bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutritional status and quality of life among breast Cancer patients undergoing treatment in Addis Ababa, Ethiopia
Authors: Adam Ruth , Haileselassie Werissaw , Solomon Nabel , Desalegn Yakob , Tigeneh Wondemagegnhu , Suga Yisihak , Gebremedhin Samson 
Published: August 2023

Abstract
Background
The prevalence of malnutrition in cancer patients ranges from 30 to 60%. While it is known that malnutrition is prevalent among cancer patients, the relationship between undernutrition and quality of life among breast cancer patients has not been adequately explored. Therefore, the present study was aimed at assessing the association between undernutrition and quality of life among Breast Cancer patients under treatment in Addis Ababa, Ethiopia.

Methods
A cross-sectional study on breast cancer patients under treatment at the outpatient and in-patient departments of oncology centers of two tertiary hospitals in Addis Ababa – Tikur Anbessa Specialized Hospital (TASH) and St. Paul Millennium Medical College (SPHMMC) oncology was conducted from May 12 to August 26,2020. Nutritional status was assessed using Subjective Global Assessment (SGA) screening tool. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cancer 30 (EORTC QLQ C30) a standard quality of life measurement scale for cancer patients. To determine the relationship between quality of life scores and nutritional status multivariable linear regression was fitted.

Results
A total of 411 breast cancer patients with mean age of 44.4 (± 11.47) years. And 393 (95.6%) of them female were included in the study. A high prevalence of moderate 127 (30.9%) and severe 106 (25.8%) malnutrition was observed. Moderate (β = −9.21 CI (− 14.59, − 4.67)) and severe (β = −17.81 CI (− 16.6, 2 − 2.91)) malnutrition were negatively associated with the overall quality of life. Malnutrition also showed negative associations with all domains of functional status (P < 0.05) and strong positive associations with symptom scores covered in the EORTC QLQ C-30 (P < 0.05).

Conclusion
This study indicated that malnutrition is a major problem among breast cancer patients and the nutritional status breast cancer patients was related to their quality of life….
Can clinical decision support systems be an asset in medical education? An experimental approach
Authors: Kafke Sean D. , Kuhlmey Adelheid , Schuster Johanna , Blüher Stefan , Czimmeck Constanze , Zoellick Jan C. , Grosse Pascal 
Published: August 2023

Abstract
Background
Diagnostic accuracy is one of the major cornerstones of appropriate and successful medical decision-making. Clinical decision support systems (CDSSs) have recently been used to facilitate physician’s diagnostic considerations. However, to date, little is known about the potential assets of CDSS for medical students in an educational setting. The purpose of our study was to explore the usefulness of CDSSs for medical students assessing their diagnostic performances and the influence of such software on students’ trust in their own diagnostic abilities.

Methods
Based on paper cases students had to diagnose two different patients using a CDSS and conventional methods such as e.g. textbooks, respectively. Both patients had a common disease, in one setting the clinical presentation was a typical one (tonsillitis), in the other setting (pulmonary embolism), however, the patient presented atypically. We used a 2x2x2 between- and within-subjects cluster-randomised controlled trial to assess the diagnostic accuracy in medical students, also by changing the order of the used resources (CDSS first or second).

Results
Medical students in their 4th and 5th year performed equally well using conventional methods or the CDSS across the two cases (t(164) = 1,30; p = 0.197). Diagnostic accuracy and trust in the correct diagnosis were higher in the typical presentation condition than in the atypical presentation condition (t(85) = 19.97; p < .0001 and t(150) = 7.67; p < .0001).These results refute our main hypothesis that students diagnose more accurately when using conventional methods compared to the CDSS.

Conclusions
Medical students in their 4th and 5th year performed equally well in diagnosing two cases of common diseases with typical or atypical clinical presentations using conventional methods or a CDSS. Students were proficient in diagnosing a common disease with a typical presentation but underestimated their own factual knowledge in this scenario. Also, students were aware of their own diagnostic limitations when presented with a challenging case with an atypical presentation for which the use of a CDSS seemingly provided no additional insights.
Meaning in life among nursing students: a latent profile analysis
Authors: Zhao Zhixin , Mei Yongxia , Wang Xiaoxuan , Jiang Hu , Wang Wenna , Lin Beilei , Zhang Zhenxiang 
Published: August 2023

Abstract
Background
Meaning in life, defined by an individual’s understanding and appreciation of life, is a vital aspect of a positive psychological state, that has a significant influence on physical and mental health. Therefore, improving the sense of meaning in life among nursing students has emerged as a crucial concern in nursing education. This study aimed to clarify the profiles and influencing factors of meaning in life among nursing students.

Methods
A descriptive cross-sectional online survey was conducted among nursing students in China from November 16, 2022, to January 17, 2023. The demographic information questionnaire and the meaning in life questionnaire (MLQ) were used to collect data. Latent profile analysis (LPA) was used to identify groups exhibiting distinct levels of meaning in life. Additionally, univariate analysis and multinominal logistic regression analysis were used to investigate the factors influencing each group. The reporting of this study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist.

Results
A total of 10,583 valid responses were received, and the analysis revealed four distinct profiles. The profiles identified were the medium meaning group (C1, 41.4%), medium fluctuation meaning-no motivation group (C2, 8.7%), lower meaning group (C3, 9.7%), and higher meaning group (C4, 40.2%). The univariate analysis revealed that age, gender, ethnicity, marital status, educational level, grade, university classification, student leadership experience, and political affiliation were factors that influenced the four latent profiles (P < 0.05). The multinomial logistic regression analysis showed that age, gender, ethnicity, education level, and student leadership experience were significant predictors of the various profiles (P < 0.05).

Conclusion
There is heterogeneous in meaning in life among nursing students in China. Nursing educators need to provide tailored guidance based on the latent classification characteristics of meaning in life among nursing students, aiming at improving their meaning in life and promoting the development of the nursing workforce.
An association between individual’s risk perceptions and delayed or foregone healthcare services during the COVID-19 pandemic in Korea
Authors: Hwang Jongnam , Kim Woong-Han , Heo Jongho 
Published: August 2023

Abstract
Background
Existing evidence highlights that the COVID-19 pandemic is associated with a large reduction in healthcare utilization for routine and less-urgent services around the world including Korea. During the COVID-19 pandemic, delayed and foregone healthcare are driven by various factors, and risk perception, a complex psychological construct, is one of them. The aim of this study was to examine how COVID-19 risk perceptions influence delayed and foregone care during the pandemic in Korea.

Methods
The Koreans’ Happiness Survey (KHS) 2020 was used to analyze responses from 13,491 individuals over 19 years of age residing in Korea. To assess delayed and foregone care, self-reported delayed or foregone care after the COVID-19 outbreak was used. COVID-19 risk perceptions were analyzed in terms of fear and severity of the pandemic based on responses from the participants. Logistic regression models, stratified by gender, were used to examine the relationship between COVID-19 risk perception and delayed/foregone healthcare.

Results
Among the total 13,491 individuals included in the study, 4.0% (n = 541) reported delayed and foregone care in 2020. The results showed that higher level of fear of COVID-19 was associated with an increased likelihood of reporting delayed and foregone care in Korean adults (OR = 1.36, 95% CI = 1.08–1.73). The gender-stratified model revealed that greater fear of COVID-19 was associated with higher odds of delayed and foregone healthcare (OR = 1.71, 95%CI = 1.23–2.39) among women while the perceived severity did not have any association. However, the perceived severity was associated with a higher likelihood of delayed and foregone care in men (OR = 1.17, 95%CI = 1.04–1.32), but no association was found between fear of COVID-19 and delayed and foregone healthcare in men.

Conclusions
To ensure the timely use of any needed healthcare services, it is worth considering establishing policy interventions to mitigate unnecessary fear and worries about COVID-19. This can be achieved by providing accurate information on the virus, protective measures, and treatment.
Diminished activation of excitatory neurons in the prelimbic cortex leads to impaired working memory capacity in mice
Authors: Jiang Li-Xin , Huang Geng-Di , Tian Yong-Lu , Cong Ri-Xu , Meng Xue , Wang Hua-Li , Zhang Chen , Yu Xin 
Published: August 2023

Abstract
Background
Working memory capacity impairment is an early sign of Alzheimer's disease, but the underlying mechanisms remain unclear. Clarifying how working memory capacity is affected will help us better understand the pathological mechanism of Alzheimer's disease. We used the olfactory working memory capacity paradigm to evaluate memory capacity in 3-month-old 5XFAD (an animal model of Alzheimer's disease) mice. Immunofluorescence staining of the prefrontal cortex was performed to detect the number of FOS-positive neurons, calmodulin-dependent protein kinase II-positive neurons, and glutamate decarboxylase-positive neurons in the prelimbic cortex and infralimbic cortex. A chemogenetic method was then used to modulate the inhibition and activation of excitatory neurons in the prelimbic cortex of wild-type and 5XFAD mice and to measure the memory capacity of mice.

Results
Working memory capacity was significantly diminished in 5XFAD mice compared to littermate wild-type mice. Neuronal activation of the prelimbic cortex, but not the infralimbic cortex, was attenuated in 5XFAD mice performing the olfactory working memory capacity task. Subsequently, the FOS-positive neurons were co-localized with both calmodulin-dependent protein kinase II-positive neurons and glutamate decarboxylase-positive neurons. The results showed that the activation of excitatory neurons in the prelimbic cortex was correlated with working memory capacity in mice. Our results further demonstrate that the chemogenetic inhibition of prelimbic cortex excitatory neurons resulted in reduced working memory capacity in wild-type mice, while the chemogenetic activation of prelimbic cortex excitatory neurons improved the working memory capacity of 5XFAD mice.

Conclusion
The diminished activation of prelimbic cortex excitatory neurons in 5XFAD mice during task performance is associated with reduced working memory capacity, and activation modulation of excitatory neurons by chemogenetic methods can improve memory capacity impairment in 5XFAD mice. These findings may provide a new direction for exploring Alzheimer's disease therapeutic approaches.
Neuroprotective effects of osmotin in Parkinson’s disease-associated pathology via the AdipoR1/MAPK/AMPK/mTOR signaling pathways
Authors: Park Jun Sung , Choe Kyonghwan , Lee Hyeon Jin , Park Tae Ju , Kim Myeong Ok 
Published: August 2023

Abstract
Background
Parkinson’s disease (PD) is the second most frequent age-related neurodegenerative disorder and is characterized by the loss of dopaminergic neurons. Both environmental and genetic aspects are involved in the pathogenesis of PD. Osmotin is a structural and functional homolog of adiponectin, which regulates the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK) via adiponectin receptor 1 (AdipoR1), thus attenuating PD-associated pathology. Therefore, the current study investigated the neuroprotective effects of osmotin using in vitro and in vivo models of PD.

Methods
The study used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and neuron-specific enolase promoter human alpha-synuclein (NSE-hαSyn) transgenic mouse models and 1-methyl-4-phenylpyridinium (MPP+)- or alpha-synuclein A53T-treated cell models. MPTP was injected at a dose of 30 mg/kg/day for five days, and osmotin was injected twice a week at a dose of 15 mg/kg for five weeks. We performed behavioral tests and analyzed the biochemical and molecular changes in the substantia nigra pars compacta (SNpc) and the striatum.

Results
Based on our study, osmotin mitigated MPTP- and α-synuclein-induced motor dysfunction by upregulating the nuclear receptor-related 1 protein (Nurr1) transcription factor and its downstream markers tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2). From a pathological perspective, osmotin ameliorated neuronal cell death and neuroinflammation by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, osmotin alleviated the accumulation of α-synuclein by promoting the AMPK/mammalian target of rapamycin (mTOR) autophagy signaling pathway. Finally, in nonmotor symptoms of PD, such as cognitive deficits, osmotin restored synaptic deficits, thereby improving cognitive impairment in MPTP- and α-synuclein-induced mice.

Conclusions
Therefore, our findings indicated that osmotin significantly rescued MPTP/α-synuclein-mediated PD neuropathology. Altogether, these results suggest that osmotin has potential neuroprotective effects in PD neuropathology and may provide opportunities to develop novel therapeutic interventions for the treatment of PD.
The clinical impact of Lumacaftor-Ivacaftor on structural lung disease and lung function in children aged 6–11 with cystic fibrosis in a real-world setting
Authors: McNally Paul , Linnane Barry , Williamson Michael , Elnazir Basil , Short Christopher , Saunders Clare , Kirwan Laura , David Rea , Kemner-Van de Corput Mariette P. C. , Tiddens Harm A.W.M. , Davies Jane C , Cox Des W 
Published: August 2023

Abstract
Background
Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV1 in children with Cystic Fibrosis (CF) aged 6–11 years and homozygous for the Phe508del mutation. It is not known whether LUM/IVA use in children can impact the progression of structural lung disease. We sought to determine the real-world impact of LUM/IVA on lung structure and function in children aged 6–11 years.

Methods
This real-world observational cohort study was conducted across four paediatric sites in Ireland over 24-months using spirometry-controlled CT scores and LCI as primary outcome measures. Children commencing LUM-/IVA as part of routine care were included. CT scans were manually scored with the PRAGMA CF scoring system and analysed using the automated bronchus-artery (BA) method. Secondary outcome measures included rate of change of ppFEV1, nutritional indices and exacerbations requiring hospitalisation.

Results
Seventy-one participants were recruited to the study, 31 of whom had spirometry-controlled CT performed at baseline, and after one year and two years of LUM/IVA treatment. At two years there was a reduction from baseline in trapped air scores (0.13 to 0.07, p = 0.016), but an increase from baseline in the % bronchiectasis score (0.84 to 1.23, p = 0.007). There was no change in overall % disease score (2.78 to 2.25, p = 0.138). Airway lumen to pulmonary artery ratios (AlumenA ratio) were abnormal at baseline and worsened over the course of the study. In 28 participants, the mean annual change from baseline LCI2.5 (-0.055 (-0.61 to 0.50), p = 0.85) measurements over two years were not significant. Improvements from baseline in weight (0.10 (0.06 to 0.15, p < 0.0001), height (0.05 (0.02 to 0.09), p = 0.002) and BMI (0.09 (0.03 to 0.15) p = 0.005) z-scores were seen with LUM/IVA treatment. The mean annual change from baseline ppFEV1 (-2.45 (-4.44 to 2.54), p = 0.66) measurements over two years were not significant.

Conclusion
In a real-world setting, the use of LUM/IVA over two years in children with CF aged 6–11 resulted in improvements in air trapping on CT but worsening in bronchiectasis scores. Our results suggest that LUM/IVA use in this age group improves air trapping but does not prevent progression of bronchiectasis over two years of treatment.
Development of the thermophilic fungus Myceliophthora thermophila into glucoamylase hyperproduction system via the metabolic engineering using improved AsCas12a variants
Authors: Zhu Zhijian , Zhang Manyu , Liu Dandan , Liu Defei , Sun Tao , Yang Yujing , Dong Jiacheng , Zhai Huanhuan , Sun Wenliang , Liu Qian , Tian Chaoguang 
Published: August 2023

Abstract
Background
Glucoamylase is an important enzyme for starch saccharification in the food and biofuel industries and mainly produced from mesophilic fungi such as Aspergillus and Rhizopus species. Enzymes produced from thermophilic fungi can save the fermentation energy and reduce costs as compared to the fermentation system using mesophiles. Thermophilic fungus Myceliophthora thermophila is industrially deployed fungus to produce enzymes and biobased chemicals from biomass during optimal growth at 45 °C. This study aimed to construct the M. thermophila platform for glucoamylase hyper-production by broadening genomic targeting range of the AsCas12a variants, identifying key candidate genes and strain engineering.

Results
In this study, to increase the genome targeting range, we upgraded the CRISPR-Cas12a-mediated technique by engineering two AsCas12a variants carrying the mutations S542R/K607R and S542R/K548V/N552R. Using the engineered AsCas12a variants, we deleted identified key factors involved in the glucoamylase expression and secretion in M. thermophila, including Mtstk-12, Mtap3m, Mtdsc-1 and Mtsah-2. Deletion of four targets led to more than 1.87- and 1.85-fold higher levels of secretion and glucoamylases activity compared to wild-type strain MtWT. Transcript level of the major amylolytic genes showed significantly increased in deletion mutants. The glucoamylase hyper-production strain MtGM12 was generated from our previously strain MtYM6 via genetically engineering these targets Mtstk-12, Mtap3m, Mtdsc-1 and Mtsah-2 and overexpressing Mtamy1 and Mtpga3. Total secreted protein and activities of amylolytic enzymes in the MtGM12 were about 35.6-fold and 51.9‒55.5-fold higher than in MtWT. Transcriptional profiling analyses revealed that the amylolytic gene expression levels were significantly up-regulated in the MtGM12 than in MtWT. More interestingly, the MtGM12 showed predominantly short and highly bulging hyphae with proliferation of rough ER and abundant mitochondria, secretion vesicles and vacuoles when culturing on starch.

Conclusions
Our results showed that these AsCas12a variants worked well for gene deletions in M. thermophila. We successfully constructed the glucoamylase hyper-production strain of M. thermophila by the rational redesigning and engineering the transcriptional regulatory and secretion pathway. This targeted engineering strategy will be very helpful to improve industrial fungal strains and promote the morphology engineering for enhanced enzyme production.
Conversion of methionine biosynthesis in Escherichia coli from trans- to direct-sulfurylation enhances extracellular methionine levels
Authors: Gruzdev Nadya , Hacham Yael , Haviv Hadar , Stern Inbar , Gabay Matan , Bloch Itai , Amir Rachel , Gal Maayan , Yadid Itamar 
Published: August 2023

AbstractMethionine is an essential amino acid in mammals and a precursor for vital metabolites required for the survival of all organisms. Consequently, its inclusion is required in diverse applications, such as food, feed, and pharmaceuticals. Although amino acids and other metabolites are commonly produced through microbial fermentation, high-yield biosynthesis of L-methionine remains a significant challenge due to the strict cellular regulation of the biosynthesis pathway. As a result, methionine is produced primarily synthetically, resulting in a racemic mixture of D,L-methionine. This study explores methionine bio-production in E. coli by replacing its native trans-sulfurylation pathway with the more common direct-sulfurylation pathway used by other bacteria. To this end, we generated a methionine auxotroph E. coli strain (MG1655) by simultaneously deleting metA and metB genes and complementing them with metX and metY from different bacteria. Complementation of the genetically modified E. coli with metX/metY from Cyclobacterium marinum or Deinococcus geothermalis, together with the deletion of the global repressor metJ and overexpression of the transporter yjeH, resulted in a substantial increase of up to 126 and 160-fold methionine relative to the wild-type strain, respectively, and accumulation of up to 700 mg/L using minimal MOPS medium and 2 ml culture. Our findings provide a method to study methionine biosynthesis and a chassis for enhancing L-methionine production by fermentation.