an O-acetyl-L-serine sulfhydrylase with an almost absolute preference for sulfide as sulfur donor. Sulfide is produced in abundance in the intestinal niche C. jejuni colonises, yet sulfide is generally viewed as highly toxic to bacteria. We conducted a series of growth experiments in sulfur-limited media and demonstrate that sulfide is an excellent sulfur source for C. jejuni at physiologically relevant concentrations, combating the view of sulfide as a purely deleterious compound to bacteria. Nonetheless, C. jejuni is indeed inhibited by elevated concentrations of sulfide and we sought to understand the targets involved. Surprisingly, we found that inactivation of the sulfide-sensitive primary terminal oxidase, the cbb3-type cytochrome c oxidase CcoNOPQ, did not explain the majority of growth inhibition by sulfide. Therefore, further work is required to reveal the cellular targets responsible for sulfide toxicity in C. jejuni.
Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition
Authors: Han Hyunho , Park Cheol Keun , Choi Young-Deuk , Cho Nam Hoon , Lee Jongsoo , Cho Kang Su
Published: January 2023

Prostate cancer is a common form of cancer in men, and androgen-deprivation therapy (ADT) is often used as a first-line treatment. However, some patients develop resistance to ADT, and their disease is called castration-resistant prostate cancer (CRPC). Identifying potential therapeutic targets for this aggressive subtype of prostate cancer is crucial. In this study, we show that statins can selectively inhibit the growth of these CRPC tumors that have lost their androgen receptor (AR) and have overexpressed the RNA-binding protein QKI. We found that the repression of microRNA-200 by QKI overexpression promotes the rise of AR-low mesenchymal-like CRPC cells. Using in silico drug/gene perturbation combined screening, we discovered that QKI-overexpressing cancer cells are selectively vulnerable to CDC42-PAK7 inhibition by statins. We also confirmed that PAK7 overexpression is present in prostate cancer that coexists with hyperlipidemia. Our results demonstrate a previously unseen mechanism of action for statins in these QKI-expressing AR-lost CRPCs. This may explain the clinical benefits of the drug and support the development of a biology-driven drug-repurposing clinical trial. This is an important finding that could help improve treatment options for patients with this aggressive form of prostate cancer.
Gene Therapy with Voretigene Neparvovec Improves Vision and Partially Restores Electrophysiological Function in Pre-School Children with Leber Congenital Amaurosis
Authors: Gerhardt Maximilian J. , Priglinger Claudia S. , Rudolph Günther , Hufendiek Karsten , Framme Carsten , Jägle Herbert , Salchow Daniel J. , Anschütz Andreas , Michalakis Stylianos , Priglinger Siegfried G.
Published: January 2023

Leber congenital amaurosis caused by mutations in the RPE65 gene belongs to the most severe early-onset hereditary childhood retinopathies naturally progressing to legal blindness. The novel gene therapy voretigene neparvovec is the first approved causative treatment option for this devastating eye disease and is specifically designed to treat RPE65-mediated retinal dystrophies. Herein, we present a follow-up of the youngest treated patients in Germany so far, including four pre-school children who received treatment with voretigene neparvovec at a single treatment center between January 2020 and May 2022. All patients underwent pars plana vitrectomy with circumferential peeling of the internal limiting membrane at the injection site and subretinal injection of voretigene neparvovec. Pre- and postoperative diagnostics included imaging (spectral domain optical coherence tomography, fundus autofluorescence, fundus wide-angle imaging), electrophysiologic examination (ERG), retinal light sensitivity measurements (FST) and visual acuity testing. Behavioral changes were assessed using a questionnaire and by observing the children’s vision-guided behavior in different levels of illumination. All children showed marked increase in vision-guided behavior shortly after therapy, as well as marked increase in visual acuity in the postoperative course up to full visual acuity in one child. Two eyes showed partial electrophysiological recovery of an ERG that was undetectable before treatment—a finding that has not been described in humans before.
Immunopathogenesis of Immune Checkpoint Inhibitor Induced Myocarditis: Insights from Experimental Models and Treatment Implications
Authors: Wong Chun-Ka , Lam Tsun-Ho , Liao Song-Yan , Lau Yee-Man , Tse Hung-Fat , So Benjamin Y. F.
Published: January 2023

Despite the extraordinary success of immune checkpoint inhibitors (ICIs) in cancer treatment, their use is associated with a high incidence of immune-related adverse events (IRAEs), resulting from therapy-related autoimmunity against various target organs. ICI-induced myocarditis is one of the most severe forms of IRAE, which is associated with risk of hemodynamic compromise and mortality. Despite increasing recognition and prompt treatment by clinicians, there remain significant gaps in knowledge regarding the pathophysiology, diagnosis and treatment of ICI-induced myocarditis. As the newly emerged disease entity is relatively rare, it is challenging for researchers to perform studies involving patients at scale. Alternatively, mouse models have been developed to facilitate research understanding of the pathogenesis of ICI-induced myocarditis and drug discovery. Transgenic mice with immune checkpoint genes knocked out allow induction of myocarditis in a highly reproducible manner. On the other hand, it has not been possible to induce ICI-induced myocarditis in wild type mice by injecting ICIs monotherapy alone. Additional interventions such as combinational ICI, tumor inoculation, cardiac sarcomere immunization, or cardiac irradiation are necessary to mimic the underlying pathophysiology in human cancer patients and to induce ICI-induced myocarditis successfully. This review focuses on the immunopathogenesis of ICI-induced myocarditis, drawing insights from human studies and animal models, and discusses the potential implications for treatment.
A Treatment Decision Support Model for Laryngeal Cancer Based on Bayesian Networks
Authors: Hikal Aisha , Gaebel Jan , Neumuth Thomas , Dietz Andreas , Stoehr Matthaeus
Published: January 2023

The increase in diagnostic and therapeutic procedures in the treatment of oncological diseases, as well as the limited capacity of experts to provide information, necessitates the development of therapy decision support systems (TDSS). We have developed a treatment decision model that integrates available patient information as well as tumor characteristics. They are assessed according to their relevance in evaluating the optimal therapy option. Our treatment model is based on Bayesian networks (BN) which integrate patient-specific data with expert-based implemented causalities to suggest the optimal therapy option and therefore potentially support the decision-making process for treatment of laryngeal carcinoma. To test the reliability of our model, we compared the calculations of our model with the documented therapy from our data set, which contained information on 97 patients with laryngeal carcinoma. Information on 92 patients was used in our analyses and the model suggested the correct treatment in 419 out of 460 treatment modalities (accuracy of 91%). However, unequally distributed clinical data in the test sets revealed weak spots in the model that require revision for future utilization.
Role of Wearable Sensing Technology to Manage Long COVID
Authors: Khondakar Kamil Reza , Kaushik Ajeet
Published: January 2023

Long COVID consequences have changed the perception towards disease management, and it is moving towards personal healthcare monitoring. In this regard, wearable devices have revolutionized the personal healthcare sector to track and monitor physiological parameters of the human body continuously. This would be largely beneficial for early detection (asymptomatic and pre-symptomatic cases of COVID-19), live patient conditions, and long COVID monitoring (COVID recovered patients and healthy individuals) for better COVID-19 management. There are multitude of wearable devices that can observe various human body parameters for remotely monitoring patients and self-monitoring mode for individuals. Smart watches, smart tattoos, rings, smart facemasks, nano-patches, etc., have emerged as the monitoring devices for key physiological parameters, such as body temperature, respiration rate, heart rate, oxygen level, etc. This review includes long COVID challenges for frequent monitoring of biometrics and its possible solution with wearable device technologies for diagnosis and post-therapy of diseases.
Polarized Micro-Raman Spectroscopy and 2D Convolutional Neural Network Applied to Structural Analysis and Discrimination of Breast Cancer
Authors: Shang Linwei , Tang Jinlan , Wu Jinjin , Shang Hui , Huang Xing , Bao Yilin , Xu Zhibing , Wang Huijie , Yin Jianhua
Published: January 2023

Raman spectroscopy has been efficiently used to recognize breast cancer tissue by detecting the characteristic changes in tissue composition in cancerization. In addition to chemical composition, the change in bio-structure may be easily obtained via polarized micro-Raman spectroscopy, aiding in identifying the cancerization process and diagnosis. In this study, a polarized Raman spectral technique is employed to obtain rich structural features and, combined with deep learning technology, to achieve discrimination of breast cancer tissue. The results reconfirm that the orientation of collagen fibers changes from parallel to vertical during breast cancerization, and there are significant structural differences between cancerous and normal tissues, which is consistent with previous reports. Optical anisotropy of collagen fibers weakens in cancer tissue, which is closely related with the tumor’s progression. To distinguish breast cancer tissue, a discrimination model is established based on a two-dimensional convolutional neural network (2D-CNN), where the input is a matrix containing the Raman spectra acquired at a set of linear polarization angles varying from 0° to 360°. As a result, an average discrimination accuracy of 96.01% for test samples is achieved, better than that of the KNN classifier and 1D-CNN that are based on non-polarized Raman spectra. This study implies that polarized Raman spectroscopy combined with 2D-CNN can effectively detect changes in the structure and components of tissues, innovatively improving the identification and automatic diagnosis of breast cancer with label-free probing and analysis.
Assessment of Rhizobium anhuiense Bacteria as a Potential Biocatalyst for Microbial Biofuel Cell Design
Authors: Reinikovaite Viktorija , Zukauskas Sarunas , Zalneravicius Rokas , Ratautaite Vilma , Ramanavicius Simonas , Bucinskas Vytautas , Vilkiene Monika , Ramanavicius Arunas , Samukaite-Bubniene Urte
Published: January 2023

The development of microbial fuel cells based on electro-catalytic processes is among the novel topics, which are recently emerging in the sustainable development of energetic systems. Microbial fuel cells have emerged as unique biocatalytic systems, which transform the chemical energy accumulated in renewable organic fuels and at the same time reduce pollution from hazardous organic compounds. However, not all microorganisms involved in metabolic/catalytic processes generate sufficient redox potential. In this research, we have assessed the applicability of the microorganism Rhizobium anhuiense as a catalyst suitable for the design of microbial fuel cells. To improve the charge transfer, several redox mediators were tested, namely menadione, riboflavin, and 9,10-phenanthrenequinone (PQ). The best performance was determined for a Rhizobium anhuiense-based bio-anode mediated by menadione with a 0.385 mV open circuit potential and 5.5 μW/cm2 maximal power density at 0.35 mV, which generated 50 μA/cm2 anode current at the same potential.