bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-resistance to isoniazid and second-line anti-tuberculosis drugs in isoniazid-resistant tuberculosis at a tertiary care hospital in Thailand
Authors: Prommi Ajala , Wongjarit Kanphai , Petsong Suthidee , Somsukpiroh Ubonwan , Faksri Kiatichai , Kawkitinarong Kamon , Payungporn Sunchai , Rotcheewaphan Suwatchareeporn
Published: February 2024

Isoniazid-resistant tuberculosis (Hr-TB) is an important drug-resistant tuberculosis (TB). In addition to rifampicin, resistance to other medications for Hr-TB can impact the course of treatment; however, there are currently limited data in the literature. In this study, the drug susceptibility profiles of Hr-TB treatment and resistance-conferring mutations were investigated for Hr-TB clinical isolates from Thailand. Phenotypic drug susceptibility testing (pDST) and genotypic drug susceptibility testing (gDST) were retrospectively and prospectively investigated using the Mycobacterium Growth Indicator Tube (MGIT), the broth microdilution (BMD) method, and whole-genome sequencing (WGS)-based gDST. The prevalence of Hr-TB cases was 11.2% among patients with TB. Most Hr-TB cases (89.5%) were newly diagnosed patients with TB. In the pDST analysis, approximately 55.6% (60/108) of the tested Hr-TB clinical isolates exhibited high-level isoniazid resistance. In addition, the Hr-TB clinical isolates presented co-resistance to ethambutol (3/161, 1.9%), levofloxacin (2/96, 2.1%), and pyrazinamide (24/118, 20.3%). In 56 Hr-TB clinical isolates, WGS-based gDST predicted resistance to isoniazid [
katG
S315T (48.2%) and
fabG1
c-15t (26.8%)], rifampicin [
rpoB
L430P and
rpoB
L452P (5.4%)], and fluoroquinolones [
gyrA
D94G (1.8%)], but no mutation for ethambutol was detected. The categorical agreement for the detection of resistance to isoniazid, rifampicin, ethambutol, and levofloxacin between WGS-based gDST and the MGIT or the BMD method ranged from 80.4% to 98.2% or 82.1% to 100%, respectively. pDST and gDST demonstrated a low co-resistance rate between isoniazid and second-line TB drugs in Hr-TB clinical isolates.

IMPORTANCE

The prevalence of isoniazid-resistant tuberculosis (Hr-TB) is the highest among other types of drug-resistant tuberculosis. Currently, the World Health Organization (WHO) guidelines recommend the treatment of Hr-TB with rifampicin, ethambutol, pyrazinamide, and levofloxacin for 6 months. The susceptibility profiles of Hr-TB clinical isolates, especially when they are co-resistant to second-line drugs, are critical in the selection of the appropriate treatment regimen to prevent treatment failure. This study highlights the susceptibility profiles of the WHO-recommended treatment regimen in Hr-TB clinical isolates from a tertiary care hospital in Thailand and the concordance and importance of using the phenotypic drug susceptibility testing or genotypic drug susceptibility testing for accurate and comprehensive interpretation of results.
Anaesthesia of a parturient with uncorrected pentalogy of Fallot undergoing caesarean section and postpartum sterilisation
Authors: Leong Rachel Wei-Li , Chen Jinghui , Mathews Abey Matthew Varughese , Kothandan Harikrishnan
Published: February 2024

Pentalogy of Fallot is a rare congenital cyanotic heart disease; few patients with uncorrected disease survive to childbearing age. Cardiovascular changes during pregnancy and delivery can lead to haemodynamic instability, while anaesthesia can cause right-to-left shunting and worsen hypoxaemia.

We present the learning points from the anaesthetic management of an obstetric patient with uncorrected pentalogy of Fallot. We describe the successful application of general anaesthesia, choice of transoesophageal echocardiography for real-time haemodynamic monitoring and management, and the comprehensive multidisciplinary care of this high cardiovascular risk obstetric patient perioperatively. We also review the literature and discuss the anaesthetic management of patients with pentalogy of Fallot going for caesarean section.
Parainfectious Brown-Séquard syndrome associated with COVID-19
Authors: Chen Lily Ye , Truong Rachel Diem-Trang , Shanmugham Sampathkumar
Published: February 2024

Acute myelitis encompasses syndromes associated with inflammation of the spinal cord. In cases of inflammatory lesions that only involve a unilateral portion of the axial plane of the cord, Brown-Séquard syndrome may occur, resulting in potential ipsilateral corticospinal, dorsal spinocerebellar, or dorsal column dysfunction or contralateral spinothalamic dysfunction below the level of the lesion. We report a case of an adult male who presented with Brown-Séquard syndrome and with a positive SARS-CoV-2 nasopharyngeal swab PCR test. Neurological symptoms rapidly resolved after initiation of high-dose methylprednisolone. The findings reported not only contribute to documenting a new presentation of neurological complications associated with SARS-CoV-2 infection but also non-exclusively supports the body of literature suggesting the immune-mediated response to this infection as a mechanism of neuropathogenesis. In this case, COVID-19-related acute myelitis responded to treatment with a short regimen of high-dose glucocorticoids.
Small bowel obstruction caused by dehydrated apple ingestion: the challenges of preoperative radiological diagnosis and surgical management
Authors: Mikhail Rama Hala Gamal , McKay Siobhan , Goodwin Mark , Yoshino Osamu
Published: February 2024

A man in his 60s with a virgin abdomen presented with sudden-onset generalised abdominal pain and fevers. The night prior, he snacked on supermarket purchased dehydrated apples. CT abdomen and pelvis revealed small bowel obstruction (SBO) to the mid ileum and small amount of free fluid within the pelvis. The patient underwent emergency exploratory laparotomy. High-grade SBO was identified, caused by large obstructing phytobezoars, with three further proximal large phytobezoars identified. All four phytobezoars were extracted and found to be rehydrated pieces of dehydrated apple that had increased in size in the gastrointestinal tract. The patient was later found to have further phytobezoars in the stomach which passed conservatively. The patient recovered well. This case demonstrates the challenges of preoperative radiological diagnosis in phytobezoar-related SBO and the significance of enterotomy orientation and closure to ensure a safe repair to withstand the passage of any residual rehydrating phytobezoars.
Study protocol of a national multicentre prospective evaluation study assessing the validity and impact of the Dutch Paediatric Early Warning Score (PEWS) in the Netherlands
Authors: Stevens Jikke , de Groot Janke , Luijmes Marie , Bouwens Janneke , Rippen Hester , Hoogervorst-Schilp Janneke , Fuijkschot Joris
Published: February 2024

Introduction

Early recognition of clinical deterioration and timely intervention are important to improve morbidity and mortality in paediatric care. The Paediatric Early Warning Score (PEWS) is a scoring system aiming to identify hospitalised children at risk for deterioration. Currently, there is a large heterogeneity of PEWS systems in the Netherlands, with a considerable number remaining unvalidated or self-designed. Therefore, a consensus-based Dutch PEWS has been developed in a national study using the Core Outcome Measures in Effectiveness Trials initiative. The Dutch PEWS is a uniform system that integrates a core set of vital parameters together with pre-existing risk factors and uses risk stratification to proactively follow-up on patients at risk (so-called ‘watcher patients’). This study aims to validate the Dutch PEWS and to determine its impact on improving patient safety in various hospital settings.

Methods and analysis

This national study will be a large multicentre evaluation study, in which the Dutch PEWS will be implemented and evaluated in 12 hospitals in the Netherlands. In this study, a mixed methods methodology will be used and evaluated on predefined outcome measures. To examine the validity of the Dutch PEWS, statistical analyses will be undertaken on quantitative data retrieved from electronic health records. Surveys among physicians and nurses; semistructured interviews with healthcare providers and parents; and daily evaluation forms are being conducted to determine the impact of the Dutch PEWS. The study is being conducted from December 2020 to June 2024.
Prevalence and causes of ocular disorders and visual impairment among preterm children in Ethiopia
Authors: Sherief Sadik Taju , Muhe Lulu M , Mekasha Amha , Demtse Asrat , Ali Asim
Published: February 2024

Objective

The aim of this study was to determine the prevalence, causes of ocular disorders and visual impairment among preterm children previously admitted to neonatal intensive care units in Addis Ababa, Ethiopia.

Methods and analysis

A prospective screening survey was conducted from February to June 2019 at the paediatric eye clinic of Menelik II Hospital. Children who were preterm at birth and who attended the eye clinic were included in the study. Data on demographic and neonatal characteristics, neonatal and maternal comorbidities and ocular disorders were collected. OR and univariate analysis were used to identify predictors of ocular diseases and visual impairment.

Results

There were 222 children included in the study with a mean age at presentation of 2.62 years (range 2.08–6.38 years), mean gestational age 34.11 weeks (range 30–36) weeks and mean birth weight 1941.72 g (range 953–3500 g). Nearly two-thirds had ocular disorders with refractive error (51.8%), strabismus (11.3%) and a history of retinopathy of prematurity (ROP) (7.2%) being more common. One-fourth of the children had visual impairment, and the prevalence of amblyopia was 40.1%. Uncorrected refractive errors, strabismus and ROP were causes for visual impairment.

Conclusion

Visual impairment and amblyopia are common in Ethiopia. There is a need to develop a screening protocol for ocular disorders for preterm children to enhance early detection and prevention of childhood visual impairment.
Bifurcation and Spatiotemporal Patterns of SI Epidemic Model with Diffusion
Authors: Ma Yani , Yuan Hailong
Published: February 2024

This paper investigates a spatiotemporal SI epidemiological model under homogeneous Neumann boundary conditions. First, the long-time behavior of the solutions is described, a priori estimates of nonconstant positive solutions are given, and the nonexistence of nonconstant positive steady states is proved by the energy method. Second, the Turing instability of the positive constant steady-state is discussed, and the existence of nonconstant positive steady states is shown by using the degree theory. Moreover, applying the bifurcation theory, we establish the local and global structures of the steady-state bifurcation from simple eigenvalues, and describe some conditions for determining the direction of bifurcation, where the techniques of space decomposition and implicit function theorem are adopted to deal with the local structure of the steady-state bifurcation from double eigenvalues. Finally, some analysis results are supplemented by numerical simulations.
Two Independent Offset Controllers in a Three-Dimensional Chaotic System
Authors: Li Chunbiao , Gao Yikai , Lei Tengfei , Li Rita Yi Man , Xu Yuanxiao
Published: February 2024

Offset boosting is a crucial passage for chaotic signal modification in chaos-based engineering. Searching an offset controller for a 3D chaotic system is usually complex, let alone two independent nonbifurcating offset constants. This paper constructs a class of chaotic systems, providing a single constant posing direct offset boosting for two dimensions. This offset boostable chaotic system regime has multiple typical control modes, including a system variable single control, synchronous common control, reverse control, and differential control. This new type of chaotic systems also finds two-dimensional offset boosting combined with amplitude control.
SWRM: Similarity Window Reweighting and Margin for Long-Tailed Recognition
Authors: Chen Qiong , Huang Tianlin , Liu Qingfa
Published: February 2024

Real-world data usually obeys a long-tailed distribution, where a few classes have higher number of samples compared to the other classes. Recent studies have been proposed to alleviate the extreme data imbalance from different perspectives. In this article, we experimentally find that due to the easily confusing visual features between some head- and tail classes, the cross-entropy model is prone to misclassify tail samples to similar head classes. Therefore, to alleviate the influence of the confusion on model performance and improve the classification of tail classes, we propose a Similarity Window Reweighting and Margin (SWRM) algorithm, where the SWRM consists of Similarity Window Reweighting (SWR) and Similarity Window Margin (SWM) algorithms. For the confusable head- and tail classes, SWR assigns larger weights to tail classes and smaller weights to head classes. Therefore, the model can enlarge the importance of tail classes and effectively improve their classification. Moreover, SWR considers the difference in label frequency and the impact of category similarity simultaneously, so that the weight coefficients are more reasonable and efficacious. SWM generates adaptive margins that are proportional to the ratio of the classifier’s weight norm, thus promoting the learning of tail classifier with small weight norm. Our SWRM effectively eliminates the confusion between head- and tail classes and alleviates the misclassification issues. Extensive experiments on three long-tailed datasets, i.e., CIFAR100-LT, ImageNet-LT, and Places-LT, verify our proposed method’s effectiveness and superiority over comparative methods.
Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog
Authors: Coate Katie C. , Ramnanan Christopher J. , Smith Marta , Winnick Jason J. , Kraft Guillaume , Irimia-Dominguez Jose , Farmer Ben , Donahue E. Patrick , Roach Peter J. , Cherrington Alan D. , Edgerton Dale S.
Published: February 2024

Glucagon rapidly stimulates hepatic glucose production, but these effects are transient. This study links the molecular and metabolic flux changes that occur in the liver over time in response to a rise in glucagon, demonstrating the strength of the dog as a translational model to couple findings in small animals and humans. In addition, this study clarifies why the rapid effects of glucagon on liver glycogen metabolism are not sustained.
Quantification of the immunometabolite protein modifications S-2-succinocysteine and 2,3-dicarboxypropylcysteine
Authors: Cox J. Hunter , McCain Richard S. , Tran Emery , Swaminathan Shoba , Smith Holland H. , Piroli Gerardo G. , Shtutman Michael , Walla Michael D. , Cotham William E. , Frizzell Norma
Published: February 2024

Itaconate and fumarate have roles as immunometabolites modulating the macrophage response to inflammation. Both immunometabolites chemically modify protein cysteine residues to modulate the immune response. Itaconate and fumarate levels change dynamically, whereas their stable protein modifications can be quantified by mass spectrometry. This method distinguishes itaconate and fumarate-derived protein modifications and will allow researchers to quantify their contributions in isolated cell types and tissues across a range of metabolic diseases.
Vitamin D promotes the folate transport and metabolism in zebrafish (Danio rerio)
Authors: Liang Shufei , Zhang Hui , Jiao Lin , Shao Rui , Lan Yawen , Liao Xinmeng , Mai Kangsen , Ai Qinghui , Wan Min
Published: February 2024

Our study has identified that VD influences intestinal uptake and transport of folate in zebrafish while also altering hepatic folate metabolism and storage. Interestingly, the regulatory effects of VD on folate transport and metabolism diminished after the gut flora was interrupted by antibiotic treatment, suggesting that the regulatory effects of VD on folate metabolism in zebrafish are most likely dependent on the intestinal flora.
The influence of postural threat-induced anxiety on locomotor learning and updating
Authors: Ellmers Toby J. , Durkin Morgan , Sriranganathan Karthigan , Harris David J. , Bronstein Adolfo M.
Published: February 2024

Safe and efficient locomotion frequently requires movements to be adapted in a feedforward (i.e., “predictive”) manner. These adaptations are not always correct, and thus inappropriate behavior must be quickly updated. Here we showed that increased threat disrupts this process. We found that locomotor actions learned in the presence of postural threat-induced anxiety are strengthened, subsequently impairing one’s ability to update (or “deadapt”) these actions when they are no longer appropriate for the current context.
Speech perception difficulty modulates theta-band encoding of articulatory synergies
Authors: Corsini Alessandro , Tomassini Alice , Pastore Aldo , Delis Ioannis , Fadiga Luciano , D’Ausilio Alessandro
Published: February 2024

Top-down processes originating from the motor system contribute to speech perception through the reconstruction of the speaker’s articulatory movement. This study investigates the role of such articulatory simulation under variable task difficulty. We show that more challenging listening tasks lead to increased encoding of articulatory kinematics in the theta band and suggest that, in such situations, fine-grained articulatory reconstruction complements acoustic encoding.
Spectral Smoothness of Ground Plane Backed Log-Periodic Dipole Antennas for Radioastronomical Applications
Authors: Kyriakou Georgios , Bolli Pietro , Bercigli Mirko
Published: February 2024

The spectral smoothness properties of the low-frequency array of the square kilometer array (SKA), namely, SKA-Low, are an important issue for its scientific objectives to be attainable. A large array of 256 log-periodic dipole antennas, installed on top of a 42 m circular ground plane, will work as an SKA-Low station in the frequency range of 50–350 MHz. In this article, the ground plane-induced effects are examined in terms of antenna beam spectral characteristics, while different antenna placements are considered. Results are produced both at the isolated antenna and at the array level in the band 50–100 MHz, by employing an approximate method for the speeding-up of array simulations. We attempt to distinguish the ground plane effect from that of mutual coupling among antennas, which appears to be more severe at specific frequencies, using 2 figures of merit. The discrete Fourier transform (DFT) components of gain pattern ratios identify the fundamental spatial components of the ripple, while the envelope correlation coefficient quantifies the penalty to considering an infinite ground plane.
The Phenolic Content of Pistacia lentiscus Leaf Extract and Its Antioxidant and Antidiabetic Properties
Authors: Bouakline Hamza , Bouknana Saliha , Merzouki Mohammed , Ziani Imane , Challioui Allal , Bnouham Mohamed , Tahani Abdesselam , EL Bachiri Ali
Published: February 2024

The aims of this study were to determine the polyphenolic profile, to estimate the total phenolic and flavonoid contents, and to evaluate the antioxidant and antidiabetic activities of the extract of Pistacia lentiscus leaves, and the hydroacetonic mixture was employed as an alternative for common solvents in the extraction process. In order to explain the antidiabetic activity, molecular docking has been performed on the main constituents of the leaf extract. The characterization of the extract has been performed by high-performance liquid chromatography (HPLC) leading to the detection of 20 compounds of which gallic acid, ellagic acid, catechin, kaempferol, and quercetin 3-glucoside were identified using authentic standards. The total phenolic and flavonoid contents, assessed using the Folin–Ciocalteu and quercetin methods, were 394.5 ± 0.08 mg gallic acid equivalent/g dry extract (mg GAE/g DE) and 101.2 ± 0.095 mg quercetin equivalent/g dry extract (mg QE/g DE), respectively. On the other hand, the antioxidant activity of leaf extract, quantified by determining the ability to neutralize the free radical DPPH and β-carotene/linoleate model system, reached the values of 0.0027 ± 0.002 mg/mL and 0.128 ± 0.04 mg/mL, respectively. Regarding the antidiabetic activity, based on the inhibition of pancreatic α-amylase activity, a significant inhibition of about 68.20% with an IC50 value of 0.266 mg/mL had been observed. This finding is consistent with the molecular docking study of the main phenolic compounds of the extracts, where a remarkable binding affinity against α-amylase was observed, with values of −7.631 (kcal/mol), −6.818 (kcal/mol), and −5.517 (kcal/mol) for the major compounds catechin, quercetin-3-glucoside, and gallic acid, respectively.
Analysis of Quality Differences in Radix Dipsaci before and after Processing with Salt Based on Quantitative Control of HPLC Multi-Indicator Components Combined with Chemometrics
Authors: Wu Hangsha , Lv Yue , Tang Rui , Zhao Mingfang , Li Yafei , Wei Feiyang , Li Changyu , Ge Weihong , Du Weifeng
Published: February 2024

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.
BLSENet: A Novel Lightweight Bilinear Convolutional Neural Network Based on Attention Mechanism and Feature Fusion Strategy for Apple Leaf Disease Classification
Authors: Fang Tianyu , Zhang Jialin , Qi Dawei , Gao Mingyu
Published: February 2024

Accurate identification of apple leaf diseases is of great significance for improving apple yield. The lesion area of the apple leaf disease image is small and vulnerable to background interference, which easily leads to low recognition accuracy. To solve this problem, a lightweight bilinear convolutional neural network (CNN) model named BLSENet based on attention mechanism is designed. The model consists of two subnetworks, and each subnetwork is embedded with a Squeeze-and-Excitation (SE) module. By using the feature extraction ability of the two subnetworks and combining the bilinear feature CONCAT operation, the multiscale features of the image are obtained. Compared with the unimproved model LeNet-5 (84.63%), BLSENet has higher accuracy in the test set, which indicates that SE module and bilinear feature fusion have a positive effect on the performance of the model, and BLSENet has the ability to identify apple leaf diseases. The model has achieved the expected goal and can provide technical support for accurate identification and real-time monitoring of apple disease images.
Application of Near-Infrared Spectroscopy to Rapidly Classify the Chinese Quince Fruits from Different Habitats
Authors: Diao Songfeng , Tang Xiaoqian , Huang Lin , Li Yanjie , Fan Xiongfei , Shao Wenhao
Published: February 2024

The ecological habitats of Chinese quince (Chaenomeles speciosa Nakai) fruits affect their phenotype. Currently, limited or no rapid method exists for classifying Chinese quince fruit from different ecosystems. This study developed a partial least squares discriminant analysis (PLS-DA) classification model to effectively and nondestructively classify 663 Chinese quince fruit samples from six environments in 2020. PLS-DA models and other variable selection approaches were used in this study. The near-infrared spectroscopy (NIRs) absorption spectra of raw Chinese quince fruit samples from six habitats showed a similar shape. The spectra of each environment showed little variance. The raw fruit spectra varied significantly among habitat categories after the first derivative preprocessing phase. The uninformative variable elimination (UVE) variable selection approach had greater calibration and validation set specificity of 0.93 and 0.98. This study found the best classification specificity using the UVE variable selection approach compared to other methods including the PLS-DA model without variable selection. The UVE approach improved Yunnan habitat categorization specificity from 86% to 88% when integrated with PLS-DA. Additionally, the validation set for quinces originating from Anhui, Chongqing, Hubei, Shandong, and Zhejiang achieved an ideal classification score of 100%. The findings of the study indicated that PLS-DA can serve as an alternative approach for classifying the habitats of Chinese quince fruits. When used in conjunction with other methods, this technique can assist researchers, scientists, and industry professionals in identifying the main factors responsible for significant variations in the habitats, composition, and quality of Chinese quince fruits.
Effects of Dietary Phytol Supplementation on Growth Performance, Immunological Parameters, Intestinal Bacteria, and Prevention of Oxidative Stress Following Transportation of Nile Tilapia, Oreochromis niloticus
Authors: Ahani Saman , Ahani Sara , Yousefi Morteza , Taheri Mirghaed Ali , Abdel Rahman Afaf N.
Published: February 2024

Nile tilapia, Oreochromis niloticus, (2.00 ± 0.02 g) were reared in 16 70‐L tanks (40 individual/tank) and fed diets (approx. 345 g/kg protein, approx. 87 g/kg crude fat) containing 0 (CTL), 75 (PH‐75), 150 (PH‐150), and 300 (PH‐300) mg/kg phytol (n = 4). After 60 days of feeding (4% daily), growth performance, humoral immune parameters, and gut bacteria were analyzed. Also, hepatic antioxidant parameters were determined before and after the fish were transported in plastic bags for 6 hr. The results showed that PH‐75 exhibited the highest final weight (P < 0.001), weight gain (P < 0.001), feed intake (P < 0.001), feed efficiency (P = 0.015), plasma lysozyme activity (P = 0.004), and intestinal Lactobacillus sp. population (P = 0.017), among the treatments. The highest plasma alternative complement activity (P = 0.006) and the lowest intestinal total viable bacteria (P = 0.027) were observed in PH‐75 and PH‐150. The highest plasma alkaline phosphatase activities were observed in PH‐75 and PH‐300 (P = 0.014). The highest blood leukocyte (P = 0.008), monocyte (P = 0.010), and eosinophil (P < 0.001) were observed in PH‐300, while the highest blood neutrophil was observed in all phytol treatments (P < 0.001). The highest hepatic lipid peroxidation was observed in PH‐300, whereas PH‐75 and PH‐150 showed the lowest values (P < 0.001). The highest hepatic reduced glutathione was observed in PH‐75, also PH‐150 exhibited significant elevation in this parameter, compared to CTL (P < 0.001). Transportation led to significant elevations in the hepatic antioxidant enzymes’ activities in CTL, PH‐75, and PH‐150; the highest activities were related to PH‐75 and PH‐150 treatments, which had also the highest post‐transportation survivals (P < 0.001). In conclusion, phytol is a suitable feed supplement for Nile tilapia, improving growth performance and welfare, particularly at 75 mg/kg.
Meta‐Analysis of Open‐Heart Surgery Pain Relief Using Transversus Thoracic Plane Blocks
Authors: Ye Xiuli , Zou Yun , Chen Yijian , Huang Guiming , Deng Ruiming , Liang Weidong , Zhong Ruipeng
Published: February 2024

Background. Severe postoperative pain is commonly reported following open‐heart surgery, necessitating the implementation of effective pain management strategies to facilitate patient recovery. The benefits of the transverse thoracic muscle plane (TTMP) block for open‐heart surgery remain unclear. Therefore, a meta‐analysis was conducted to systematically evaluate the effect of TTMP on postoperative analgesia and recovery in patients undergoing open‐heart surgery. Methods. A computer search was performed in PubMed, Cochrane, Embase, CNKI, and Wangfang databases. The primary outcome was 24‐hour postoperative opioid consumption, and the secondary outcomes were 12‐ and 24‐hour postoperative resting and motor pain scores, time of first analgesia demand, extubation time, length of stay in the intensive care unit (ICU), time of first feces, incidence of nausea and vomiting, and length of hospitalization. Results. Thirteen randomized controlled trials (RCTs) involving a total of 766 patients were included in this meta‐analysis. Compared with the control group, the TTMP group showed a significant reduction in opioid consumption within 24 h postoperatively (mean difference = −41.88 mg; 95% confidence interval: −51.99, −31.77; p < 0.001; and I2 = 98%). However, the 12‐ and 24‐hour postoperative resting and moment VAS pain scores were significantly lower in the TTMP group. In addition, the TTMP group had a longer time of first analgesic demand; shorter endotracheal intubation time, ICU stay duration, time of first feces, and length of hospital stay; and a lower incidence of nausea and vomiting. Conclusions. Perioperative TTMP block can reduce the use of opioids in patients undergoing open‐heart surgery for 24 h postoperatively, decrease the early postoperative pain scores, prolong the time of first analgesic demand, shorten the time of extubation and the length of ICU stay and hospitalization, and reduce the incidence of nausea and vomiting, which are all conducive to the recovery of patients. Registration. This trial is registered with PROSPERO database (CRD42022312435).
FDA Approval Summary: Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell Lymphoma
Authors: Elmacken Mona , Peredo-Pinto Helkha , Wang Cong , Xu Zhenzhen , Tegenge Million , Jaigirdar Adnan A. , Theoret Marc R. , Purohit-Sheth Tejashri , Kasamon Yvette L.
Published: February 2024

In June 2022, the FDA extended the indication for lisocabtagene maraleucel (liso-cel) to include adults with large B-cell lymphoma (LBCL) who have refractory disease or relapse within 12 months of first-line chemoimmunotherapy (CIT), as well as transplant-ineligible adults with refractory disease or relapse after first-line CIT. Two clinical trials evaluating a single infusion of liso-cel preceded by lymphodepleting chemotherapy supported the second-line indications. TRANSFORM is a randomized, phase 3, open-label trial comparing liso-cel with standard second-line therapy, including planned autologous hematopoietic stem cell transplantation (HSCT), in 184 transplant-eligible patients. On interim analysis, event-free survival (EFS) by independent review committee (IRC) assessment was statistically significantly improved for the liso-cel arm, with a stratified hazard ratio of 0.34 [95% confidence interval (CI), 0.22–0.51; P < 0.0001]; the estimated median EFS was 10.1 months in the liso-cel arm versus 2.3 months in the control arm. PILOT is a single-arm phase 2 trial of second-line liso-cel in patients who were transplant-ineligible due to age or comorbidities but had adequate organ function for chimeric antigen receptor (CAR) T-cell therapy. Among 61 patients who received liso-cel (median age, 74 years), the IRC-assessed complete response rate was 54% (95% CI, 41–67). Among patients achieving complete response, the estimated 1-year rate of continued response was 68% (95% CI, 45–83). Of the 268 patients combined who received liso-cel as second-line therapy for LBCL, cytokine release syndrome occurred in 45% (Grade 3, 1.3%) and CAR T-cell–associated neurologic toxicities occurred in 27% (Grade 3, 7%), warranting a continued risk evaluation and mitigation strategy.
ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies
Authors: Zammarchi Francesca , Havenith Karin E. , Sachini Nikoleta , Janghra Narinder , Chivers Simon , Idusogie Esohe , Gaudio Eugenio , Tarantelli Chiara , Bertelli Francois , Santos Kathleen , Tyrer Peter , Corbett Simon , Spriano Filippo , Golino Gaetanina , Cascione Luciano , Bertoni Francesco , Hartley John A. , van Berkel Patrick H.
Published: February 2024

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed. CD22 is an attractive target for antibody–drug conjugates (ADCs), being highly expressed in R/R B-ALL with rapid internalization kinetics. ADCT-602 is a novel CD22-targeting ADC, consisting of humanized mAb hLL2-C220, site specifically conjugated to the pyrrolobenzodiazepine dimer–based payload tesirine. In preclinical studies, ADCT-602 demonstrated potent, specific cytotoxicity in CD22-positive lymphomas and leukemias. ADCT-602 was specifically bound, internalized, and trafficked to lysosomes in CD22-positive tumor cells; after cytotoxin release, DNA interstrand crosslink formation persisted for 48 hours. In the presence of CD22-positive tumor cells, ADCT-602 caused bystander killing of CD22-negative tumor cells. A single ADCT-602 dose led to potent, dose-dependent, in vivo antitumor activity in subcutaneous and disseminated human lymphoma/leukemia models. Pharmacokinetic analyses (rat and cynomolgus monkey) showed excellent stability and tolerability of ADCT-602. Cynomolgus monkey B cells were efficiently depleted from circulation after one dose. Gene signature association analysis revealed IRAK1 as a potential marker for ADCT-602 resistance. Combining ADCT-602 + pacritinib was beneficial in ADCT-602–resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematologic cancers.
Trastuzumab-MMAU Antibody-Auristatin Conjugates: Valine-Glucoserine Linker with Stabilized Maleimide Conjugation Improves In Vivo Efficacy and Tolerability
Authors: Goldberg Shalom D. , Satomaa Tero , Aina Olulanu , Aitio Olli , Burke Krista , Dudkin Vadim , Geist Brian , Irrechukwu Onyi , Hänninen Anna-Liisa , Heiskanen Annamari , Helin Jari , Hiltunen Jukka O. , Kinyamu-Akunda Jacqueline , Klein Donna M. , Kohli Neeraj , Kotiranta Titta , Lähteenmäki Tuula , Niemelä Ritva , Pitkänen Virve , Pynnönen Henna , Rittase William , Wiley Kristen , Zhou Junguo , Saarinen Juhani
Published: February 2024

Antibody–drug conjugates (ADC) have shown impressive clinical activity with approval of many agents in hematologic and solid tumors. However, challenges remain with both efficacy and safety of ADCs. This study describes novel trastuzumab–auristatin conjugates with the hydrophilic monomethylauristatin E (MMAE) prodrug MMAU, and optimization of a glycopeptide linker leading to a wider therapeutic window. Trastuzumab was conjugated with auristatin payloads via a series of linkers using a stabilized maleimide handle. The ADCs were characterized in vitro and their relative in vivo antitumor efficacies were assessed in HER2+ xenograft models. Relative linker stabilities and the mechanism of linker cleavage were studied using in vitro assays. Toxicity and toxicokinetics of the best performing ADC were evaluated in cynomolgus monkey (cyno). The trastuzumab–MMAU ADC with stabilized glycopeptide linker showed maleimide stabilization and higher resistance to cleavage by serum and lysosomal enzymes compared with a valine–citrulline conjugated trastuzumab ADC (trastuzumab–vc-MMAE). A single dose of 1 or 2 mg/kg of trastuzumab–MMAU at drug-to-antibody ratios (DAR) of eight and four respectively resulted in xenograft tumor growth inhibition, with superior efficacy to trastuzumab–vc-MMAE. Trastuzumab–MMAUDAR4 was tolerated at doses up to 12 mg/kg in cyno, which represents 2- to 4-fold higher dose than that observed with vedotin ADCs, and had increased terminal half-life and exposure. The optimized trastuzumab–MMAU ADC showed potent antitumor activity and was well tolerated with excellent pharmacokinetics in nonhuman primates, leading to a superior preclinical therapeutic window. The data support potential utility of trastuzumab–MMAU for treatment of HER2+ tumors.
Coregulation of NDC80 Complex Subunits Determines the Fidelity of the Spindle-Assembly Checkpoint and Mitosis
Authors: Kim Sehong , Lau Thomas T.Y. , Liao Man Kit , Ma Hoi Tang , Poon Randy Y.C.
Published: February 2024

NDC80 complex (NDC80C) is composed of four subunits (SPC24, SPC25, NDC80, and NUF2) and is vital for kinetochore–microtubule (KT–MT) attachment during mitosis. Paradoxically, NDC80C also functions in the activation of the spindle-assembly checkpoint (SAC). This raises an interesting question regarding how mitosis is regulated when NDC80C levels are compromised. Using a degron-mediated depletion system, we found that acute silencing of SPC24 triggered a transient mitotic arrest followed by mitotic slippage. SPC24-deficient cells were unable to sustain SAC activation despite the loss of KT–MT interaction. Intriguingly, our results revealed that other subunits of the NDC80C were co-downregulated with SPC24 at a posttranslational level. Silencing any individual subunit of NDC80C likewise reduced the expression of the entire complex. We found that the SPC24–SPC25 and NDC80–NUF2 subcomplexes could be individually stabilized using ectopically expressed subunits. The synergism of SPC24 downregulation with drugs that promote either mitotic arrest or mitotic slippage further underscored the dual roles of NDC80C in KT–MT interaction and SAC maintenance. The tight coordinated regulation of NDC80C subunits suggests that targeting individual subunits could disrupt mitotic progression and provide new avenues for therapeutic intervention.

Implications:

These results highlight the tight coordinated regulation of NDC80C subunits and their potential as targets for antimitotic therapies.
Liver Fibrosis Is Associated with Poorer Overall Survival and Higher Recurrence Rate in Patients with Cholangiocarcinoma
Authors: Steffani Marcella , Nitsche Ulrich , Ollesky Johanna , Kaufmann Benedikt , Schulze Sarah , Novotny Alexander , Friess Helmut , Hüser Norbert , Stoess Christian , Hartmann Daniel
Published: February 2024

Introduction: Cholangiocarcinoma is the second most common primary liver tumour worldwide with an increasing incidence in recent decades. While the effects of fibrosis on hepatocellular carcinoma have been widely demonstrated, the impact on cholangiocarcinoma remains unclear. The aim of this study was to evaluate the impact of liver fibrosis on overall survival (OS) and disease-free survival (DFS) in patients who have undergone liver resection for cholangiocarcinoma. Methods: Eighty patients with cholangiocarcinoma who underwent curatively intended liver surgery between January 2007 and December 2020 were included in this retrospective single-centre study. Clinical and histopathological features were analysed. The primary endpoint was cause-specific survival. Secondary endpoints were DFS and identification of prognostic factors. Results: The present study shows that the median OS is significantly reduced in patients with fibrosis (p < 0.001). The median OS in patients with fibrosis was three times shorter than in the group without fibrosis. In addition, a significantly shorter DFS was observed in patients with fibrosis (p < 0.002). Multivariate analysis showed that fibrosis is the strongest independent factor with a negative impact on OS and DFS. Conclusion: Liver fibrosis has a significant impact on OS and DFS in patients with cholangiocarcinoma. Patients with known liver fibrosis require thorough perioperative care and postoperative follow-up.
Associations between Sleep Disorders and Impulsive-Compulsive Behaviors in Parkinson’s Disease: A Prospective Cohort Study
Authors: Ye Meijie , Kang Xiaoying , Karlsson Ida K. , Wang Yu , Ji Qianqian , Liu Qi , Xu Xiaowei , Hägg Sara , Fang Fang , Wirdefeldt Karin , Zhan Yiqiang
Published: February 2024

Objective: To examine the associations of excessive daytime sleepiness (EDS) and probable rapid eye movement sleep behavior disorder (pRBD), respectively, with impulsive-compulsive behaviors (ICBs) over a 5-year follow-up in patients with early Parkinson’s disease (PD). Methods: The Parkinson’s Progression Markers Initiative is a multicenter cohort study based on an ongoing and open-ended registry. Longitudinal associations of sleep disorders with ICB over 5-year follow-up visits were estimated using generalized linear mixed-effects models among PD participants. Results: A total of 825 PD participants were enrolled at baseline. The study sample had a median baseline age of 63.1 (interquartile range: 55.6–69.3) years and comprised 496 (61.5%) men. Among them, 201 (24.9%) had ICB at baseline. In the generalized mixed-effects models, EDS (odds ratio [OR] = 1.09, 95% confidence interval [CI] 1.05, 1.12) and RBD (OR = 1.07, 95% CI 1.03, 1.12) were substantially associated with higher odds of developing ICB over time in PD patients, after multivariate adjustment including age, gender, family history, GDS score, STAI-Y score, MDS-UPDRS part III score, LEDD, and disease duration. Consistent results were observed when stratifying by age at baseline, gender, and PD family history. Conclusions: The study findings suggest a longitudinal association between EDS and pRBD with an increased risk of developing ICB in patients with PD. The findings emphasize the significance of evaluating and addressing sleep disorders in PD patients as a potential approach to managing ICB.
As representações da marca Amazônia usadas na comunicação do governador do estado do Pará, Helder Barbalho
Authors: Marques Rodolfo Silva , Santos Luiz Cezar Silva dos
Published: February 2024

The Amazônia brand generates several discussions about consumption, representations, repercussion and significance. This article first discusses the Amazon as a brand, pointing out power relations based on the actions of Helder Barbalho (MDB), who began his second term as state governor in 2023, in Pará. This debate proposes a literature review with conceptual reflections, while using the case study methodology to analyze the Amazônia brand in the actions of Barbalho’s administration. To reinforce this correlation between the Amazonian image and the construction of Barbalho government’s brand, we recall his protagonism in the region, the use of Instagram and X (formerly Twitter) in his institutional communication, propaganda tools and his appearance in global events. In conclusion, by expanding the visibility of the Amazônia brand, Barbalho strengthened his political image while strengthening his power relations with the federal government and international organizations.
LA ESTRATEGIA PUBLICITARIA DE JeB ESPAÑA EN TORNO A LA DIVERSIDAD DE IDENTIDAD DE GÉNERO Y ORIENTACIÓN SEXUAL
Authors: Hernández Gómez Onésimo Samuel
Published: February 2024

La publicidad emerge como una herramienta poderosa para impulsar el cambio social al adoptar y comunicar valores que convierten a las marcas en defensoras de diversas causas. Ante la competencia feroz en el mercado, las empresas, como la marca de bebidas JeB, buscan diferenciarse al alinearse con valores en tendencia en la sociedad. En el periodo entre 2021 y 2023, JeB ha forjado una estrategia publicitaria que posiciona a la marca como defensora de la diversidad de género y sexual, fundamentando su enfoque en conceptos como el sexilio y la "homosexoledad navideña". Este enfoque no solo busca sensibilizar a audiencias urbanas y rurales sobre estas realidades, sino que también pretende proyectar a la marca como moderna y progresista. A través de estrategias innovadoras, narrativas impactantes y el uso de símbolos poderosos, JeB se erige como un referente en la promoción de valores de respeto y tolerancia en su identidad de marca.
propriedade da terra no Brasil e o ensino de História: permanências e rupturas ao longo do processo de formação da sociedade brasileira
Authors: Pinto Gilson Mateus
Published: February 2024

Este artigo trata sobre uma breve evolução jurídica do direito à terra no Brasil e quais as possibilidades que o docente tem em trazer essas discussões à escola básica. Busca-se, portanto, entender como a questão fundiária pode vir a se constituir em conteúdo significativo para a compreensão da sociedade brasileira. Para o desenvolvimento deste estudo, fez-se uso de pesquisa bibliográfica de abordagem qualitativa, bem como recorreu-se aos documentos jurídicos que remontam aos recortes temporais estabelecidos, como as cartas de sesmarias, as ordenações régias de 1695 e 1697, além do texto da lei de terra em 1850, em conjunto às regulamentações jurídicas atuais. Por fim, não apenas objetiva-se estabelecer essa discussão jurídica historicizada, mas também entender a transformação dessas fontes históricas em materiais didáticos.
A Ordem Econômica Constitucional entre Serviços Públicos e Atividades Econômicas
Authors: Antonacci Leonardo
Published: February 2024

It exposes the legal theory that proposes that the Brazilian constitutional economic order is divided into a dichotomy between public services and economic activities in the strict sense. From a historical recovery of the doctrine, it is analyzed that this traditional theory of categorization of the economic order in Brazil derives directly from the French tradition of public service, which was incorporated into the national doctrine since the mid-twentieth century by different authors, until composing its most current formulation by the hands of Eros Grau and Celso Antônio Bandeira de Mello. After this presentation, the traditional theory is confronted with new political and legal contexts that transformed the economic order, as well as the recent doctrinal criticisms about the applicability of this dichotomy in Brazilian law.
Desafios à consensualização no direito administrativo sancionador disciplinar: reflexões à luz da literatura jurídica, da legislação e da prática administrativa
Authors: Lima Cesar Henrique
Published: February 2024

The purpose of this article is to address the challenges imposed on the implementation of consensual solutions within the scope of Brazilian disciplinary administrative law. The main idea of this text is to discuss the principal obstacles to the adoption of concerted solutions by the Brazilian Public Administration in the field of disciplinary law. Will be analyzed some contributions on the subject contained in the specialized legal literature will be exposed, the legal norms relevant to the subject existing at the federal level will be highlighted, as well as some contributions arising from administrative practice regarding the matter.
O impacto da hipernormatividade da Lei 8.666/93 em pequenos municípios paulistas
Authors: Almeida Gabriel Schroeder de
Published: February 2024

Questo articolo è il risultato di una ricerca empirica, basata su interviste semi-direttive condotte con dipendenti di piccoli Comuni nello stato di San Paolo, sullo svolgimento di offerte da parte di queste unità di potere locali e sulla visione dei loro agenti in merito alla Legge Federale 8.666 /1993. Il lavoro presenta l'idea che la legge 8.666/93 sia caratterizzata da un'ipernormatività, rappresentata dalla sua pretesa di regolamentare meticolosamente tutti i processi di assunzione sviluppati in Brasile, in tutti gli ambiti federativi. In considerazione di ciò, sono stati intervistati gli agenti municipali coinvolti negli appalti pubblici per identificare se le preoccupazioni circa gli impatti dell'ipernormatività sulla qualità della gestione municipale sarebbero state confermate. Il lavoro conclude che i dipendenti dei settori appaltanti dei piccoli comuni hanno un atteggiamento di relativa indifferenza rispetto al carattere della legge 8.666/93 o si sentono tutelati dal suo dettaglio. Anche altri argomenti relativi ai processi di gara sono affrontati nelle interviste e sviluppati nel testo.