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Frontiers in Plant Science 2024is one of the most important oil crops in the world. Breeding oilseed rape with colorful flowers can greatly enhance the ornamental value of and thus improve the...
is one of the most important oil crops in the world. Breeding oilseed rape with colorful flowers can greatly enhance the ornamental value of and thus improve the economic benefits of planting. As water-soluble flavonoid secondary metabolites, anthocyanins are very important for the synthesis and accumulation of pigments in the petals of plants, giving them a wide range of bright colors. Despite the documentation of over 60 distinct flower shades in , the intricacies underlying flower color variation remain elusive. Particularly, the mechanisms driving color development across varying flower color backgrounds necessitate further comprehensive investigation. This research undertook a comprehensive exploration through the integration of transcriptome and metabolome analyses to pinpoint pivotal genes and metabolites underpinning an array of flower colors, including beige, beige-red, yellow, orange-red, deep orange-red, white, light-purple, and purple. First, we used a two-way BLAST search to find 275 genes in the reference genome of Darmor v10 that were involved in making anthocyanins. The subsequent scrutiny of RNA-seq outcomes underscored notable upregulation in the structural genes and , alongside the , , and transcriptional regulators within petals, showing anthocyanin accumulation. By synergizing this data with a weighted gene co-expression network analysis, we identified , , , , and as the key players driving anthocyanin synthesis in beige-red, orange-red, deep orange-red, light-purple, and purple petals. By integrating transcriptome and weighted gene co-expression network analysis findings with anthocyanin metabolism data, it is hypothesized that the upregulation of , which, in turn, enhances expression, plays a pivotal role in the development of pigmented oilseed rape flowers. These findings help to understand the transcriptional regulation of anthocyanin biosynthesis in and provide valuable genetic resources for breeding varieties with novel flower colors.
PubMed: 38933465
DOI: 10.3389/fpls.2024.1419508 -
Frontiers in Oncology 2024Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human...
INTRODUCTION
Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR).
PATIENTS AND METHODS
Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model.
RESULTS
Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925).
CONCLUSION
In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.
PubMed: 38933451
DOI: 10.3389/fonc.2024.1377842 -
Frontiers in Oncology 2024This study aims to explore the clinical application of bronchial artery chemoembolization (BACE) in managing refractory central lung cancer with atelectasis.
OBJECTIVE
This study aims to explore the clinical application of bronchial artery chemoembolization (BACE) in managing refractory central lung cancer with atelectasis.
METHODS
The retrospective case series includes patients diagnosed with refractory central lung cancer and atelectasis who underwent BACE treatment at Yueyang Integrated Traditional Chinese and Western Medicine Hospital, affiliated with Shanghai University of Traditional Chinese Medicine, from January 2012 to December 2021.
RESULTS
All 30 patients with lung cancer successfully underwent BACE procedures. Their ages ranged from 62 to 88 years, with an average age of 67.53. The treatment interval was 21 days, and the treatment cycle ranged from 2 to 12 times, averaging 4.13 times. During the BACE procedures, the Karnofsky Performance Status (KPS) score after 2 to 3 BACE cycles showed a significant improvement (82.0 ± 10.1 vs 68.3 ± 14.0, P < 0.001) than that of before BACE. Only nutritional support and symptomatic treatment were performed after BACE, and no major hemoptysis were observed. During follow-up, 23 cases resulted in mortality, while seven survived. The median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% CI: 4.6-9.4) and 10.0 (95% CI: 6.2-13.8) months, respectively, with 1-, 2-, and 3-year survival rates of 84.0%, 53.5%, and 11.3%, respectively. Eight cases exhibited bronchial recanalization and relief of atelectasis. According to the RECIST scale, there were 4 cases of complete response (CR), 16 cases of partial response (PR), 9 cases of stable disease (SD), and 1 case of progressive disease (PD). No serious adverse events were reported.
CONCLUSION
BACE might be a safe intervention for refractory central lung cancer accompanied by atelectasis. The procedure exhibits satisfactory outcomes in tumor control, atelectasis relief, and enhancement of quality of life, warranting further investigation.
PubMed: 38933450
DOI: 10.3389/fonc.2024.1343324 -
The Pan African Medical Journal 2024tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study...
INTRODUCTION
tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs).
METHODS
a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05).
RESULTS
two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109).
CONCLUSION
site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.
Topics: Humans; Nigeria; HIV Infections; Adult; Female; Antitubercular Agents; Male; Tuberculosis; Middle Aged; Coinfection; Treatment Outcome; Young Adult; Anti-HIV Agents; Isoniazid; Retrospective Studies; Tuberculosis, Pulmonary
PubMed: 38933432
DOI: 10.11604/pamj.2024.47.149.35719 -
European Heart Journal Open May 2024Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon...
AIMS
Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon ablation (CBA) and pulsed field ablation (PFA) using a pentaspline catheter, has gained prominence. Recent studies hypothesize that PFA might be superior to CBA, although procedural efficacy and safety data are inconsistent. A meta-analysis was conducted to compare both energy sources for the treatment of AF.
METHODS AND RESULTS
A structured systematic database search and meta-analysis were performed on studies investigating outcomes, periprocedural complications, and/or procedural parameters of AF patients treated by either CBA or PFA. Eleven studies reporting data from 3805 patients were included. Pulmonary vein isolation by PFA was associated with a significantly lower recurrence of atrial fibrillation/atrial tachycardia [odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.54-0.98, I = 20%] and fewer periprocedural complications (OR = 0.62, 95% CI = 0.40-0.96, I = 6%) compared to CBA. The lower complication rate following PFA was mainly driven by fewer phrenic nerve injuries (OR = 0.19, 95% CI = 0.08-0.43, I = 0%). However, there were more cases of cardiac tamponades after PFA (OR = 2.56, 95% CI = 1.01-6.49, I = 0%). Additionally, using PFA for PVI was associated with shorter total procedure times [mean difference (MD) = -9.68, 95% CI = -14.92 to -4.43 min, I = 92%] and lower radiation exposure (MD = -148.07, 95% CI = -276.50 to -19.64 µGy·mI = 7%).
CONCLUSION
Our results suggest that PFA for PVI, compared to CBA, enables shorter procedure times with lower arrhythmia recurrence and a reduced risk of periprocedural complications. Randomized controlled trials need to confirm our findings.
PubMed: 38933428
DOI: 10.1093/ehjopen/oeae044 -
European Heart Journal Open May 2024Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and...
AIMS
Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.
METHODS AND RESULTS
To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38-0.51, = 2.6e-28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39-0.76, = 4.2e-04) but not with bleeding (OR = 1.13, 95% CI = 0.93-1.36, = 2.2e-01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58-0.64, = 4.1e-85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69-0.86, = 4.1e-06) but not with bleeding (OR = 1.01, 95% CI = 0.95-1.08, = 7.5e-01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.
CONCLUSION
These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.
PubMed: 38933427
DOI: 10.1093/ehjopen/oeae043 -
Health Science Reports Jun 2024Although the clinical benefit of percutaneous coronary intervention (PCI) on cardiovascular outcomes has been widely investigated, the impact of this revascularization...
BACKGROUND AND AIMS
Although the clinical benefit of percutaneous coronary intervention (PCI) on cardiovascular outcomes has been widely investigated, the impact of this revascularization strategy compared to other alternatives on the degree of left ventricular function recovery is poorly demonstrated. In this regard, we investigated whether time delays between the presentation of ST-segment elevation myocardial infarction (STEMI) and PCI in reperfusion strategies have different impacts on left ventricular function recovery.
METHODS
In this single-center study, all the patients who presented with STEMI and a reduced left ventricular ejection fraction (LVEF ≤ 40%) were enrolled. Included patients were subjected to four different treatment groups of primary, rescue (immediate transfer for angioplasty due to failed fibrinolytic therapy), facilitated (fibrinolytic therapy followed by angioplasty within 24 h), and deferred (successful fibrinolytic therapy and PCI after 24 h) PCI based on hospital facilities. Echocardiography was performed for all the patients at the time of hospitalization and 6 months later.
RESULTS
A total of 128 patients were included in this study. The LVEF improved by 15.3 ± 6.3%, 11.5 ± 3.61%, 4.0 ± 1.0%, and -1.3 ± 7.0% in primary, rescue, facilitated, and deferred PCI groups, respectively ( < 0.001). Patients undergoing deferred PCI experienced a significantly lower improvement in LVEF compared with primary and rescue PCI ( < 0.001).
CONCLUSION
Primary PCI demonstrated the most promising recovery in left ventricular function following STEMI compared to other alternative strategies. Performing PCI as soon as possible provides better recovery of LVEF.
PubMed: 38933425
DOI: 10.1002/hsr2.2220 -
Health Science Reports Jun 2024Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C...
BACKGROUND
Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Men who have sex with men (MSM) represent a vulnerable population in terms of HIV infection. We aimed to determine the prevalence of HCV, HBV among HIV-infected MSM.
METHODS
This systematic review and meta-analysis searched PubMed, Cochrane, Scopus, Web of Science, and ProQuest up-to 2023/04/22. All studies reporting the prevalence of HBV or HCV infection in MSM PLHIV were included. Meta-analysis used random effect model for synthesis and along with prediction interval for heterogeneity. Subgroup analysis based on continent and meta-regression for study size, average age and year of publication were used to explore heterogeneity. Modified Newcastle-Ottawa Scale was used to evaluate the quality of studies according to the protocol (PROSPERO: CRD42023428764).
RESULTS
Fifty-six of 5948 studies are included. In 53 studies with 3,07,589 participants, a pooled prevalence of 7% (95% confidence interval [CI]: 5-10) was found for HCV among MSM PLHIV, while a 9% (95% CI: 4-18) prevalence was found for HBV infection from five studies which included 5641 MSM PLHIV. Asia reported the lowest pooled prevalence at 5.84% (95% CI: 2.98-11.13) for HCV while Europe reported the highest pooled prevalence at 7.76% (95% CI: 4.35-13.45). Baujat plot and influence diagnostic identified contributors to influence and between-study heterogeneity. Sensitivity analyses omitting these studies result in considerably more precise estimates. Another sensitivity analysis as leave-one-out meta-analysis did not change any pooled estimate significantly.
CONCLUSION
There is a significant burden of HCV and HBV among MSM PLHIV worldwide, with varying prevalence rates. Future studies should focus on these multimorbidity clusters and investigate factors influencing disease burden, long-term outcomes, optimal testing strategies, and tailored interventions.
PubMed: 38933421
DOI: 10.1002/hsr2.2206 -
BMJ Open Sport & Exercise Medicine 2024No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity...
No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity and motor performance, as well as the range of motion of Paralympic athletes. The study will be a triple-blinded, randomised controlled trial. Twenty-four athletes aged 18-45 in T35-T38 groups of the International Paralympic Committee classification will be included in the study. Twelve participants will receive dry needling of the quadriceps and gastrocnemius muscles, and 12 will receive placebo treatment with sham needles at similar points. We will assess the spasticity of the quadriceps and gastrocnemius muscles using the Modified Ashworth Scale, evaluate motor function using the Selective Control Assessment of the Lower Extremity Scale and measure ankle range of motion (ROM) with a goniometer. Considering our hypothesis, the athletes who will undergo the dry needling are supposed to achieve better improvements in spasticity, ROM and motor performance. This study can provide useful information to help better decide on managing complications in Paralympics and its long-term outcomes, to cover the current lack in the literature.
PubMed: 38933371
DOI: 10.1136/bmjsem-2024-002096 -
Frontiers in Neurology 2024For children who are unable to cooperate due to severe dental anxiety (DA), dental treatment of childhood caries under Dental General Anesthesia (DGA) is a safe and...
BACKGROUND
For children who are unable to cooperate due to severe dental anxiety (DA), dental treatment of childhood caries under Dental General Anesthesia (DGA) is a safe and high-quality treatment method. This study aims to evaluate the impact on neurocognitive functions and the growth and development of children 2 years after dental procedure based on previous research, and further establish a causal relationship between general anesthesia (GA) and changes in children's neurocognitive functions by incorporating Mendelian Randomization (MR) analysis.
METHODS
Data were collected and analyzed from 340 cases of S-ECC procedures of preschool children conducted in 2019. This involved comparing the neurocognitive outcomes 2 years post-operation of preschool children receiving dental procedures under general anesthesia or local anesthesia. Physical development indicators such as height, weight, and body mass index (BMI) of children were also compared at baseline, half a year post-operation, and 2 years post-operation. We performed a Mendelian randomization analysis on the causal relationship between children's cognitive development and general anesthesia, drawing on a large-scale meta-analysis of GWAS for anesthesia, including multiple general anesthesia datasets.
RESULTS
Outcome data were obtained for 111 children in the general anesthesia group and 121 children in the local anesthesia group. The mean FSIQ score for the general anesthesia group was 106.77 (SD 6.96), while the mean score for the local anesthesia group was 106.36 (SD 5.88). FSIQ scores were equivalent between the two groups. The incidence of malnutrition in children in the general anesthesia group was 27.93% ( < 0.001) before surgery and decreased to 15.32% ( > 0.05) after 2 years, which was not different from the general population. The IVW method suggested that the causal estimate ( = 0.99 > 0.05, OR = 1.04, 95% CI = 5.98 × 10-1.82 × 10) was not statistically significant for disease prevalence. This indicates no genetic cause-and-effect relationship between anesthesia and childhood intelligence.
CONCLUSION
There were no adverse outcomes in neurocognitive development in 2 years after severe early childhood caries (S-ECC) procedure under total sevoflurane-inhalation in preschool children. The malnutrition condition in children can be improved after S-ECC procedure under general anesthesia. Limited MR evidence does not support a correlation between genetic susceptibility to anesthesia and an increased risk for intelligence in children.
PubMed: 38933327
DOI: 10.3389/fneur.2024.1389203