Nevin Manimala

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

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

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

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

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

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

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

Cell Signal. 2023 Sep 22:110901. doi: 10.1016/j.cellsig.2023.110901. Online ahead of print.

ABSTRACT

Cancer cachexia is a systemic inflammation-driven syndrome, characterized by muscle atrophy and adipose tissue wasting, with progressive weight loss leading to serious impairment of physiological function. Extracellular vesicles (EVs) derived from cancer cells play a significant role in adipocyte lipolysis, yet the mechanism remain uneclucidated. In this study, EVs derived from Lewis lung carcinoma (LLC) cells were extracted and characterized. 3 T3-L1 and HIB1B adipocytes were cultured with conditioned medium or EVs from LLC, and LLC cells were used to establish a cancer cachexia mouse model. EVs derived from LLC cells were taken up by 3 T3-L1 and HIB1B adipocytes, and derived exosomal EIF5A protein-induced lipolysis of adipocytes. High level of EIF5A was expressed in EVs from LLC cells, exosomal EIF5A is linked to lipid metabolism. Elevated expression of EIF5A is associated with shorter overall survival in lung cancer patients. Western blots, glycerol release and Oil red O staining assays were used to evaluate lipolysis of adipocytes. The reduction of lipolysis in 3 T3-L1 and HIB1B adipocytes is achieved through silencing EIF5A or treating with pharmacologic inhibitor GC7 in vitro, and suppressing the expression of EIF5A in LLC cells by infected with shRNA or GC7 treatment partly alleviated white and brown adipose tissue lipolysis in vivo. Mechanistically, EIF5A directly binds with G protein-coupled bile acid receptor 1 (GPBAR1) mRNA to promote its translation and then activates cAMP response element binding protein (CREB) signaling pathway to induce lipolysis. This study demonstrates that exosomal EIF5A from LLC cells, with hypusinated EIF5A, has a lipolytic effect on adipocyte and adipose tissues in cancer cachexia model. Exosomal EIF5A could be involved in lipolysis and these findings indicate that a novel regulator and potential target for cachexia treatment.

PMID:37743008 | DOI:10.1016/j.cellsig.2023.110901

Am J Obstet Gynecol MFM. 2023 Sep 22:101168. doi: 10.1016/j.ajogmf.2023.101168. Online ahead of print.

ABSTRACT

BACKGROUND: Continuous support during labor has many benefits, including lower use of obstetrical interventions. However, implementation remains limited. Insights into birth outcomes as well as peripartum costs are essential to assess whether continuous care by a maternity care assistant is a potentially (cost) effective program to provide for all women.

OBJECTIVE: Continuous care during labor, provided by maternity care assistants, will reduce the use of epidural analgesia and peripartum costs due to a reduction in interventions.

STUDY DESIGN: A randomized controlled trial, comparing continuous support during labor (intervention group) to care-as-usual (control group) with pre-specified intention-to-treat and per-protocol analyses. The primary outcome was epidural analgesia use. Secondary outcomes were use of other analgesia, referrals from midwife- to obstetrician-led care, modes of birth, hospital stay, sense of control (evaluated with the Labor Agentry Scale), maternal and neonatal adverse outcomes and peripartum costs. Data were collected using questionnaires. Anticipating incomplete adherence to providing continuous care, both intention-to-treat and per-protocol analyses were planned. Peripartum costs were estimated using a healthcare perspective. Mean costs per woman and cost differences between the intervention and control group were calculated.

RESULTS: The population consisted of 1076 women with 54 exclusions and 30 discontinuations, leaving 992 women to be analyzed (515 continuous care and 477 care-as-usual). Intention-to-treat analyses showed statistically non-significant differences between the intervention and control group for epidural use (RR 0.88, 95%-CI 0.74 to 1.04, p=0.14) and peripartum costs (mean difference € 185.83, 95%-CI -€ 204.22 to € 624.54). Per-protocol analyses showed statistically significant decreases in epidural analgesia (RR 0.64, 95%-CI 0.48 to 0.84, p=0.001), other analgesia (RR 0.59, 95%-CI 0.37 to 0.94, p=0.02), cesarean sections (RR 0.53, 95%-CI 0.29 to 0.95, p=0.03) and increase in spontaneous vaginal births (RR 1.09, 95%-CI 1.01 to 1.18, p=0.001) in the intervention group, but difference in total peripartum costs remained statistically non-significant (mean difference € 246.55, 95%-CI -€ 539.14 to € 13.50).

CONCLUSION: If the provision of continuous care given by maternity care assistants during labor can be secured, continuous care leads to more vaginal births and less epidural use, pain medication and cesarean sections, while not leading to a difference in peripartum costs compared to care-as-usual.

PMID:37742999 | DOI:10.1016/j.ajogmf.2023.101168

Sci Total Environ. 2023 Sep 22:167288. doi: 10.1016/j.scitotenv.2023.167288. Online ahead of print.

ABSTRACT

Limited information is available regarding the pollution status of organophosphate esters (OPEs) in the environment of the Yellow River estuary. Here, n = 51 sediment samples were collected from the Yellow River estuary in 2021, and further analyzed by using the integrated target, suspect, and feature fragment-dependent nontarget OPE screening strategy developed in our laboratory. Among the 30 target OPEs, 19 were detectable in at least one of the analyzed samples, with total concentrations (Σ₁₉OPEs) ranging from of 41.4 to 1930 ng/g dry weight (dw). On the basis of an in-house suspect compound database, we further tentatively identified 11 suspect OPEs, and they were semi-quantified. Furthermore, four other interesting findings were observed and described as follows: 1) a statistically significant difference existed in the concentrations of OPEs in sediment samples between the lower reaches of the Yellow River (n = 5 samples), and the Yellow River estuary (n = 46 samples) (unpaired t-test, p < 0.001); 2) tris(2,4-di-tert-butylphenyl)phosphate (TDTBPP) exhibited the greatest concentrations (ranging from 30.7 to 1920 ng/g dw) among all OPEs detected in the sediment samples; 3) samples from the north of the Yellow River estuary had higher OPE concentrations than those from the south; and 4) a suspect screening strategy allowed us to identify a novel OPE structure (tert-butyl)phenyl (ethyne-oxidane) bis(2,4-di-tert-butylphenyl) phosphate (TPBDTP) that exhibited a highly positive correlation relationship with TDTBPP (r = 0.749; p < 0.001). Overall, this study provided evidence that OPEs (especially TDTBPP) were ubiquitous in the sediment environment of the Yellow River estuary; thus, we emphasize that continuous monitoring of OPE pollution should be conducted in this region.

PMID:37742975 | DOI:10.1016/j.scitotenv.2023.167288