bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and prognostic efficacy of optic nerve sheath diameter in patients with dysnatremia
Authors: Kuru Berika Kavaz , Baydın Ahmet , Ocak Metin , Aksoy İskender
Published: February 2024

Aim: This study aimed to investigate the diagnostic and prognostic value of optic nerve sheath diameter (ONSD) measurement in patients with dysnatremia.Material and methods: This prospective clinical study included patients aged ≥18 years who were diagnosed with dysnatremia on admission to the emergency department.Results: The present study included 65 patients (35 with hypernatremia [hypernatremia group] and 30 with hyponatremia [hyponatremia group]) and 14 healthy volunteers (control group). Comparison of these groups in terms of ONSD revealed that the right and left ONSDs were significantly higher in the hypernatremia and hyponatremia groups comparing to the control group (p<0.001). According to the optimal cutoff values determined, the right ONSD detected hypernatremia with 91.4% sensitivity and 92.9% specificity and the left ONSD detected the condition with 88.6% sensitivity and 85.7% specificity. Furthermore, the right ONSD detected hyponatremia with 83.3% sensitivity and 92.9% specificity, and the left ONSD detected it with 93.0% sensitivity and 86.0% specificity. Finally, ONSD was found to be an independent predictor of mortality in patients with hypernatremia.Conclusion: ONSD is a noninvasive, easy, cheap, and reproducible measurement and can be used as an effective and powerful tool for the diagnosis of patients with dysnatremia and the prognosis of patients with hypernatremia.
Active design of diffuse acoustic fields in enclosures
Authors: Aquino Wilkins , Rouse Jerry , Bonnet Marc
Published: February 2024

This paper presents a numerical framework for designing diffuse fields in rooms of any shape and size, driven at arbitrary frequencies. That is, we aim at overcoming the Schroeder frequency limit for generating diffuse fields in an enclosed space. We formulate the problem as a Tikhonov regularized inverse problem and propose a low-rank approximation of the spatial correlation that results in significant computational gains. Our approximation is applicable to arbitrary sets of target points and allows us to produce an optimal design at a computational cost that grows only linearly with the (potentially large) number of target points. We demonstrate the feasibility of our approach through numerical examples where we approximate diffuse fields at frequencies well below the Schroeder limit.
Sensitizing methicillin-resistant
Staphylococcus aureus
(MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine
Authors: Ersoy Selvi C. , Proctor Richard A. , Rose Warren E. , Abdelhady Wessam , Fan Sook-Ha , Madrigal Sabrina L. , Elsayed Ahmed M. , Chambers Henry F. , Sobral Rita G. , Bayer Arnold S.
Published: February 2024

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains are a major challenge for clinicians due, in part, to their resistance to most β-lactams, the first-line treatment for methicillin-susceptible
S. aureus
. A phenotype termed “NaHCO
3
-responsiveness” has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care β-lactams in the presence of physiologically relevant concentrations of NaHCO
3
,
in vitro
and
ex vivo
; moreover, such “NaHCO
3
-responsive” isolates can be effectively cleared by β-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO
3
exposure on NaHCO
3
-responsive MRSA is to repress WTA synthesis. This NaHCO
3
effect mimics the phenotype of
tarO
-deficient MRSA, including sensitization to the PBP2-targeting β-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO
3
exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO
3
and/or TCP enhanced susceptibility to CFX
in vitro
, by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an
ex vivo
simulated endocarditis vegetations (SEV) model, in NaHCO
3
-responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO
3
), pre-exposure to TCP prior to infection sensitized the NaHCO
3
-responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO
3
is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific β-lactam agents.
Molecular diagnosis of Cytomegalovirus infection: clinical performance of the Aptima transcription-mediated amplification assay toward conventional qPCR chemistry on whole blood samples
Authors: Bottino Paolo , Pastrone Lisa , Zanotto Elisa , Sidoti Francesca , Cavallo Rossana , Costa Cristina
Published: February 2024

Human Cytomegalovirus (HCMV) infection is life-threatening for immunocompromised patients. Quantitative molecular assays on whole blood or plasma are the gold standard for the diagnosis of invasive HCMV infection and for monitoring antiviral treatment in individuals at risk of HCMV disease. For these reasons, an accurate standardization toward the WHO 1st International Standard among different centers and diagnostic kits represents an effort for better clinical management of HCMV-positive patients. Herein, we evaluate, for the first time, the performance of a new transcription-mediated amplification (TMA) assay versus quantitative polymerase chain reaction (qPCR) chemistry, used as a routine method, on whole blood samples. A total of 755 clinical whole blood specimens were collected and tested simultaneously with TMA and qPCR assays. The data showed a qualitative agreement of 99.27% for positive quantified samples and 89.39% for those undetected between the two tested methods. Evaluation of viremia in positive samples highlighted a good correlation between TMA and qPCR chemistries in terms of International Units (ΔLog
10
IU/mL: −0.29 ± 0.40). The TMA assay showed a significant correlation with qPCR in patients monitored for up to 3 months, thus allowing an accurate assessment of viremia in transplant patients. Therefore, TMA chemistry showed good agreement with qPCR testing, used as a current diagnostic routine. It also offers important advantages, such as FDA approval on plasma and
In Vitro
Diagnostic (IVD) on both plasma and whole blood, automated workflow with minimal hands-on time, and random access loading, thus enabling a rapid and reliable diagnostic in HCMV-infected patients.

IMPORTANCE

In this paper, we describe the clinical performance of a novel transcription-mediated amplification (TMA) assay for the detection and quantification of human Cytomegalovirus (HCMV) DNA from whole blood samples. This is a pivotal analysis in immunocompromised patients [transplanted, HIV-positive, and Hematopoietic Stem Cell (HSC) recipients], and molecular tests with high sensitivity and specificity are necessary to evaluate the HCMV viral load in these patients. To our knowledge, this is the first in-depth evaluation of TMA chemistry for HCMV diagnosis on whole blood samples. Moreover, also technical aspects of this assay make it suitable for clinical diagnostics.
Lyssavirus M protein degrades neuronal microtubules by reprogramming mitochondrial metabolism
Authors: Yuan Yueming , Fang An , Wang Haoran , Wang Caiqian , Sui Baokun , Zhao Jianqing , Fu Zhen F. , Zhou Ming , Zhao Ling
Published: February 2024

Infection with neurotropic viruses may result in changes in host behavior, which are closely associated with degenerative changes in neurons. The lyssavirus genus comprises highly neurotropic viruses, including the rabies virus (RABV), which has been shown to induce degenerative changes in neurons, marked by the self-destruction of axons. The underlying mechanism by which the RABV degrades neuronal cytoskeletal proteins remains incomplete. In this study, we show that infection with RABV or overexpression of its M protein can disrupt mitochondrial metabolism by binding to Slc25a4. This leads to a reduction in NAD
+
production and a subsequent influx of Ca
2+
from the endoplasmic reticulum and mitochondria into the cytoplasm of neuronal cell lines, activating Ca
2+
-dependent proteinase calpains that degrade α-tubulin. We further screened the M proteins of different lyssaviruses and discovered that the M protein of the dog-derived RABV strain (DRV) does not degrade α-tubulin. Sequence analysis of the DRV M protein and that of the lab-attenuated RABV strain CVS revealed that the 57th amino acid is vital for M-induced microtubule degradation. We generated a recombinant RABV with a mutation at the 57th amino acid position in its M protein and showed that this mutation reduces α-tubulin degradation
in vitro
and axonal degeneration
in vivo
. This study elucidates the mechanism by which lyssavirus induces neuron degeneration.

IMPORTANCE

Previous studies have suggested that RABV (rabies virus, the representative of lyssavirus) infection induces structural abnormalities in neurons. But there are few articles on the mechanism of lyssavirus’ effect on neurons, and the mechanism of how RABV infection induces neurological dysfunction remains incomplete. The M protein of lyssavirus can downregulate cellular ATP levels by interacting with Slc25a4, and this decrease in ATP leads to a decrease in the level of NAD
+
in the cytosol, which results in the release of Ca
2+
from the intracellular calcium pool, the endoplasmic reticulum, and mitochondria. The presence of large amounts of Ca
2+
in the cytoplasm activates Ca
2+
-dependent proteases and degrades microtubule proteins. The amino acid 57 of M protein is the key site determining its disruption of mitochondrial metabolism and subsequent neuron degeneration.
Two complete 1918 influenza A/H1N1 pandemic virus genomes characterized by next-generation sequencing using RNA isolated from formalin-fixed, paraffin-embedded autopsy lung tissue samples along with evidence of secondary bacterial co-infection
Authors: Xiao Yongli , Sheng Zong-Mei , Williams Stephanie L. , Taubenberger Jeffery K.
Published: February 2024

The 1918 influenza pandemic was the most devastating respiratory pandemic in modern human history, with 50–100 million deaths worldwide. Here, we characterized the complete genomes of influenza A virus (IAV) from two fatal cases during the fall wave of 1918 influenza A (H1N1) pandemic in the United States, one from Walter Reed Army Hospital in Washington, DC, and the other from Camp Jackson, SC. The two complete IAV genomes were obtained by combining Illumina deep sequencing data from both total RNA and influenza viral genome-enriched libraries along with Sanger sequencing data from PCR across the sequencing gaps. This study confirms the previously reported 1918 IAV genomes and increases the total number of available complete or near-complete influenza viral genomes of the 1918 pandemic from four to six. Sequence comparisons among them confirm that the genomes of the 1918 pandemic virus were highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases. Interestingly, in the Washington, DC, case, evidence is presented of the first reported
Rhodococcus
-influenza virus co-infection.

IMPORTANCE

This study applied modern molecular biotechnology and high-throughput sequencing to formalin-fixed, paraffin-embedded autopsy lung samples from two fatal cases during the fall wave of the 1918 influenza A (H1N1) pandemic in the United States. Complete influenza genomes were obtained from both cases, which increases the total number of available complete or near-complete influenza genomes of the 1918 pandemic virus from four to six. Sequence analysis confirms that the 1918 pandemic virus was highly conserved during the main wave of the pandemic with geographic separation in North America and Europe. Metagenomic analyses revealed bacterial co-infections in both cases, including the first reported evidence of
Rhodococcus
-influenza co-infection. Overall, this study offers a detailed view at the molecular level of the very limited samples from the most devastating influenza pandemic in modern human history.
The effect of site-specific recombinases XerCD on the removal of over-replicated chromosomal DNA through outer membrane vesicles in bacteria
Authors: Mansky Johannes , Wang Hui , Wagner-Döbler Irene , Tomasch Jürgen
Published: February 2024

Outer membrane vesicles (OMVs) are universally produced by Gram-negative bacteria and play important roles in symbiotic and pathogenic interactions. The DNA from the lumen of OMVs from the Alphaproteobacterium
Dinoroseobacter shibae
was previously shown to be enriched for the region around the terminus of replication
ter
and specifically for the recognition sequence
dif
of the two site-specific recombinases XerCD. These enzymes are highly conserved in bacteria and play an important role in the last phase of cell division. Here, we show that a similar enrichment of
ter
and
dif
is found in the DNA inside OMVs from
Prochlorococcus marinus
,
Pseudomonas aeruginosa, Vibrio cholerae,
and
Escherichia coli
. The deletion of
xerC
or
xerD
in
E. coli
reduced the enrichment peak directly at the
dif
sequence, while the enriched DNA region around
ter
became broader, demonstrating that either enzyme influences the DNA content inside the lumen of OMVs. We propose that the intra-vesicle DNA originated from over-replication repair and the XerCD enzymes might play a role in this process, providing them with a new function in addition to resolving chromosome dimers.

IMPORTANCE

Imprecise termination of replication can lead to over-replicated parts of bacterial chromosomes that have to be excised and removed from the dividing cell. The underlying mechanism is poorly understood. Our data show that outer membrane vesicles (OMVs) from diverse Gram-negative bacteria are enriched for DNA around the terminus of replication
ter
and the site-specific XerCD recombinases influence this enrichment. Clearing the divisome from over-replicated parts of the bacterial chromosome might be a so far unrecognized and conserved function of OMVs.
Detection of resistance to macrolides and fluoroquinolones in
Mycoplasma genitalium
by targeted next-generation sequencing
Authors: Chiribau Calin B. , Schmedes Sarah , Dong Yibo , Tarigopula Namratha , Tekin Omer , Cannons Andrew , Roberts Jill , Haiduven Donna , Crowe Susanne R.
Published: February 2024

Mycoplasma genitalium
is fastidious to culture, and its detection in human clinical specimens relies mainly on molecular methods. Phenotypic determination of antibiotic susceptibility for this bacterium is not a timely or feasible option for most clinical laboratories. This study sought to determine whether next-generation sequencing technologies can effectively be employed in determining genetic mutations associated with drug resistance in
M. genitalium
samples collected in Aptima Hologic tubes and possibly integrating them into viable workflows in public health laboratories. Following analysis by a custom-designed bioinformatics pipeline, at least one mutation/sample has been identified in 94/98 specimens in at least one of seven loci (macrolides:
rrl
,
rplD
,
rplV
; fluoroquinolones:
parC
,
parE
,
gyrA
,
gyrB
) described previously to be connected to antibiotic resistance. This method identified a total of 469 single nucleotide polymorphisms (SNPs) (452 mutations): 134 of 23S rRNA SNPs and 318 amino acid mutations: 114 substitutions and 204 synonymous; the turnaround time (sample to analyzed sequence) was typically 3 days. The assays and workflows described in this work demonstrated that the determination of a drug resistance profile for macrolides and fluoroquinolones of
M. genitalium
samples by using next-generation sequencing in clinical samples is a feasible approach that can be implemented in clinical laboratories, following thorough and extensive validation studies.

IMPORTANCE

The mechanisms of drug resistance in
Mycoplasma genitalium
are complex and involve several genetic loci. The molecular methods for accurately characterizing resistance to fluoroquinolones and macrolides in this organism are often not available or approved for patient use and do not cover all genetic determinants. To this end, we propose a next-generation sequencing-based method with a turnaround time of 3 days that includes the investigation of all drug resistance loci of
M. genitalium
. Following adaptation, validation, and verification for routine clinical use, assays based on this method may yield molecular results that can be used to guide proper treatment regimens and for surveillance of drug resistance in the general population.
Liquid biopsy approach to monitor the efficacy and response to CAR-T cell therapy
Authors: Shishido Stephanie N , Hart Olivia , Jeong Sujin , Moriarty Aidan , Heeke Darren , Rossi John , Bot Adrian , Kuhn Peter
Published: February 2024

Background

Chimeric antigen receptor (CAR)-T cells are approved for use in the treatment of hematological malignancies. Axicabtagene ciloleucel (YESCARTA) and brexucabtagene autoleucel (TECARTUS) genetically modified autologous T cells expressing an anti-CD19 scFv based on the FMC63 clone have shown impressive response rates for the treatment of CD19+B cell malignancies, but there remain challenges in monitoring long-term persistence as well as the functional characterization of low-level persisting CAR-T cells in patients. Furthermore, due to CD19-negative driven relapse, having the capability to monitor patients with simultaneous detection of the B cell malignancy and persisting CAR-T cells in patient peripheral blood is important for ensuring timely treatment optionality and understanding relapse.

Methods

This study demonstrates the development and technical validation of a comprehensive liquid biopsy, high-definition single cell assay (HDSCA)-HemeCAR for (1) KTE-X19 CAR-T cell identification and analysis and (2) simultaneously monitoring the CD19-epitope landscape on neoplastic B cells in cryopreserved or fresh peripheral blood. Proprietary anti-CD19 CAR reagents, healthy donor transduced CAR-T cells, and patient samples consisting of malignant B cell fractions from manufacturing were used for assay development.

Results

The CAR-T assay showed an approximate limit of detection at 1 cell in 3 million with a sensitivity of 91%. Genomic analysis was additionally used to confirm the presence of the CAR transgene. This study additionally reports the successful completion of two B cell assays with multiple CD19 variants (FMC63 and LE-CD19) and a unique fourth channel biomarker (CD20 or CD22). In patient samples, we observed that CD19 isoforms were highly heterogeneous both intrapatient and interpatient.

Conclusions

With the simultaneous detection of the CAR-T cells and the B cell malignancy in patient peripheral blood, the HDSCA-HemeCAR workflow may be considered for risk monitoring and patient management.
Apparent migration and natal homing of a small minnow in a large ancient lake
Authors: Kikko Takeshi , Sato Takuya , Kanaiwa Minoru , Ishizaki Daisuke , Kuwamura Kunihiko , Okamoto Haruo , Ide Atsuhiko , Nemoto Morihito , Takeoka Shoichiro , Kai Yoshiaki , Nakayama Kouji , Fujioka Yasuhiro
Published: February 2024

Migratory freshwater fish species are particularly susceptible to population decline because they rely on multiple habitats and open passages to complete their life cycle. Understanding the migratory patterns of cyprinids is thus essential for their management and conservation. Gnathopogon caerelescens, a small cyprinid species endemic to Lake Biwa (Japan), is one of the most important targets of inland fisheries. However, their abundance has dramatically decreased. By using an extensive alizarin complexone-mark-and-recapture program for of G. caerelescens juveniles, together with the collaboration of commercial fishermen, this cyprinid fish was demonstrated as: (1) migrating from a nursery lagoon toward the main lake and moving along the near-shore from spring to autumn; (2) migrating from the near-shore shallow habitats to off-shore deep habitats from autumn to winter; and (3) migrating to a nursery lagoon from off-shore deep habitats from winter to spring. These results highlighted the importance of protecting individual spawning/nursery habitats, and maintaining connectivity between each spawning/nursery habitat and the lake system.
Three-family supersymmetric Pati–Salam models with symplectic groups from intersecting D6-branes
Authors: Mansha Adeel , Li Tianjun , Sabir Mudassar , Wu Lina
Published: February 2024

We construct new three-family $${{\mathcal {N}}}=1$$

N
=
1

supersymmetric Pati–Salam models from intersecting D6-branes with original gauge group $$\textrm{U}(4)_C \times \textrm{USp}(2)_L \times \textrm{U}(2)_R$$

U

(
4
)

C

×
USp

(
2
)

L

×
U

(
2
)

R

on a Type IIA $${\mathbb {T}}^6/({\mathbb {Z}}_2\times {\mathbb {Z}}_2)$$

T

6

/

(

Z
2

×

Z
2

)

orientifold. We find that replacing a $$\textrm{U}(2)$$

U
(
2
)

with a $$\textrm{USp}(2)$$

USp
(
2
)

group severely restricts the number of three-generation supersymmetric models such that there are only five inequivalent models. Exchanging the left and right sectors, we obtain five dual models with gauge group $$\textrm{U}(4)_C \times \textrm{U}(2)_L \times \textrm{USp}(2)_R$$

U

(
4
)

C

×
U

(
2
)

L

×
USp

(
2
)

R

. These ten models have different gauge coupling relations at string scale. The highest wrapping number is 4, and one of the models contains no filler O6-planes. Moreover, we discuss in detail the particle spectra, the composite particles through strong coupling dynamics, and the exotic particle decouplings. Also, we study how to realize the string-scale gauge coupling relations in some models.
Mechanisms driving fasting-induced protection from genotoxic injury in the small intestine
Authors: Deans-Fielder Kali , Wu Timothy , Nguyen Thanh , To Sarah , Huang Yang-Zhe , Bark Steven J. , Mills Jason C. , Shroyer Noah F.
Published: February 2024

New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting’s crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.
Astragaloside IV Protects against Shear Stress‐Induced Glycocalyx Damage and Alleviates Abdominal Aortic Aneurysm by Regulating miR‐17‐3p/Syndecan‐1
Authors: Li Guojian , Yang Qionghui , Luo Kaikai , Xu Ankou , Hou Lijuan , Li Zhaoxiang , Du Lingjuan
Published: February 2024

Background. The present study aimed to analyze the impact of astragaloside IV (AS‐IV) on abdominal aortic aneurysm (AAA) and the glycocalyx, elucidating the potential mechanism of AS‐IV. Methods. Rat models of AAA were established using porcine pancreatic elastase. The effects of intraperitoneal AS‐IV injection on the morphology, diameter, and glycocalyx of the aorta and the expression of miR‐17‐3p and Syndecan‐1 (SDC1) protein were examined. Differentially expressed miRNAs from peripheral blood samples of healthy individuals, untreated patients with AAA, and treated patients with AAA were identified through sequencing. The relationship between miR‐17‐3p and SDC1 was validated using a dual‐luciferase reporter assay. In vitro, shear stress was induced in human aortic endothelial cells (HAECs) to simulate AAA. Overexpression of miR‐17‐3p was performed to assess the effects of AS‐IV on miR‐17‐3p and SDC1 expressions, apoptosis, and glycocalyx in HAECs. Results. AS‐IV mitigated aortic damage in AAA rats, reducing the aortic diameter and alleviating glycocalyx damage. In addition, it suppressed the increase in miR‐17‐3p expression and promoted SDC1 expression in AAA rats. Peripheral blood miR‐17‐3p levels were significantly higher in patients with AAA than in healthy individuals. miR‐17‐3p inhibited the SDC1 protein expression in HAECs. In the in vitro AAA environment, miR‐17‐3p was upregulated and SDC1 was downregulated in HAECs. AS‐IV inhibited miR‐17‐3p expression, promoted SDC1 expression, and mitigated shear stress‐induced apoptosis and glycocalyx damage in HAECs. Overexpression of miR‐17‐3p blocked AS‐IV–induced SDC1 expression promotion, glycocalyx protection, and apoptosis suppression in HAECs. Conclusion. miR‐17‐3p may damage the glycocalyx of aortic endothelial cells by targeting SDC1. AS‐IV may promote SDC1 expression by inhibiting miR‐17‐3p, thereby protecting the glycocalyx and alleviating AAA.
Chronic Ultrasound Prenatal Stress Altered the Brain’s Neurochemical Systems in Newborn Rats
Authors: Abramova Olga , Zorkina Yana , Pavlov Konstantin , Ushakova Valeria , Morozova Anna , Zubkov Eugene , Pavlova Olga , Storozheva Zinaida , Gurina Olga , Chekhonin Vladimir
Published: February 2024

Prenatal stress (PS) affects the development and functioning of the central nervous system, but the exact mechanisms underpinning this effect have not been pinpointed yet. A promising model of PS is one based on chronic exposure of pregnant rodents to variable-frequency ultrasound (US PS), as it mimics the PS with a psychic nature that most adequately captures the human stressors in modern society. The aim of this study was to investigate the effects of US PS on the brain neurotransmitter, neuropeptide, and neurotrophic systems of newborn Wistar rats. We determined the concentration of neurotransmitters and their metabolites (serotonin, HIAA, dopamine, DOPAC, and norepinephrine), neuropeptides (α-MSH, β-endorphin, neurotensin, oxytocin, and substance P), and the neurotrophin brain-derived neurotrophic factor (BDNF) in rat brain tissues by HPLC-ED, ELISA, and multiplex ELISA. Correlation analysis and principal component analysis (PCA) were used to get a sense of the relationship between the biochemical parameters of the brain. The results demonstrated that US PS increases the concentration of serotonin (p=0.004) and DOPAC (p=0.04) in the hippocampus has no effect on the neurotransmitter systems of the frontal cortex, reduces the concentration of BDNF in the entirety of the brain of males (p=0.008), and increases the neuropeptides α-MSH (p=0.02), β-endorphin (p=0.01), oxytocin (p=0.008), and substance P (p<0.001) in the entire brain. A degree of complexity in the neurotransmitter system network in the frontal cortex and network change in the hippocampus after exposure to US PS have been observed. PCA revealed a similar pattern of neurotransmitter system interactions in the frontal cortex and hippocampus in males and females after exposure to US PS. We suggest that US PS can alter neurodevelopment, which is mediated by changes in the studied neurochemical systems that thus affect the behavioral phenotype in animals.
Pod Production Dynamics and Pod Size Distribution of Theobroma cacao L. Clone CCN 51 in Full Sunlight
Authors: Jaimez Ramón E. , Barragan Luigy , Fernández-Niño Miguel , Larreal B Oswaldo J. , Flores Byron
Published: February 2024

Cacao fruit production dynamics vary from one location to another and are conditioned by the number of pods produced per tree. During cocoa pod development, the strength of the carbon sink varies depending on the demand exerted by the pods, which is proportional to the size. The relationship between cocoa pod production dynamics and size distribution is still poorly understood. Dissecting this relationship is an important step toward further improving cocoa crop management. In this study, the annual yield dynamics and quantity of cocoa pods produced by popular, highly productive, and widespread clone CCN 51 were investigated, based on six size classes observed during its fructification. Growth parameters were determined as weekly increments of pod length and diameter, whereas daily increments were estimated using the logistic Richards model. The fruiting cycle was characterized by the coexistence of fruits of various sizes where the number of pods belonging to each size class changes throughout the fruiting season. Fruit production varied following a seasonal pattern, reaching a maximum of 36 pods/tree, in trees cultivated in full sunlight, of which approximately 55% matured and were harvested. The peak carbon sink demand occurs when the tree pods have the highest numbers of pods. During this period, 65% of the pods had lengths between 5 and 15 cm, which corresponds to the period of the highest pod growth rate. The average length values of the harvested pods were generally below 23 cm and rarely exceeded 7 pods/tree. The Richard model proved to describe accurately the pod growth rates for CCN 51. This represents a promising tool to determine pod growth in other cultivars of relevance for the cocoa industry, which is essential to improve cocoa crop management.
Transcanthal Canthopexy for Involutional Lower Eyelid Entropion Corrects Horizontal Laxity
Authors: Kono Shinjiro , Kamei Motohiro
Published: February 2024

In this prospective observational study, we aimed to examine improvements in horizontal laxity after lower eyelid retractor advancement and transcanthal canthopexy for involutional lower eyelid entropion. The study included 19 sides in 15 patients with involutional entropion who underwent transcanthal canthopexy with the advancement of the lower eyelid retractor. Using the pinch test, the distance from the lowest part of the corneal limbus to the eyelid margin was measured using callipers. All measurements were performed preoperatively and at postoperative 3 and 6 months. Using the pinch test, the distance from the lowest part of the corneal limbus to the lower eyelid margin was significantly shortened during each postoperative follow-up period. None of the included cases experienced recurrence. Our results indicated that transcanthal canthopexy could preserve postoperative horizontal tightness.
Medical Image Description Based on Multimodal Auxiliary Signals and Transformer
Authors: Tan Yun , Li Chunzhi , Qin Jiaohua , Xue Youyuan , Xiang Xuyu
Published: February 2024

Medical image description can be applied to clinical medical diagnosis, but the field still faces serious challenges. There is a serious problem of visual and textual data bias in medical datasets, which are the imbalanced distribution of health and disease data. This can greatly affect the learning performance of data-driven neural networks and finally lead to errors in the generated medical image descriptions. To address this problem, we propose a new medical image description network architecture named multimodal data-assisted knowledge fusion network (MDAKF), which introduces multimodal auxiliary signals to guide the Transformer network to generate more accurate medical reports. In detail, audio auxiliary signals provide clear abnormal visual regions to alleviate the visual data bias problem. However, the audio modality signals with similar pronunciation lack recognizability, which may lead to incorrect mapping of audio labels to medical image regions. Therefore, we further fuse the audio with text features as the auxiliary signal to improve the overall performance of the model. Through the experiments on two medical image description datasets, IU-X-ray and COV-CTR, it is found that the proposed model is superior to the previous models in terms of language generation evaluation indicators.
Electromechanical Coupling Model for Ionic Liquid Gel Soft Actuators
Authors: Zhang Chenghong , Zhang Chengguang , Tian Guangping , Gu Xun
Published: February 2024

A soft robot is composed of soft materials, which exhibit continuous deformation and driving structure integration and can arbitrarily change shapes and sizes over wide ranges. It shows strong adaptability to unstructured environments and has broad application prospects in military reconnaissance, medical rescues, agricultural production, etc. Soft robots based on ionic electroactive polymers (EAPs) have low-driving voltages, large-actuation displacements, fast responses, light weights, and low powers and have become a hot research field of bionic robots. Ionic liquid gels (ILGs) are new ionic EAPs. In this study, a new soft actuator was designed based on an ILG, and the electromechanical coupling model of an ILG soft actuator was studied in detail. Based on the system transfer function method, a mechatronic coupling model for the soft actuator was developed. According to the material characteristics and current response law of the ILG-containing EAP, an equivalent circuit model was used to describe transfer of the output current and input voltage. Based on the equivalent transformer model for ionic polymer–metal composite (IPMC) actuators proposed by Claudia Bonomo, the electromechanical coupling equation and a driving equation of the ILG soft actuator were established. The least-squares method was used with the coupling model of an ILG soft actuator to identify the system parameters for the model, and the effects of the structural parameters on the end displacement and driving force of the soft actuator were analyzed.
Nursing Instructors’ and Students’ Experiences of Transition from Face-to-Face Education to Virtual Education during the Coronavirus Disease 2019 Pandemic
Authors: Salehpoor-Emran Mohammad , Ghorbani Azam , Abbasi Dolatabadi Zahra , Delkhosh Marjan
Published: February 2024

Introduction. The coronavirus disease 2019 (COVID-19) pandemic necessitated the suspension of most educational activities and a shift from face-to-face (FTF) education to virtual education (VE). These changes were associated with new educational experiences for both instructors and students. This study aimed to explore nursing instructors’ and students’ experiences of VE during the COVID-19 pandemic. Method. This descriptive qualitative study was carried out in 2021. Participants were 21 bachelor’s, master’s, and Ph.D. nursing students and six nursing instructors purposively selected from the Faculty of Nursing and Midwifery of Tehran University of Medical Sciences, Tehran, Iran. Data were gathered through FTF or online in-depth semistructured interviews and were analyzed through conventional qualitative content analysis as proposed by Graneheim and Lundman (2004). Results. Eight subthemes and three main themes were developed during data analysis. The main themes and subthemes were VE as a double-edged sword (VE as a threat, VE as an opportunity, and necessity to improve VE), weaknesses in clinical education (reduced quality of clinical education and necessity to compensate for students’ retarded clinical learning), and reduced reliability of virtual student evaluation (cheating as a problem of virtual evaluation, stresses and tensions of virtual evaluation, and necessity to use new strategies in virtual evaluation). Conclusion. Despite the different shortcomings and challenges of VE during the COVID-19 pandemic, educational experiences gained in this period can be used to improve the quality of nursing VE in future epidemics and pandemics.
Supplementary Table 6 from EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas
Authors: DuCote Tanner J. , Song Xiulong , Naughton Kassandra J. , Chen Fan , Plaugher Daniel R. , Childress Avery R. , Gellert Abigail R. , Skaggs Erika M. , Qu Xufeng , Liu Jinze , Liu Jinpeng , Li Fei , Wong Kwok-Kin , Brainson Christine F.
Published: February 2024

Supplementary Table 6 shows gene highly expressed in each of the 4 neutrophil clusters called in the single cell RNA-sequencing from murine lung and lung squamous cell carcinoma samples.
Supplementary Figure 3 from EZH2 Inhibition Promotes Tumor Immunogenicity in Lung Squamous Cell Carcinomas
Authors: DuCote Tanner J. , Song Xiulong , Naughton Kassandra J. , Chen Fan , Plaugher Daniel R. , Childress Avery R. , Gellert Abigail R. , Skaggs Erika M. , Qu Xufeng , Liu Jinze , Liu Jinpeng , Li Fei , Wong Kwok-Kin , Brainson Christine F.
Published: February 2024

Supplementary Figure 3 shows changes in gene expression and Gene Set Enrichment Analysis in lung squamous cell carcinoma tumoroids in response to EZH2 inhibitor and interferon-gamma treatment.
Artificial Intelligence in Heart Failure and Acute Kidney Injury: Emerging Concepts and Controversial Dimensions
Authors: Cheungpasitporn Wisit , Thongprayoon Charat , Kashani Kianoush B.
Published: February 2024

Background: The growing complexity of patient data and the intricate relationship between heart failure (HF) and acute kidney injury (AKI) underscore the potential benefits of integrating artificial intelligence (AI) and machine learning into healthcare. These advanced analytical tools aim to improve the understanding of the pathophysiological relationship between kidney and heart, provide optimized, individualized, and timely care, and improve outcomes of HF with AKI patients.
Summary: This comprehensive review article examines the transformative potential of AI and machine learning solutions in addressing the challenges within this domain. The article explores a range of methodologies, including supervised and unsupervised learning, reinforcement learning, and AI-driven tools like chatbots and large language models. We highlight how these technologies can be tailored to tackle the complex issues prevalent among HF patients with AKI. The potential applications identified span predictive modeling, personalized interventions, real-time monitoring, and collaborative treatment planning. Additionally, we emphasize the necessity of thorough validation, the importance of collaborative efforts between cardiologists and nephrologists, and the consideration of ethical aspects. These factors are critical for the effective application of AI in this area.
Key Messages: As the healthcare field evolves, the synergy of advanced analytical tools and clinical expertise holds significant promise to enhance the care and outcomes of individuals who deal with the combined challenges of HF and AKI.
КЛІНІКО-ФУНКЦІОНАЛЬНІ АСПЕКТИ У ХВОРИХ НА МІОКАРДИТ ІЗ СЕРЦЕВОЮ НЕДОСТАТНІСТЮ
Authors: Миндзів К. В. , Ярема Н. І.
Published: February 2024

РЕЗЮМЕ. Міокардит, що належить до групи запальних захворювань серцевого м’яза, за оцінкою Всесвітньої федерації серця, є однією з провідних причин раптової смерті, дилатаційної кардіоміопатії та застійної серцевої недостатності.
Мета – проаналізувати клінічні прояви хронічного міокардиту в дорослих пацієнтів різного віку та статі, залежно від фракції викиду, а також дослідити динаміку маркерів запалення і лізису кардіоміоцитів, серцевої недостатності та їх зв’язок із фактором росту фібробластів FGF-23.
Матеріал і методи. В обстеження включили 65 хворих з хронічним міокардитом, які перебували на стаціонарному лікуванні в кардіологічному відділенні та амбулаторному лікуванні в кардіодиспансері Тернопільської обласної клінічної лікарні впродовж 2019–2022 років. Хворим проводили клініко-анамнестичне та лабораторно-інструментальне обстеження. Статистичну обробку отриманих результатів досліджень здійснювали з використанням сформованої бази даних обстежених пацієнтів у програмі StatSoft Statistica v 10.0.
Результати. У хворих на хронічний міокардит із помірно зниженою та зниженою ФВ ЛШ запальний синдром проявлявся зростанням ШОЕ і фібриногену порівняно з контрольною групою. Цитолітичний синдром проявлявся достовірним підвищенням КФК-МВ у всіх груп обстежених пацієнтів із хронічним міокардитом, незалежно від величини ФВ ЛШ, а підвищення тропоніну Т, порівняно з контролем, було достовірним лише у групі хворих на ХМ із помірно зниженою і зниженою ФВ ЛШ. Установлена пряма достовірна кореляція FGF-23 з СРП (r=0,410513, р=0,001) та з фібриногеном (r=0,462285, р=0,001), що підтверджує роль хронічного запального процесу в активації профіброзних процесів у міокарді. У хворих на хронічний міокардит виявлена пряма достовірна кореляція середньої сили між FGF-23 і NT-proBNP (r=0,495400, р=0,0001), що відображає участь профіброзних процесів у прогресуванні серцевої недостатності.
МАРКЕРИ КІСТКОВОГО ОБМІНУ В ЛІКУВАННІ ТА КОНТРОЛІ КОМПЛЕКСНОЇ ТЕРАПІЇ ГЕНЕРАЛІЗОВАНОГО ПАРОДОНТИТУ
Authors: Горб-Гаврильченко І. В.
Published: February 2024

РЕЗЮМЕ. Пошук та обґрунтування застосування засобів патогенетичної терапії, диференційоване призначення лікарських засобів відповідно до клініки пародонтиту, стоматологічного статусу та загальносоматичного стану хворих є основним напрямком сучасної пародонтології. Відомо, що одним із основних показників ефективності лікування генералізованого пародонтиту є віддалені результати після проведеного лікування, які дають об’єктивну інформацію про кількісні та якісні зміни клінічних та параклінічних ознак стану тканин пародонта, дозволяють судити про наявність або відсутність клініко-рентгенологічної стабілізації.
Мета – оцінити ефективність лікування генералізованого пародонтиту в жінок після оваріоектомії за станом процесів ремоделювання кісткової тканини.
Матеріал і методи. Було проведено клініко-рентгенологічне дослідження тканин пародонта та лабораторне дослідження маркерів кісткового метаболізму в 60 жінок, що перенесли оваріоектомію та страждають на генералізований пародонтит.
Результати. У віддалені терміни після проведеного лікування спостерігалося зниження індексу активності остеопорозу в усіх групах спостереження. Позитивна динаміка індексу остеопорозного процесу в альвеолярному відростку означала гальмування підвищених резорбтивних процесів та посилення остеогенезу. Про нормалізацію кісткового обміну свідчили і зниження показників оксипроліну та підвищення рівнів остеокальцину в пацієнтів першої та другої груп спостереження.
Висновок. Результати дослідження підтверджують необхідність виділення трьох форм активності остеопорозного процесу в альвеолярній кістці, для подальшого диференційованого підходу в комплексному лікуванні генералізованого пародонтиту. Жінкам з малоактивними вогнищами остеопорозного процесу в альвеолярному відростку доцільне застосування Кальцій-D3 Нікомеду. За наявності середньоактивних та активних вогнищ остеопорозу в кісткових структурах пародонта доцільнішим є призначення препаратів кальцію та антирезорбтивних засобів у комплексі з препаратами, які нормалізують гормональний фон. Зважаючи на встановлені особливості розроблено та апробовано комплексний патогенетично обґрунтований метод лікування генералізованого пародонтиту в даного контингенту хворих. Він передбачає, поряд із засобами базової терапії, призначення Кальцій-D3 Нікомед, Фосамакса та Прогінова.
ЯКІСТЬ ЖИТТЯ ПАЦІЄНТІВ З ПЕРВИННИМ ОСТЕОАРТРОЗОМ У КОМОРБІДНОСТІ ЗІ ЗАХВОРЮВАННЯМИ, ЯКІ СУПРОВОДЖУЮТЬСЯ ЕКЗОКРИННОЮ НЕДОСТАТНІСТЮ ПІДШЛУНКОВОЇ ЗАЛОЗИ
Authors: Галабіцька І. М.
Published: February 2024

РЕЗЮМЕ. Остеоартроз (ОА) – це гетерогенна група захворювань різної етіології, але зі схожими біологічними, морфологічними і клінічними проявами та наслідками. Це захворювання впливає на всі компоненти суглоба, зокрема хрящ, субхондральну кістку, синовіальну оболонку, зв’язки та м’язи, що оточують суглоб. ОА є постійно прогресуючою хворобою, яка серйозно впливає на якість життя, особливо, якщо дане захворювння перебігає за умов коморбідності з хронічними захворюваннями, які супроводжуються екзокринною недостатністю підшлункової залози (ЕкНПЗ).

Мета дослідження – проаналізувати зміни показників якості життя за шкалами опитувальника SF-36 у пацієнтів з первинним ОА за умов коморбідності зі захворюваннями шлунково-кишкового тракту (ШКТ), що супроводжуються ЕкНПЗ.

Матеріал і методи дослідження. Було обстежено 304 пацієнти з первинним ОА у коморбідності зі захворюваннями ШКТ, що супроводжуються ЕкНПЗ, поза загостренням. Групу порівняння склали 30 практично здорових осіб, які не мали клініко-анамнестичних та інструментальних ознак захворювань ШКТ і суглобів.

Для оцінки якості життя хворих на первинний ОА в коморбідності зі захворюваннями, що супроводжуються ЕкНПЗ, використовувався загальний опитувальник SF-36.

Результати й обговорення. Встановлено статистично достовірний вплив коморбідної гастроентерологічної патології при первинному ОА на показники шкал фізичного та психологічного здоров’я опитувальника SF-36 (р<0,05).

Висновок. Проведений post hoc аналіз показав наступний рейтинг коморбідної гастроентерологічної патології, що супроводжується ЕкНПЗ, при первинному ОА за рівнем показників шкал фізичного і психологічного здоров’я опитувальника SF-36, починаючи з найнижчого: ЦД2 > ХП > хронічний некаменевий холецистит і функціональні захворювання жовчного міхура та жовчновидільної системи > хронічний гастродуоденіт (р<0,05).
ДОСЛІДЖЕННЯ АСОЦІАЦІЙ МІЖ ПОЛІМОРФІЗМОМ ГЕНА PON1 -108C/T ТА КЛІНІКО-НЕВРОЛОГІЧНИМИ, НЕЙРОВІЗУАЛІЗАЦІЙНИМИ, ГЕМОДИНАМІЧНИМИ ХАРАКТЕРИСТИКАМИ ТА КОГНІТИВНОЮ ДИСФУНКЦІЄЮ У ХВОРИХ ІЗ СУДИННОЮ ЕНЦЕФАЛОПАТІЄЮ ПРИ ХРОНІЧНІЙ ІШЕМІЇ МОЗКУ
Authors: Дуве Х. В.
Published: February 2024

РЕЗЮМЕ. Оксидативний стрес є важливою ланкою патогенезу судинної енцефалопатії при хронічній ішемії мозку (ХСЕ). Параоксоназа-1(PON1) є основним ензимом крові, що здійснює гідроліз окиснених ліпідів у складі ліпопротеїнів, проявляючи значну антиоксидантну та кардіопротекторну дію залежно від поліморфізму гена PON1.

Мета – встановити ймовірні асоціації поліморфного варіанта -108C/T гена PON1 з клініко-неврологічними, нейровізуалізаційними гемодинамічними характеристиками та когнітивною дисфункцією у пацієнтів з ХСЕ.

Матеріал і методи. У групу дослідження ввійшли 145 пацієнтів з ХСЕ, з них 18-ти пацієнтам проводилось молекулярно-генетичне дослідження поліморфного варіанта -108C/T гена PON1; контрольну групу склали 12 практично здорових осіб, репрезентативних за віком і статтю. Застосовано стандартні клініко-неврологічні, інструментальні та нейропсихологічні методи дослідження. Молекулярно-генетичне дослідження поліморфного варіанта -108C/T гена PON1 проводилось в молекулярно-генетичній лабораторії державного закладу «Референс-центр з молекулярної діагностики МОЗ України», м. Київ. Статистичну обробку результатів здійснювали за допомогою програми «STATISTICA 13.0».

Результати. Аналізуючи залежність клініко-неврологічних синдромів, нейровізуалізаційних, гемодинамічних характеристик та когнітивної дисфункції від поліморфного варіанта -108C/T гена PON1 у пацієнтів з ХСЕ вірогідні відмінності у розподілі частот генотипів встановлено лише для клініко-неврологічних синдромів (астенічний синдром виявлено у 100 % носіїв генотипу Т/Т та у 66,67 % носіїв генотипу С/Т; c2=6,43; p=0,040) і когнітивної дисфункції (75,00 % пацієнтів з помірним когнітивним дефектом були носіями Т/Т генотипу та 61,54 % пацієнтів з легким когнітивним дефектом були носіями С/Т генотипу; c2=19,74; р<0,001).

Висновки. Отримані результати свідчать про доцільність подальшого вивчення асоціації поліморфного варіанта -108C/T гена PON1 та когнітивного функціонування із залученням більшої вибірки пацієнтів з ХСЕ, що допоможе пояснити молекулярні механізми, які зумовлюють когнітивні порушення, та оцінити діагностичну значимість включення даного поліморфізму до генетичної панелі дослідження хворих з ХСЕ.