Tag: nevin manimala

J Cancer Res Clin Oncol. 2023 Feb 16. doi: 10.1007/s00432-023-04638-w. Online ahead of print.

ABSTRACT

PURPOSE: An increasing infiltration of FoxP3-positive T-regs is associated with a higher grade of cervical intraepithelial neoplasia. The T-reg-recruiting chemokine CCL22 is expressed in various tumour entities. Aim of our study was to investigate the role of CCL22 in the progression and regression of cervical intraepithelial neoplasias, especially in patients with intermediate cervical intraepithelial neoplasias (CIN II). Furthermore, our aim was to characterize the CCL22-producing cells and explore the role of innate immunity in the process of cells recruitment.

METHODS: CCL22 expression was analyzed immunohistochemically in 169 patient samples. The immunoreactive score as well as the median numbers of positive cells were calculated in each slide and correlated with the histological CIN grade and FoxP3 expression. Additionally, CD68/CCL22 as well as CD68/PPARγ and CD68/FoxP3 expression were examined by double immunofluorescence. Statistical analysis was performed by SPSS 26.

RESULTS: A significantly higher expression of epithelial CCL22 in CIN II with progression in comparison to CIN II with regression (p = 0.006) could be detected. CCL22 was correlated with FoxP3 (Spearman’s Rho: 0.308; p < 0.01). In 88%, CCL22-positive cells were positive for CD68, and 71% of CD68-positive macrophages expressed PPARγ. Colocalization of CD68 and FoxP3 was detected in 12%.

CONCLUSION: We could demonstrate that increased expression of CCL22, mainly produced by macrophages, correlates with elevated potential of malignancy. CCL22 expression could act as a predictor for regression and progression in cervical intraepithelial neoplasia, and it may help in the decision process regarding surgical treatment versus watchful waiting strategy in order to prevent conisation-associated risks. Furthermore, our findings support the potential of CCL22-producing cells as a target for immune therapy in cervical cancer patients.

PMID:36792811 | DOI:10.1007/s00432-023-04638-w

Commun Biol. 2023 Feb 15;6(1):132. doi: 10.1038/s42003-023-04490-1.

ABSTRACT

Jaguars (Panthera onca) exert critical top-down control over large vertebrates across the Neotropics. Yet, this iconic species have been declining due to multiple threats, such as habitat loss and hunting, which are rapidly increasing across the New World tropics. Based on geospatial layers, we extracted socio-environmental variables for 447 protected areas across the Brazilian Amazon to identify those that merit short-term high-priority efforts to maximize jaguar persistence. Data were analyzed using descriptive statistics and comparisons of measures of central tendency. Our results reveal that areas containing the largest jaguar densities and the largest estimated population sizes are precisely among those confronting most anthropogenic threats. Jaguars are threatened in the world’s largest tropical forest biome by deforestation associated with anthropogenic fires, and the subsequent establishment of pastures. By contrasting the highest threats with the highest jaguar population sizes in a bivariate plot, we provide a shortlist of the top-10 protected areas that should be prioritized for immediate jaguar conservation efforts and 74 for short-term action. Many of these are located at the deforestation frontier or in important boundaries with neighboring countries (e.g., Peruvian, Colombian and Venezuelan Amazon). The predicament of a safe future for jaguars can only be ensured if protected areas persist and resist downgrading and downsizing due to both external anthropogenic threats and geopolitical pressures (e.g., infrastructure development and frail law enforcement).

PMID:36792802 | DOI:10.1038/s42003-023-04490-1

World J Microbiol Biotechnol. 2023 Feb 16;39(4):100. doi: 10.1007/s11274-023-03536-0.

ABSTRACT

Plant growth-promoting rhizobacteria (PGPR) have multifarious beneficial activities for plant growth promotion; act as source of metabolites, enzymes, nutrient mobilization, biological control of pests, induction of disease resistance vis-a-vis bioremediation potentials by phytoextraction and detoxification of heavy metals, pollutants and pesticides. Agrochemicals and synthetic pesticides are currently being utilized widely in all major field crops, thereby adversely affecting human and animal health, and posing serious threats to the environments. Beneficial microorganisms like PGPR could potentially substitute and supplement the toxic chemicals and pesticides with promising application in organic farming leading to sustainable agriculture practices and bioremediation of heavy metal contaminated sites. Among field crops limited bio-formulations have been prepared till now by utilization of PGPR strains having plant growth promotion, metabolites, enzymes, nutrient mobilization and biocontrol activities. The present review contributes comprehensive description of PGPR applications in field crops including commercial, oilseeds, leguminous and cereal crops to further extend the utilization of these potent groups of beneficial microorganisms so that even higher level of crop productivity and quality produce of field crops could be achieved. PGPR and bacteria based commercialized bio-formulations available worldwide for its application in the field crops have been compiled in this review which can be a substitute for the harmful synthetic chemicals. The current knowledge gap and potential target areas for future research have also been projected.

PMID:36792799 | DOI:10.1007/s11274-023-03536-0

Transl Stroke Res. 2023 Feb 16. doi: 10.1007/s12975-023-01140-w. Online ahead of print.

ABSTRACT

Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1β and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log₁₀ (IL-1.ra/IL-1β). Based on the derivation cohort, multivariate logistic analysis showed that IL-1β (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability.

PMID:36792794 | DOI:10.1007/s12975-023-01140-w

Surg Endosc. 2023 Feb 15. doi: 10.1007/s00464-023-09926-7. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with Roux-en-Y gastric bypass (RYGB) anatomy, laparoscopic endoscopic retrograde cholangiopancreatography (LA-ERCP) and enteroscopy-assisted ERCP (E-ERCP) have been utilized to achieve pancreaticobiliary access. Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) has recently emerged as an alternate and efficient approach. As data regarding EDGE continues to evolve, concerns about safety and efficacy remain, limiting wide adoptability. We performed a systematic review and meta-analysis to assess the safety and efficacy of EDGE and compare it to the current standard of care.

METHODS: A comprehensive search of major databases (inception to Nov 2022) identified published studies on EDGE. A random-effects model was used to calculate the pooled rates and heterogeneity (I²). Risk ratio (RR) and standardized difference in means (SMD) were utilized for head-to-head comparison analysis between EDGE vs. LA-ERCP and EDGE vs. E-ERCP. Primary outcomes assessed pooled EDGE safety (adverse events) and efficacy (technical/clinical success). Secondary outcomes assessed efficacy and safety profiles via a comparative analysis of EDGE vs. LA-ERCP and EDGE vs. E-ERCP.

RESULTS: A total of 16 studies (470 patients) were included. EDGE pooled technical success (TS) rate was 96% (95% CI 92-97.6, I² = 0), and clinical success was 91% (85-95, I² = 0). Pooled rate of all adverse events with EDGE was 17% (14-24.6, I² = 32%). On sub-group analysis, these included failure of fistula closure 17% (10-25.5, I² = 48%), stent migration 7% (4-12, I² = 51%), bleeding 5% (3.2-7.9, I² = 0), post-EDGE weight gain 4% (2-9, I² = 0), perforation 4% (2.1-5.8, I² = 0), and post-ERCP pancreatitis 2% (1-5, I² = 0). EDGE TS was comparable to LA-ERCP (97% vs. 98%; RR, 1.00; CI, 0.85-1.17, p = 0.95) and E-ERCP (100% vs. 66%; RR, 1.26; CI, 0.99-1.6, p = 0.06). No statistical difference was noted in adverse events between EDGE and LA-ERCP (13% vs. 17.6%; RR, 0.61; CI, 0.28-1.35, p = 0.52) and E-ERCP (9.6% vs. 16%; RR, 0.61; CI, 0.28-1.35, p = 0.22). EDGE procedure time and hospital stay were shorter than LA-ERCP and E-ERCP (p < 0.001).

CONCLUSION: Our analysis shows that EDGE is safe and efficacious to the current standard of care. Further head-to-head comparative trials are needed to validate our findings.

PMID:36792784 | DOI:10.1007/s00464-023-09926-7

Surg Endosc. 2023 Feb 15. doi: 10.1007/s00464-023-09892-0. Online ahead of print.

ABSTRACT

BACKGROUND: High-energy devices allow better vessel sealing compared with monopolar electrocautery and could improve the outcomes of surgical operations. The objective of the study was to compare tissue dissection by the LigaSure™ device with that by monopolar electrocoagulation for thoracoscopic lobectomy and lymphadenectomy.

METHODS: This pragmatic, parallel group, prospective randomized controlled trial was funded by the Medtronic External Research Program (ISR-2016-10,756) and registered at www.

CLINICALTRIALS: gov (NCT03125798). The study included patients aged 18 years or older, who had undergone thoracoscopic lobectomy with lymphadenectomy at the Department of Thoracic Surgery of Poznan University of Medical Sciences between May 3, 2018, and November 4, 2021. Using simple randomization, the patients were assigned to undergo tissue dissection with either the LigaSure device (study group) or monopolar electrocautery (control group). Participants and care givers, except operating surgeons, were blinded to group assignment. The primary outcome was postoperative chest drainage volume. Secondary outcomes were change of the esophageal temperature during subcarinal lymphadenectomy and C-reactive protein level 72 h after surgery.

RESULTS: Study outcomes were analyzed in 107 patients in each group. We found no differences between the study and control groups in terms of chest drainage volume (550 vs. 600 mL, respectively; p = 0.315), changes in esophageal temperature (- 0.1 °C vs. – 0.1 °C, respectively; p = 0.784), and C-reactive protein levels (72.8 vs. 70.8 mg/L, respectively; p = 0.503). The mean numbers of lymph nodes removed were 12.9 (SD: 3.1; 95% CI, 12.4 to 13.5) in the study group and 11.6 (SD: 3.2; 95% CI, 11.0 to 12.2) in the control group (p < 0.001).

CONCLUSIONS: The use of the LigaSure device did not allow to decrease the chest drainage volume, local thermal spread, and systemic inflammatory response. The number of lymph nodes removed was higher in patients operated with the LigaSure device, which indicated better quality of lymphadenectomy.

PMID:36792782 | DOI:10.1007/s00464-023-09892-0

Nat Rev Drug Discov. 2023 Feb 15. doi: 10.1038/s41573-023-00638-0. Online ahead of print.

ABSTRACT

The pharmaceutical industry and its global regulators have routinely used frequentist statistical methods, such as null hypothesis significance testing and p values, for evaluation and approval of new treatments. The clinical drug development process, however, with its accumulation of data over time, can be well suited for the use of Bayesian statistical approaches that explicitly incorporate existing data into clinical trial design, analysis and decision-making. Such approaches, if used appropriately, have the potential to substantially reduce the time and cost of bringing innovative medicines to patients, as well as to reduce the exposure of patients in clinical trials to ineffective or unsafe treatment regimens. Nevertheless, despite advances in Bayesian methodology, the availability of the necessary computational power and growing amounts of relevant existing data that could be used, Bayesian methods remain underused in the clinical development and regulatory review of new therapies. Here, we highlight the value of Bayesian methods in drug development, discuss barriers to their application and recommend approaches to address them. Our aim is to engage stakeholders in the process of considering when the use of existing data is appropriate and how Bayesian methods can be implemented more routinely as an effective tool for doing so.

PMID:36792750 | DOI:10.1038/s41573-023-00638-0

Sci Rep. 2023 Feb 15;13(1):2730. doi: 10.1038/s41598-023-29463-6.

ABSTRACT

Octopus vulgaris (Cuvier, 1797) is a cephalopod species with great economic value. In western Asturias (northwest of Spain), O. vulgaris artisanal fisheries are relatively well monitored and conditionally eco-labeled by the Marine Stewardship Council (MSC). Despite this, the Asturian octopus stocks have not been genetically assessed so far. In order to improve the current fishery plan and contrast the octopus eco-label validity in Asturias, 539 individuals from five regions of the O. vulgaris geographic distribution, including temporal samplings in Asturias, were collected and genotyped at thirteen microsatellite loci. All the samples under analysis were in agreement with Hardy-Weinberg expectations. Spatial levels of genetic differentiation were estimated using F-statistics, multidimensional scaling, and Bayesian analyses. Results suggested that the O. vulgaris consists of at least four genetically different stocks coming from two ancestral lineages. In addition, temporal analyses showed stability in terms of genetic variation and high N_E (> 50) for several generations in different localities within Asturias, pointing out to indeed sustainable fishery exploitation levels. Even though, the current Asturias fishery plan shows no significant genetic damages to the stocks, the regional-specific management plans need systematic genetic monitoring schemes as part of an efficient and preventive regional fishery regulation strategy.

PMID:36792695 | DOI:10.1038/s41598-023-29463-6

Commun Biol. 2023 Feb 15;6(1):175. doi: 10.1038/s42003-023-04546-2.

ABSTRACT

Visual cortex contains regions of selectivity for domains of ecological importance. Food is an evolutionarily critical category whose visual heterogeneity may make the identification of selectivity more challenging. We investigate neural responsiveness to food using natural images combined with large-scale human fMRI. Leveraging the improved sensitivity of modern designs and statistical analyses, we identify two food-selective regions in the ventral visual cortex. Our results are robust across 8 subjects from the Natural Scenes Dataset (NSD), multiple independent image sets and multiple analysis methods. We then test our findings of food selectivity in an fMRI “localizer” using grayscale food images. These independent results confirm the existence of food selectivity in ventral visual cortex and help illuminate why earlier studies may have failed to do so. Our identification of food-selective regions stands alongside prior findings of functional selectivity and adds to our understanding of the organization of knowledge within the human visual system.

PMID:36792693 | DOI:10.1038/s42003-023-04546-2

Commun Biol. 2023 Feb 15;6(1):169. doi: 10.1038/s42003-023-04511-z.

ABSTRACT

Identifying network architecture from observed neural activities is crucial in neuroscience studies. A key requirement is knowledge of the statistical input-output relation of single neurons in vivo. By utilizing an exact analytical solution of the spike-timing for leaky integrate-and-fire neurons under noisy inputs balanced near the threshold, we construct a framework that links synaptic type, strength, and spiking nonlinearity with the statistics of neuronal population activity. The framework explains structured pairwise and higher-order interactions of neurons receiving common inputs under different architectures. We compared the theoretical predictions with the activity of monkey and mouse V1 neurons and found that excitatory inputs given to pairs explained the observed sparse activity characterized by strong negative triple-wise interactions, thereby ruling out the alternative explanation by shared inhibition. Moreover, we showed that the strong interactions are a signature of excitatory rather than inhibitory inputs whenever the spontaneous rate is low. We present a guide map of neural interactions that help researchers to specify the hidden neuronal motifs underlying observed interactions found in empirical data.

PMID:36792689 | DOI:10.1038/s42003-023-04511-z