bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiogram of Bacteria Isolated from Bloodstream Infection‐Suspected Patients at the University of Gondar Comprehensive Specialized Hospital in Northwest Ethiopia: A Retrospective Study
Authors: Worku Minichil , Molla Tigist , Kasew Desie , Assefa Muluneh , Geteneh Alene , Aynalem Melak , Gizachew Mucheye , Biset Sirak
Published: July 2024

Background. Bacterial bloodstream infections (BSIs) are the leading cause of sepsis‐related morbidity and mortality worldwide. The emergence and spread of antimicrobial resistance (AMR) in bacteria is also a growing global concern. As a result, data on bacterial profile and their antibiogram are essential for strategies to contain drug resistance, improve the quality of patient care, and strengthen health systems. Methods. Retrospective data from bacteriological results of blood samples of BSI‐suspected patients from 2018 to 2021 were collected using a data collection sheet. Standard bacteriological techniques were followed during sample collection, culture preparation, bacterial identification, and antibiotic susceptibility testing (AST). We used Epi Info version 7 to enter and clean the data and then exported it to SPSS version 26 for analysis. Logistic regression models were used to measure the association between variables. A p value <0.05 with a 95% confidence interval was considered as statistically significant. Result. Of the total 2,795 blood culture records, 455 (16.3%) were culture positive for bacteria, with Klebsiella pneumoniae (26%) and Staphylococcus aureus (24.6%) being the leading isolates. The isolates were highly resistant to common antibiotics, with more than 80% of them being resistant to ceftriaxone and penicillin. Moreover, about 43% of isolates were multidrug resistant (MDR), with Klebsiella pneumoniae (65.5%), Acinetobacter species (56.7%), and Citrobacter species (53.8%) being the most common MDR isolates. Age and diagnosis year were significantly associated with the presence of bacterial BSIs (p value <0.05). Conclusion. Bacterial BSI and AMR were growing concerns in the study area. Bacteremia was more common in children under the age of five, and it decreased as the patient’s age increased. The alarming rate of AMR, such as MDR blood isolates, calls for periodic and continuous monitoring of antibiotic usage in the study area.
Monitoring of Aflatoxins B1, G1, B2, and G2 in Spices from Riyadh Markets by Liquid Chromatography Coupled to Tandem Mass Spectrometry
Authors: Khabbouchi Mohamed , Guesmi Nour , Sultan Abdulhameed bin , Alkhuzayyim Abdulaziz , Abdo Gharib Abdelhalim , Alhotan Adel , Aljarbou Walid
Published: July 2024

A total of 1053 samples of spices were collected from Riyadh markets during 2022. The contamination with aflatoxins (AF) B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2) was determined via liquid chromatography coupled to tandem mass spectrometry. AF extraction from spices was performed using an acetonitrile‐formic acid mixture. The results obtained show that the highest value for AFB1 (3.865 μg/kg) was detected in the bay leaf sample, while the highest value for AFB2 (3.461 μg/kg) was found in red chili powder. The values of AFG1 and AFG2 did not exceed 2.59 μg/kg. The AF analysis shows that 24 out of 1053 samples (2.3%) contained one or more of these AFs. The highest percentage of contaminated samples was detected in black pepper. AFB1 was found in 21 samples of six types of spices, while AFG2 was detected in eight samples of four types of spices. Also, none of the samples exceeded the Saudi Food and Drug Authority and EU limits of 10 μg/kg. The present research is not a comprehensive study; however, it provides valuable information on AFB1, AFB2, AFG1, and AFG2 levels in the Kingdom of Saudi Arabia spices.
Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer
Authors: Dilly Julien , Hoffman Megan T. , Abbassi Laleh , Li Ziyue , Paradiso Francesca , Parent Brendan D. , Hennessey Connor J. , Jordan Alexander C. , Morgado Micaela , Dasgupta Shatavisha , Uribe Giselle A. , Yang Annan , Kapner Kevin S. , Hambitzer Felix P. , Qiang Li , Feng Hanrong , Geisberg Jacob , Wang Junning , Evans Kyle E. , Lyu Hengyu , Schalck Aislyn , Feng Ningping , Lopez Anastasia M. , Bristow Christopher A. , Kim Michael P. , Rajapakshe Kimal I. , Bahrambeigi Vahid , Roth Jennifer A. , Garg Kavita , Guerrero Paola A. , Stanger Ben Z. , Cristea Simona , Lowe Scott W. , Baslan Timour , Van Allen Eliezer M. , Mancias Joseph D. , Chan Emily , Anderson Abraham , Katlinskaya Yuliya V. , Shalek Alex K. , Hong David S. , Pant Shubham , Hallin Jill , Anderes Kenna , Olson Peter , Heffernan Timothy P. , Chugh Seema , Christensen James G. , Maitra Anirban , Wolpin Brian M. , Raghavan Srivatsan , Nowak Jonathan A. , Winter Peter S. , Dougan Stephanie K. , Aguirre Andrew J.
Published: July 2024

KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated with adagrasib or sotorasib, mutations in PIK3CA and KRAS, and amplifications of KRASG12C, MYC, MET, EGFR, and CDK6 emerged at acquired resistance. In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy. MRTX1133 treatment of the KrasLSL-G12D/+; Trp53LSL-R172H/+; p48-Cre (KPC) mouse model yielded deep tumor regressions, but drug resistance ultimately emerged, accompanied by amplifications of Kras, Yap1, Myc, Cdk6, and Abcb1a/b, and co-evolution of drug-resistant transcriptional programs. Moreover, in KPC and PDX models, mesenchymal and basal-like cell states displayed increased response to KRAS inhibition compared to the classical state. Combination treatment with KRASG12D inhibition and chemotherapy significantly improved tumor control in PDAC mouse models. Collectively, these data elucidate co-evolving resistance mechanisms to KRAS inhibition and support multiple combination therapy strategies.

Significance: Acquired resistance may limit the impact of KRAS inhibition in patients with PDAC. Using clinical samples and multiple preclinical models, we define heterogeneous genetic and non-genetic mechanisms of resistance to KRAS inhibition that may guide combination therapy approaches to improve the efficacy and durability of these promising therapies for patients.

See related commentary by Marasco and Misale, p. 2018
Atrioventricular Synchrony Delivered by a Dual-Chamber Leadless Pacemaker System
Authors: Ip James E. , Rashtian Mayer , Exner Derek V. , Reddy Vivek Y. , Doshi Rahul , Badie Nima , Nevo Jordan R. , Goil Aditya , Defaye Pascal , Canby Robert , Bongiorni Maria Grazia , Shoda Morio , Hindricks Gerhard , Knops Reinoud E.
Published: July 2024

BACKGROUND:

A dual-chamber leadless pacemaker system has been designed for atrioventricular synchronous pacing using wireless, beat-to-beat, implant-to-implant (i2i) communication between distinct atrial and ventricular leadless pacemakers. The atrioventricular synchrony achieved across various ambulatory scenarios has yet to be systematically evaluated.

METHODS:

A prospective, single-arm, unblinded, multicenter, international clinical trial of the leadless pacemaker system was conducted in patients with a conventional dual-chamber pacing indication enrolled from February 2022 to March 2023. Leadless pacemaker systems were implanted, and 12-lead Holter electrocardiographic recordings were collected 3 months after implantation over various postures/activities: sitting, supine, left lateral recumbent, right lateral recumbent, standing, normal walk, and fast walk. An independent Holter core laboratory performed a manual adjudication of the percent of atrioventricular synchronous beats using the standard 300-millisecond PR interval limit. Atrium-to-ventricle and ventricle-to-atrium i2i communication success rates were also assessed. Post hoc summary statistics describing the relationships between atrioventricular synchrony and i2i success, posture/activity, implantation indication, atrioventricular event, and heart rate were calculated.

RESULTS:

In the evaluable population (n=384 of 464 enrolled [83%]; 61% male; age, 70 years; weight, 82 kg; 60% ejection fraction; 95% of beats evaluable), the mean atrioventricular synchrony of 98% of beats observed across all postures using the standard 300-millisecond limit was greater than both atrial-to-ventricular i2i (94%) and ventricular-to-atrial i2i (94%;
P
<0.001), exceeding both i2i values in 95% of patients. Atrioventricular synchrony was achieved in >95% of evaluable beats across all postures/activities, implantation indications, atrioventricular paced/sensed event combinations, and heart rate ranges (including >100 bpm).

CONCLUSIONS:

This dual-chamber leadless pacemaker system demonstrated atrioventricular synchrony in 98% of evaluable beats at 3 months after implantation. Atrioventricular synchrony was maintained across postures/activities and remained robust for heart rates >100 bpm.
Multi-scale structural characterization of ceramic-based photonic glasses for structural colors
Authors: Häntsch Yen , Diaz Ana , Holler Mirko , Krekeler Tobias , Ritter Martin , Rosenfeldt Sabine , Retsch Markus , Furlan Kaline P.
Published: July 2024

Structural colors arise from selective light interaction with (nano)structures, which give them advantages over pigmented colors such as resistance to fading and possibility to be fabricated out of traditional low-cost and non-toxic materials. Since the color arises from the photonic (nano)structures, different structural features can impact their photonic response and thus, their color. Therefore, the detailed characterization of their structural features is crucial for further improvement of structural colors. In this work, we present a detailed multi-scale structural characterization of ceramic-based photonic glasses by using a combination of high-resolution ptychographic X-ray computed tomography and small angle X-ray scattering. Our results uncover the structure-processing-properties’ relationships of such nanoparticles-based photonic glasses and point out to the need of a review of the structural features used in simulation models concomitantly with the need for further investigations by experimentalists, where we point out exactly which structural features need to be improved.
Differential gene expression of salt-tolerant alfalfa in response to salinity and inoculation by Ensifer meliloti
Authors: Lundell Seth , Biligetu Bill
Published: July 2024

Background

Alfalfa (Medicago sativa L.) experiences many negative effects under salinity stress, which may be mediated by recurrent selection. Salt-tolerant alfalfa may display unique adaptations in association with rhizobium under salt stress.

Results

To elucidate inoculation effects on salt-tolerant alfalfa under salt stress, this study leveraged a salt-tolerant alfalfa population selected through two cycles of recurrent selection under high salt stress. After experiencing 120-day salt stress, mRNA was extracted from 8 random genotypes either grown in 0 or 8 dS/m salt stress with or without inoculation by Ensifer meliloti. Results showed 320 and 176 differentially expressed genes (DEGs) modulated in response to salinity stress or inoculation x salinity stress, respectively. Notable results in plants under 8 dS/m stress included upregulation of a key gene involved in the Target of Rapamycin (TOR) signaling pathway with a concomitant decrease in expression of the SNrK pathway. Inoculation of salt-stressed plants stimulated increased transcription of a sulfate-uptake gene as well as upregulation of the Lysine-27-trimethyltransferase (EZH2), Histone 3 (H3), and argonaute (AGO, a component of miRISC silencing complexes) genes related to epigenetic and post-transcriptional gene control.

Conclusions

Salt-tolerant alfalfa may benefit from improved activity of TOR and decreased activity of SNrK1 in salt stress, while inoculation by rhizobiumstimulates production of sulfate uptake- and other unique genes.
Genome-wide identification and analysis of monocot-specific chimeric jacalins (MCJ) genes in Maize (Zea mays L.)
Authors: Jiang Hailong , Peng Jiajian , Li Qian , Geng Siqian , Zhang Hualei , Shu Yuting , Wang Rui , Zhang Bin , Li Changsheng , Xiang Xiaoli
Published: July 2024

Background

The monocot chimeric jacalins (MCJ) proteins, which contain a jacalin-related lectin (JRL) domain and a dirigent domain (DIR), are specific to Poaceae. MCJ gene family is reported to play an important role in growth, development and stress response. However, their roles in maize have not been thoroughly investigated.

Results

In this study, eight MCJ genes in the maize genome (designated as ZmMCJs) were identified, which displayed unequal distribution across four chromosomes. Phylogenetic relationships between the ZmMCJs were evident through the identification of highly conserved motifs and gene structures. Analysis of transcriptome data revealed distinct expression patterns among the ZmMCJ genes, leading to their classification into four different modules, which were subsequently validated using RT-qPCR. Protein structures of the same module are found to be relatively similar. Subcellular localization experiments indicated that the ZmMCJs are mainly located on the cell membrane. Additionally, hemagglutination and inhibition experiments show that only part of the ZmMCJs protein has lectin activity, which is mediated by the JRL structure, and belongs to the mannose-binding type. The cis-acting elements in the promoter region of ZmMCJ genes predicted their involvement response to phytohormones, such as abscisic acid and jasmonic acid. This suggests that ZmMCJ genes may play a significant role in both biotic and abiotic stress responses.

Conclusions

Overall, this study adds new insights into our understanding of the gene-protein architecture, evolutionary characteristics, expression profiles, and potential functions of MCJ genes in maize.
Unveiling the mysteries of HvANS: a study on anthocyanin biosynthesis in qingke (hordeum vulgare L. var. Nudum hook. f.) seeds
Authors: Wang Yan , Yao Youhua , Cui Yongmei , An Likun , Li Xin , Bai Yixiong , Ding Baojun , Yao Xiaohua , Wu Kunlun
Published: July 2024

Background

Based on our previous research, a full-length cDNA sequence of HvANS gene was isolated from purple and white Qingke. The open reading frame (ORF) in the purple variety Nierumuzha was 1320 base pairs (bp), encoding 439 amino acids, while the ORF in the white variety Kunlun 10 was 1197 bp, encoding 398 amino acids. A nonsynonymous mutation was found at the position of 1195 bp (T/C) in the coding sequence (CDS) of the HvANS gene. We carried out a series of studies to further clarify the relationship between the HvANS gene and anthocyanin synthesis in Qingke.

Results

The conservative structural domain prediction results showed that the encoded protein belonged to the PLN03178 superfamily. Multiple comparisons showed that this protein had the highest homology with Hordeum vulgare, at 88.61%. The approximately 2000 bp promoter sequence of the HvANS gene was identical in both varieties. The real-time fluorescence PCR (qRT-PCR) results revealed that HvANS expression was either absent or very low in the roots, stems, leaves, and awns of Nierumuzha. In contrast, the HvANS expression was high in the seed coats and seeds of Nierumuzha. Likewise, in Kunlun 10, HvANS expression was either absent or very low, indicating a tissue-specific and variety-specific pattern for HvANS expression. The subcellular localization results indicated that HvANS was in the cell membrane. Metabolomic results indicated that the HvANS gene is closely related to the synthesis of three anthocyanin substances (Idaein chloride, Kinetin 9-riboside, and Cyanidin O-syringic acid). Yeast single hybridization experiments showed that the HvANS promoter interacted with HvANT1, which is the key anthocyanin regulatory protein. In a yeast two-hybrid experiment, we obtained two significantly different proteins (ZWY2020 and POMGNT2-like) and verified the results by qRT-PCR.

Conclusions

These results provide a basis for further studies on the regulatory mechanism of HvANS in the synthesis of anthocyanins in Qingke purple grains.
The ten-year evaluation of clinical characteristics in congenital lung anomaly in pediatrics; a retrospective study in North of Iran
Authors: Lashkarbolouk Narges , Mazandarani Mahdi , Azari Ali Ahani , Ghorbani Somayeh , Shahkar Lobat
Published: July 2024

Introduction

Congenital lung anomalies (CLA) are a group of anomalies, including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestrations (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts (BC). The prevalence of these rare anomalies has risen in recent years, according to various population-based studies due to advances in fetal ultrasound technology.

Method

This retrospective study examines the diagnosis of CLA, and was conducted on 72 patients between March 2014 and March 2024 at Taleghani Pediatric Hospital in Gorgan, Iran.

Result

The average age was 18.8 ± 30.3 months, with the majority being boys (62.5%). Most participants had CCAM (41.7%), followed by CLE (18.1%), BPS (16.7%), pulmonary hypoplasia (9.7%), BC (8.3%), and hybrid lesion (5.6%). The majority of patients were Fars (62.5%), and the average hospitalization days was 9.4 ± 4.5 days. Cardiac anomalies were observed in 19.4% of the patients. 62 patients (86.1%) exhibited respiratory symptoms, and prenatal screening during pregnancy led to the diagnosis in 51 patients (70.8%). Most patients had left lung anomalies (43; 59.7%), and the majority (90.3%) survived. There is a statistically significant relation between needed for surgical treatment and patients’ type of pulmonary lesions (p-value: 0.02). In addition, there was a significant relation between the Fars ethnicity and the presence of cardiac anomalies (p-value: 0.04).

Conclusion

Some CLAs remain undiagnosed or untreated due to the rare nature of congenital lung anomalies. Nevertheless, improvements in ultrasound and other imaging methods will make diagnosing and managing these anomalies during the prenatal period more prevalent, resulting in enhanced understanding.
Knowledge, attitudes, and practice related to tooth loss and dentures among patients with dental arch deficiencies
Authors: Sun Jing , Meng Junru , Shan Jianliang , Lu Huijun , Wei Wei , Zhang Shengnan , Zhang Li
Published: July 2024

Background

Tooth loss is a common problem that affects many people worldwide. Exploring knowledge, attitude, and practice (KAP) among patients can identify barriers and challenges in following recommended practices, providing valuable insights for dental healthcare providers, policymakers, and researchers. This study aimed to explore the KAP of patients with dental arch deficiencies regarding tooth loss and dentures.

Methods

This web-based, cross-sectional study was conducted among patients with dental arch deficiencies using a self-designed questionnaire.

Result

3166 valid questionnaires were included. Participants’ mean KAP scores were 6.84 ± 2.27 (possible range: 0 ~ 12), 39.4 ± 3.72 (possible range: 9 ~ 45), and 27.7 ± 4.36 (possible range: 8 ~ 40), respectively. Multivariable logistic regression analysis showed that knowledge (OR = 1.383), employed (OR = 1.805), family history (OR = 2.158), and treatment (OR = 1.683) were independently associated with attitude. Moreover, knowledge (OR = 1.239), attitude (OR = 1.250), female (OR = 0.619), age (OR = 0.967), college/bachelor (OR = 0.373), and master and above degree (OR = 0.418), employed (OR = 0.554) or student (OR = 0.434), with 10,001–20,000 Yuan household income per month (OR = 0.492), have been married (OR = 0.609), smoking (OR = 0.595), drinking (OR = 0.397), disease duration (OR = 0.972), with family history (OR = 1.676), and with treatment (OR = 3.492) were independently associated with practice (all P < 0.05).

Conclusion

Patients with dental arch deficiencies have insufficient knowledge, positive attitudes, and moderate practice toward tooth loss and dentures, which might be affected by multiple demographic factors.
The impact of a culturally adapted lifestyle intervention on the glycaemic profile of mothers with GDM one year after delivery – a community-based, cluster randomized trial in Sri Lanka
Authors: Sundarapperuma Thamudi D. , Katulanda Prasad , Wijesinghe Champa J. , Hettiarachchi Priyadarshika , Wasalathanthri Sudharshani
Published: July 2024

Background

A woman with a history of GDM has a high risk of developing type two diabetes (T2DM) in her future life. Lifestyle modifications are known to attenuate the progression of GDM to T2DM. Therefore, the aim of this study was to assess the impact of a simple, cost effective, culturally acceptable lifestyle intervention programme on the trajectory towards T2DM in women with a history of GDM.

Methods

This cluster randomized trial was conducted in 100 postpartum women in three selected districts of Sri Lanka. The subjects were divided into intervention (n = 50) and control groups (n = 50) by cluster randomization method. A culturally adapted protocol (comprised of dietary and physical activity modifications) was administered to the intervention group. The glycemic profile was assessed using fasting and 2-hour post-OGTT plasma glucose and HbA1c, and insulin resistance by HOMA-IR at baseline and after one year of intervention.

Results

The mean age (SD) of the subjects in the intervention and control groups were 33.0 (5.1) and 34.3 (6.5) years respectively. All glycemic and insulin resistance parameters (i.e. Fasting plasma glucose- FPG, 2-hour post-OGTT plasma glucose, HbA1c and HOMA-ir) were comparable (p > 0.05) between the two groups at baseline. FPG, 2 h post OGTT, HbA1c and HOMA-ir values between intervention vs. control (p) at 12 months were 87.3 vs. 123.2 (< 0.01); 106.5 vs. 156.1 (0.01); 5.3 vs. 6.8 (< 0.01) and 0.9 vs. 2.3 (< 0.01) respectively. All glycemic parameters showed a significant reduction in the intervention group at 12 months compared to baseline. In contrast, the control group showed a significant increase in FPG, 2-hour post-OGTT plasma glucose and HbA1c at 12 months compared to baseline. In multiple linear regression model adjusted for age, parity and family history, the control group showed an approximately 33 times risk of developing insulin resistance compared to the intervention group.

Conclusion

The culturally acceptable and individualized lifestyle intervention was able to produce remarkable reductions in glycaemic and insulin resistance parameters among postpartum women with a history of GDM.

Trial registration

Ethical clearance was obtained from the Ethics Review Committee of the University of Sri Jayewardenepura, Sri Lanka (ERC 52/14), Sri Lanka Clinical trial registration number Sri Lanka Clinical Trials Registry (SLCTR/2015/021 date 25.09.2015).
The meaning of culture in nursing at the end of life – an interview study with nurses in specialized palliative care
Authors: Mian Rasha , Rejnö Åsa
Published: July 2024

Background

The countries of the world are becoming increasingly multicultural and diverse, both as a result of growing migration, of people fleeing countries at war but also due to increased mobility related to labour immigration. Culture is a broad concept where the definitions focus on learned and shared values, traditions, and beliefs of a group of individuals. People’s culture affects health and perceptions of illness as well as treatment, symptoms, and care. Moreover, people who are at the end of life, live and exist within all levels and contexts of care. Specialized palliative care requires that the nurse has sufficient knowledge and skills to be responsible for meeting the patient’s nursing needs also on a cultural level, regardless of cultural affiliation. The aim of the study was to highlight nurses’ experiences of the meaning of culture when caring for patients at the end of life in specialized palliative care.

Methods

The study was conducted with a qualitative design and inductive approach. Semi-structured interviews were conducted with twelve nurses in western Sweden. Data were analysed using qualitative content analysis.

Results

The nurses had an awareness of culture as a phenomenon and how it affected palliative care at the end of life. The results showed two categories, Awareness of the impact of culture on nursing and Culture’s impact and influence on the nurse’s mindset and approach, consisting of seven subcategories that highlight the nurse’s experience. It emerged that there are differences between cultures regarding notions of dying and death, who should be informed, and treatments. There were also challenges and emotions that arose when cultural preferences differed among everyone involved. A person-centred approach allowed for recognition of the dying person’s culture, to meet diverse cultural needs and wishes.

Conclusion

Providing culturally competent care is a major challenge. There are often no routines or methods prescribed for how nurses should relate to and handle the diversity of cultural notions that may differ from the values and cornerstones of palliative care. Having a person-centred approach as strategy can help to better manage the situation and provide equitable care on terms that respect cultural diversity.
SNMP1 is critical for sensitive detection of the desert locust aromatic courtship inhibition pheromone phenylacetonitrile
Authors: Lehmann Joris , Günzel Yannick , Khosravian Maryam , Cassau Sina , Kraus Susanne , Libnow Johanna S. , Chang Hetan , Hansson Bill S. , Breer Heinz , Couzin-Fuchs Einat , Fleischer Joerg , Krieger Jürgen
Published: July 2024

Background

Accurate detection of pheromones is crucial for chemical communication and reproduction in insects. In holometabolous flies and moths, the sensory neuron membrane protein 1 (SNMP1) is essential for detecting long-chain aliphatic pheromones by olfactory neurons. However, its function in hemimetabolous insects and its role for detecting pheromones of a different chemical nature remain elusive. Therefore, we investigated the relevance of SNMP1 for pheromone detection in a hemimetabolous insect pest of considerable economic importance, the desert locust Schistocerca gregaria, which moreover employs the aromatic pheromone phenylacetonitrile (PAN) to govern reproductive behaviors.

Results

Employing CRISPR/Cas-mediated gene editing, a mutant locust line lacking functional SNMP1 was established. In electroantennography experiments and single sensillum recordings, we found significantly decreased electrical responses to PAN in SNMP1-deficient (SNMP1−/−) locusts. Moreover, calcium imaging in the antennal lobe of the brain revealed a substantially reduced activation of projection neurons in SNMP1−/− individuals upon exposure to PAN, indicating that the diminished antennal responsiveness to PAN in mutants affects pheromone-evoked neuronal activity in the brain. Furthermore, in behavioral experiments, PAN-induced effects on pairing and mate choice were altered in SNMP1−/− locusts.

Conclusions

Our findings emphasize the importance of SNMP1 for chemical communication in a hemimetabolous insect pest. Moreover, they show that SNMP1 plays a crucial role in pheromone detection that goes beyond long-chain aliphatic substances and includes aromatic compounds controlling reproductive behaviors.
Myocardial transcriptomic analysis of diabetic patients with aortic stenosis: key role for mitochondrial calcium signaling
Authors: Cherpaz Maelle , Meugnier Emmanuelle , Seillier Gaultier , Pozzi Matteo , Pierrard Romain , Leboube Simon , Farhat Fadi , Vola Marco , Obadia Jean-François , Amaz Camille , Chalabreysse Lara , May Chloe , Chanon Stephanie , Brun Camille , Givre Lucas , Bidaux Gabriel , Mewton Nathan , Derumeaux Genevieve , Bergerot Cyrille , Paillard Melanie , Thibault Helene
Published: July 2024

Background

Type 2 diabetes (T2D) is a frequent comorbidity encountered in patients with severe aortic stenosis (AS), leading to an adverse left ventricular (LV) remodeling and dysfunction. Metabolic alterations have been suggested as contributors of the deleterious effect of T2D on LV remodeling and function in patients with severe AS, but so far, the underlying mechanisms remain unclear. Mitochondria play a central role in the regulation of cardiac energy metabolism.

Objectives

We aimed to explore the mitochondrial alterations associated with the deleterious effect of T2D on LV remodeling and function in patients with AS, preserved ejection fraction, and no additional heart disease.

Methods

We combined an in-depth clinical, biological and echocardiography phenotype of patients with severe AS, with (n = 34) or without (n = 50) T2D, referred for a valve replacement, with transcriptomic and histological analyses of an intra-operative myocardial LV biopsy.

Results

T2D patients had similar AS severity but displayed worse cardiac remodeling, systolic and diastolic function than non-diabetics. RNAseq analysis identified 1029 significantly differentially expressed genes. Functional enrichment analysis revealed several T2D-specific upregulated pathways despite comorbidity adjustment, gathering regulation of inflammation, extracellular matrix organization, endothelial function/angiogenesis, and adaptation to cardiac hypertrophy. Downregulated gene sets independently associated with T2D were related to mitochondrial respiratory chain organization/function and mitochondrial organization. Generation of causal networks suggested a reduced Ca2+ signaling up to the mitochondria, with the measured gene remodeling of the mitochondrial Ca2+ uniporter in favor of enhanced uptake. Histological analyses supported a greater cardiomyocyte hypertrophy and a decreased proximity between the mitochondrial VDAC porin and the reticular IP3-receptor in T2D.

Conclusions

Our data support a crucial role for mitochondrial Ca2+ signaling in T2D-induced cardiac dysfunction in severe AS patients, from a structural reticulum-mitochondria Ca2+ uncoupling to a mitochondrial gene remodeling. Thus, our findings open a new therapeutic avenue to be tested in animal models and further human cardiac biopsies in order to propose new treatments for T2D patients suffering from AS.

Trial registration

URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01862237.

Graphical abstract
Combined conventional factors and the radiomics signature of coronary plaque texture could improve cardiac risk prediction
Authors: Kahmann Jannik , Nörenberg Dominik , Papavassiliu Theano , Dar Salman Ul Hassan , Engelhardt Sandy , Schoenberg Stefan O. , Froelich Matthias F. , Ayx Isabelle
Published: July 2024

Objectives

This study aims to investigate how radiomics analysis can help understand the association between plaque texture, epicardial adipose tissue (EAT), and cardiovascular risk. Working with a Photon-counting CT, which exhibits enhanced feature stability, offers the potential to advance radiomics analysis and enable its integration into clinical routines.

Methods

Coronary plaques were manually segmented in this retrospective, single-centre study and radiomic features were extracted using pyradiomics. The study population was divided into groups according to the presence of high-risk plaques (HRP), plaques with at least 50% stenosis, plaques with at least 70% stenosis, or triple-vessel disease. A combined group with patients exhibiting at least one of these risk factors was formed. Random forest feature selection identified differentiating features for the groups. EAT thickness and density were measured and compared with feature selection results.

Results

A total number of 306 plaques from 61 patients (mean age 61 years +/− 8.85 [standard deviation], 13 female) were analysed. Plaques of patients with HRP features or relevant stenosis demonstrated a higher presence of texture heterogeneity through various radiomics features compared to patients with only an intermediate stenosis degree. While EAT thickness did not significantly differ, affected patients showed significantly higher mean densities in the 50%, HRP, and combined groups, and insignificantly higher densities in the 70% and triple-vessel groups.

Conclusion

The combination of a higher EAT density and a more heterogeneous plaque texture might offer an additional tool in identifying patients with an elevated risk of cardiovascular events.

Clinical relevance statement

Cardiovascular disease is the leading cause of mortality globally. Plaque composition and changes in the EAT are connected to cardiac risk. A better understanding of the interrelation of these risk indicators can lead to improved cardiac risk prediction.

Key Points

Cardiac plaque composition and changes in the EAT are connected to cardiac risk.

Higher EAT density and more heterogeneous plaque texture are related to traditional risk indicators.

Radiomics texture analysis conducted on PCCT scans can help identify patients with elevated cardiac risk.

Graphical Abstract
Comprehensive characterization of the neurogenic and neuroprotective action of a novel TrkB agonist using mouse and human stem cell models of Alzheimer’s disease
Authors: Charou Despoina , Rogdakis Thanasis , Latorrata Alessia , Valcarcel Maria , Papadogiannis Vasileios , Athanasiou Christina , Tsengenes Alexandros , Papadopoulou Maria Anna , Lypitkas Dimitrios , Lavigne Matthieu D. , Katsila Theodora , Wade Rebecca C. , Cader M. Zameel , Calogeropoulou Theodora , Gravanis Achille , Charalampopoulos Ioannis
Published: July 2024

Background

Neural stem cell (NSC) proliferation and differentiation in the mammalian brain decreases to minimal levels postnatally. Nevertheless, neurogenic niches persist in the adult cortex and hippocampus in rodents, primates and humans, with adult NSC differentiation sharing key regulatory mechanisms with development. Adult neurogenesis impairments have been linked to Alzheimer’s disease (AD) pathology. Addressing these impairments by using neurotrophic factors is a promising new avenue for therapeutic intervention based on neurogenesis. However, this possibility has been hindered by technical difficulties of using in-vivo models to conduct screens, including working with scarce NSCs in the adult brain and differences between human and mouse models or ethical limitations.

Methods

Here, we use a combination of mouse and human stem cell models for comprehensive in-vitro characterization of a novel neurogenic compound, focusing on the brain-derived neurotrophic factor (BDNF) pathway. The ability of ENT-A011, a steroidal dehydroepiandrosterone derivative, to activate the tyrosine receptor kinase B (TrkB) receptor was tested through western blotting in NIH-3T3 cells and its neurogenic and neuroprotective action were assessed through proliferation, cell death and Amyloid-β (Aβ) toxicity assays in mouse primary adult hippocampal NSCs, mouse embryonic cortical NSCs and neural progenitor cells (NPCs) differentiated from three human induced pluripotent stem cell lines from healthy and AD donors. RNA-seq profiling was used to assess if the compound acts through the same gene network as BDNF in human NPCs.

Results

ENT-A011 was able to increase proliferation of mouse primary adult hippocampal NSCs and embryonic cortical NSCs, in the absence of EGF/FGF, while reducing Aβ-induced cell death, acting selectively through TrkB activation. The compound was able to increase astrocytic gene markers involved in NSC maintenance, protect hippocampal neurons from Αβ toxicity and prevent synapse loss after Aβ treatment. ENT-A011 successfully induces proliferation and prevents cell death after Aβ toxicity in human NPCs, acting through a core gene network shared with BDNF as shown through RNA-seq.

Conclusions

Our work characterizes a novel BDNF mimetic with preferable pharmacological properties and neurogenic and neuroprotective actions in Alzheimer’s disease via stem cell-based screening, demonstrating the promise of stem cell systems for short-listing competitive candidates for further testing.
Automation of systematic reviews of biomedical literature: a scoping review of studies indexed in PubMed
Authors: Tóth Barbara , Berek László , Gulácsi László , Péntek Márta , Zrubka Zsombor
Published: July 2024

Background

The demand for high-quality systematic literature reviews (SRs) for evidence-based medical decision-making is growing. SRs are costly and require the scarce resource of highly skilled reviewers. Automation technology has been proposed to save workload and expedite the SR workflow. We aimed to provide a comprehensive overview of SR automation studies indexed in PubMed, focusing on the applicability of these technologies in real world practice.

Methods

In November 2022, we extracted, combined, and ran an integrated PubMed search for SRs on SR automation. Full-text English peer-reviewed articles were included if they reported studies on SR automation methods (SSAM), or automated SRs (ASR). Bibliographic analyses and knowledge-discovery studies were excluded. Record screening was performed by single reviewers, and the selection of full text papers was performed in duplicate. We summarized the publication details, automated review stages, automation goals, applied tools, data sources, methods, results, and Google Scholar citations of SR automation studies.

Results

From 5321 records screened by title and abstract, we included 123 full text articles, of which 108 were SSAM and 15 ASR. Automation was applied for search (19/123, 15.4%), record screening (89/123, 72.4%), full-text selection (6/123, 4.9%), data extraction (13/123, 10.6%), risk of bias assessment (9/123, 7.3%), evidence synthesis (2/123, 1.6%), assessment of evidence quality (2/123, 1.6%), and reporting (2/123, 1.6%). Multiple SR stages were automated by 11 (8.9%) studies. The performance of automated record screening varied largely across SR topics. In published ASR, we found examples of automated search, record screening, full-text selection, and data extraction. In some ASRs, automation fully complemented manual reviews to increase sensitivity rather than to save workload. Reporting of automation details was often incomplete in ASRs.

Conclusions

Automation techniques are being developed for all SR stages, but with limited real-world adoption. Most SR automation tools target single SR stages, with modest time savings for the entire SR process and varying sensitivity and specificity across studies. Therefore, the real-world benefits of SR automation remain uncertain. Standardizing the terminology, reporting, and metrics of study reports could enhance the adoption of SR automation techniques in real-world practice.
Economic burden of psoriasis in Southern Iran in 2022
Authors: Ravangard Ramin , Mirzaei Moslem , Ghahartars Mehdi , Jafari Abdosaleh
Published: July 2024

Introduction

Psoriasis is a common, chronic, and non-contagious skin disease that has no known cause or treatment. Various medical costs for skin disorders, including psoriasis, can be expensive and lifelong. The purpose of the present study was to determine the economic burden of psoriasis in patients admitted to general hospitals affiliated with Shiraz University of Medical Sciences, Iran in 2022.

Materials and methods

This research was a descriptive, cross-sectional, cost of illness study from a societal perspective. All psoriasis patients (N = 118) admitted to the hospitals affiliated with Shiraz University of Medical Sciences in 2022 were examined. 7 participants refused to cooperate and were excluded from the study and, the information of 111 patients was collected. A researcher-made data collection form was used to collect data. A prevalence-based approach was used to prepare cost data, and the costing approach was bottom-up. The productivity lost due to the absenteeism of patients and their companions was estimated using the human capital approach. Microsoft Excel ® 2016 was applied to analyze the data.

Results

The mean annual cost per psoriasis patient was estimated to be US$ 30,374.21. Its highest and lowest share was related to direct medical costs (88.61%), direct non-medical costs (7.3%) and indirect costs (4.09%), respectively. Also, the highest mean direct medical, direct non-medical, and indirect costs per patient were related to those of medicine (93.11%), transportation (51.65%), and absenteeism of the patients’ companions due to patient care (71.73%).

Conclusion

Considering that the major contributor in the direct medical cost of treating psoriasis patients was related to medicine, designing appropriate mechanisms for insurance coverage, and allocating government subsidies for the purchase of medicine, are suggested. The result of the current study has important implications for policymakers in developing guidelines for early diagnosis of this disease and reducing the health economic burden.
Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data
Authors: Li Yun , Cao Yuan , Wang Min , Wang Lu , Wu Yiqi , Fang Yuan , Zhao Yan , Fan Yong , Liu Xiaoli , Liang Hong , Yang Mengmeng , Yuan Rui , Zhou Feihu , Zhang Zhengbo , Kang Hongjun
Published: July 2024

Background

Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay.

Methods

Utilizing patient data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets.

Results

The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay.

Conclusions

The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.
Chinese version of the Tendency to Avoid Physical Activity and Sport (TAPAS) scale: testing unidimensionality, measurement invariance, concurrent validity, and known-group validity among Taiwanese youths
Authors: Lin Yi-Ching , Chen Jung-Sheng , Bevan Nadia , O’Brien Kerry S. , Strong Carol , Tsai Meng-Che , Fung Xavier C. C. , Chen Ji-Kang , Lin I-Ching , Latner Janet D. , Lin Chung-Ying
Published: July 2024

Background and objectives

Psychosocial factors affect individuals’ desire for physical activity. A newly developed instrument (Tendency to Avoid Physical Activity and Sport; TAPAS) has been designed to assess the avoidance of physical activity. Considering cultural differences could be decisive factors, the present study aimed to translate and validate the TAPAS into Chinese (Mandarin) for Taiwanese youths, and further cultural comparisons are expected.

Methods

Standard translation procedure (i.e., forward translation, back translation, and reconciliation) was used to translate the English TAPAS into the Chinese TAPAS. Following translation, 608 youths (mean [SD] age 29.10 [6.36] years; 333 [54.8%] women) participated in the study via a snowballing sampling method with an online survey. All participants completed the Chinese TAPAS and additional instruments assessing weight stigma and psychological distress. Confirmatory factor analysis (CFA) was used to examine the factor structure of the Chinese TAPAS and multigroup CFA to examine measurement invariance across gender (men vs. women) and weight status (overweight vs. non-overweight). Pearson correlations were used to examine the concurrent validity; independent t-tests between gender groups and weight status groups were used to examine the known-group validity.

Results

Consistent with the English version, the Chinese TAPAS was found to have a one-factor structure evidenced by CFA results. The structure was invariant across gender and weight status groups evidenced by multigroup CFA results. Concurrent validity was supported by significant associations with the related constructs assessed (r = 0.326 to 0.676; p < 0.001). Known-group validity was supported by the significant differences in TAPAS total scores between gender and weight status groups (p = 0.004 and < 0.001; Cohen’s d = 0.24 and 0.48).

Conclusion

The Chinese version of the TAPAS is a valid and reliable instrument assessing individuals’ avoidance of physical activity and sports due to underlying psychosocial issues among Taiwanese youths. It is anticipated to be applied within a large Asian population, as well as cross-cultural comparisons, for further explorations in health, behavioral and epidemiological research and practice.
Comparison of simulation tools for optimizing borehole heat exchanger field operation
Authors: Heim Elisa , Stoffel Phillip , Düber Stephan , Knapp Dominique , Kümpel Alexander , Müller Dirk , Klitzsch Norbert
Published: July 2024

Model predictive control (MPC) is a promising approach for optimizing the performance of borehole heat exchangers (BHEs) in ground-source heat pump systems. The central element of MPC is the forward model that predicts the thermal dynamics in the ground. In this work, we validate the prediction accuracy of four BHE modeling approaches against real-world measurement data across various operational events and timescales. We simulate the fluid temperature leaving a BHE using a fully discretized 3-D numerical model, a resistance–capacitance model, a g-function model, and a hybrid model. The simulated temperatures are compared to measured temperatures using three validation metrics that quantify temperature offset, noise, and accuracy. The main reason for a mismatch between measured and modeled temperatures is a temperature offset of the simulated temperature. To remove this effect, the models were calibrated for their most sensitive parameter, the ground temperature, and their prediction accuracy over 4 years was evaluated. Thereby, model calibration seems to be a viable solution to account for an unknown load history. The results show that the resistance–capacitance model provides decent predictions in the short term and the g-function model in the long term. However, both models are strongly dependent on accurate calibration. The hybrid model provides the most accurate short and long-term predictions and is less dependent on calibration. Still, its integration into optimization syntax poses challenges compared to the other models. Although not yet applied in model predictive control, the hybrid model stands out as a promising choice for optimizing BHE field operations across various timescales.