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Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways

World J Gastrointest Oncol. 2023 Sep 15;15(9):1505-1519. doi: 10.4251/wjgo.v15.i9.1505.

ABSTRACT

Pancreatic cancer (PanCa) presents a catastrophic disease with poor overall survival at advanced stages, with immediate requirement of new and effective treatment options. Besides genetic mutations, epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target. Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails. Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients. Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies. Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance. Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions, and novel pharmacological strategies that target these components could potentially lead to breakthroughs. We aim to highlight the possibilities that exist and the potential therapeutic interventions.

PMID:37746645 | PMC:PMC10514732 | DOI:10.4251/wjgo.v15.i9.1505

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Multidisciplinary discussion and management of synchronous colorectal liver metastases: A single center study in China

World J Gastrointest Oncol. 2023 Sep 15;15(9):1616-1625. doi: 10.4251/wjgo.v15.i9.1616.

ABSTRACT

BACKGROUND: The multidisciplinary team (MDT) has been carried out in many large hospitals now. However, given the costs of time and money and with little strong evidence of MDT effectiveness being reported, critiques of MDTs persist.

AIM: To evaluate the effects of MDTs on patients with synchronous colorectal liver metastases and share our opinion on management of synchronous colorectal liver metastases.

METHODS: In this study we collected clinical data of patients with synchronous colorectal liver metastases from February 2014 to February 2017 in the Chinese People’s Liberation Army General Hospital and subsequently divided them into an MDT+ group and an MDT- group. In total, 93 patients in MDT+ group and 169 patients in MDT- group were included totally.

RESULTS: Statistical increases in the rate of chest computed tomography examination (P = 0.001), abdomen magnetic resonance imaging examination (P = 0.000), and preoperative image staging (P = 0.0000) were observed in patients in MDT+ group. Additionally, the proportion of patients receiving chemotherapy (P = 0.019) and curative resection (P = 0.042) was also higher in MDT+ group. Multivariable analysis showed that the population of patients assessed by MDT meetings had higher 1-year [hazard ratio (HR) = 0.608, 95% confidence interval (CI): 0.398-0.931, P = 0.022] and 5-year (HR = 0.694, 95%CI: 0.515-0.937, P = 0.017) overall survival.

CONCLUSION: These results proved that MDT management did bring patients with synchronous colorectal liver metastases more opportunities for comprehensive examination and treatment, resulting in better outcomes.

PMID:37746642 | PMC:PMC10514728 | DOI:10.4251/wjgo.v15.i9.1616

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A chatbot-delivered intervention for optimizing social media use and reducing perceived isolation among rural-living LGBTQ+ youth: Development, acceptability, usability, satisfaction, and utility

Internet Interv. 2023 Sep 9;34:100668. doi: 10.1016/j.invent.2023.100668. eCollection 2023 Dec.

ABSTRACT

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) youth are at higher risk of isolation and depression than their heterosexual peers. Having access to tailored mental health resources is a documented concern for rural living LGBTQ+ youth. Social media provides access to connections to a broader and like-minded community of peers, but it also is a vehicle for negative interactions. We developed REALbot, an automated, social media-based educational intervention to improve social media efficacy, reduce perceived isolation, and bolster connections for rural living LGBTQ+ youth. This report presents data on the acceptability, feasibility, and utility of REALbot among its target audience of rural living LGBTQ+ youth.

METHODS: We conducted a week-long exploratory study with a single non-comparison group of 20 rural-living LGBTQ+ youth aged 14-19 recruited from social media to test our Facebook- and Instagram-delivered chatbot. We assessed pre- and post-test scores of social media self-efficacy, social isolation (4-item Patient-Reported Outcomes Measurement System – PROMIS), and depressive symptoms (Patient Health Questionnaire, Adolescent Version – PHQ-A). At post-test, we assessed acceptability (User Experience Questionnaire – UEQ-S), usability (Chatbot Usability Questionnaire -CUQ and Post-Study Satisfaction and Usability Questionnaire -PSSUQ), and satisfaction with the chatbot (Client Satisfaction Questionnaire – CSQ), along with two open-ended questions on ‘likes’ and ‘dislikes’ about the intervention. We compared pre- and post-test scores with standard univariate statistics. Means and standard deviations were calculated for usability, acceptability, and satisfaction. To analyze the responses to post-test open-end questions, we used a content analysis approach.

RESULTS: Acceptability of REALbot was high with UEQ-S 5.3 out of 7 (SD = 1.1) and received high usability scores with CUQ and PSSUQ (mean score (M) = 78.0, SD = 14.5 and M = 86.9, SD = 25.2, respectively), as well as high user satisfaction with CSQ (M = 24.9, SD = 5.4). Themes related to user ‘likes’ and ‘dislikes’ were organized in two main categories: usability and content provided. Participants were engaged with the chatbot, sending an average of 49.3 messages (SD = 43.6, median = 30). Pre-/post- changes in scores of perceived isolation, depressive symptoms and social media self-efficacy were not significant (p’s > 0.08).

CONCLUSION: REALbot deployment was found to be feasible and acceptable, with good usability and user satisfaction scores. Participants reported changes from pre- to post-test in most outcomes of interest and effect sizes were small to medium. Additional development and a formal evaluation of feasibility and engagement with behavioral targets is warranted.

PMID:37746640 | PMC:PMC10511780 | DOI:10.1016/j.invent.2023.100668

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Comprehensive and realistic simulation of tumour genomic sequencing data

NAR Cancer. 2023 Sep 22;5(3):zcad051. doi: 10.1093/narcan/zcad051. eCollection 2023 Sep.

ABSTRACT

Accurate identification of somatic mutations and allele frequencies in cancer has critical research and clinical applications. Several computational tools have been developed for this purpose but, in the absence of comprehensive ‘ground truth’ data, assessing the accuracy of these methods is challenging. We created a computational framework to simulate tumour and matched normal sequencing data for which the source of all loci that contain non-reference bases is known, based on a phased, personalized genome. Unlike existing methods, we account for sampling errors inherent in the sequencing process. Using this framework, we assess accuracy and biases in inferred mutations and their frequencies in an established somatic mutation calling pipeline. We demonstrate bias in existing methods of mutant allele frequency estimation and show, for the first time, the observed mutation frequency spectrum corresponding to a theoretical model of tumour evolution. We highlight the impact of quality filters on detection sensitivity of clinically actionable variants and provide definitive assessment of false positive and false negative mutation calls. Our simulation framework provides an improved means to assess the accuracy of somatic mutation calling pipelines and a detailed picture of the effects of technical parameters and experimental factors on somatic mutation calling in cancer samples.

PMID:37746635 | PMC:PMC10516706 | DOI:10.1093/narcan/zcad051

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Noninvasive magnetic resonance-guided focused ultrasound for tendon disruption: an in vivo Animal study

Int J Hyperthermia. 2023;40(1):2260129. doi: 10.1080/02656736.2023.2260129. Epub 2023 Sep 24.

ABSTRACT

PURPOSE: Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons.

MATERIAL AND METHODS: In vivo Achilles tendons (n = 28) from 15-20kg Yorkshire pigs (n = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed.

RESULTS: Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16° to 27°. There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm2, 53.2mm2, 77.8mm2 and 91.6mm2. The average areas of skin necrosis were 5.4mm2, 21.8mm2, 37.2mm2, and 91.4mm2. Histologic analysis confirmed tissue ablation and structural collagen fiber disruption.

CONCLUSIONS: This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions.

PMID:37743063 | DOI:10.1080/02656736.2023.2260129

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Comparison between the effects of virtual supervision and minimal supervision in a 12-week home-based physical exercise program on mental health and quality of life of older adults: Secondary analysis from a randomized clinical trial

Geriatr Gerontol Int. 2023 Sep 24. doi: 10.1111/ggi.14673. Online ahead of print.

ABSTRACT

AIM: The objective of this study was to compare the effects of virtual supervision and minimal supervision in a 12-week home-based physical exercise program on the mental health and quality of life of community-dwelling older adults.

METHODS: This study presents a secondary analysis of a randomized clinical trial conducted during the COVID-19 pandemic. The sample comprised 38 elderly men and women (81.6% women, mean age 68 ± 6.4 years; mean weight 69.8 ± 12.1 km) without physical and/or cognitive impairments. The volunteers were divided into two groups: one group received virtual supervision (monitored via videoconference), while the other group received minimal supervision (monitored through weekly text messages). Both groups followed the same home-based physical exercise program, consisting of three sessions per week, differing only in the supervision strategy. Mental health was assessed using the Depression, Anxiety, and Stress Scale (DASS-21) in conjunction with the POMS questionnaire, which evaluates mood, and quality of life was assessed using the WHOQOL-OLD questionnaire.

RESULTS: Our findings demonstrated statistically significant superiority of virtual supervision compared with minimal supervision in relation to depression (-2.92, 95% confidence interval = -5.22 to -0.63). Conversely, minimal supervision exhibited superiority over virtual supervision regarding quality of life (-6.70, 95% confidence interval = -11.66 to -1.73).

CONCLUSIONS: Virtual supervision yielded better outcomes for the depression indicator, while minimal supervision favored the quality of life of older adults at the conclusion of the 12-week home-based physical exercise program. Geriatr Gerontol Int 2023; ••: ••-••.

PMID:37743056 | DOI:10.1111/ggi.14673

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Effect of salt, alkali and combined stresses on root system architecture and ion profiling in a diverse panel of oat (Avena spp.)

Funct Plant Biol. 2023 Sep 25. doi: 10.1071/FP23031. Online ahead of print.

ABSTRACT

The co-occurrence of salinisation and alkalisation is quite frequent in problematic soils and poses an immediate threat to food, feed and nutritional security. In the present study, root system architectural traits (RSAs) and ion profiling were evaluated in 21 genotypes of Avena species to understand the effect of salinity-alkalinity stress. The oat genotypes were grown on germination paper and 5-day-old seedlings were transferred to a hydroponic system for up to 30days. These seedlings were subjected to seven treatments: T0, treatment control (Hoagland solution); T1, moderate salinity (50mM); T2, high salinity (100mM); T3, moderate alkalinity (15mM); T4, high alkalinity (30mM); T5, combined moderate salinity-alkalinity (50mM+15mM); and T6, combined high salinity-alkalinity (100mM and 30mM) by using NaCl+Na2SO4 (saline) and NaHCO3+Na2CO3 (alkaline) salts equivalently. The root traits, such as total root area (TRA), total root length (TRL), total root diameter (TRD), total root volume (TRV), root tips (RT), root segments (RS), root fork (RF) and root biomass (RB) were found to be statistically significant (P<0.01) among the different genotypes, treatments and their interactions. Na+ and K+ content analysis in root and shoot tissues revealed the ion homeostasis capacity of different Avena accessions under stress treatments. Principal component analysis (PCA) covered almost 83.0% of genetic variation and revealed that the sharing of TRA, RT, RS and RF traits was significantly high. Biplot analysis showed a highly significant correlation matrix (P<0.01) between the pairs of RT and RS, TRL and RS, and RT and RF. Based on PCA ranking and relative value for stress tolerance, IG-20-1183, IG-20-894, IG-20-718 and IG-20-425 expressed tolerance to salinity (T2), IG-20-425 (alkalinity; T4) and IG-20-1183, IG-20-894 and IG-20-1004 were tolerant to salt-alkali treatment (T6). Multi-trait stability index (MTSI) analysis identified three stable oat genotypes (IG-20-714, IG-20-894 and IG-20-425) under multiple environments and these lines can be used in salinity-alkalinity affected areas after yield trials or as donor lines for combined stresses in future breeding programs.

PMID:37743054 | DOI:10.1071/FP23031

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Trends in Soccer-Related Craniomaxillofacial Injuries, United States 2003-2022

J Oral Maxillofac Surg. 2023 Sep 9:S0278-2391(23)01092-3. doi: 10.1016/j.joms.2023.09.001. Online ahead of print.

ABSTRACT

BACKGROUND: Soccer is one of the most popular sports worldwide. However, it has risks of injury to craniomaxillofacial regions such as the head, neck, and mouth.

PURPOSE: The purpose of this study is to determine which demographic and injury characteristics among soccer players with craniomaxillofacial injuries are associated with increased hospitalizations.

STUDY DESIGN, SETTING, AND SAMPLE: This is a retrospective cohort study utilizing the National Electronic Injury Surveillance System. Subjects included in this study experienced an injury to a craniomaxillofacial area from soccer between January 1, 2003, and December 31, 2022.

PREDICTOR VARIABLE: The predictor variables included demographics (age, sex, race) and injury characteristics (craniomaxillofacial region, diagnosis).

MAIN OUTCOME VARIABLE: The primary outcome variable was injury severity defined as hospitalization outcome after injury (yes/no). The secondary outcome variable was the trends in the incidence of soccer craniomaxillofacial injuries over time (2003-2022).

COVARIATES: The covariates were the heterogenous set of predictor variables in this study.

ANALYSES: Descriptive statistics and univariate analyses were computed. Survey-weighted univariate and multivariate logistic regression were used to measure the association of demographic and injury variables with hospitalization outcome. Statistical significance was defined as P < .05.

RESULTS: The study sample included 26,642 subjects (national estimate, 799,393). The national incidence of craniomaxillofacial soccer injuries generally increased between 2003 and 2012 and decreased between 2016 and 2020. Subjects in the ≥30 age group had increased odds of hospitalization compared to those in the 10-19 age group (odds ratio [OR], 2.12; P < .001). Compared to females, males had significantly higher odds of hospitalization (OR, 1.53; P < .001). Head (OR, 8.42; P < .001) and neck (OR, 15.8; P < .001) injuries had increased odds of hospitalization compared to facial injuries. Relative to contusions/abrasions, subjects with fractures (OR, 94.7; P < .001), dental injuries (OR, 41.3; P < .001), and concussions (OR, 5.33; P = .017) were at significantly higher odds of hospitalization.

CONCLUSION AND RELEVANCE: Age, sex, craniomaxillofacial region, and diagnosis were significant predictors of hospitalization outcome after craniomaxillofacial soccer injury. Safer playing styles, use of mouthguards, and proper medical management may reduce future risks of craniomaxillofacial injury from soccer.

PMID:37743045 | DOI:10.1016/j.joms.2023.09.001

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Does Clockwise Rotation of Maxillomandibular Complex Using Surgery-First Approach to Correct Mandibular Prognathism Improve Facial Appearance?

J Oral Maxillofac Surg. 2023 Sep 5:S0278-2391(23)01091-1. doi: 10.1016/j.joms.2023.08.226. Online ahead of print.

ABSTRACT

BACKGROUND: Facial aesthetics may be optimized based on a deeper understanding of soft tissue changes after orthognathic surgery.

PURPOSE: The purpose of the study was to delineate facial soft tissue changes after clockwise rotation (CWR) of the maxillomandibular complex (MMC) to correct mandibular prognathism using the surgery-first approach.

STUDY DESIGN, SETTING, SAMPLE: This prospective cohort study enrolled patients over 18 years of age with skeletal Class III malocclusion in the craniofacial center. The patients were excluded with previous history of craniofacial syndrome, orthognathic surgery trauma, infection at surgical sites, chin deviation (menton deviation ≥4 mm), 2 or more missing data points after surgery, or without informed consent. This study compared significant facial changes before (T0) and after orthodontic debonding (T1) in the CWR and control groups.

PREDICTOR VARIABLE: The patients were divided in accordance with maxillary occlusal plane change (OPC) after surgery into CWR (OPC >4°) and control (OPC ≤4°) groups.

MAIN OUTCOME VARIABLE: The primary outcome variable was frontal lip curvature (FLC: Right Cheilion-Stomion-Left Cheilion, degree) with or without upper lip curving upward at T1, where upper lip curving upward was considered more favorable.

COVARIATES: The covariates included age, sex, and various cephalometric measurements.

ANALYSES: The Mann-Whitney U test, paired, and independent t-test were implemented to compare the intragroup and intergroup differences. Statistical significance was indicated by P value <.05.

RESULTS: The study comprised 34 patients (21 women) in the control group and 37 (29 women) in the CWR group; their mean ages were 23.64 ± 4.38 and 24.21 ± 3.84 years, respectively (P value = .562). At T1, the CWR group had significant increased FLC (P value = .001), alar width (P value = .034), and lower vermilion height (P value = .018), and decreased lower lip length (P value = .004). The high FLC group had significant decreased upper lip projection (P value = .002) and increased NLA (P value = .013). The significant relationship between CWR and high FLC was supported by the χ2 test (P value = .018) and multiple logistic regression (P value = .017).

CONCLUSION: Greater CWR of the MMC increased FLC and lower vermilion height and reduced lower lip length. High FLC resulting from the CWR of the MMC improved facial appearance by moving the upper lip curve upward.

PMID:37743044 | DOI:10.1016/j.joms.2023.08.226

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Changing Patterns of Zygomaticomaxillary Complex Fractures: A Retrospective Study

J Oral Maxillofac Surg. 2023 Sep 9:S0278-2391(23)01090-X. doi: 10.1016/j.joms.2023.08.225. Online ahead of print.

ABSTRACT

BACKGROUND: Limited research exists regarding the incidence and variations of zygomaticomaxillary complex (ZMC) fracture patterns and their correlation with the mechanism of injury. Hence, further research is indicated.

PURPOSE: The purpose of this study was to analyze the different ZMC fracture patterns in relation to its etiology using computed tomography scans.

STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study was conducted at a single institution. The medical records of maxillofacial trauma patients from 2016 to 2020 were analyzed. Patients from any gender and all age groups with complete records diagnosed with isolated ZMC fractures were included in the study.

PREDICTOR VARIABLE: The etiology of trauma was the primary predictor variable. It was categorized as road traffic accidents (RTAs), falls, interpersonal violence, fall from height, sports injuries, etc. MAIN OUTCOME VARIABLES: The primary outcome variable was the ZMC fracture patterns observed and was defined as similar to or different from the classical fracture patterns. Any type of variation noted from the classical fracture lines was defined as the secondary outcome variable.

COVARIATES: Covariates included demographic variables such as age, gender, the type of vehicle involved, the type of RTA, side of fracture, associated orbital fractures, and number of ZMC points fractured.

ANALYSES: Descriptive and bivariate statistics were used to measure association between the predictor and outcome variables using multiple proportions χ2 test. Statistical significance was defined at P value of <.05.

RESULTS: Out of the 232 scans assessed, a total of 163 cases were included in this study. A majority of the cases belonged to a range of 21 to 30 years and showed a male predilection. The most common mode of injury was found to be RTAs (88.3%). Most cases had fracture patterns different from the classical fracture patterns (65.64%). A statistically significant association was found between the types of ZMC fracture patterns and etiology of trauma (RTA P = <.0001, falls P = .0001, and interpersonal violence P = .0001). Five different variations in ZMC fracture patterns were found and had a statistically significant association with the classical fracture lines (P < .0001).

CONCLUSION AND RELEVANCE: The authors conclude that the variations in fracture patterns encountered today may be attributed to the mechanism of injury. With due consideration to the limitations of this study, the authors suggest that the treatment plan may require slight modification based on the variation of the fracture pattern. Additional intervention may also be indicated.

PMID:37743043 | DOI:10.1016/j.joms.2023.08.225