bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer
Authors: Hyung Sujin , Ko Jihoon , Heo You Jeong , Blum Steven M. , Kim Seung Tae , Park Se Hoon , Park Joon Oh , Kang Won Ki , Lim Ho Yeong , Klempner Samuel J. , Lee Jeeyun
Published: November 2023

Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXO
Ascites
) in cancer progression and use modified exosomes as resources for cancer therapy. EXO
Ascites
from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXO
Ascites
concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In
MET
-amplified GC, EXO
Ascites
contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived
MET
-amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a
MET
non-amplified GC model.
MET
-amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC.
Periportal necrosis and successful liver transplantation following Lamotrigine drug-induced liver injury in a child
Authors: Couper Michael Richard , Brown Rachel M , Nath Stuart , Parida Amitav , Kelgeri Chayarani
Published: November 2023

Lamotrigine is one of the most prescribed antiepileptics in children and a well-known cause of drug-induced liver injury (DILI). The typical presentation usually includes a drug rash with eosinophilia and systemic symptoms (DRESS syndrome). Cases are typically mild and self-limiting, requiring supportive care only. We report a severe Lamotrigine-induced DILI with a non-typical presentation with hyperammonaemia and rapid clinical deterioration. We present a literature review exploring contributing factors, transplant considerations and liver histology. Histology showed periportal necrosis, which is recognised as a pattern of DILI but has not been previously described with Lamotrigine. Our patient proceeded to transplant and is the first reported liver transplant for Lamotrigine DILI in a child. A directed and rapid diagnostic approach is crucial to avoid delays and rule out multisystemic metabolic and genetic conditions that preclude liver transplantation.
Impact of a capacity-building intervention on views and perceptions of healthcare providers towards the provision of adolescent sexual and reproductive health services in southeast Nigeria: a cross-sectional qualitative study
Authors: Agu Ifunanya Clara , Agu Chibuike , Mbachu Chinyere , Onwujekwe Obinna
Published: November 2023

Objectives

Negative views of healthcare providers towards adolescent sexual and reproductive health (SRH) services deter adolescents from seeking vital SRH services. This paper assessed the impact of an intervention on the views and perceptions of healthcare providers towards the provision of adolescent SRH services.

Design and setting

A descriptive, cross-sectional, qualitative study was conducted between 14 October and 19 November 2021 in six local government areas (LGAs) in Ebonyi state, southeast Nigeria, after the implementation of an intervention comprising of training and supportive supervision.

Participants and data collection

Data were collected through: (1) two in-depth interviews (IDIs) with LGA healthcare managers; (2) six IDIs with LGA adolescent health programme managers; (3) two focus group discussions (FGDs) with 15 primary healthcare facility managers; (4) two FGDs with 20 patent medicine vendors and (5) two FGDs with 17 community health volunteers. A total of six FGDs were held with 52 healthcare providers. The interviews were conducted using pretested interview guides. Transcripts were coded in NVivo (V.12) and themes were identified through inductive analysis.

Results

As a result of the intervention, most healthcare providers started recognising the rights of adolescents to obtain contraceptive services and no longer deny them access to contraceptive services. The providers also became friendlier and were no longer harsh in their interactions with adolescents. There were some unique findings relative to whether the providers were formal or informal healthcare providers. It was found that the informal healthcare providers were bolder and more comfortable delivering SRH services to adolescents and reported improved patronage by the adolescents. The formal healthcare providers made their facilities more conducive for adolescents by creating safe spaces and introducing extracurricular activities.

Conclusion

These findings highlight the importance of the constant capacity building of both formal and informal healthcare providers, which can address healthcare providers’ biases, views and perceptions of delivering SRH services to adolescents.
Integrative multiomics enhancer activity profiling identifies therapeutic vulnerabilities in cholangiocarcinoma of different etiologies
Authors: Hong Jing Han , Yong Chern Han , Heng Hong Lee , Chan Jason Yongsheng , Lau Mai Chan , Chen Jianfeng , Lee Jing Yi , Lim Abner Herbert , Li Zhimei , Guan Peiyong , Chu Pek Lim , Boot Arnoud , Ng Sheng Rong , Yao Xiaosai , Wee Felicia Yu Ting , Lim Jeffrey Chun Tatt , Liu Wei , Wang Peili , Xiao Rong , Zeng Xian , Sun Yichen , Koh Joanna , Kwek Xiu Yi , Ng Cedric Chuan Young , Klanrit Poramate , Zhang Yaojun , Lai Jiaming , Tai David Wai Meng , Pairojkul Chawalit , Dima Simona , Popescu Irinel , Hsieh Sen-Yung , Yu Ming-Chin , Yeong Joe , Kongpetch Sarinya , Jusakul Apinya , Loilome Watcharin , Tan Patrick , Tan Jing , Teh Bin Tean
Published: November 2023

Objectives

Cholangiocarcinoma (CCA) is a heterogeneous malignancy with high mortality and dismal prognosis, and an urgent clinical need for new therapies. Knowledge of the CCA epigenome is largely limited to aberrant DNA methylation. Dysregulation of enhancer activities has been identified to affect carcinogenesis and leveraged for new therapies but is uninvestigated in CCA. Our aim is to identify potential therapeutic targets in different subtypes of CCA through enhancer profiling.

Design

Integrative multiomics enhancer activity profiling of diverse CCA was performed. A panel of diverse CCA cell lines, patient-derived and cell line-derived xenografts were used to study identified enriched pathways and vulnerabilities. NanoString, multiplex immunohistochemistry staining and single-cell spatial transcriptomics were used to explore the immunogenicity of diverse CCA.

Results

We identified three distinct groups, associated with different etiologies and unique pathways. Drug inhibitors of identified pathways reduced tumour growth inin vitroandin vivomodels. The first group (ESTRO), with mostly fluke-positive CCAs, displayed activation in estrogen signalling and were sensitive to MTOR inhibitors. Another group (OXPHO), with mostlyBAP1andIDH-mutant CCAs, displayed activated oxidative phosphorylation pathways, and were sensitive to oxidative phosphorylation inhibitors. Immune-related pathways were activated in the final group (IMMUN), made up of an immunogenic CCA subtype and CCA with aristolochic acid (AA) mutational signatures. Intratumour differences in AA mutation load were correlated to intratumour variation of different immune cell populations.

Conclusion

Our study elucidates the mechanisms underlying enhancer dysregulation and deepens understanding of different tumourigenesis processes in distinct CCA subtypes, with potential significant therapeutics and clinical benefits.
First-in-human trial of a self-expandable, temporary dilation system for intracranial atherosclerotic disease in patients presenting with acute ischemic stroke
Authors: Ohta Tsuyoshi , Takeuchi Masataka , Yamagami Hiroshi , Tsuto Kazuma , Yamamoto Shiro , Asai Katsunori , Ishii Akira , Imamura Hirotoshi , Yoshimura Shinichi , Fukumitsu Ryu , Sakai Chiaki , Sakai Nobuyuki , Tateshima Satoshi
Published: November 2023

Background

Intracranial atherosclerotic disease (ICAD) significantly contributes to ischemic stroke, especially among Asian populations. Large vessel occlusion (LVO) due to underlying ICAD accounts for 15–35% of acute ischemic stroke cases requiring endovascular therapy. However, the successful recanalization rate of ICAD-related LVO remains lower. The TG dilator is a self-expandable device, temporarily dilating ICAD-related blocked blood vessels.

Objective

To demonstrate TG dilator safety and efficacy for ICAD-related acute ischemic stroke.

Methods

This was a single-arm, open-label, non-randomized, prospective, multicenter, and investigator-initiated trial that involved patients undergoing TG dilator application for acute ischemic stroke caused by ICAD-related LVO or severe stenosis.

Results

We enrolled 10 patients in this trial between November 2022 and April 2023. The median (IQR) age was 68 (59.3–75.3) years. Before using the dilator, seven patients received stent retriever treatment. All 10 patients were prescribed a loading dose of aspirin with prasugrel. The median application time was 10 (10–12) min. At the end of the procedure, we achieved significant recanalization immediately in all patients. The stenosis/occlusion decreased from 100% (100–100) to 68% (56.3–75.3). No patient experienced recurrent ischemic stroke or reocclusion within 90 days. We achieved a modified Rankin scale score of 0–2 in 8 patients by day 90. We detected no cases of intracranial hemorrhage, equipment failure, distal embolism, vasospasm, dissection, or perforation requiring intervention.

Conclusions

Acute revascularization using the TG dilator on patients with ICAD-related LVO or severe stenosis did not cause any significant adverse event, and consistently improved blood flow at 90 days.
Recurrentde-novo gain-of-functionmutation inSPTLC2confirms dysregulated sphingolipid production to cause juvenile amyotrophic lateral sclerosis
Authors: Dohrn Maike F , Beijer Danique , Lone Museer A , Bayraktar Elif , Oflazer Piraye , Orbach Rotem , Donkervoort Sandra , Foley A Reghan , Rose Aubrey , Lyons Michael , Louie Raymond J , Gable Kenneth , Dunn Teresa , Chen Sitong , Danzi Matt C , Synofzik Matthis , Bönnemann Carsten G , Nazlı Başak A , Hornemann Thorsten , Zuchner Stephan
Published: November 2023

Background

Amyotrophic lateral sclerosis (ALS) leads to paralysis and death by progressive degeneration of motor neurons. Recently, specificgain-of-functionmutations inSPTLC1were identified in patients with juvenile form of ALS. SPTLC2encodes the second catalytic subunit of the serine-palmitoyltransferase (SPT) complex.

Methods

We used the GENESIS platform to screen 700 ALS whole-genome and whole-exome data sets for variants inSPTLC2. Thede-novostatus was confirmed by Sanger sequencing. Sphingolipidomics was performed using liquid chromatography and high-resolution mass spectrometry.

Results

Two unrelated patients presented with early-onset progressive proximal and distal muscle weakness, oral fasciculations, and pyramidal signs. Both patients carried the novelde-novo SPTLC2mutation, c.203T>G, p.Met68Arg. This variant lies within a single short transmembrane domain of SPTLC2, suggesting that the mutation renders the SPT complex irresponsive to regulation through ORMDL3. Confirming this hypothesis, ceramide and complex sphingolipid levels were significantly increased in patient plasma. Accordingly, excessive sphingolipid production was shown in mutant-expressing human embryonic kindney (HEK) cells.

Conclusions

Specificgain-of-functionmutations in both core subunits affect the homoeostatic control of SPT.SPTLC2represents a new Mendelian ALS gene, highlighting a key role of dysregulated sphingolipid synthesis in the pathogenesis of juvenile ALS. Given the direct interaction of SPTLC1 and SPTLC2, this knowledge might open new therapeutic avenues for motor neuron diseases.
Recurrent de novoSPTLC2variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis
Authors: Syeda Safoora B , Lone Museer A , Mohassel Payam , Donkervoort Sandra , Munot Pinki , França Marcondes C , Galarza-Brito Juan Eli , Eckenweiler Matthias , Asamoah Alexander , Gable Kenneth , Majumdar Anirban , Schumann Anke , Gupta Sita D , Lakhotia Arpita , Shieh Perry B , Foley A Reghan , Jackson Kelly E , Chao Katherine R , Winder Thomas L , Catapano Francesco , Feng Lucy , Kirschner Janbernd , Muntoni Francesco , Dunn Teresa M , Hornemann Thorsten , Bönnemann Carsten G
Published: November 2023

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specificSPTLC1variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant inSPTLC2c.778G>A [p.Glu260Lys] manifesting with juvenile ALS.

Methods

Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients’ blood and fibroblasts, was performed.

Results

All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate thatSPTLC2variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causingSPTLC2variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reportedSPTLC1ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic inSPTLC1andSPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS.

Conclusions

SPTLC2is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further.
Pragmatic computerised perfusion diagnostics for non-convulsive status epilepticus: a prospective observational study
Authors: Merli Elena , Romoli Michele , Galluzzo Simone , Bevacqua Lorenzo , Cece Emanuele Saverio , Ricci Gabriele , Testoni Stefania , Zaniboni Anna , Viola Maria Maddalena , Simonetti Luigi , Bisulli Francesca , Contardi Sara , Tinuper Paolo , Zini Andrea
Published: November 2023

Background

Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow.

Methods

We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard.

Results

Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1).

Conclusion

CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.
Five-day evaluation of the acceptability and comfort of wearable technology at four anatomical locations during military training
Authors: Taylor Natalie , Carroll A , Gifford R M
Published: November 2023

Introduction

Wearable sensor technologies enable Defence to optimise human performance, remotely identify physiological abnormalities and enhance medical support. Maximising the acceptability of devices will ensure they are worn alongside other equipment. This study assessed the acceptability and comfort of four devices at different anatomical locations during military training.

Method

A cross-sectional pilot study during a live firing infantry exercise or adventurous training assessed four anatomical locations concurrently over 5 days: finger, wrist, upper arm and chest. Participants rated comfort, acceptability and preference using a standardised questionnaire after 12 hours and 5 days of wear.

Results

Twenty-one regular British Army personnel soldiers participated, aged 24.4 (4.3) years. The upper arm location received the highest rating by participants for comfort, followed in order by wrist, finger and chest (p=0.002, Χ2=40.0). The finger was most commonly identified as uncomfortable during specific activities (76%), followed by chest (48%), wrist (23%) and upper arm devices (14%). There was no significant difference in participant confidence in the devices to collect data or allow movement, but there was a trend towards greater confidence in upper arm and wrist locations to stay in position than the others (p=0.059, Χ2=28.0). After 5 days of wear, 43% of participants said they preferred the upper arm for comfort, followed by wrist (36%), finger (24%) and chest (10%). 73% and 71% would wear the wrist and upper arm devices on deployed operations, compared with 29% and 24% for chest and finger devices, respectively.

Conclusion

The upper arm location offered greater acceptability and comfort than finger, wrist or chest locations. It is essential to consider such findings from occupationally relevant settings when selecting wearable technology. A larger service evaluation in diverse settings is recommended to guide the choice of the most acceptable wearable devices across different equipment, roles and environments.
Accuracy of heart rate measured by military-grade wearable ECG monitor compared with reference and commercial monitors
Authors: Lindsey Bryndan , Hanley C , Reider L , Snyder S , Zhou Y , Bell E , Shim J , Hahn J-O , Vignos M , Bar-Kochba E
Published: November 2023

Introduction

Physiological monitoring of soldiers can indicate combat readiness and performance. Despite demonstrated use of wearable devices for HR monitoring, commercial options lack desired military features. A newly developed OMNI monitor includes desired features such as long-range secure data transmission. This study investigated the accuracy of the OMNI to measure HR via accuracy of R-R interval duration relative to research-grade ECG and commercial products.

Methods

54 healthy individuals (male/female=37/17, age=22.2±3.6 years, height=173.0±9.1 cm, weight=70.1±11.2 kg) completed a submaximal exercise test while wearing a reference ECG (Biopac) and a randomly assigned chest-based monitor (OMNI, Polar H10, Equivital EQ-02, Zephyr Bioharness 3). All participants also wore two wrist-based photoplethysmography (PPG) devices, Garmin fēnix 6 and Empatica E4. Bland-Altman analyses of agreement, concordance correlation coefficient (CCC) and root-mean-squared error (RMSE) were used to determine accuracy of the OMNI and commercial devices relative to Biopac. Additionally, a linear mixed-effects model evaluated the effects of device and exercise intensity on agreement.

Results

Chest-based devices showed superior agreement with Biopac for measuring R-R interval compared with wrist-based ones in terms of mean bias, CCC and RMSE, with OMNI demonstrating the best scores on all metrics. Linear mixed-effects model showed no significant main or interaction effects for the chest-based devices. However, significant effects were found for Garmin and Empatica devices (p<0.001) as well as the interaction effects between both Garmin and Empatica and exercise intensity (p<0.001).

Conclusions

Chest-based ECG devices are preferred to wrist-based PPG devices due to superior HR accuracy over a range of exercise intensities, with the OMNI device demonstrating equal, if not superior, performance to other commercial ECG monitors. Additionally, wrist-based PPG devices are significantly affected by exercise intensity as they underestimate HR at low intensities and overestimate HR at high intensities.
Selection effects on early life history traits and thermal resistance in brook charr Salvelinus fontinalis
Authors: Gourtay Clémence , Rivolet Marine , Ghinter Léopold , Bernatchez Louis , Garant Dany , Audet Céline
Published: November 2023

In the context of climate change, it is crucial to understand whether animals that have been domesticated and (or) selected maintain their abilities to adapt to changes in their thermal environment. Here, we tested how selection for absence of early sexual maturation combined with better growth performance may have impacted thermal resistance and gene expression response in the presence of thermal stress in brook charr Salvelinus fontinalis (Mitchill, 1814). We performed temperature challenge tests on brook charr 0+ juveniles and studied the expression of genes involved in the response to oxidative stress, in synthesis of heat shock proteins, or involved in regulation of apoptosis, in heart and liver tissues. Juveniles from the selected lineage had a higher thermal resistance than controls and a loss of equilibrium occurred on average 1 °C above what was observed for the controls. The relative expressions of catalase and HSP70 were significantly higher in juveniles from the selection program. Overall, thermally sensitive fish were characterized by low mass and length and lower relative expressions of genes associated with stress response. Our results indicate that selection for traits of interests may be indirectly related to the significant lineage effect on growth in early stages of development.
gLSM: Using GPGPU to Accelerate Compactions in LSM-tree-based Key-value Stores
Authors: Sun Hui , Xu Jinfeng , Jiang Xiangxiang , Chen Guanzhong , Yue Yinliang , Qin Xiao
Published: November 2023

Log-structured-merge tree or LSM-tree is a technological underpinning in key-value (KV) stores to support a wide range of performance-critical applications. By conducting data re-organization in the background by virtue of compaction operations, the KV stores have the potential to swiftly service write requests with sequential batched disk writes and read requests for KV items constantly sorted by the compaction. Compaction demands high I/O bandwidth and CPU speed to facilitate quality service to user read/write requests. With the emergence of high-speed SSDs, CPUs are increasingly becoming a performance bottleneck. To mitigate the bottleneck limiting the KV-store’s performance and that of the applications supported by the store, we propose a system -
gLSM
- to leverage GPGPU to remarkably accelerate the compaction operations. gLSM fully utilizes the parallelism and computational capability inside GPGPUs to improve the compaction performance. We design a driver framework to parallelize compaction operations handled between a pair of CPU and GPGPU. We employ data independence and GPGPU-orient radix-sorting algorithm to concurrently conduct compaction. A key-value separation method is devised to slash the transfer of data volume from CPU-side memory to the GPGPU counterpart. The results reveal that gLSM improves the throughput and compaction bandwidth by up to a factor of 2.9 and 26.0, respectively, compared with the four state-of-the-art KV stores. gLSM also reduces the write latency by 73.3%. gLSM exhibits a performance improvement by up to 45% compared against its variant where there are no KV separation and collaboration sort modules.
Application of Smart Insoles for Recognition of Activities of Daily Living: A Systematic Review
Authors: D’arco Luigi , Mccalmont Graham , Wang Haiying , Zheng Huiru
Published: November 2023

Recent years have witnessed the increasing literature on using smart insoles in health and well-being, and yet, their capability of daily living activity recognition has not been reviewed. This paper addressed this need and provided a systematic review of smart insole-based systems in the recognition of Activities of Daily Living (ADLs). The review followed the PRISMA guidelines, assessing the sensing elements used, the participants involved, the activities recognised, and the algorithms employed. The findings demonstrate the feasibility of using smart insoles for recognising ADLs, showing their high performance in recognising ambulation and physical activities involving the lower body, ranging from 70% to 99.8% of Accuracy, with 13 studies over 95%. The preferred solutions have been those including machine learning. A lack of existing publicly available datasets has been identified, and the majority of the studies were conducted in controlled environments. Furthermore, no studies assessed the impact of different sampling frequencies during data collection, and a trade-off between comfort and performance has been identified between the solutions. In conclusion, real-life applications were investigated showing the benefits of smart insoles over other solutions and placing more emphasis on the capabilities of smart insoles.
MEK1-ERK1/2 signaling regulates the cardiomyocyte non-sarcomeric actin cytoskeletal network
Authors: Grimes Kelly M. , Maillet Marjorie , Swoboda Casey O. , Bowers Stephanie L. K. , Millay Doug P. , Molkentin Jeffery D.
Published: November 2023

Here, we performed an unbiased analysis of the total phosphoproteome downstream of MEK1-ERK1/2 kinase signaling in cardiomyocytes. Pathway analysis suggested that proteins of the non-sarcomeric cytoskeleton were the most differentially affected. We showed that cytoplasmic β-actin and γ-actin isoforms, regulated by MEK1-ERK1/2, are localized to the subcortical space at both lateral membranes and intercalated discs of adult cardiomyocytes suggesting how MEK1-ERK1/2 signaling might underlie directional growth of adult cardiomyocytes.
Patchable Transparent Standalone Piezoelectric P(VDF-TrFE) Film for Radial Artery Pulse Detection
Authors: Hu Yian , Huang Shunyao , Gao Yujia , Lee Jaeyeon , Jin Zhangsiyuan , An Geon-Hyoung , Cho Yuljae
Published: November 2023

Wearable or patchable biosensors have attracted tremendous attention due to their continuous health-monitoring capabilities. In particular, self-powered passive biosensors based on a piezoelectric nanogenerator (PENG) have demonstrated measurements of physiological signals from which cardiovascular information can be analyzed such as heart rate and blood pressure. However, challenges still remain with regard to both material and device aspects. For the effective and accurate measurement of extremely weak physiological signals, various methods have been introduced, including employment of inorganic lead-based piezoelectric materials and design of a complex material or device structure. In spite of their effectiveness in enhancing the piezoelectric output response, the introduced methods brought concomitant issues, such as toxicity and complexity. We present unique methods to produce a transparent standalone piezoelectric polymer film which can be directly transferred to any surface such as the human skin. Through a room temperature solvent vapor annealing process, we further enhance the crystallinity and a portion of the ferroelectric β-phase of the transparent standalone polymer film, resulting in an improved piezoelectric output response. Based on these two new methods introduced, we demonstrate a simple sandwich-structured, transparent, and patchable biosensor based on PENG for radial artery detection with significantly reduced complex manufacturing processes, providing great practical value.
Comparison of the Diagnostic Performance of Five Clinical Questionnaires for Chronic Obstructive Pulmonary Disease
Authors: Bastidas Alirio R. , Tuta-Quintero Eduardo , Arias José S. , Cufiño Diana , Moya Diana , Martin Daniel , Rodríguez Faure , Aponte-Murcia Carolina , Pumarejo Doris M. , Bejarano Maria A. , Ospina Geraldine , Morales Lina M. , Portella Adriana M. , Barragán Maria D. , Álvarez Daniela A. , Hernández José M.
Published: November 2023

Background. Chronic obstructive pulmonary disease (COPD) remains one of the most prevalent pathologies in the world and is among the leading causes of mortality and morbidity, partially due to underdiagnosis. The use of clinical questionnaires to identify high-risk individuals to take them to further diagnostic procedures has emerged as a strategy to address this problem. Objective. To compare the performance of the COULD IT BE COPD, CDQ, COPD-PS, LFQ, and PUMA questionnaires for COPD diagnosis. Methods. A cross-sectional study was carried out on subjects who underwent spirometry in the third-level center. Data were collected between January 2015 and March 2020. Bivariate analysis was performed between the study variables and the presence of COPD. The area under the receiver operating characteristics curve (AUC-ROC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR−) for each questionnaire were calculated. The AUC-ROCs were compared with the DeLong test, considering a

p

value <0.05 statistically significant. Results. 681 subjects met the inclusion criteria and were taken to the final analysis. The prevalence of COPD was 27.5% (187/681). The mean age of the subjects was 65.9 years (SD ± 11.79); 46.3% (315/681) were female, and 83.6% (569/681) reported respiratory symptoms. Statistically significant relationship was found for COPD diagnosis with male sex, older age, respiratory symptoms, and exposure to wood smoke (

p

value <0.05). The AUC-ROCs of the questionnaires were between 0.581 and 0.681. The COULD IT BE COPD questionnaire had a lower discriminatory capacity AUC-ROC of 0.581, concerning the other scores (DeLong test,

p

 = 0.0002). Conclusion. The CDQ, COPD-PS, LFQ, PUMA, and COULD IT BE COPD questionnaires have acceptable performance for the diagnosis of COPD together with low sensitivity and specificity. Therefore, its use must be complemented with other diagnostic tests or techniques such as pulmonary function tests.
Diabetes Mellitus and HIV Infection among Newly Diagnosed Pulmonary Tuberculosis Patients in the North West Region of Cameroon: A Cross-Sectional Study
Authors: Sama Leonard Fonkeng , Sadjeu Sidoine , Tchouangueu Thibau Flaurant , Dabou Solange , Kuh Georges Ful , Ngouateu Omer Bebe , Noubom Michel
Published: November 2023

Objective. To determine the prevalence rate of HIV and diabetes among tuberculosis (TB) patients and also the comorbidity rate. Design. Cross-sectional study. Setting. This study was carried out at the Tuberculosis Reference Laboratory, Regional Hospital Bamenda, North West Region of Cameroon, from January 2017 to December 2019. Participants. 1115 cases of pulmonary tuberculosis aged ≥14 years (mean 42.5 ± 15.28 years). Methods. Sputum samples collected were acid-fast stained and examined macroscopically as well as inoculated for culture. A chest X-ray was performed for further confirmation of TB diagnosis. After the TB diagnosis was done, fasting blood glucose, 2 h-PG test, HbA1c, and biochemical enzymatic tests were performed for the diagnosis of diabetes. Rapid strip test and enzyme-linked immunosorbent assay were used to diagnose HIV infection. Interventions. No intervention was done during the period of study. Outcome Measures. The prevalence of TB/HIV and TB/HIV/DM, signs and symptoms, imaging results, and bacteriology status among TB/HIV, TB/HIV/DM coinfected, and comorbidity cases. Results. Of 1115 participants, 38.57% had TB/HIV, and 5.83% had TB/HIV/DM. Among TB/HIV/DM cases, 20.39% had a cough for more than 2 weeks [

p
 
<
 
0.0001

; OR (95%CI): 4.866 (3.170–7.404)], and 35.71% had a fever for at least 2 weeks [

p
 
<
 
0.0001

; OR (95%CI): 7.824 (5.336–11.36)]. The majority of TB/HIV/DM patients (77.42%) had chest pain for at least 2 weeks [

p
 
<
 
0.0001

; OR (95%CI): 114.3 (59.78–207.1)]. 7.41%, 14.18%, and 9.09% of TB/HIV/DM, respectively, had chest abnormality, positive smear, and positive culture (p = 0.018). Significant differences were observed between signs and symptoms, imaging results, bacteriology, treatment history for TB cases and those with HIV and/or DM, and those without HIV and/or DM coinfection and comorbidity. Conclusion. This study reports a high prevalence of DM comorbidity and HIV coinfection among active TB patients in the North West Region of Cameroon as well as TB/HIV/DM comorbidity.
Efficient One-Pot Synthesis of Novel Caffeic Acid Derivatives as Potential Antimalarials
Authors: Sidoryk Katarzyna , Parapini Silvia , Basilico Nicoletta , Zaremba-Czogalla Magdalena , Kubiszewski Marek , Cybulski Marcin , Gubernator Jerzy , Zagórska Agnieszka , Jaromin Anna
Published: November 2023

New protocol for the preparation of the novel caffeic acid derivatives using the Wittig reaction has been applied to follow the principles of green chemistry. The compounds have been evaluated against chloroquine-sensitive and chloroquine-resistant P. falciparum strains. Their cytotoxicity to normal human dermal fibroblasts and their propensity to induce hemolysis have been also determined. Ethyl (2E)-3-(2,3,4-trihydroxyphenyl)-2-methylpropenoate has exhibited the highest antiplasmodial activity against P. falciparum strains without the cytotoxic and hemolytic effects. This derivative is significantly more potent than caffeic acid parent structure. The application of our one-step procedure has been shown to be rapid and efficient. It allows for an easy increase of input data to refine the structure-activity relationship model of caffeates as the antimalarials. The one-step approach meets the conditions of “atom economy” and eliminates hazardous materials. Water has been used as the effective medium for the Wittig reaction to avoid toxic organic solvents.
Investigation of the Proportion of Brucella abortus and Brucella melitensis in Sheep and Goat Milk
Authors: Rostami Saeid , Rashidian Ehsan , Jaydari Amin , Rahimi Heidar
Published: November 2023

Despite the implementation of brucellosis eradication programs in Iran, this disease is still endemic and highly prevalent among ruminants in this country. The infection of small ruminants with Brucella abortus may play a significant role in the continuation of brucellosis among the herds of ruminants. This study investigated the proportion of B. abortus and Brucella melitensis in 150 samples of sheep and goat’s raw milk which were obtained from Lorestan and Hamadan provinces in the western part of Iran using the PCR method. The results revealed that among the Brucella spp. positive samples, 26.5% and 73.4% of the samples were infected with B. abortus and B. melitensis, respectively. The incidence rates of B. abortus among the sheep and goats samples were 6.8% and 12.5%, respectively. There was a significant difference between goats and sheep regarding the proportion of B. abortus. Three samples (2%) (2 goats and one sheep) were simultaneously infected with both B. melitensis and B. abortus. This article renews our knowledge about the causative agent of brucellosis in small ruminants and shows that B. abortus has a relatively high prevalence among those animals in the western regions of Iran, and its role as one of the main factors of abortion among small ruminants should not be ignored. The information provided in the present study is important for the surveillance program, as eradication programs and strategies to prevent the spread of B. abortus among small ruminants that have not been vaccinated against this microorganism may be adapted accordingly.
Orientin Reduces the Effects of Repeated Procedural Neonatal Pain in Adulthood: Network Pharmacology Analysis, Molecular Docking Analysis, and Experimental Validation
Authors: Guo Dong-Dong , Huang Hai-Yan , Liu Hai-E. , Liu Kun , Luo Xing-Jing
Published: November 2023

Background. Premature infants often undergo painful procedures and consequently experience repeated procedural neonatal pain. This can elicit hyperalgesia and cognitive impairment in adulthood. Treatments for neonatal pain are limited. Orientin is a flavonoid C-glycoside that has repeatedly been shown to have pharmacological effects in the past decades. The aim of this study was to systematically explore the effect of orientin on repeated procedural neonatal pain using network pharmacology, molecular docking analysis, and experimental validation. Methods. Several compound-protein databases and disease-protein databases were employed to identify proteins that were both predicted targets of orientin and involved in neonatal pain. A protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential mechanism of action. Molecular docking analysis was employed to calculate the binding energy and visualize the interactions between orientin and potential target proteins. Finally, a mouse model of repeated procedural neonatal pain was established and orientin was administered for 6 days. The mechanical and thermal pain thresholds were assessed in neonates and adult mice. A Morris water maze was employed to investigate cognitive impairment in adult mice. Results. A total of 286 proteins that were both predicted targets of orientin and involved in neonatal pain were identified. The hub proteins were SRC, HSP90AA1, MAPK1, RHOA, EGFR, AKT1, PTPN11, ESR1, RXRA, and HRAS. GO analysis indicated that the primary biological process (BP), molecular function (MF), and cellular component (CC) were protein phosphorylation, protein kinase activity, and vesicle lumen, respectively. KEGG analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway may be the key to the mechanism of action. Molecular docking analysis showed the high binding affinities of orientin for MAPK1, MAPK8, and MAPK14. In mice, orientin inhibited the hyperalgesia in the pain threshold tests in neonates and adult mice and cognitive impairment in adult mice. Immunofluorescence showed that phosphorylated MAPK1 (p-ERK) protein levels in the hippocampus and spinal dorsal horn were downregulated by orientin. Conclusion. The findings suggested that orientin alleviates neonatal pain, and the MAPK signaling pathway is involved.
An Analytical View of Nonlinear Fractional Burger’s Equations Using Conformable Double Elzaki Transform
Authors: Abd Elmohmoud Eltaib M. , Mohamed Mohamed Z. , Magzoub M. , Elsheikh Alla Mahmoud
Published: November 2023

The conformable double Elzaki composition technique (CDET) and the Adomian decomposition technique are combined in this work to provide a novel approach for dealing with nonlinear partial issues under certain specified conditions. The conformable double Elzaki composition (CDEC) approach is the name we give to this novel technique. We also outline and discuss the main traits and major conclusions connected to the recommended technique. The new technique provides an estimated succession of answers that finally get close to the exact solution. This method has the advantage of generating findings rapidly since it generates analytical series solutions for the target equations without the requirement for discretization, transformation, or limited assumptions. We also present some numerical applications to back up our conclusions. The results demonstrate the strength and potency of the recommended strategy in dealing with a variety of problems in the fields of engineering and physics in symmetry with other strategies.
A Case of Symptomatic Intraluminal Internal Carotid Artery Thrombus in a Patient with Essential Thrombocythemia Surgically Treated by CEA
Authors: Takahashi Satoshi , Katsumata Masahiro , Nogawa Hirotsugu , Takahara Kento , Nakahara Jin , Toda Masahiro
Published: November 2023

We report a patient with a symptomatic intraluminal internal carotid artery thrombus clinically revealed by cerebral infarction. In the preoperative evaluation, it was revealed that essential thrombocythemia existed in the background. Therefore, medical treatment with antithrombotic agents in conjunction with hydroxycarbamide for essential thrombocythemia was initiated, but the thrombus was not dissolved by three weeks. At this time, the patient underwent carotid endarterectomy, which removed the thrombus completely with its adjacent plaque without any perioperative stroke. The possibility of essential thrombocythemia may also be kept in mind when an increased platelet count is observed in patients with internal carotid artery thrombus. It is a reasonable option to precede medical treatment, including anticoagulant therapy, by setting the time limit for surgical intervention in such a disease state.
СТАН ІМУННОЇ СИСТЕМИ ТА ХАРАКТЕР ІМУННИХ ПОРУШЕНЬ У ВЗАЄМОЗВ’ЯЗКУ З НАПРУЖЕНІСТЮ ІМУНІТЕТУ ДО ДИФТЕРІЇ ТА ПРАВЦЯ В ОСІБ, ЯКІ ПЕРЕХВОРІЛИ НА ХВЕБІ
Authors: Лядова Т. І. , Попова А. М.
Published: November 2023

Епштейна-Барр вірусна інфекція (ВЕБ-інфекція) є однією із найпоширеніших у світі. Вірусом Епштейна-Барр інфіковано біля 90 % населення планети.

Активна проліферація вірусу у лімфоїдних органах може призводити до значних структурних змін і функціональної активності, спричиняти лімфаденопатію, гепато- та спленомегалію, індукувати імунодефіцитний стан, лімфопроліферативні та онкологічні процеси, синдром хронічної втоми.

Мета роботи – вивчити стан імунної системи і визначити характер імунних порушень в осіб, які перехворіли на ХВЕБІ, у взаємозв’язку з напруженістю імунітету до дифтерії та правця.

Матеріали і методи. Було вивчено стан імунної системи і характер імунних порушень у дорослих, які перенесли ХВЕБІ, серед яких 16 осіб (1-а група), які не мають одночасно захисного рівня антитіл (АТ) до дифтерії та правця та у 16 дорослих (2-а група), в яких є захисний рівень АТ до цих інфекцій. Контрольну групу склали 20 осіб. Середній вік обстежених становив (20,3±2,3) року. Вивчали стан Т-, В- і фагоцитарної ланки імунітету. Результати досліджень було опрацьовано методом варіаційної та кореляційної статистики з використанням програми «Statistica 10,0 for Windows».

Результати досліджень та їх обговорення. Встановлено, що в осіб 1-ї і 2-ї групи, які перехворіли на ХВЕБІ, після повного клінічного одужання спостерігаються порушення в імунній системі, які зачіпають всі ланки імунітету. Так, у Т-ланці відбувається вірогідне зниження бласттрансформувальної здатності Т-лімфоцитів, підвищення вмісту CD8+ та CD16+-клітин у крові, підвищення рівня лімфоцитів, які експресують молекули апоптозу СD95+, Bcl-2, порушення співвідношення CD4+/CD8+-клітин та CD8+CD28+/CD8+CD28- за рахунок підвищення вмісту серед лімфоцитів клітин із цитотоксичними і супресорними властивостями. У фагоцитарній ланці відбувається вірогідне зниження поглинальної та перетравлювальної здатності лейкоцитів крові. В осіб 2-ї групи серед основних класів імуноглобулінів реєструється вірогідне підвищення рівня IgG.

Висновок. В осіб, які перехворіли на ВЕБ-інфекцію, спостерігаються розлади в Т-, В- і фагоцитарній ланках імунітету. Відсутність захисного рівня АТ до дифтерії та правця в осіб, які перехворіли на ХВЕБІ, асоціюється з дисбалансом серед Т-регуляторних клітин, низьким вмістом Т-хелперів, високим відсотком Т-супресорів, низьким рівнем проліферативної активності Т-лімфоцитів, високим відсотком лімфоцитів, які експресують маркери апоптозу.
АЦИНЕТОБАКТЕРНА ІНФЕКЦІЯ У ХВОРИХ НА COVID-19
Authors: Бондаренко А. В. , Чумаченко І. В. , Бондаренко О. В. , Кацапов Д. В. , Доценко Н. В. , Крохмаль І. В.
Published: November 2023

Розробка стратегії запобігання нозокоміальним інфекціям нерозривно пов’язана з розумінням причин і механізмів їх поширення. Під час пандемії COVID-19 в Україні, як і в усьому світі, значно зросли ризики виникнення таких інфекцій. Всі медичні заклади є осередками підвищеного ризику передачі збудників, що найчастіше демонструють стійкість до антибіотиків та є причиною більшості нозокоміальних інфекцій (ESKAPE), але передусім стаціонари для лікування хворих на COVID-19.

Наведено інформацію про ко-інфекції та вторинні інфекції у хворих на COVID-19, що обумовлені Acinetobacter baumannii. A. baumannii займає лідируючі позиції серед збудників нозокоміальних інфекцій, що виникають у хворих на COVID-19. Захворювання має тяжкий клінічний перебіг й високу смертність через значну стійкість мікроорганізму до більшості антибактерійних препаратів. Основною причиною цього є зміна властивостей A. baumannii через некоректне використання антимікробних засобів і створення умов для відбору полі- та панрезистентних штамів у медичних закладах, зокрема за рахунок міжвидової передачі генів антибіотикорезистентності. Особливо це стосується аерозольної передачі, оскільки майже всі госпіталізовані пацієнти зі зниженою сатурацією та підозрою на інфікованість SARS-CoV-2 потребують госпіталізації і кисневої терапії.

Розвиток A. baumanii-інфекції призводить до подовження тривалості лікування, збільшення летальних випадків, матеріальних збитків і негативно впливає на психологічний стан хворих. Для успішного уникнення таких ситуацій важливо дотримуватися суворих принципів інфекційного контролю. Для забезпечення ефективності протиепідемічних і профілактичних заходів необхідна Agile-трансформація систем надання медичних послуг шляхом підвищення адаптивності та резельєнтності процесів ресурсного забезпечення в умовах пандемій та воєнних конфліктів.