bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of pulmonary Scedosporium apiospermum infection from bronchoalveolar lavage fluid by metagenomic next-generation sequencing in an immunocompetent female patient with normal lung structure: a case report and literature review
Authors: Han Jingru , Liang Lifang , Li Qingshu , Deng Ruihang , Liu Chenyang , Wu Xuekai , Zhang Yuxin , Zhang Ruowen , Dai Haiyun
Published: March 2024

Background

Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency.

Case presentation

A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient’s symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up.

Conclusion

This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.
Bloodstream infection clusters for critically ill patients: analysis of two-center retrospective cohorts
Authors: Wang Lei , Zhang Li , Huang Xiaolong , Xu Hao , Huang Wei
Published: March 2024

Background

Bloodstream infections (BSI) are highly prevalent in hospitalized patients requiring intensive care. They are among the most serious infections and are highly associated with sepsis or septic shock, which can lead to prolonged hospital stays and high healthcare costs. This study aimed at establishing an easy-to-use nomogram for predicting the prognosis of patients with BSI.

Methods

In retrospective study, records of patients with BSI admitted to the intensive care unit (ICU) over the period from Jan 1st 2016 to Dec 31st 2021 were included. We used data from two different China hospitals as development cohort and validation cohort respectively. The demographic and clinical data of patients were collected. Based on all baseline data, k-means algorithm was applied to discover the groups of BSI phenotypes with different prognostic outcomes, which was confirmed by Kaplan-Meier analysis and compared using log-rank tests. Univariate Cox regression analyses were used to estimate the risk of clusters. Random forest was used to identified discriminative predictors in clusters, which were utilized to construct nomogram based on multivariable logistic regression in the discovery cohort. For easy clinical applications, we developed a bloodstream infections clustering (BSIC) score according to the nomogram. The results were validated in the validation cohort over a similar period.

Results

A total of 360 patients in the discovery cohort and 310 patients in the validation cohort were included in statistical analyses. Based on baseline variables, two distinct clusters with differing prognostic outcomes were identified in the discovery cohort. Population in cluster 1 was 211 with a ICU mortality of 17.1%, while population in cluster 2 was 149 with an ICU mortality of 41.6% (p < 0.001). The survival analysis also revealed a higher risk of death for cluster 2 when compared with cluster 1 (hazard ratio: 2.31 [95% CI, 1.53 to 3.51], p < 0.001), which was confirmed in validation cohort. Four independent predictors (vasoconstrictor use before BSI, mechanical ventilation (MV) before BSI, Deep vein catheterization (DVC) before BSI, and antibiotic use before BSI) were identified and used to develop a nomogram. The nomogram and BSIC score showed good discrimination with AUC of 0.96.

Conclusion

The developed score has potential applications in the identification of high-risk critically ill BSI patients.
Strabismus management in retinoblastoma survivors
Authors: Masoomian Babak , Shields Carol L. , Esfahani Hamid Riazi , Khalili Atefeh , Ghassemi Fariba , Rishi Pukhraj , Akbari Mohammad Reza , Khorrami-Nejad Masoud
Published: March 2024

Purpose

To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients.

Methods

A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist.

Results

A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2–39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4–9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor’s group was D (n = 11), C (n = 4), B (n = 2) and E (n = 1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n = 8, 47%), intra-arterial chemotherapy (n = 7, 41%) and both (n = 3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12–84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P = 0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30–60) prism diopter (PD) for esotropic and 35.7 ± 7.9 (range, 25–50) PD for exotropic patients (P = 0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9 ± 6.7 PD in exotropic cases (P < 0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10–24) months, in which, 3 (17%) patients needed a second surgery.

Conclusion

Strabismus surgery in treated Rb is safe and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis.
Pandemic lockdowns: who feels coerced and why? - a study on perceived coercion, perceived pressures and procedural justice during the UK COVID-19 lockdowns
Authors: Ranieri V. , Gordon C. , Kamboj S. K. , Edwards S. J.
Published: March 2024

Background

This study examined perceptions of coercion, pressures and procedural injustice and how such perceptions influenced psychological well-being in those who experienced a UK COVID-19 lockdown, with a view to preparing for the possibility of future lockdowns.

Methods

40 individuals categorised as perceiving the lockdown(s) as either highly or lowly coercive took part in one of six asynchronous virtual focus groups (AVFGs).

Results

Using thematic analysis, the following key themes were identified in participants’ discussions: (1) Choice, control and freedom; (2) threats; (3) fairness; (4) circumstantial factors; and (5) psychological factors.

Conclusions

As the first qualitative study to investigate the psychological construct of perceived coercion in relation to COVID-19 lockdowns, its findings suggest that the extent to which individuals perceived pandemic-related lockdowns as coercive may have been linked to their acceptance of restrictions. Preparing for future pandemics should include consideration of perceptions of coercion and efforts to combat this, particularly in relation to differences in equity, in addition to clarity of public health messaging and public engagement.
Effect of parenting style on the emotional and behavioral problems among Chinese adolescents: the mediating effect of resilience
Authors: Wang Jiana , Huang Xinyuan , Li Zhe , Chen Kun , Jin Zhiyu , He Jing , Han Bingsong , Feng Lin , Meng Nana , Yang Cong , Liu Zhuang
Published: March 2024

Background

Although previous studies have found that parenting style significantly predicts emotional and behavioral problems (EBPs) among Chinese adolescents, the mechanism between different parenting styles and EBPs requires in-depth investigation. In our study, we aimed to investigate the mediating effect of resilience, a positive psychological characteristic, between parenting style and EBPs among Chinese adolescents.

Methods

In this cross-sectional study, we used a multistage stratified cluster random sampling method to collect data in Shenyang, Liaoning Province from November to December 2019. Self-developed questionnaires were distributed to 1028 adolescents aged 10–18. Finally, the study consisted of 895 participants. The bootstrap method was used to investigate the role of resilience as a mediator in the relationship between different parenting styles and EBPs from a positive psychology perspective.

Results

The mean score of EBPs was 12.71 (SD = 5.77). After controlling for variables such as gender, age, left-behind children, family type and family income, resilience partially played a mediating role in the associations of paternal rejection (a × b = 0.051 BCa95%CI:0.023,0.080), maternal rejection (a × b = 0.055 BCa95%CI: 0.024, 0.086), paternal emotional warmth (a × b = -0.139 BCa95%CI: -0.182, -0.099) and maternal emotional warmth (a × b = -0.140 BCa95%CI: -0.182, -0.102), with EBPs. The effect sizes were11.28%, 11.51%, 40.76%, and 38.78%, respectively.

Conclusions

Resilience could partially mediate the relationship between parenting style and EBPs, highlighting that parents should adopt a positive parenting style and that resilience improvement could be effective in reducing EBPs among Chinese adolescents.
Impact of psychosocial work factors on risk of medically certified sick leave due to common mental disorders: a nationwide prospective cohort study of Norwegian home care workers
Authors: Knutsen Rigmor Harang , Nielsen Morten Birkeland , Lunde Lars-Kristian , Skare Øivind , Johannessen Håkon A.
Published: March 2024

Background

The Norwegian home care services experience a high level of sick leave, a large proportion of which is due to common mental disorders. A substantial number of such cases can be attributed to psychosocial factors at work, but more knowledge about occupation-specific risk factors is needed to develop targeted preventive measures to reduce sick leave levels. The aim of this study is to identify the most prominent psychosocial work factors influencing the risk of sick leave spells due to common mental disorders.

Methods

Employees from a random sample of 130 Norwegian home care services (N = 1.819) completed a baseline survey on 15 psychosocial work factors. Participants were subsequently followed up for 26 months using registry data on sick leave. The outcome measure was the number of medically certified sick leave spells due to common mental disorders during follow-up in the Norwegian social insurance database. Incidence risk ratios (IRR) and 95% confidence intervals (CIs) were calculated using negative binomial regression with robust standard errors.

Results

Emotional dissonance (IRR 1.30, 95% CI 1.05–1.60) and emotional demands (IRR 1.35, 95% CI 1.14–1.58) were associated with an excess risk of sick leave, while control over work pacing (IRR 0.78, 95% CI 0.62–0.98) was associated with a reduced risk. An estimated 30% (95% CI 8.73–48.82) of sick leave cases were attributable to emotional dissonance and 27% (95% CI 4.80-46.33) were attributable to emotional demands. Control over work pacing was estimated to have prevented 20% (95% CI 1.32–37.78) of the sick leave cases.

Conclusions

This study found that emotional dissonance and emotional demands were robust risk factors for sick leave due to common mental disorders, and that control of work pacing constituted a robust protective factor against sick leave.
Predictive models for perceived convenience of accessing outdoor activities among elderly with physical disabilities in rural China
Authors: Xu Qi , Lin Youyi , He Yiqi , Zhou Xianhong , Liu Jinhai , Shen Dewang , Wu Fan , Lin Xin , Zhang Yun , Li Taibiao , Yan Tiebin
Published: March 2024

Background

The elderly, especially those with physical disabilities, often encounter barriers that prevent them from accessing outdoor activities. Their perceptions of the convenience of accessing outdoor activities may be influenced by various factors including their health, the social context, and/or planned behavior. This study aimed to develop predictive models that identify the principal determinants of perceived convenience among this demographic, and it also examined the disparities observed between genders.

Methods

This was a cross-sectional survey of 1216 community-dwelling older people with physical disabilities in rural China. Grounded on the rehabilitation concepts and the theory of planned behavior, structural equation models integrated health and social behavior factors were constructed to predict perceived convenience of accessing outdoor activities. The standardized coefficients explained the contributions of various factors to the variance.

Results

The final structural models demonstrated good fit for both female and male participants. Perceptions of the convenience of accessing outdoor activities among both women and men were directly impacted by their physical functioning and their intention to participate, and indirectly by medical expenditure, subjective norms, pain, and role limitation in emotional interactions. Positive mental health was more influential for women, while men were more influenced by subjective norms.

Conclusions

Structural equation models have effectively predicted the self-reported convenience of accessing outdoor activities, underscoring the importance of functional and behavioral rehabilitation. Furthermore, gender-sensitive rehabilitation programs are advised to promote engagement in outdoor activities among elderly individuals with physical disabilities.
The mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation
Authors: Wang Rong , Xu Fei , Yang Zhengjia , Cao Jian , Hu Liqi , She Yangyang
Published: March 2024

Background

Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Phosphofructokinase 1 (PFK-1) is one of member of PFK, which plays an important role in reprogramming cancer metabolism, such as lactylation modification. Zinc finger E-box-binding homeobox 1 (ZEB1) has been demonstrated to be a oncogene in many cancers. Therefore, this study was performed to explore the effects of PFK-1 on the lactylation of ZEB1 in BC development.

Methods

Cell viability was measured using the CCK-8 kit. The glucose assay kit and lactate assay kit were used to detect glucose utilization and lactate production. The DNA was purified and quantified by qRT-PCR.

Results

In the present study, we found that ZEB1 expression levels were significantly elevated in bladder cancer cells. Impaired PFK-1 expression inhibits proliferation, migration, and invasion of BC cells and suppresses tumour growth in vivo. We subsequently found that knockdown of PFK-1 decreases glycolysis, including reduced glucose consumption, lactate production and total extracellular acidification rate (ECAR). Mechanistically, PFK-1 inhibits histone lactylation of bladder cancer cells, and thus inhibits the transcription activity of ZEB1.

Conclusion

Our results suggest that PFK-1 can inhibit the malignant phenotype of bladder cancer cells by mediating the lactylation of ZEB1. These findings suggested PFK-1 to be a new potential target for bladder cancer therapy.
Effect of the antirheumatic medication methotrexate (MTX) on biomechanical compressed human periodontal ligament fibroblasts (hPDLFs)
Authors: Welte-Jzyk Claudia , Plümer Vera , Schumann Sven , Pautz Andrea , Erbe Christina
Published: March 2024

Background

The aim of this study was to investigate the in vitro effect of the antirheumatic drug methotrexate (MTX) on biomechanically compressed human periodontal ligament fibroblasts (hPDLFs), focusing on the expression of interleukin 6 (IL-6), as its upregulation is relevant to orthodontic tooth movement.

Methods

Human PDLFs were subjected to pressure and simultaneously treated with MTX. Cell proliferation, viability and morphology were studied, as was the gene and protein expression of IL-6.

Results

Compared with that in untreated fibroblasts, IL-6 mRNA expression in mechanically compressed ligament fibroblasts was increased (two to sixfold; ****p < 0.0001). Under compression, hPDLFs exhibited a significantly more expanded shape with an increase of cell extensions. MTX with and without pressure did not affect IL-6 mRNA expression or the morphology of hPDLFs.

Conclusion

MTX has no effect on IL-6 expression in compressed ligament fibroblasts.
Clinical reasoning skill of nurses working in teaching medical centers in dealing with practical scenarios of King’s model concepts
Authors: Borzo Seyyed Reza , Cheraghi Fatemeh , Khatibian Mahnaz , Noveiri Marzieh Jahani Sayad
Published: March 2024

Background

The present study was conducted to determine clinical reasoning of nurses working in teaching medical centers in dealing with practical scenarios of King’s concepts.

Methods

The study population in this cross-sectional descriptive-analytical study comprised 133 nurses. Data were collected using scenarios based on the King’s model. Data were analyzed in SPSS-16.

Findings

Mean age of the participating nurses was 27.71 ± 8.1 years.The clinical reasoning score was less than average in most participating nurses, and had a significant relationship with education(P < 0.05), service ward(P < 0.001)and organizational position(P < 0.05). In the multivariate analysis of factors relating to clinical reasoning, higher education level (B = 9.5, P = 0.018) and organizational position (B = 4.3, P = 0.017) were predictors of clinical reasoning score.

Discussion

Existing nursing models such as King’s, which is closely related to clinical reasoning, can be used more in educational and clinical systems, and as a clinical guide for promoting the clinical reasoning of nurses and students.
Missed nursing care and its relationship with nurses’ moral sensitivity: a descriptive-analytical study
Authors: Ahansaz Naiier , Adib-Hajbaghery Mohsen , Baghaei Rahim
Published: March 2024

Background

Missed care rates are an indicator of healthcare quality. Missed nursing care can reduce patient safety and lead to adverse events. Moral sensitivity enables nurses to interpret and respond to clients’ needs according to ethical principles. Despite the importance of moral sensitivity and its role in the quality of care, the relationship between nurses' moral sensitivity and missed nursing care has not been extensively studied. This raises the question of whether there is an association between nurses' moral sensitivity and missed care. This study was conducted to investigate the relationship between nurses’ moral sensitivity and missed nursing care in the medical and surgical departments of Imam Khomeini Hospital in Urmia, Iran.

Methods

A cross-sectional study was conducted in 2022, on 202 nurses working in the medical and surgical departments of Imam Khomeini Medical Education Center, Urmia, Iran. Stratified random sampling was used to select the participants. A questionnaire on demographic characteristics, Kalisch's missed care questionnaire, and Lutzen's moral sensitivity questionnaire were used to collect data. Data were analyzed using the Pearson correlation test and linear regression analysis.

Results

Most participants (52.97%) showed moderate moral sensitivity. Nurses’ mean moral sensitivity and total missed care scores were 149.07 ± 21.60 and 59.45 ± 4.87, respectively. Pearson correlation test showed no significant correlation between moral sensitivity scores and the total missed care scores (r = 0.041,p = 0.152). However, in the regression analysis, moral sensitivity (β = 0.213,p < 0.001), age (β = 0.131,p < 0.001), working in rotating shifts (β = 0.183,p < 0.001), monthly income (β = 0.079,p = 0.004), work experience (β = 0.030,p = 0.010), and monthly work hours (β = 0.247,p = 0.010) influenced missed care. Approximately, 0.98% of the variance in the missed care was explained by these variables.

Conclusion

Our nurses reported moderate levels of moral sensitivity and a concerning level of missed care. Missed care can have detrimental effects on patient safety. Therefore, nursing managers must address this issue promptly.
Views and experiences of healthcare professionals and patients on the implementation of a 23-hour accelerated enhanced recovery programme: a mixed-method study
Authors: Sier Misha A. T. , Godina Eva , Tweed Thaís T. T. , Daher Imane , Stoot Jan H. M. B.
Published: March 2024

Background

An accumulating body of research suggests that an accelerating enhanced recovery after colon surgery protocol is beneficial for patients, however, to obtain these effects, adherence to all elements of the protocol is important. The implementation of complex interventions, such as the Enhanced Recovery After Surgery protocol (ERAS), and their strict adherence have proven to be difficult. The same challenges can be expected in the implementation of the accelerated Enhanced Recovery Pathways (ERPs). This study aimed to understand the perspectives of both healthcare professionals (HCPs) and patients on the locally studied acCelerated enHanced recovery After SurgEry (CHASE) protocol.

Methods

For this mixed-method study, HCPs who provided CHASE care and patients who received CHASE care were recruited using purposive sampling. Ethical approval was obtained by the Medical Ethical Committee of the Zuyderland Medical Centre (NL71804.096.19, METCZ20190130, October 2022). Semi-structured, in-depth, one-on-one interviews were conducted with HCPs (n = 13) and patients (n = 11). The interviews consisted of a qualitative and quantitative part, the protocol evaluation and the Measurement Instrument or Determinant of Innovations-structured questionnaire. We explored the perspectives, barriers, and facilitators of the CHASE protocol implementation. The interviews were audiotaped, transcribed verbatim and analysed independently by two researchers using direct content analysis.

Results

The results showed that overall, HCPs support the implementation of the CHASE protocol. The enablers were easy access to the protocol, the relevance of the intervention, and thorough patient education. Some of the reported barriers included the difficulty of recognizing CHASE patients, the need for regular feedback, and the updates on the implementation progress. Most patients were enthusiastic about early discharge after surgery and expressed satisfaction with the care they received. On the other hand, the patients sometimes received different information from different HCPs, considered the information to be too extensive and few experienced some discomfort with CHASE care.

Conclusion

Bringing CHASE care into practice was challenging and required adaptation from HCPs. The experiences of HCPs showed that the protocol can be improved further, and the mostly positive experiences of patients are a motivation for this improvement. These results yielded practical implications to improve the implementation of accelerated ERPs.
The fitness trade-off between growth and stress resistance determines the phenotypic landscape
Authors: Kim Dongsan , Hwang Chae Young , Cho Kwang-Hyun
Published: March 2024

Background

A central challenge in biology is to discover a principle that determines individual phenotypic differences within a species. The growth rate is particularly important for a unicellular organism, and the growth rate under a certain condition is negatively associated with that of another condition, termed fitness trade-off. Therefore, there should exist a common molecular mechanism that regulates multiple growth rates under various conditions, but most studies so far have focused on discovering those genes associated with growth rates under a specific condition.

Results

In this study, we found that there exists a recurrent gene expression signature whose expression levels are related to the fitness trade-off between growth preference and stress resistance across various yeast strains and multiple conditions. We further found that the genomic variation of stress-response, ribosomal, and cell cycle regulators are potential causal genes that determine the sensitivity between growth and survival. Intriguingly, we further observed that the same principle holds for human cells using anticancer drug sensitivities across multiple cancer cell lines.

Conclusions

Together, we suggest that the fitness trade-off is an evolutionary trait that determines individual growth phenotype within a species. By using this trait, we can possibly overcome anticancer drug resistance in cancer cells.
Mitochondrial perturbation in immune cells enhances cell-mediated innate immunity in Drosophila
Authors: Vesala Laura , Basikhina Yuliya , Tuomela Tea , Nurminen Anssi , Siukola Emilia , Vale Pedro F. , Salminen Tiina S.
Published: March 2024

Background

Mitochondria participate in various cellular processes including energy metabolism, apoptosis, autophagy, production of reactive oxygen species, stress responses, inflammation and immunity. However, the role of mitochondrial metabolism in immune cells and tissues shaping the innate immune responses are not yet fully understood. We investigated the effects of tissue-specific mitochondrial perturbation on the immune responses at the organismal level. Genes for oxidative phosphorylation (OXPHOS) complexes cI-cV were knocked down in the fruit flyDrosophila melanogaster, targeting the two main immune tissues, the fat body and the immune cells (hemocytes).

Results

While OXPHOS perturbation in the fat body was detrimental, hemocyte-specific perturbation led to an enhanced immunocompetence. This was accompanied by the formation of melanized hemocyte aggregates (melanotic nodules), a sign of activation of cell-mediated innate immunity. Furthermore, the hemocyte-specific OXPHOS perturbation induced immune activation of hemocytes, resulting in an infection-like hemocyte profile and an enhanced immune response against parasitoid wasp infection. In addition, OXPHOS perturbation in hemocytes resulted in mitochondrial membrane depolarization and upregulation of genes associated with the mitochondrial unfolded protein response.

Conclusions

Overall, we show that while the effects of mitochondrial perturbation on immune responses are highly tissue-specific, mild mitochondrial dysfunction can be beneficial in immune-challenged individuals and contributes to variation in infection outcomes among individuals.
Cytoplasmic genome contributions to domestication and improvement of modern maize
Authors: Cao Shuai , Zhang Huanhuan , Liu Yang , Sun Yi , Chen Z. Jeffrey
Published: March 2024

Background

Studies on maize evolution and domestication are largely limited to the nuclear genomes, and the contribution of cytoplasmic genomes to selection and domestication of modern maize remains elusive. Maize cytoplasmic genomes have been classified into fertile (NA and NB) and cytoplasmic-nuclear male-sterility (CMS-S, CMS-C, and CMS-T) groups, but their contributions to modern maize breeding have not been systematically investigated.

Results

Here we report co-selection and convergent evolution between nuclear and cytoplasmic genomes by analyzing whole genome sequencing data of 630 maize accessions modern maize and its relatives, including 24 fully assembled mitochondrial and chloroplast genomes. We show that the NB cytotype is associated with the expansion of modern maize to North America, gradually replaces the fertile NA cytotype probably through unequal division, and predominates in over 90% of modern elite inbred lines. The mode of cytoplasmic evolution is increased nucleotypic diversity among the genes involved in photosynthesis and energy metabolism, which are driven by selection and domestication. Furthermore, genome-wide association study reveals correlation of cytoplasmic nucleotypic variation with key agronomic and reproductive traits accompanied with the diversification of the nuclear genomes.

Conclusions

Our results indicate convergent evolution between cytoplasmic and nuclear genomes during maize domestication and breeding. These new insights into the important roles of mitochondrial and chloroplast genomes in maize domestication and improvement should help select elite inbred lines to improve yield stability and crop resilience of maize hybrids.
Low awareness of the transitivity assumption in complex networks of interventions: a systematic survey from 721 network meta-analyses
Authors: Spineli Loukia M. , Kalyvas Chrysostomos , Yepes-Nuñez Juan Jose , García-Sierra Andrés Mauricio , Rivera-Pinzón Diana C. , Seide Svenja E. , Papadimitropoulou Katerina
Published: March 2024

Background

The transitivity assumption is the cornerstone of network meta-analysis (NMA). Violating transitivity compromises the credibility of the indirect estimates and, by extent, the estimated treatment effects of the comparisons in the network. The present study offers comprehensive empirical evidence on the completeness of reporting and evaluating transitivity in systematic reviews with multiple interventions.

Methods

We screened the datasets of two previous empirical studies, resulting in 361 systematic reviews with NMA published between January 2011 and April 2015. We updated our evidence base with an additional 360 systematic reviews with NMA published between 2016 and 2021, employing a pragmatic approach. We devised assessment criteria for reporting and evaluating transitivity using relevant methodological literature and compared their reporting frequency before and after the PRISMA-NMA statement.

Results

Systematic reviews published after PRISMA-NMA were more likely to provide a protocol (odds ratio (OR): 3.94, 95% CI: 2.79–5.64), pre-plan the transitivity evaluation (OR: 3.01, 95% CI: 1.54–6.23), and report the evaluation and results (OR: 2.10, 95% CI: 1.55–2.86) than those before PRISMA-NMA. However, systematic reviews after PRISMA-NMA were less likely to define transitivity (OR: 0.57, 95% CI: 0.42–0.79) and discuss the implications of transitivity (OR: 0.48, 95% CI: 0.27–0.85) than those published before PRISMA-NMA. Most systematic reviews evaluated transitivity statistically than conceptually (40% versus 12% before PRISMA-NMA, and 54% versus 11% after PRISMA-NMA), with consistency evaluation being the most preferred (34% before versus 47% after PRISMA-NMA). One in five reviews inferred the plausibility of the transitivity (22% before versus 18% after PRISMA-NMA), followed by 11% of reviews that found it difficult to judge transitivity due to insufficient data. In justifying their conclusions, reviews considered mostly the comparability of the trials (24% before versus 30% after PRISMA-NMA), followed by the consistency evaluation (23% before versus 16% after PRISMA-NMA).

Conclusions

Overall, there has been a slight improvement in reporting and evaluating transitivity since releasing PRISMA-NMA, particularly in items related to the systematic review report. Nevertheless, there has been limited attention to pre-planning the transitivity evaluation and low awareness of the conceptual evaluation methods that align with the nature of the assumption.
Effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological profiles during transition period in dromedary camels
Authors: El-Sayed Ahmed , Ebissy Eman , Mohamed Ragab , Ateya Ahmed
Published: March 2024

Background

Nutrition has a primary role for optimum expression of genetic potential, and most of the farmers have limited resources of green fodder. Hence, a fat-soluble vitamin, especially vitamin A and E and trace elements remained most critical in the animal’s ration and affects their productive and reproductive performance adversely. Animals cannot be able to produce these vitamins in their bodies; hence, an exogenous regular supply is needed to fulfil the physiological needs and to maintain high production performance. This study elucidated effects of antioxidant vitamins (A, D, E) and trace elements (Cu, Mn, Se, Zn) administration on gene expression, metabolic, antioxidants and immunological parameters in dromedary camels during transition period.

Results

At 0 day, there were no appreciable differences in the expression patterns of the metabolic (IGF-I, ACACA, SCD, FASN, LPL, and BTN1A1) genes between the control and treatment groups, despite lower levels. A substantial variation in the mRNA levels of SOD1, SOD3, PRDX2, PRDX3, PRDX4, PRDX6, and AhpC/TSA was observed between the control and treatment groups, according to the antioxidant markers. In comparison to the control group, the treatment group displayed a significant up-regulation at 0 and 21 days. The treatment and control groups exhibited substantial differences in the mRNA values of IL-1α, IL-1β, IL-6, and TNFα, as indicated by immunological markers. In comparison to the control group, there was a noticeable down-regulation in the treatment group at 0 and + 21 days. But IL10 produced the opposite pattern. No significant difference was observed in glucose, cholesterol, triglyceride, HDL, total protein, NEFA, BHBA, cortisol and IGF-1 levels between control and treatment group. The activity of serum GPx, SOD and TAC was significantly affected by time and treatment x time in supplemented groups as compared with control group. IL-1, IL-1, IL-6, and TNF were noticeably greater in the control group and lower in the treatment group. Additionally, in all groups, the concentration of all pro-inflammatory cytokines peaked on the day of delivery and its lowest levels showed on day 21 following calving. The IL-10 level was at its peak 21 days prior to calving and was lowest on calving day.

Conclusion

The results demonstrated a beneficial effect of antioxidant vitamins and trace elements on the metabolic, antioxidant and immunological markers in dromedary camels throughout their transition period.
Improving furfural tolerance in a xylose-fermenting yeast Spathaspora passalidarum CMUWF1–2 via adaptive laboratory evolution
Authors: Saengphing Thanyalak , Sattayawat Pachara , Kalawil Thitisuda , Suwannarach Nakarin , Kumla Jaturong , Yamada Mamoru , Panbangred Watanalai , Rodrussamee Nadchanok
Published: March 2024

Background

Spathaspora passalidarum is a yeast with the highly effective capability of fermenting several monosaccharides in lignocellulosic hydrolysates, especially xylose. However, this yeast was shown to be sensitive to furfural released during pretreatment and hydrolysis processes of lignocellulose biomass. We aimed to improve furfural tolerance in a previously isolated S. passalidarum CMUWF1−2, which presented thermotolerance and no detectable glucose repression, via adaptive laboratory evolution (ALE).

Results

An adapted strain, AF2.5, was obtained from 17 sequential transfers of CMUWF1−2 in YPD broth with gradually increasing furfural concentration. Strain AF2.5 could tolerate higher concentrations of furfural, ethanol and 5-hydroxymethyl furfuraldehyde (HMF) compared with CMUWF1−2 while maintaining the ability to utilize glucose and other sugars simultaneously. Notably, the lag phase of AF2.5 was 2 times shorter than that of CMUWF1−2 in the presence of 2.0 g/l furfural, which allowed the highest ethanol titers to be reached in a shorter period. To investigate more in-depth effects of furfural, intracellular reactive oxygen species (ROS) accumulation was observed and, in the presence of 2.0 g/l furfural, AF2.5 exhibited 3.41 times less ROS accumulation than CMUWF1−2 consistent with the result from nuclear chromatins diffusion, which the cells number of AF2.5 with diffuse chromatins was also 1.41 and 1.24 times less than CMUWF1−2 at 24 and 36 h, respectively.

Conclusions

An enhanced furfural tolerant strain of S. passalidarum was achieved via ALE techniques, which shows faster and higher ethanol productivity than that of the wild type. Not only furfural tolerance but also ethanol and HMF tolerances were improved.
Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis
Authors: Gamal Asmaa , Fikry Eman , Tawfeek Nora , El-Shafae Azza M. , El-Sayed Ashraf S. A. , El-Domiaty Maher M.
Published: March 2024

The biosynthetic potency of Taxol by fungi raises their prospective to be a platform for commercial production of Taxol, nevertheless, the attenuation of its productivity with the fungal storage, is the challenge. Thus, screening for a novel fungal isolate inhabiting ethnopharmacological plants, with a plausible metabolic stability for Taxol production could be one of the most affordable approaches. Aspergillus niger OR414905.1, an endophyte of Encephalartos whitelockii, had the highest Taxol productivity (173.9 μg/L). The chemical identity of the purified Taxol was confirmed by HPLC, FTIR, and LC–MS/MS analyses, exhibiting the same molecular mass (854.5 m/z) and molecular fragmentation pattern of the authentic Taxol. The purified Taxol exhibited a potent antiproliferative activity against HepG-2, MCF-7 and Caco-2, with IC50 values 0.011, 0.016, and 0.067 μM, respectively, in addition to a significant activity against A. flavus, as a model of human fungal pathogen. The purified Taxol displayed a significant effect against the cellular migration of HepG-2 and MCF-7 cells, by ~ 52–59% after 72 h, compared to the control, confirming its interference with the cellular matrix formation. Furthermore, the purified Taxol exhibited a significant ability to prompt apoptosis in MCF-7 cells, by about 11-fold compared to control cells, suppressing their division at G2/M phase. Taxol productivity by A. niger has been optimized by the response surface methodology with Plackett–Burman Design and Central Composite Design, resulting in a remarkable ~ 1.6-fold increase (279.8 μg/L), over the control. The biological half-life time of Taxol productivity by A. niger was ~ 6 months of preservation at 4 ℃, however, the Taxol yield by A. niger was partially restored in response to ethyl acetate extracts of E. whitelockii, ensuring the presence of plant-derived signals that triggers the cryptic Taxol encoding genes.
Cancer cell-specific and pro-apoptotic SMAC peptide-doxorubicin conjugated prodrug encapsulated aposomes for synergistic cancer immunotherapy
Authors: Kim Jinseong , Shim Man Kyu , Moon Yujeong , Kim Jeongrae , Cho Hanhee , Yun Wan Su , Shim Nayeon , Seong Joon-Kyung , Lee Yonghyun , Lim Dong-Kwon , Kim Kwangmeyung
Published: March 2024

Background

Immunogenic cell death (ICD) is a crucial approach to turn immunosuppressive tumor microenvironment (ITM) into immune-responsive milieu and improve the response rate of immune checkpoint blockade (ICB) therapy. However, cancer cells show resistance to ICD-inducing chemotherapeutic drugs, and non-specific toxicity of those drugs against immune cells reduce the immunotherapy efficiency.

Methods

Herein, we propose cancer cell-specific and pro-apoptotic liposomes (Aposomes) encapsulating second mitochondria-derived activator of caspases mimetic peptide (SMAC-P)-doxorubicin (DOX) conjugated prodrug to potentiate combinational ICB therapy with ICD. The SMAC-P (AVPIAQ) with cathepsin B-cleavable peptide (FRRG) was directly conjugated to DOX, and the resulting SMAC-P-FRRG-DOX prodrug was encapsulated into PEGylated liposomes.

Results

The SMAC-P-FRRG-DOX encapsulated PEGylated liposomes (Aposomes) form a stable nanostructure with an average diameter of 109.1 ± 5.14 nm and promote the apoptotic cell death mainly in cathepsin B-overexpressed cancer cells. Therefore, Aposomes induce a potent ICD in targeted cancer cells in synergy of SMAC-P with DOX in cultured cells. In colon tumor models, Aposomes efficiently accumulate in targeted tumor tissues via enhanced permeability and retention (EPR) effect and release the encapsulated prodrug of SMAC-P-FRRG-DOX, which is subsequently cleaved to SMAC-P and DOX in cancer cells. Importantly, the synergistic activity of inhibitors of apoptosis proteins (IAPs)-inhibitory SMAC-P sensitizing the effects of DOX induces a potent ICD in the cancer cells to promote dendritic cell (DC) maturation and stimulate T cell proliferation and activation, turning ITM into immune-responsive milieu.

Conclusions

Eventually, the combination of Aposomes with anti-PD-L1 antibody results in a high rate of complete tumor regression (CR: 80%) and also prevent the tumor recurrence by immunological memory established during treatments.

Graphical Abstract
Nitric oxide nano-reactor DNMF/PLGA enables tumor vascular microenvironment and chemo-hyperthermia synergetic therapy
Authors: Wang Ruoyao , Cheng Long , He Lingyun , Du Chier , Wang Haiyang , Peng Bohao , Yu Xiaoqing , Liu Weiwei , Luo Wenpei , Ran Haitao , Yang Lu
Published: March 2024

Background

Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis. Timely diagnosis and precise treatment of TNBC are substantially challenging. Abnormal tumor vessels play a crucial role in TNBC progression and treatment. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis, while effective NO delivery can normalize the tumor vasculature. Accordingly, we have proposed here a tumor vascular microenvironment remodeling strategy based on NO-induced vessel normalization and extracellular matrix collagen degradation with multimodality imaging-guided nanoparticles against TNBC called DNMF/PLGA.

Results

Nanoparticles were synthesized using a chemotherapeutic agent doxorubicin (DOX), a NO donor L-arginine (L-Arg), ultrasmall spinel ferrites (MnFe2O4), and a poly (lactic-co-glycolic acid) (PLGA) shell. Nanoparticle distribution in the tumor was accurately monitored in real-time through highly enhanced magnetic resonance imaging and photoacoustic imaging. Near-infrared irradiation of tumor cells revealed that MnFe2O4 catalyzes the production of a large amount of reactive oxygen species (ROS) from H2O2, resulting in a cascade catalysis of L-Arg to trigger NO production in the presence of ROS. In addition, DOX activates niacinamide adenine dinucleotide phosphate oxidase to generate and supply H2O2. The generated NO improves the vascular endothelial cell integrity and pericellular contractility to promote vessel normalization and induces the activation of endogenous matrix metalloproteinases (mainly MMP-1 and MMP-2) so as to promote extravascular collagen degradation, thereby providing an auxiliary mechanism for efficient nanoparticle delivery and DOX penetration. Moreover, the chemotherapeutic effect of DOX and the photothermal effect of MnFe2O4 served as a chemo-hyperthermia synergistic therapy against TNBC.

Conclusion

The two therapeutic mechanisms, along with an auxiliary mechanism, were perfectly combined to enhance the therapeutic effects. Briefly, multimodality image-guided nanoparticles provide a reliable strategy for the potential application in the fight against TNBC.

Graphical Abstract
Older adult drug overdose: an application of latent class analysis to identify prevention opportunities
Authors: Mason Maryann , Pandya Kaveet , Lundberg Alexander
Published: March 2024

Background

Older adult overdose death rates have increased significantly in recent years. However, research for prevention of drug overdose death specific to older adults is limited. Our objective is to identify profiles based on missed intervention points (touchpoints) to inform prevention of future older adult unintentional overdose deaths.

Methods

We used latent class analysis methods to identify profiles of decedents aged 55 + years in the Illinois Statewide Unintentional Drug Overdose Reporting System. This system collects data on 92.6% of all unintentional overdose deaths in Illinois and includes data from death certificates, coroner/medical examiner, toxicology, and autopsy reports. Data include decedent demographics, circumstances leading up to and surrounding the fatal overdose and details regarding the overdose. Variables in the latent class analysis model included sex, race, alcohol test result, social isolation, recent emergency department (ED) visit, chronic pain, and pain treatment.

Results

We identified three distinct decent profiles. Class 1 (13% of decedents) included female decedents who were in pain treatment, had physical health problems, and had greater likelihood of a recent ED visit before their death. Class 2 (35% of decedents) decedents were most likely to be socially connected (live with others, employed, had social or family relationships) but less likely to have recent healthcare visits. Class 3 (52% of decedents) decedents had higher social isolation (lived alone, unemployed, unpartnered), were mostly male, had fewer known physical health conditions, and more alcohol positivity at time of death. White decedents are clustered in class 1 while Black decedents are predominant in classes 2 and 3.

Conclusions

These profiles link to potential touchpoint opportunities for substance use disorder screening harm reduction and treatment. Class 1 members were most likely to be reachable in healthcare settings. However, most decedents were members of Classes 2 and 3 with less engagement in the healthcare system, suggesting a need for screening and intervention in different contexts. For Class 2, intervention touchpoints might include education and screening in work or social settings such as senior centers given the higher degree of social connectivity. For Class 3, the most isolated group, touchpoints may occur in the context of harm reduction outreach and social service delivery.