bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two protocols for the generation of iPSC-derived human astrocytes
Authors: Mulica Patrycja , Venegas Carmen , Landoulsi Zied , Badanjak Katja , Delcambre Sylvie , Tziortziou Maria , Hezzaz Soraya , Ghelfi Jenny , Smajic Semra , Schwamborn Jens , Krüger Rejko , Antony Paul , May Patrick , Glaab Enrico , Grünewald Anne , Pereira Sandro L.
Published: September 2023

Background

Astrocytes have recently gained attention as key contributors to the pathogenesis of neurodegenerative disorders including Parkinson’s disease. To investigate human astrocytes in vitro, numerous differentiation protocols have been developed. However, the properties of the resulting glia are inconsistent, which complicates the selection of an appropriate method for a given research question. Thus, we compared two approaches for the generation of iPSC-derived astrocytes. We phenotyped glia that were obtained employing a widely used long, serum-free (“LSF”) method against an in-house established short, serum-containing (“SSC”) protocol which allows for the generation of astrocytes and midbrain neurons from the same precursor cells.

Results

We employed high-content confocal imaging and RNA sequencing to characterize the cultures. The astrocytes generated with the LSF or SSC protocols differed considerably in their properties: while the former cells were more labor-intense in their generation (5 vs 2 months), they were also more mature. This notion was strengthened by data resulting from cell type deconvolution analysis that was applied to bulk transcriptomes from the cultures to assess their similarity with human postmortem astrocytes.

Conclusions

Overall, our analyses highlight the need to consider the advantages and disadvantages of a given differentiation protocol, when designing functional or drug discovery studies involving iPSC-derived astrocytes.
Genome-wide identification, phylogenetic and expression pattern analysis of HSF family genes in the Rye (Secale cereale L.)
Authors: Ren Yanyan , Ma Rui , Xie Muhua , Fan Yue , Feng Liang , Chen Long , Yang Hao , Wei Xiaobao , Wang Xintong , Liu Kouhan , Cheng Peng , Wang Baotong
Published: September 2023

Background

Heat shock factor (HSF), a typical class of transcription factors in plants, has played an essential role in plant growth and developmental stages, signal transduction, and response to biotic and abiotic stresses. The HSF genes families has been identified and characterized in many species through leveraging whole genome sequencing (WGS). However, the identification and systematic analysis of HSF family genes in Rye is limited.

Results

In this study, 31 HSF genes were identified in Rye, which were unevenly distributed on seven chromosomes. Based on the homology of A. thaliana, we analyzed the number of conserved domains and gene structures of ScHSF genes that were classified into seven subfamilies. To better understand the developmental mechanisms of ScHSF family during evolution, we selected one monocotyledon (Arabidopsis thaliana) and five (Triticum aestivum L., Hordeum vulgare L., Oryza sativa L., Zea mays L., and Aegilops tauschii Coss.) specific representative dicotyledons associated with Rye for comparative homology mapping. The results showed that fragment replication events modulated the expansion of the ScHSF genes family. In addition, interactions between ScHSF proteins and promoters containing hormone- and stress-responsive cis-acting elements suggest that the regulation of ScHSF expression was complex. A total of 15 representative genes were targeted from seven subfamilies to characterize their gene expression responses in different tissues, fruit developmental stages, three hormones, and six different abiotic stresses.

Conclusions

This study demonstrated that ScHSF genes, especially ScHSF1 and ScHSF3, played a key role in Rye development and its response to various hormones and abiotic stresses. These results provided new insights into the evolution of HSF genes in Rye, which could help the success of molecular breeding in Rye.
Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients
Authors: Bittaye Sheikh Omar , Kambi Abubacarr , Tekanyi Momodou A. I. , Tamba Saydiba , Sanneh Lamin , Sisawo Momodou Musa , Jatta Abdoulie , Fatty Gibril , Jeng Adam , Jallow Momodou Salieu , Leigh Ousman , Njie Ramou
Published: September 2023

Background

As a result of the lack of screening programs and the difficulty in making a proper diagnosis, the majority of hepatocellular carcinoma (HHC) patients present late in low-resource countries. The study therefore assesses the clinical features, stage and prognostic variables of patients with HCC in The Gambia.

Methods

From December 2015 to January 2019, patients with a confirmed diagnosis of HCC were enrolled. All patients’ medical history, ultrasound scan, FibroScan and laboratory details were collected.

Results

Two hundred and sixty (260) patients were enrolled. The mean age of HCC patients was 40 years, and 210 (80.7%) of them were male. The most common gastrointestinal symptoms were early satiety 229 (88.1%) and abdominal pain 288 (87.7%), while the most common constitutional symptoms were weight loss 237 (91.2%) and easy fatiguability 237 (91.2%). Hepatomegaly 205 (78.8%) was the most common sign. On ultrasound scan, lesions were mostly multifocal 175 (67.3%), and the median FibroScan score was 75 kPa. The median fibrosis 4 and aspartate transferase platelet ratio index were 4.6 and 2.2, respectively. Hepatitis B surface antigen (HBsAg) was positive in 170 (65.4%) patients, and the median AFP level was 3263 ng/ml. HCC patients with positive HBsAg were more likely to be male 145 (85.3%) vs 62 (72.1%) (p = 0.011), much younger 39.9 vs 51.4 yrs (p =  < 0.0001), more likely to have abdominal pain 156 (91.8%) vs 68 (79.1%) (p = 0.002), jaundice 78 (45.9%) vs 29 (33.7%) (p = 0.042), dark urine 117 (68.8%) vs 46 (53.5%) (p = 0.018), raised transaminases (Aspartate transaminases 224.5 (32–7886) vs 153 (18–610), p =  < 0.01, Alanine transferases 71 (5–937) vs 47 (8–271), p =  < 0.001) and decreased platelet count 207 (33–941) vs 252 (52- 641) (p = 0.021) compared to patients with HCC who were HBsAg-negative.

Conclusions

The prognosis of patients with HCC is poor in developing countries such as The Gambia, where screening programs and treatment modalities are scarce. Young males are disproportionately affected, and HBV is a major cause of HCC in The Gambia.
Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme
Authors: Cheng Wen-Yu , Shen Chiung-Chyi , Liang Yea-Jiuen , Chiao Ming-Tsang , Yang Yi-Chin , Hsieh Wan-Yu , Lin Cheng-Hui , Chen Jun-Peng
Published: September 2023

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.
Corrected analysis of “the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial” that accounts for clustering and nesting verifies conclusions
Authors: Jamshidi-Naeini Yasaman , Golzarri-Arroyo Lilian , Siddique Abu Bakkar , Vorland Colby J. , Rodriguez Miriam Jocelyn , Holden Richard J. , Allison David B.
Published: September 2023

In this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.
Effect of short implant crown-to-implant ratio on stress distribution in anisotropic bone with different osseointegration rates
Authors: Yuan Xi , Liu Yuchen , Yang Yunhe , Ren Mingfa , Luo Lailong , Zheng Lang , Liu Yang
Published: September 2023

Objective

This study aimed to provide evidence for the clinical application of single short implants by establishing an anisotropic, three-dimensional (3D) finite element mandible model and simulating the effect of crown-to-implant ratio (CIR) on biomechanics around short implants with different osseointegration rates.

Methods

Assuming that the bone is transversely isotropic by finite element method, we created four distinct models of implants for the mandibular first molar. Subsequently, axial and oblique forces were applied to the occlusal surface of these models. Ultimately, the Abaqus 2020 software was employed to compute various mechanical parameters, including the maximum von Mises stress, tensile stress, compressive stress, shear stress, displacement, and strains in the peri-implant bone tissue.

Results

Upon establishing consistent osseointegration rates, the distribution of stress exhibited similarities across models with varying CIRs when subjected to vertical loads. However, when exposed to inclined loads, the maximum von Mises stress within the cortical bone escalated as the CIR heightened. Among both loading scenarios, notable escalation in the maximum von Mises stress occurred in the model featuring a CIR of 2.5 and an osseointegration rate of 25%. Conversely, other models displayed comparable strength. Notably, stress and strain values uniformly increased with augmented osseointegration across all models. Furthermore, an increase in osseointegration rate correlated with reduced maximum displacement for both cortical bone and implants.

Conclusions

After fixing osseointegration rates, the stress around shorter implants increased as the CIR increased under inclined loads. Thus, the effect of lateral forces should be considered when selecting shorter implants. Moreover, an implant failure risk was present in cases with a CIR ≥ 2.5 and low osseointegration rates. Additionally, the higher the osseointegration rate, the more readily the implant can achieve robust stability.
Preliminary in vitro cytotoxic evaluation of Uncaria gambier (Hunt) Roxb extract as a potential herbal-based pulpotomy medicament
Authors: Tan Bee Chin , Mahyuddin Alida , Sockalingam S. Nagarajan M. P. , Zakaria Ahmad Shuhud Irfani
Published: September 2023

Background

The downfall of formocresol as a pulpotomy medicament highlights the importance of cytotoxic evaluation and the establishment of a safe concentration of dental material prior to its usage in the oral cavity. Uncaria gambir is an herbal plant that possesses antimicrobial, anti-inflammatory and antioxidant properties, suggesting its potential as an alternative medicament for pulpotomy. However, there are not many studies published on its cytotoxicity, with some using non-standardised techniques and reported variable outcomes. Here, we investigated the concentration and time-dependent toxicity of Uncaria gambir extract towards the M3CT3-E1 cell line and compared it with the gold standard pulpotomy medicament: mineral trioxide aggregate (MTA).

Methods

Uncaria gambir extracts at concentrations ranging from 1000 to 7.8 µg/ml and MTA eluates at 4- and 48 h setting times were prepared. 10% dimethyl sulfoxide (DMSO) and culture media were used as positive and negative controls respectively. Cell viability on days 1, 2, 3 and 7 was analysed using Alamar Blue and Live and Dead Cell assay. Any morphological cellular changes were evaluated using transmission electron microscopes (TEM). Data were analysed using a two-way mixed Analysis of Variance (ANOVA).

Results

The interaction between the concentration and exposure time on the fluorescence intensity of Uncaria gambir extract and MTA 48 h was found to be statistically significant (p < 0.001). No cytotoxic effects on the cells were exerted by both MTA 48 h and Uncaria gambir extract at a concentration below 500 µg/mL. TEM analysis and Live and Dead Cell assay for both materials were comparable to the negative control. No significant differences in fluorescent intensity were observed between Uncaria gambir extract at 500 µg/mL and MTA 48 h (p > 0.05).

Conclusion

Uncaria gambir extracts at a maximum concentration of 500 μg/mL are non-cytotoxic over time and are comparable to the MTA.
Providing culturally responsive care in a pediatric setting: are our trainees ready?
Authors: Chen Anna , Blatman Zachary , Chan Amy , Hossain Anna , Niles Chavon , Atkinson Adelle , Narang Indra
Published: September 2023

Background

Extensive data consistently demonstrates inequities in access and delivery of healthcare for patients from historically marginalized populations, resulting in poorer health outcomes. To address this systemic oppression in healthcare, it is necessary to embed principles of equity, diversity, and inclusion (EDI) at an early stage within medical education. This study aimed to assess pediatric trainees’ perceived interest in EDI curricula as well as their confidence in applying this knowledge to provide culturally responsive care.

Methods

An anonymous online survey was distributed to pediatric trainees at the University of Toronto. Closed-ended questions used a Likert scale to assess respondents’ confidence and interest in providing culturally responsive care to patients. Open-ended questions explored trainees’ perceptions of effective EDI learning modalities. A mixed methods approach was utilized, where quantitative data was summarized using descriptive statistics and descriptive content analysis was used to highlight themes within qualitative data.

Results

116 pediatric trainees completed the survey, of which 72/116 (62%) were subspecialty residents/fellows and 44/116 (38%) were core residents. 97% of all responses agreed or strongly agreed that it was important to learn about providing culturally responsive care to patients from historically marginalized communities; however, many trainees lacked confidence in their knowledge of providing culturally responsive care (42%) and applying their knowledge in clinical practice (47%). Respondents identified direct clinical exposure through rotations, immersive experiences, and continuity clinics as effective EDI teaching modalities. Identified barriers included time constraints in the clinical environment, burnout, and lack of exposure to diverse patient populations.

Conclusion

Most pediatric trainees want to provide culturally responsive care to patients from historically marginalized communities, but do not feel confident in their knowledge to do so. Trainees value learning about EDI through direct clinical exposure and immersive experiences, rather than didactic lectures or modules. These study findings will be utilized to develop and implement an enhanced EDI education curriculum for pediatric trainees at the University of Toronto and other postgraduate residency programs.
Factors associated with intention of clinical pharmacists and candidates to provide pharmaceutical care: application of theory planned behaviour
Authors: Tecen-Yucel Kamer , Ozdemir Nesligul , Kara Emre , Demirkan Kutay , Sancar Mesut , Okuyan Betul
Published: September 2023

Background

Postgraduate education programs in clinical pharmacy have become widespread in Türkiye. This study aimed to identify factors associated with the intention of Turkish clinical pharmacists and candidates (who were graduates and students of postgraduate clinical pharmacy programs) to provide pharmaceutical care.

Methods

This prospective observational study was conducted between June 2021 and May 2022. After searching relevant studies, an expert panel discussion, translation, cultural adaptation, and a pilot study developed a 52-item Turkish scale based on the Theory of Planned Behavior (TBP). Cronbach alpha for each construct was calculated after an explanatory factor and test–retest reliability analysis. An online survey link was sent to all graduates or candidates of postgraduate clinical pharmacy programs in Türkiye. After univariate regression analysis, the multiple linear regression model was performed.

Results

One hundred fifty-six participants completed the survey (response rate: 59.1%). The Cronbach’s alpha for attitude (9 items), subjective norm (6 items), perceived behavioural control (5 items), self-efficacy (6 items), intention (11 items) and past behaviour (15 items) were 0.945, 0.720, 0.751, 0.864, 0.934 and 0.955 respectively. The multiple linear regression analysis found a higher score of the subjective norm (p = 0.016), a higher score of self-efficacy (p < 0.001), younger age (p < 0.001) and having PhD (p = 0.038) were associated with increased intention score.

Conclusions

It was shown that higher self efficacy and positive beliefs of their peers and other healthcare professionals were associated with their higher intention score for providing pharmaceutical care. Younger age and having a PhD were other factors associated with their intention to provide pharmaceutical care.
The impact of journal clubs on postgraduate medical education in China
Authors: Li Yujuan , Zhang Yue , Liu Rong , Hao Yi , Xiong Jing
Published: September 2023

Purpose

Journal clubs hold significant importance in medical education, with numerous studies highlighting their contributions worldwide. However, studies specifically examining their role in China, particularly among Chinese medical postgraduates categorized into academic and clinical types, remain scarce. This research aims to investigate the participation, performance, and benefits of journal clubs, and explore the influence of student type and study phase on these aspects.

Method

A survey encompassing demographic information, participation rates, performance evaluations, and perceived improvements was distributed to postgraduates at Tongji Medical College of Huazhong University of Science and Technology. A total of 232 completed questionnaires were included for further analysis. Statistical analysis employed the Mann–Whitney U test and Gamma tests, with statistical significance set at p-value < 0.05.

Results

Overall participation and performance in journal clubs among Chinese medical postgraduates were comparable to global findings. Notably, academic postgraduates exhibited higher levels of attendance rate and gained more research assistance than clinical postgraduates, while their performance levels were similar. When considering the study phase, a downward trend in academic postgraduates' attendance rate and listening attitude and an upward trend in clinical postgraduates' participation were observed with the seniority phase. Additionally, presentation comments, post-presentation progress, and research assistance showed improvements over time for both student types.

Conclusions

This study reveals academic postgraduates' fatigue, contrasting with clinical postgraduates' enthusiasm, and underscores academic postgraduates' superior research assistance. To address these findings, we recommend supporting and encouraging scientific research training for clinical postgraduates, aiding academic postgraduates in better time management and reducing non-essential responsibilities, and implementing critical appraisal skill education.
Prospective prescription review system correlated with more rational PPI medication use, better clinical outcomes and reduced PPI costs: experience from a retrospective cohort study
Authors: Fan Xiucong , Chen Danxia , Bao Siwei , Dong Xiaohui , Fang Fang , Bai Rong , Zhang Yuyi , Zhang Xiaogang , Tang Weijun , Ma Yabin , Zhai Xiaobo
Published: September 2023

Introduction

Proton pump inhibitor (PPI) abuse poses an overwhelming threat to the allocation of medical resources and places a heavy burden on global medical expenses. In this study, we put forward our prospective prescription review system and evaluated the effects of this system on clinical outcomes, rational medication use and costs related to PPIs.

Methods

A retrospective cohort study was conducted in which the included patients were divided into a preintervention group (2019.10–2020.09) and a postintervention group (2020.10–2021.09). To reduce the bias of patients’ baseline characteristics, the propensity score matching (PSM) method was employed. The primary endpoints were the incidence of stress ulcers (SUs), the improvement and cure rates of gastrointestinal haemorrhage, the defined daily dose (DDD), the drug utilization index (DUI) and the DDD/100 patient-days. The secondary endpoints included the types of unreasonable medication orders for PPIs, the PPI utilization rate and PPI costs.

Results

A total of 53,870 patients were included to evaluate the secondary endpoints, and 46,922 patients were paired by PSM and assessed to evaluate the primary endpoints. The number of PPIs used and PPI costs were significantly lower in the postintervention group than in the preintervention group (P < 0.001). The rationality evaluation results showed that the frequency of PPI use and the number of drug interactions were significantly higher in the preintervention group than in the postintervention group (P < 0.01). The proportion of patients taking oral PPIs was significantly increased in the postintervention group (29.30% vs. 34.56%, p < 0.01). For the utilization of PPIs both for prevention and treatment, the DUI and DDD/100 patient-days were substantially decreased in the postintervention group (P < 0.001 and P < 0.05, respectively). The incidence of SUs in the postintervention group was 44.95%, and that in the preintervention group was 51.93% (p < 0.05).

Conclusion

The implementation of the prospective prescription review system on rational PPI use correlated with reduced PPI costs, more rational PPI medication use and better clinical outcomes, and this system is worthy of long-term implementation for further improvement of rational drug use.
Formulation of cost-effective medium and optimization studies for enhanced production of rapamycin
Authors: K. Ganesh Sanjeev. , C Subathra Devi
Published: September 2023

Background

Enhancing rapamycin production using a cost-effective medium is crucial for wider accessibility, reduced manufacturing costs, sustainable pharmaceutical practices, and advancements in therapeutic applications. It promotes global health, biotechnological innovation, research collaboration, and societal well-being through affordable and effective treatments. This study focuses on the development of a novel cost-effective production medium for the synthesis of rapamycin from Streptomyces hygroscopicus.

Results

In the initial screening, more rapamycin production was observed in medium A. Initially, the organism produced 10 µg/mL rapamycin. Based on the OFT results, a novel cost-effective medium composition was designed, incorporating soyabean, sugarcane juice, and dried tomato components. Using RSM, soyabean and tomato was found to be more significant in rapamycin production than sugarcane. In the optimized medium, the production of rapamycin increased significantly to 24 µg/mL. Furthermore, a comparative analysis of the growth kinetics between the production normal medium (referred to as production medium A) and the newly optimized cost-effective production medium revealed that the optimized cost-effective production medium significantly enhanced the production of rapamycin.

Conclusion

Overall, this study demonstrates the successful development of a cost-effective production medium for rapamycin synthesis from S. hygroscopicus. The findings highlight the potential of using a cost-effective medium to enhance the production of a valuable secondary metabolite, rapamycin, while reducing production costs.
Small-area estimation and analysis of HIV/AIDS indicators for precise geographical targeting of health interventions in Nigeria. a spatial microsimulation approach
Authors: Abubakar Eleojo Oluwaseun , Cunningham Niall
Published: September 2023

Background

Precise geographical targeting is well recognised as an indispensable intervention strategy for achieving many Sustainable Development Goals (SDGs). This is more cogent for health-related goals such as the reduction of the HIV/AIDS pandemic, which exhibits substantial spatial heterogeneity at various spatial scales (including at microscale levels). Despite the dire data limitations in Low and Middle Income Countries (LMICs), it is essential to produce fine-scale estimates of health-related indicators such as HIV/AIDS. Existing small-area estimates (SAEs) incorporate limited synthesis of the spatial and socio-behavioural aspects of the HIV/AIDS pandemic and/or are not adequately grounded in international indicator frameworks for sustainable development initiatives. They are, therefore, of limited policy-relevance, not least because of their inability to provide necessary fine-scale socio-spatial disaggregation of relevant indicators.

Methods

The current study attempts to overcome these challenges through innovative utilisation of gridded demographic datasets for SAEs as well as the mapping of standard HIV/AIDS indicators in LMICs using spatial microsimulation (SMS).

Results

The result is a spatially enriched synthetic individual-level population of the study area as well as microscale estimates of four standard HIV/AIDS and sexual behaviour indicators. The analysis of these indicators follows similar studies with the added advantage of mapping fine-grained spatial patterns to facilitate precise geographical targeting of relevant interventions. In doing so, the need to explicate socio-spatial variations through proper socioeconomic disaggregation of data is reiterated.

Conclusions

In addition to creating SAEs of standard health-related indicators from disparate multivariate data, the outputs make it possible to establish more robust links (even at individual levels) with other mesoscale models, thereby enabling spatial analytics to be more responsive to evidence-based policymaking in LMICs. It is hoped that international organisations concerned with producing SDG-related indicators for LMICs move towards SAEs of such metrics using methods like SMS.
Variables influencing the prediction of fluid responsiveness: a systematic review and meta-analysis
Authors: Alvarado Sánchez Jorge Iván , Caicedo Ruiz Juan Daniel , Diaztagle Fernández Juan José , Cruz Martínez Luís Eduardo , Carreño Hernández Fredy Leonardo , Santacruz Herrera Carlos Andrés , Ospina-Tascón Gustavo Adolfo
Published: September 2023

Introduction

Prediction of fluid responsiveness in acutely ill patients might be influenced by a number of clinical and technical factors. We aim to identify variables potentially modifying the operative performance of fluid responsiveness predictors commonly used in clinical practice.

Methods

A sensitive strategy was conducted in the Medline and Embase databases to search for prospective studies assessing the operative performance of pulse pressure variation, stroke volume variation, passive leg raising (PLR), end-expiratory occlusion test (EEOT), mini-fluid challenge, and tidal volume challenge to predict fluid responsiveness in critically ill and acutely ill surgical patients published between January 1999 and February 2023. Adjusted diagnostic odds ratios (DORs) were calculated by subgroup analyses (inverse variance method) and meta-regression (test of moderators). Variables potentially modifying the operative performance of such predictor tests were classified as technical and clinical.

Results

A total of 149 studies were included in the analysis. The volume used during fluid loading, the method used to assess variations in macrovascular flow (cardiac output, stroke volume, aortic blood flow, volume‒time integral, etc.) in response to PLR/EEOT, and the apneic time selected during the EEOT were identified as technical variables modifying the operative performance of such fluid responsiveness predictor tests (p < 0.05 for all adjusted vs. unadjusted DORs). In addition, the operative performance of fluid responsiveness predictors was also influenced by clinical variables such as the positive end-expiratory pressure (in the case of EEOT) and the dose of norepinephrine used during the fluid responsiveness assessment for PLR and EEOT (for all adjusted vs. unadjusted DORs).

Conclusion

Prediction of fluid responsiveness in critically and acutely ill patients is strongly influenced by a number of technical and clinical aspects. Such factors should be considered for individual intervention decisions.
Thermal stability of levopimaric acid and its oxidation products
Authors: Li Yuanlin , Chen Hongqin , Yan Heng , Xu Yangyong , Tang Jinwen , Wang Runsen , Yan Mengru , Dai Yuqiao , Huang Yongguang , Liu Xiongmin
Published: September 2023

Biofuels are renewable alternatives to fossil fuels. Levopimaric acid‒base biofuels have attracted increasing attention. However, their stability remains a critical issue in practice. Thus, there is a strong impetus to evaluate the thermal stability of levopimaric acid. Through thermogravimetry (TG) and a custom-designed mini closed pressure vessel test (MCPVT) operating under isothermal and stepped temperature conditions, we investigated thermal oxidation characteristics of levopimaric acid under oxygen atmosphere. Thin-layer chromatography (TLC) and iodimetry were used to measure the hydrogen peroxides generated by levopimaric acid oxidation. A high pressure differential scanning calorimeter (HPDSC) was used to assess hydroperoxide thermal decomposition characteristics. Gas chromatography-mass spectrometry (GC-MS) was used to characterize the oxidation products. The thermal decomposition kinetics of levopimaric acid were thus elucidated, and a high peroxide value was detected in the levopimaric acid. The decomposition heat (QDSC) and exothermic onset temperature (Tonset) of hydroperoxides were 338.75 J g−1 and 375.37 K, respectively. Finally, levopimaric acid underwent a second-stage oxidation process at its melt point (423.15 K), resulting in complex oxidation products. Thermal oxidation of levopimaric acid could yield potential thermal hazards, indicating that antioxidants must be added during levopimaric acid application to protect against such hazardous effects.
Integrated study of systemic and local airway transcriptomes in asthma reveals causal mediation of systemic effects by airway key drivers
Authors: Zhang Lingdi , Chun Yoojin , Irizar Haritz , Arditi Zoe , Grishina Galina , Grishin Alexander , Vicencio Alfin , Bunyavanich Supinda
Published: September 2023

Background

Systemic and local profiles have each been associated with asthma, but parsing causal relationships between system-wide and airway-specific processes can be challenging. We sought to investigate systemic and airway processes in asthma and their causal relationships.

Methods

Three hundred forty-one participants with persistent asthma and non-asthmatic controls were recruited and underwent peripheral blood mononuclear cell (PBMC) collection and nasal brushing. Transcriptome-wide RNA sequencing of the PBMC and nasal samples and a series of analyses were then performed using a discovery and independent test set approach at each step to ensure rigor. Analytic steps included differential expression analyses, coexpression and probabilistic causal (Bayesian) network constructions, key driver analyses, and causal mediation models.

Results

Among the 341 participants, the median age was 13 years (IQR = 10–16), 164 (48%) were female, and 200 (58.7%) had persistent asthma with mean Asthma Control Test (ACT) score 16.6 (SD = 4.2). PBMC genes associated with asthma were enriched in co-expression modules for NK cell-mediated cytotoxicity (fold enrichment = 4.5, FDR = 6.47 × 10−32) and interleukin production (fold enrichment = 2.0, FDR = 1.01 × 10−15). Probabilistic causal network and key driver analyses identified NK cell granule protein (NKG7, fold change = 22.7, FDR = 1.02 × 10−31) and perforin (PRF1, fold change = 14.9, FDR = 1.31 × 10−22) as key drivers predicted to causally regulate PBMC asthma modules. Nasal genes associated with asthma were enriched in the tricarboxylic acid (TCA) cycle module (fold enrichment = 7.5 FDR = 5.09 × 10−107), with network analyses identifying G3BP stress granule assembly factor 1 (G3BP1, fold change = 9.1 FDR = 2.77 × 10−5) and InaD-like protein (INADL, fold change = 5.3 FDR = 2.98 × 10−9) as nasal key drivers. Causal mediation analyses revealed that associations between PBMC key drivers and asthma are causally mediated by nasal key drivers (FDR = 0.0076 to 0.015).

Conclusions

Integrated study of the systemic and airway transcriptomes in a well-phenotyped asthma cohort identified causal key drivers of asthma among PBMC and nasal transcripts. Associations between PBMC key drivers and asthma are causally mediated by nasal key drivers.
Identification of potential susceptibility genes in patients with primary Sjögren’s syndrome-associated pulmonary arterial hypertension through whole exome sequencing
Authors: Li Mucong , Shi Yue , Zhao Jiuliang , Wang Qian , Li Mengtao , Zhao Xiuli
Published: September 2023

Background

Pulmonary arterial hypertension (PAH) is a rare complication of primary Sjögren’s syndrome (pSS). Several genes have proven to be associated with pSS and PAH. However, there is no study specifically addressing the genetic susceptibility in pSS combined with PAH.

Methods

Thirty-four unrelated patients with pSS-PAH were recruited from April 2019 to July 2021 at Peking Union Medical College Hospital. Demographic and clinical data were recorded in detail, and peripheral blood samples were collected for whole-exome sequencing (WES). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to predict the functional effect of mutant genes. Genetic variants identified by WES were confirmed by polymerase chain reaction (PCR)-Sanger sequencing.

Results

We totally identified 141 pathogenic variant loci of 129 genes in these 34 pSS-PAH patients, using WES analysis. Patients with a family history of rheumatic diseases are more likely to carry FLG mutations or carry gene variations related to the biosynthesis of the amino acids pathway (p < 0.05). According to Sanger sequencing confirmation and pathogenicity validation, we totally identified five candidate pathogenic variants including FLG c.12064A > T, BCR c.3275_3278dupCCGG, GIGYF2 c.3463C > A, ITK c.1741C > T, and SLC26A4 c.919-2A > G.

Conclusion

Our findings provide preliminary data of exome sequencing to identify susceptibility loci for pSS-PAH and enriched our understanding of the genetic etiology for pSS-PAH. The candidate pathogenic genes may be the potential genetic markers for early warning of this disease.
Antioxidative phenolic compounds from the aerial parts of Cyperus exaltatus var. iwasakii and their HPLC analysis
Authors: Choi Jungwon , Lee Hak-Dong , Cho Hyejin , Lee Chang-Dae , Tran Gia Han , Kim Hoon , Moon Sung-Kwon , Lee Sanghyun
Published: September 2023

The constituents and antioxidant activities of Cyperus exaltatus var. iwasakii (CE) have not been studied to date. In this study, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6 sulfonic acid) (ABTS) assays were used to evaluate the radical-scavenging activities of the ethanol extract, four fractions, and isolated compounds of CE. In addition, phenolic acids and flavonoids were isolated from the ethanol extract of CE using column chromatography. The compounds identified by spectroscopy were gallic acid, protocatechuic acid, vanillic acid, p-coumaric acid, rutin, ferulic acid, isoquercitrin, astragalin, quercetin, luteolin, apigenin, tricin, and kaempferol. Quantitative analysis using high-performance liquid chromatography (HPLC) revealed that the major flavonoids of CE were astragalin and tricin and that the major phenolic acid was p-coumaric acid. In addition, comparative analysis of CE from Ganghwa and Hampyeong habitats using HPLC showed that the Hampyeong CE had a higher phytochemical content. Comparative analyses of the isolated compounds were also conducted among five Cyperus species. The highest antioxidant activities were found in the ethyl acetate (EtOAc) fraction, and among the compounds isolated from CE, vanillic acid and quercetin showed remarkable antioxidant activity even when compared with ascorbic acid. The results demonstrate the usefulness of CE, which has not been sufficiently studied previously, and will facilitate the evaluation of its potential effectiveness as antioxidant functional plant material.
Electrical signal of pepper during cropping period affected by different amount of fertilizer
Authors: Kim Jeong Yeon , Sin Su Kyeong , Park Jin Hee
Published: September 2023

Precision agriculture requires supply of adequate amount of fertilizer application to increase crop yield and prevent environmental contamination. Objective of the study was to evaluate response of pepper under different fertigation method and amount using plant induced electrical signal (PIES) for precision agriculture. Pepper was fertigated 10 times with recommended additional nitrogen fertilizer and set as a control. Low fertilizer treatment did not receive additional urea and high fertilizer received three times higher amount of nitrogen fertilizer. Conventional treatment was fertigated as basal fertilizer and once with additional fertilizer. The PIES decreased during vegetative stage and remained constant at reproductive stage because of reduced nutrient and water uptake. The PIES showed positive relationship with soil NH4+, NO3−, stem NO3− and leaf N, which resulted in highest PIES value during reproductive stage in high fertilizer treated pepper. Plant growth parameters were also related with the PIES although yield was not affected by different fertilizer treatment.
singleCellBase: a high-quality manually curated database of cell markers for single cell annotation across multiple species
Authors: Meng Fan-Lin , Huang Xiao-Ling , Qin Wen-Yan , Liu Kun-Bang , Wang Yan , Li Ming , Ren Yong-Hong , Li Yan-Ze , Sun Yi-Min
Published: September 2023

Annotating cells in the analysis of single-cell RNA-seq (scRNA-seq) data is one of the most challenging tasks that researchers are actively addressing. Manual cell annotation is generally considered the gold standard method, although it is labor intensive and independent of prior knowledge. At present, the relationship between high-quality, known marker genes and cell types is very limited, especially for a variety of species other than humans and mice. The singleCellBase is a manually curated resource of high-quality cell types and gene markers associations across multiple species. In details, it offers 9,158 entries spanning a total of 1,221 cell types and linking with 8,740 genes (cell markers), covering 464 diseases/status, and 165 types of tissues across 31 species. The singleCellBase provides a user-friendly interface to the scientific community to browse, search, download and submit records of marker genes and cell types. The resource providing ineluctable prior knowledge required by manual cell annotation, which is valuable to interpret scRNA-seq data and elucidate what cell type or cell state that a cell population represents.
The accuracy of an Online Sequential Extreme Learning Machine in detecting voice pathology using the Malaysian Voice Pathology Database
Authors: Za'im Nur Ain Nabila , Al-Dhief Fahad Taha , Azman Mawaddah , Alsemawi Majid Razaq Mohamed , Abdul Latiff Nurul Mu′azzah , Mat Baki Marina
Published: September 2023

Background

A multidimensional voice quality assessment is recommended for all patients with dysphonia, which requires a patient visit to the otolaryngology clinic. The aim of this study was to determine the accuracy of an online artificial intelligence classifier, the Online Sequential Extreme Learning Machine (OSELM), in detecting voice pathology. In this study, a Malaysian Voice Pathology Database (MVPD), which is the first Malaysian voice database, was created and tested.

Methods

The study included 382 participants (252 normal voices and 130 dysphonic voices) in the proposed database MVPD. Complete data were obtained for both groups, including voice samples, laryngostroboscopy videos, and acoustic analysis. The diagnoses of patients with dysphonia were obtained. Each voice sample was anonymized using a code that was specific to each individual and stored in the MVPD. These voice samples were used to train and test the proposed OSELM algorithm. The performance of OSELM was evaluated and compared with other classifiers in terms of the accuracy, sensitivity, and specificity of detecting and differentiating dysphonic voices.

Results

The accuracy, sensitivity, and specificity of OSELM in detecting normal and dysphonic voices were 90%, 98%, and 73%, respectively. The classifier differentiated between structural and non-structural vocal fold pathology with accuracy, sensitivity, and specificity of 84%, 89%, and 88%, respectively, while it differentiated between malignant and benign lesions with an accuracy, sensitivity, and specificity of 92%, 100%, and 58%, respectively. Compared to other classifiers, OSELM showed superior accuracy and sensitivity in detecting dysphonic voices, differentiating structural versus non-structural vocal fold pathology, and between malignant and benign voice pathology.

Conclusion

The OSELM algorithm exhibited the highest accuracy and sensitivity compared to other classifiers in detecting voice pathology, classifying between malignant and benign lesions, and differentiating between structural and non-structural vocal pathology. Hence, it is a promising artificial intelligence that supports an online application to be used as a screening tool to encourage people to seek medical consultation early for a definitive diagnosis of voice pathology.
Influence of exposure of customized dental implant abutments to different cleaning procedures: an in vitro study using AI-assisted SEM/EDS analysis
Authors: Hofmann Paul , Kunz Andreas , Schmidt Franziska , Beuer Florian , Duddeck Dirk
Published: September 2023

Purpose

Dental implant abutments are defined as medical devices by their intended use. Surfaces of custom-made CAD/CAM two-piece abutments may become contaminated during the manufacturing process in the dental lab. Inadequate reprocessing prior to patient care may contribute to implant-associated complications. Risk-adapted hygiene management is required to meet the requirements for medical devices.

Methods

A total of 49 CAD/CAM-manufactured zirconia copings were bonded to prefabricated titanium bases. One group was bonded, polished, and cleaned separately in dental laboratories throughout Germany (LA). Another group was left untreated (NC). Five groups received the following hygiene regimen: three-stage ultrasonic cleaning (CP and FP), steam (SC), argon–oxygen plasma (PL), and simple ultrasonic cleaning (UD). Contaminants were detected using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) and segmented and quantified using interactive machine learning (ML) and thresholding (SW). The data were statistically analysed using non-parametric tests (Kruskal–Wallis test, Dunn’s test).

Results

Significant differences in contamination levels with the different cleaning procedures were found (p ≤ 0.01). The FP–NC/LA groups showed the most significant difference in contamination levels for both measurement methods (ML, SW), followed by CP–LA/NC and UD–LA/NC for SW and CP–LA/NC and PL–LA/NC for ML (p ≤ 0.05). EDS revealed organic contamination in all specimens; traces of aluminum, silicon, and calcium were detected.

Conclusions

Chemothermal cleaning methods based on ultrasound and argon–oxygen plasma effectively removed process-related contamination from zirconia surfaces. Machine learning is a promising assessment tool for quantifying and monitoring external contamination on zirconia abutments.

Graphical Abstract
Undifferentiated pleomorphic sarcoma of the spleen: a case report and literature review
Authors: Gatt Raphael , Casingena Luca , Pisani David , Agius Rachel , Cassar Noel
Published: September 2023

Background

Undifferentiated pleomorphic sarcoma is an uncommon sarcoma and its presence in the spleen is even rarer, with only a handful of cases reported in English literature. It is typically only diagnosed following histological analysis. Its rarity also means that there is little consensus over ideal management.

Case presentation

This report presents a case of a 40-year-old Caucasian male who was found to have a splenic mass after presenting with non-specific abdominal pain and generalized malaise. Numerous imaging modalities were used which demonstrated a large partially solid and partially cystic lesion in spleen with no evidence of metastasis. As core biopsies were undiagnostic, he was planned for a diagnostic and therapeutic splenectomy. However, despite magnetic resonance imaging 11 days prior to his operation showed no evidence of liver metastasis, a massive splenic tumour with hepatic metastases was identified intraoperatively. An open splenectomy, distal pancreatectomy and liver metastasectomy was hence carried out. Histological analysis confirmed liver metastasis secondary to a splenic undifferentiated pleomorphic sarcoma. The patient recovered well and was discharged home. He presented again three weeks after his operation with lower back pain, abdominal pain and fever. Computed tomography demonstrated extensive recurrent disease burden in the peritoneum and liver. The patient passed away a month after surgery.

Conclusion

Splenic undifferentiated pleomorphic sarcoma is a rare tumour which may pose a significant diagnostic challenge on both clinical and histopathological grounds. Following diagnosis and treatment, its aggressive nature often results in a poor prognosis. Current literature fails to delineate any superior management strategy to increase survival.