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Frontiers in Genome Editing 2024With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes...
Horizon scanning of potential environmental applications of terrestrial animals, fish, algae and microorganisms produced by genetic modification, including the use of new genomic techniques.
With scientific progress and the development of new genomic techniques (NGTs), the spectrum of organisms modified for various purposes is rapidly expanding and includes a wide range of taxonomic groups. An improved understanding of which newly developed products may be introduced into the market and released into the environment in the near and more distant future is of particular interest for policymakers, regulatory authorities, and risk assessors. To address this information need, we conducted a horizon scanning (HS) of potential environmental applications in four groups of organisms: terrestrial animals (excluding insects and applications with gene drives), fish, algae and microorganisms. We applied a formal scoping review methodology comprising a structured search of the scientific literature followed by eligibility screening, complemented by a survey of grey literature, and regulatory websites and databases. In all four groups of organisms we identified a broad range of potential applications in stages of basic as well as advanced research, and a limited number of applications which are on, or ready to be placed on, the market. Research on GM animals including fish is focused on farmed animals and primarily targets traits which increase performance, influence reproduction, or convey resistance against diseases. GM algae identified in the HS were all unicellular, with more than half of the articles concerning biofuel production. GM algae applications for use in the environment include biocontrol and bioremediation, which are also the main applications identified for GM microorganisms. From a risk assessor's perspective these potential applications entail a multitude of possible pathways to harm. The current limited level of experience and limited amount of available scientific information could constitute a significant challenge in the near future, for which risk assessors and competent authorities urgently need to prepare.
PubMed: 38938511
DOI: 10.3389/fgeed.2024.1376927 -
Cancers Jun 2024While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated.... (Review)
Review
BACKGROUND
While several risk factors for recurrences have been defined, the topographic pattern of meningioma recurrences after surgical resection has been scarcely investigated. The possibility of theoretically predicting the site of recurrence not only allows us to better understand the pathogenetic bases of the disease and consequently to drive the development of new targeted therapies, but also guides the decision-making process for treatment strategies and tailored follow-ups to decrease/prevent recurrence.
METHODS
The authors performed a comprehensive and detailed systematic literature review of the EMBASE and MEDLINE electronic online databases regarding the topographic pattern of recurrence after surgical treatment for intracranial meningiomas. Demographics and histopathological, neuroradiological and treatment data, pertinent to the topography of recurrences, as well as time to recurrences, were extracted and analyzed.
RESULTS
Four studies, including 164 cases of recurrences according to the inclusion criteria, were identified. All studies consider the possibility of recurrence at the previous dural site; three out of four, which are the most recent, consider 1 cm outside the previous dural margin to be the main limit to distinguish recurrences closer to the previous site from those more distant. Recurrences mainly occur within or close to the surgical bed; higher values of proliferation index are associated with recurrences close to the original site rather than within it.
CONCLUSIONS
Further studies, including genomic characterization of different patterns of recurrence, will better clarify the main features affecting the topography of recurrences. A comparison between topographic classifications of intracranial meningioma recurrences after surgery and after radiation treatment could provide further interesting information.
PubMed: 38927972
DOI: 10.3390/cancers16122267 -
Biomedicines May 2024The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the... (Review)
Review
Neurobiological Effects of Transcranial Direct Current Stimulation over the Inferior Frontal Gyrus: A Systematic Review on Cognitive Enhancement in Healthy and Neurological Adults.
The neurobiological effects of transcranial direct current stimulation (tDCS) have still not been unequivocally clarified. Some studies have suggested that the application of tDCS over the inferior frontal gyrus (IFG) enhances different aspects of cognition in healthy and neurological individuals, exerting neural changes over the target area and its neural surroundings. In this systematic review, randomized sham-controlled trials in healthy and neurological adults were selected through a database search to explore whether tDCS over the IFG combined with cognitive training modulates functional connectivity or neural changes. Twenty studies were finally included, among which twelve measured tDCS effects through functional magnetic resonance (fMRI), two through functional near-infrared spectroscopy (fNIRS), and six through electroencephalography (EEG). Due to the high heterogeneity observed across studies, data were qualitatively described and compared to assess reliability. Overall, studies that combined fMRI and tDCS showed widespread changes in functional connectivity at both local and distant brain regions. The findings also suggested that tDCS may also modulate electrophysiological changes underlying the targeted area. However, these outcomes were not always accompanied by corresponding significant behavioral results. This work raises the question concerning the general efficacy of tDCS, the implications of which extend to the steadily increasing tDCS literature.
PubMed: 38927353
DOI: 10.3390/biomedicines12061146 -
World Journal of Surgical Oncology Jun 2024The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS.
METHODS
We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460).
RESULTS
From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53-1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50-0.99]; P = 0.04).
CONCLUSIONS
This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.
Topics: Female; Humans; Carcinoma, Ovarian Epithelial; Fertility Preservation; Neoplasm Recurrence, Local; Neoplasm Staging; Organ Sparing Treatments; Ovarian Neoplasms; Prognosis; Survival Rate
PubMed: 38918840
DOI: 10.1186/s12957-024-03440-3 -
International Journal of Molecular... May 2024Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and... (Review)
Review
Porocarcinoma (PC) is a rare adnexal tumor, mainly found in the elderly. The tumor arises from the acrosyringium of eccrine sweat glands. The risk of lymph node and distant metastasis is high. Differential diagnosis with squamous cell carcinoma is difficult, although NUT expression and YAP1 fusion products can be very useful for diagnosis. Currently, wide local excision is the main surgical treatment, although Mohs micrographic surgery is promising. To date, there is no consensus regarding the role of sentinel lymph node biopsy and consequential lymph node dissection. No guidelines exist for radiotherapy, which is mostly performed based on tumor characteristics and excision margins. Only a few studies report systemic treatment for advanced PC, although therapy with pembrolizumab and EGFR inhibitors show promise. In this review, we discuss epidemiology, clinical features, histopathological features, immunohistochemistry and fusion products, surgical management and survival outcomes according to stage, surgical management, radiotherapy and systemic therapy.
Topics: Humans; Eccrine Porocarcinoma; Immunohistochemistry; Sweat Gland Neoplasms; Biomarkers, Tumor; YAP-Signaling Proteins
PubMed: 38891945
DOI: 10.3390/ijms25115760 -
Oncology Letters Jul 2024The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung...
Effectiveness and safety of segmentectomy vs. wedge resection for the treatment of patients with operable non‑small cell lung cancer: A meta‑analysis and systematic review.
The present study compared the differences in effectiveness and safety between segmentectomy (ST) and wedge resection (WR) in patients with operable non-small cell lung cancer (NSCLC). The PubMed, EMBASE, Cochrane Library and Web of Science databases were searched for papers published from inception until July 2023. The inclusion criteria were based on the population, intervention, comparator, outcomes and study designs. ROBINS-I was selected to assess the risk of bias and quality of evidence in the included non-randomised studies. Appropriate effect sizes were selected, and subgroup analyses, heterogeneity tests, sensitivity analyses and publication bias were applied. A total of 18 retrospective studies were included, involving 19,381 patients with operable NSCLC. The 5-year overall survival rate [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.04, 0.34; P=0.014; I=76.3%], lung cancer-specific survival rate (HR, 0.3; 95% CI, 0.21, 0.38; P<0.01; I=13.8%) and metastasis rate [odds ratio (OR), 1.56; 95% CI, 1.03, 2.38; P=0.037] in patients with operable NSCLC treated with WR were worse than those in patients treated with ST. The incidence of postoperative complications (OR, 0.44; 95% CI, 0.23, 0.82) in the WR group was lower than in the ST treatment group. There was no difference in postoperative recurrence (OR, 2.15; 95% CI, 0.97, 4.74; P=0.058) and mortality (risk difference, 0.04; 95% CI, -0.03, 0.11; P=0.287) between groups. Based on current evidence, patients with NSCLC treated with ST surgery have better postoperative survival but more complications than those patients treated with WT, while the effect of WR and ST on the recurrence rate and distant metastasis rate remains controversial.
PubMed: 38846430
DOI: 10.3892/ol.2024.14469 -
JAMA Network Open Jun 2024Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.
OBJECTIVE
To assess the efficacy and tolerability of TNT protocols for LARC.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024.
STUDY SELECTION
Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria.
DATA EXTRACTION AND SYNTHESIS
Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival.
RESULTS
Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63).
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.
Topics: Rectal Neoplasms; Humans; Neoadjuvant Therapy; Network Meta-Analysis; Female; Middle Aged; Male; Randomized Controlled Trials as Topic; Adult
PubMed: 38833249
DOI: 10.1001/jamanetworkopen.2024.14702 -
PeerJ 2024To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal... (Meta-Analysis)
Meta-Analysis
Systematic evaluation and meta-analysis of the prognosis of down-staging human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma using cetuximab combined with radiotherapy instead of cisplatin combined with radiotherapy.
OBJECTIVE
To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV OPSCC).
DESIGN
Meta-analysis and systematic evaluation.
DATA SOURCES
The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE).
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data.
RESULTS
A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], = 0.0004; HR = 1.79, 95% CI [1.40-2.29], < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], < 0.0001; HR = 1.66, 95% CI [1.07-2.58], = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], = 0.28).
CONCLUSIONS
Cisplatin + radiotherapy remains the standard treatment for HPV OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies.
PROSPERO REGISTRATION NUMBER
CRD42023445619.
Topics: Humans; Cetuximab; Oropharyngeal Neoplasms; Cisplatin; Chemoradiotherapy; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck; Neoplasm Staging; Papillomaviridae; Antineoplastic Agents, Immunological; Progression-Free Survival; Human Papillomavirus Viruses
PubMed: 38784388
DOI: 10.7717/peerj.17391 -
BMC Cancer May 2024The 17-gene Genomic Prostate Score (GPS) test has been clinically employed to predict adverse prognosis in prostate cancer. In this meta-analysis, we aimed to evaluate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 17-gene Genomic Prostate Score (GPS) test has been clinically employed to predict adverse prognosis in prostate cancer. In this meta-analysis, we aimed to evaluate the prognostic value of the 17-gene GPS in patients with prostate cancer.
METHODS
Potentially relevant studies were obtained by searching PubMed, Web of Science, Embase databases from their inception to December 1, 2023. Studies were considered eligible if they evaluated the association of the 17-gene GPS with distant metastases, biochemical recurrence, or prostate cancer-specific mortality (PCSM) in prostate cancer patients. To estimate the prognostic value, we pooled the adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the high versus low GPS group or per 20-unit increase in GPS.
RESULTS
Seven cohort studies that reported on 8 articles comprising 1,962 patients satisfied the eligibility criteria. Meta-analysis showed that per 20-unit increase in GPS was significantly associated with distant metastases (HR 2.99; 95% CI 1.97-4.53), biochemical recurrence (HR 2.18; 95% CI 1.64-2.89), and PCSM (HR 3.14; 95% CI 1.86-5.30). Moreover, patients with high GPS (> 40 points) had an increased risk of distant metastases (HR 5.22; 95% CI 3.72-7.31), biochemical recurrence (HR 4.41; 95% CI 2.29-8.49), and PCSM (HR 3.81; 95% CI 1.74-8.33) than those with low GPS (≤ 40 points).
CONCLUSIONS
A higher 17-gene GPS significantly predicts distant metastases, biochemical recurrence, and PCSM in men with clinically localized prostate cancer. However, large-scale multicenter prospective studies are necessary to further validate these findings.
Topics: Humans; Male; Prostatic Neoplasms; Prognosis; Biomarkers, Tumor; Genomics; Neoplasm Recurrence, Local
PubMed: 38783246
DOI: 10.1186/s12885-024-12389-1 -
Frontiers in Oncology 2024Fibroblast activation protein-α (FAP-α) is a vital surface marker of cancer-associated fibroblasts, and its high expression is associated with a higher tumor grade and...
INTRODUCTION
Fibroblast activation protein-α (FAP-α) is a vital surface marker of cancer-associated fibroblasts, and its high expression is associated with a higher tumor grade and metastasis. A systematic review and a meta-analysis were performed to associate future metastasis with FAP-α expression in cancer.
METHODS
In our meta-analysis, relevant studies published before 20 February 2024 were systematically searched through online databases that included PubMed, Scopus, and Web of Science. The association between FAP-α expression and metastasis, including distant metastasis, lymph node metastasis, blood vessel invasion, vascular invasion, and neural invasion, was evaluated. A pooled odds ratio (OR) with 95% confidence intervals (CI) was reported as the measure of association.
RESULTS
A total of 28meta-analysis. The random-effects model for five parameters showed that a high FAP-α expression was associated with blood vessel invasion (OR: 3.04, 95% CI: 1.54-5.99, = 63%, = 0.001), lymphovascular invasion (OR: 3.56, 95% CI: 2.14-5.93, = 0.00%, < 0.001), lymph node metastasis (OR: 2.73, 95% CI: 1.96-3.81, = 65%, < 0.001), and distant metastasis (OR: 2.59; 95% CI: 1.16-5.79, = 81%, < 0.001). However, our analysis showed no statistically significant association between high FAP-α expression and neural invasion (OR: 1.57, 95% CI: 0.84-2.93, = 38%, = 0.161).
CONCLUSIONS
This meta-analysis indicated that cancer cells with a high FAP-α expression have a higher risk of metastasis than those with a low FAP-α expression. These findings support the potential importance of FAP-α as a biomarker for cancer metastasis prediction.
PubMed: 38751814
DOI: 10.3389/fonc.2024.1339050