Αρχειοθήκη ιστολογίου

Δευτέρα 13 Φεβρουαρίου 2023

Associations between genetically predicted levels of blood metabolites and pancreatic cancer risk

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies, which is featured by systematic metabolism. Thus, a better understanding of metabolic dysregulation in PDAC is important to better characterize its etiology. Here, we performed a large metabolome-wide association study (MWAS) to systematically explore associations between genetically predicted metabolite levels in blood and PDAC risk. Using data from 881 subjects of European descent in the TwinsUK Project, comprehensive genetic models were built to predict serum metabolite levels. These prediction models were applied to the genetic data of 8,280 cases and 6,728 controls included in the PanScan (I, II, and III) and PanC4 consortia. After assessing the metabolite-PDAC risk associations by a slightly modified TWAS/FUSION framework, we identified five metabolites (including two dipeptides) showing significant associations with PDAC risk at false discovery rate (FDR)<0.05. Integrated with gut m icrobial information, two-sample Mendelian randomization (MR) analyses were further performed to investigate the relationship among serum metabolites, gut microbiome features, and PDAC. The flavonoid-degrading bacteria Flavonifractor sp90199495 was found to be associated with metabolite X – 21849, and it was also shown to be associated with PDAC risk. Collectively, our study identified novel candidate metabolites for PDAC risk, which could lead to new insights into the etiology of PDAC and improved treatment options.
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Exosomes: Mediators in Microenvironment of Colorectal Cancer

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Abstract

Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely unclear. In this review, we summarized the relationship between TME and CRC based on recent literature. Then, we revealed the unique impacts and signal molecules of exosomes on account of their regulatory role in the flora, hypoxia, inflammatory, and immunological microenvironment of CRC. Finally, we summarized the therapeutically effective of exosomes in CRC microenvironment and discussed their current status and prospects, aiming to provide new molecular targets and a theoretical basis for th e CRC treatment.
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Pain mitigation and management strategies for anti‐GD2 infusions: An expert consensus

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Abstract

Monoclonal antibodies (mAbs) targeting disialoganglioside 2 (GD2) are an important treatment advance for high-risk neuroblastoma, including in patients with refractory or relapsed disease. Dinutuximab and dinutuximab beta are administered for ≥8 hours (and up to 10 days for dinutuximab beta), whereas naxitamab is administered over 0.5 to 2 hours as tolerated. As acute pain is a class effect of anti-GD2 mAbs, effective pain management is crucial to successful treatment. Here, we provide an overview of current pain-management strategies for anti-GD2 mAb infusions, with a focus on strategies suitable for naxitamab infusions, which cause a more rapid onset of often severe pain. We discuss opioid analgesics, ketamine, gabapentin, and other similar agents and nonpharmacologic approaches. Potential future pain-management options are also discussed, in addition to the use of sedatives to reduce the anxiety that may be associated with infusion-related pain. In this expert conse nsus paper, specific guidance for pain management during naxitamab infusions is provided, as these infusions are administered over 0.5 to 2 hours and may not need overnight hospitalization based on the physician's assessment, and require rapid-onset analgesia options suitable for potential outpatient administration.
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The adult outcome of childhood quasi‐autism arising following extreme institutional deprivation

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Background

Rutter and colleagues' seminal observation that extended early life exposure to extreme institutional deprivation can result in what he termed quasi-autism (QA), informed both our understanding of the effects of adversity on development and the nature of autism. Here we provide the first detailed analysis of the adult outcomes of the group of institutionally deprived-then-adopted children identified as displaying QA.

Methods

Twenty-six adult adoptees identified with QA in childhood (Childhood QA+) were compared to 75 adoptees who experienced extended institutional deprivation (>6 months) but no QA (Childhood QA−), and 116 adoptees exposed to Low/No institutional deprivation. The outcomes were child-to-adult developmental trajectories of neuro-developmental symptoms (autism, attention-deficit/hyperactivity disorder (ADHD), disinhibited social engagement (DSE) and cognitive impairment), adult functioning, life satisfaction and mental health.

Results

Childhood QA+ was associated with elevated and persistent trajectories of broad-based autism-related difficulties, ADHD and DSE symptoms and low IQ, as well as adult mental health difficulties and functional impairment, including high rates of low educational attainment and unemployment. Life satisfaction and self-esteem were unaffected. Autism-related communication problems, in particular, predicted negative adult outcomes. Childhood QA+ was still associated with poor outcomes even when ADHD, DSE and IQ were controlled.

Conclusions

Early and time-limited institutional deprivation has a critical impact on adult functioning, in part via its association with an early established and persistent variant of autism, especially related to communication difficulties. Apparent similarities and differences to non-deprivation related autism are discussed.
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Effectiveness and Accuracy of MRI‐Ultrasound Fusion Targeted Biopsy Based on PI‐RADS v2.1 Category in Transition/Peripheral Zone of the Prostate

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Background

MRI-ultrasound fusion targeted biopsy (MRI-TBx) improves the clinically significant prostate cancer (csPCa) detection with fewer cores. However, whether systematic biopsy-guided by transrectal ultrasound (TRUS-SBx) can be omitted when undergoing MRI-TBx in transition zone (TZ) and peripheral zone (PZ) remains unclear.

Purpose

To assess the performance and effectiveness of MRI-TBx based on PI-RADS v2.1 for csPCa diagnosis in TZ and PZ, respectively.

Study Type

Retrospective.

Subjects

A total of 309 selected cases (median age 70 years) with 356 lesions who underwent both MRI-TBx and TRUS-SBx were enrolled.

Field Strength/Sequence

A 3.0 T, multiparametric MRI (mp-MRI) including T2-weighted turbo-spin echo imaging (T2WI), diffusion-weighted spin-echo echo planar imaging (DWI), dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging (DCE).

Assessment

Mp-MRI was assessed by two radiologists using PI-RADS v2.1. The csPCa detection rates provided by MRI-TBx, TRUS-SBx and combined biopsy in TZ and PZ were calculated, respectively.

Statistical Tests

McNemar test was used to compare the csPCa detection rates in TZ and PZ, respectively. The frequencies and distribution of all detected prostate cancers by different biopsy methods were also compared. P < 0.05 was considered statistically significant.

Results

Among 356 lesions in 309 patients, 208 (68 in TZ, 140 in PZ) were pathologically confirmed as csPCa. In TZ, there were significant differences for csPCa detection with PI-RADS 3 between combined biopsy and TRUS-SBx (23.5% vs. 15.3%), MRI-TBx (23.5% vs. 16.3%), respectively. MRI-TBx detected 23% (19/83) cases missed by TRUS-SBx in which 68% (13/19) were csPCa. In PZ, there were no statistical differences between MRI-TBx and combined biopsy with PI-RADS 3–5 (P = 0.21, 0.25, 0.07, respectively). In 9% (14/152) cases only detected by MRI-TBx, 86% (12/14) were clinically significant. Five percent (7/152) of cases only detected by TRUS-SBx were completely nonclinically significant.

Data Conclusion

MRI-TBx played a positive role on csPCa diagnosis in TZ, but combined biopsy might be the best choice especially in the subgroup PI-RADS 3. In PZ, MRI-TBx had an advantage over TRUS-SBx for csPCa detection.

Evidence Level

2.

Technical Efficacy

Stage 2.
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WHOLE‐GENOME SINGLE MOLECULE REAL‐TIME SEQUENCING OF SARS‐CoV‐2 OMICRON

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ABSTRACT

New variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome can only be identified using accurate sequencing methods. Single molecule real-time (SMRT) sequencing has been used to characterize Alpha and Delta variants, but not Omicron variants harbouring numerous mutations in the SARS-CoV-2 genome. This study assesses the performance of a target capture SMRT sequencing protocol for whole genome sequencing (WGS) of SARS-CoV-2 Omicron variants and compared it to that of an amplicon SMRT sequencing protocol optimized for Omicron variants. The failure rate of the target capture protocol (6%) was lower than that of the amplicon protocol (34%, p<0.001) on our dataset, and the median genome coverage with the target capture protocol (98.6% [IQR: 86-99.4]) was greater than that with the amplicon protocol (76.6% [IQR: 66-89.6], (p<0.001)). The percentages of samples with >95% whole genome coverage were 64% with the target capture pro tocol and 19% with the amplicon protocol (p<0.05). The clades of 96 samples determined with both protocols were 93% concordant and the lineages of 59 samples were 100% concordant. Thus, target capture SMRT sequencing appears to be an efficient method for WGS, genotyping and detecting mutations of SARS-CoV-2 Omicron variants.

This article is protected by copyright. All rights reserved.
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Adaptive changes in sexual behavior in the high‐risk population in response to human monkeypox transmission in Canada can help control the outbreak: insights from a two‐group, two‐route epidemic model

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Abstract

Monkeypox, a zoonotic disease, is emerging as a potential sexually transmitted infection/disease, with underlying transmission mechanisms still unclear. We devised a risk-structured, compartmental model, incorporating sexual behavior dynamics. We compared different strategies targeting the high-risk population: a scenario of control policies geared towards the use of condoms and/or sexual abstinence (robust control strategy) with risk compensation behavior change, and a scenario of control strategies with behavior change in response to the doubling rate (adaptive control strategy). Monkeypox's basic reproduction number is 1.464, 0.0066, and 1.461 in the high-risk, low-risk, and total populations, respectively, with the high-risk group being the major driver of monkeypox spread. Policies imposing condom use or sexual abstinence need to achieve a 35% minimum compliance rate to stop further transmission, while a combination of both can curb the spread with 10% compliance to abstinence and 25% to condom use. With risk compensation, the only option is to impose sexual abstinence by at least 35%. Adaptive control is more effective than robust control where the daily sexual contact number is reduced proportionally and remains constant thereafter, shortening the time to epidemic peak, lowering its size, facilitating disease attenuation, and playing a key role in controlling the current outbreak.

This article is protected by copyright. All rights reserved.
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Autophagy: A challengeable paradox in cancer treatment

AlexandrosSfakianakis shared this article with you from Inoreader

Abstract

Objective

Autophagy is an intracellular degradation pathway conserved in all eukaryotes from yeast to humans. This process plays a quality-control role by destroying harmful cellular components under normal conditions, maintaining cell survival, and establishing cellular adaptation under stressful conditions. Hence, there are various studies indicating dysfunctional autophagy as a factor involved in the development and progression of various human diseases, including cancer. In addition, the importance of autophagy in the development of cancer has been highlighted by paradoxical roles, as a cytoprotective and cytotoxic mechanism. Despite extensive research in the field of cancer, there are many questions and challenges about the roles and effects suggested for autophagy in cancer treatment. The aim of this study was to provide an overview of the paradoxical roles of autophagy in different tumors and related cancer treatment options.

Methods

In this study, to find articles, a search was made in PubMed and Google scholar databases with the keywords Autophagy, Autophagy in Cancer Management, and Drug Design.

Results

According to the investigation, some studies suggest that several advanced cancers are dependent on autophagy for cell survival, so when cancer cells are exposed to therapy, autophagy is induced and suppresses the anti-cancer effects of therapeutic agents and also results in cell resistance. However, enhanced autophagy from using anti-cancer drugs causes autophagy-mediated cell death in several cancers. Because autophagy also plays roles in both tumor suppression and promotion further research is needed to determine the precise mechanism of this process in cancer treatment.

Conclusion

We concluded in this article, autophagy manipulation may either promote or hinder the growth and development of cancer according to the origin of the cancer cells, the type of cancer, and the behavior of the cancer cells exposed to treatment. Thus, before starting treatment it is necessary to determine the basal levels of autophagy in various cancers.
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Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019

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Characteristics and outcomes of gallbladder cancer patients at the Tata Medical Center, Kolkata 2017–2019

The curative approach for gallbladder cancer (GBC) is radical cholecystectomy with adjuvant chemotherapy. GBC has non-specific symptoms, so screening/early detection is not possible. We report that 90% of GBC patients presented with late-stage inoperable disease. Patients with late-stage disease who received chemotherapy had significantly better survival over those who did not (p < 0.0001). Our real-world data suggests that GBC is a chemosensitive disease. Clinical trials in low-middle income countries to reposition available therapies are urgently required.


Abstract

Background

The north and north-eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India.

Methods

Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed.

Results

There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50–65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2-year overall survival (OS) was 100% (95% CI: 100–100); 61% (95% CI: 45–83); 30% (95% CI: 21–43); and 9% (95% CI: 6–13) for stages I–IV, respectively (p = <0.0001).   For all patients, the 2-year OS in patients who had a radical cholecystectomy followed by adjuvant therapy (N = 36) was 50% (95% CI: 39–64), compared to 29% (95% CI: 22–38) for those who had a simple cholecystectomy and/or chemotherapy (N = 265) and 9% (95% CI: 6–14) in patients who were palliated (N = 107) (p = <0.0001).

Conclusion

The combined surgical/chemotherapy approach for patients with stage II GBC showed the best outcomes. Early detection of GBC remains problematic with the majority of patients presenting with stage III–IV and who have a median survival of 9.1 months. Our data suggests that the tumor is chemoresponsive and multi-center collaborative clinical trials to identify alternative therapies are urgently required.
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Intelligent Headband System for Evaluating Rehabilitation Effectiveness

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Stroke is an acute cerebrovascular condition causing damage to cranial nerves and requires subsequent rehabilitation treatment. In clinical practice, the effectiveness of rehabilitation is usually subjectively assessed by experienced physicians or using global prognostic scales. Several brain imaging techniques, such as positron emissio n tomography, functional magnetic resonance imaging, and computed tomography angiography, can be applied in rehabilitation effectiveness evaluation, but their complexity and long measurement times limit the activity of patients during measurement. This paper proposes an intelligent headband system based on near-infrared spectroscopy. An optical headband continuously and noninvasively monitors changes in hemoglobin parameters in the brain. The system's wearable headband and wireless transmission provide convenience of use. According to the change of hemoglobin parameters during rehabilitation exercise, several indexes were also defined to evaluate the state of cardiopulmonary function and further build the neural network model of the cardiopulmonary function evaluation. Finally, the relationship between the defined indexes and the cardiopulmonary function state were investigated and the neural network model for the cardiopulmonary function evaluation was also applied in the rehabil itation effect evaluation. The experimental results show the cardiopulmonary function state could reflect on most of the defined indexes and the output of neural network model, and the rehabilitation therapy could also improve the cardiopulmonary function.
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