Category: Nevin Manimala

Sci Rep. 2023 Apr 8;13(1):5778. doi: 10.1038/s41598-023-30826-2.

ABSTRACT

We developed a novel prediction model for recurrence and survival in patients with localized renal cell carcinoma (RCC) after surgery and a novel statistical method of machine learning (ML) to improve accuracy in predicting outcomes using a large Asian nationwide dataset, updated KOrean Renal Cell Carcinoma (KORCC) database that covered data for a total of 10,068 patients who had received surgery for RCC. After data pre-processing, feature selection was performed with an elastic net. Nine variables for recurrence and 13 variables for survival were extracted from 206 variables. Synthetic minority oversampling technique (SMOTE) was used for the training data set to solve the imbalance problem. We applied the most of existing ML algorithms introduced so far to evaluate the performance. We also performed subgroup analysis according to the histologic type. Diagnostic performances of all prediction models achieved high accuracy (range, 0.77-0.94) and F1-score (range, 0.77-0.97) in all tested metrics. In an external validation set, high accuracy and F1-score were well maintained in both recurrence and survival. In subgroup analysis of both clear and non-clear cell type RCC group, we also found a good prediction performance.

PMID:37031280 | DOI:10.1038/s41598-023-30826-2

Clin Proteomics. 2023 Apr 8;20(1):17. doi: 10.1186/s12014-023-09394-0.

ABSTRACT

INTRODUCTION: Proteomic analysis of human plasma by LC-ESI-MS/MS has discovered a limited number of new cellular protein biomarkers that may be confirmed by independent biochemical methods. Analysis of COVID-19 plasma has indicated the re-purposing of known biomarkers that might be used as prognostic markers of COVID-19 infection. However, multiple molecular approaches have previously indicated that the SARS-COV2 infection cycle is linked to the biology of mitochondria and that the response to infections may involve the action of heme containing oxidative enzymes.

METHODS: Human plasma from COVID-19 and ICU-ARDS was analyzed by classical analytical biochemistry techniques and classical frequency-based statistical approaches to look for prognostic markers of severe COVID-19 lung damage. Plasma proteins from COVID-19 and ICU-ARDS were identified and enumerated versus the controls of normal human plasma (NHP) by LC-ESI-MS/MS. The observation frequency of proteins detected in COVID-19 and ICU-ARDS patients were compared to normal human plasma, alongside random and noise MS/MS spectra controls, using the Chi Square (χ²) distribution.

RESULTS: PCR showed the presence of MT-ND1 DNA in the plasma of COVID-19, ICU-ARDS, as well as normal human plasma. Mitochondrial proteins such as MRPL, L2HGDH, ATP, CYB, CYTB, CYP, NDUF and others, were increased in COVID-19 and ICU-ARDS plasma. The apparent activity of the cytochrome components were tested alongside NHP by dot blotting on PVDF against a purified cytochrome c standard preparation for H₂O₂ dependent reaction with luminol as measured by enhanced chemiluminescence (ECL) that showed increased activity in COVID-19 and ICU-ARDS patients.

DISCUSSION: The results from PCR, LC-ESI-MS/MS of tryptic peptides, and cytochrome ECL assays confirmed that mitochondrial components were present in the plasma, in agreement with the established central role of the mitochondria in SARS-COV-2 biology. The cytochrome activity assay showed that there was the equivalent of at least nanogram amounts of cytochrome(s) in the plasma sample that should be clearly detectable by LC-ESI-MS/MS. The release of the luminol oxidase activity from cells into plasma forms the basis of a simple and rapid test for the severity of cell damage and lung injury in COVID-19 infection and ICU-ARDS.

PMID:37031181 | DOI:10.1186/s12014-023-09394-0

Radiat Oncol. 2023 Apr 8;18(1):66. doi: 10.1186/s13014-023-02248-x.

ABSTRACT

OBJECTIVE: To evaluate the impact of bone marrow (BM) irradiation dose on acute haematologic toxicity (HT) in concurrent chemoradiotherapy for cervical cancer.

METHODS: Sixty-nine patients with cervical cancer treated with curative or postoperative adjuvant therapy received weekly cisplatin concurrent chemotherapy (CCT) and intensity-modulated radiation therapy (IMRT). The whole pelvic bone marrow (PBM) was delineated and divided into three subsites: ilium (IL), lower pelvis (LP), and lumbosacral spine (LS). Associations between clinical variables, dose volume of BM, including PBM, IL, LP, and LS in the form of x-Vy (volume receiving y Gy for x), and blood cell count nadir were tested using linear regression models. Receiver operating characteristic (ROC) curve analysis was further used to analyse the cutoff values of the variables with p < 0.05 in the multivariate analysis.

RESULTS: In 69 patients, the haemoglobin nadir was positive correlated with baseline haemoglobin (p < 0.001), negative correlated with relative LP-V10 (p = 0.005), relative LP-V25 (p = 0.002), relative LP-V50 (p = 0.007), relative LP-mean (p = 0.003), absolute LP-V15 (p = 0.049), absolute LP-V25 (p = 0.004) and absolute LP-V30 (p = 0.009). The platelet nadir was positive correlated with baseline platelets (p = 0.048) and negative correlated with relative LP-V40 (p = 0.028), but there was no significant variable in absolute radiation volume by multivariate analysis. No variables related to the neutrophil nadir were found, and the 69 patients were divided into group A (43 cases) receiving 3-4 cycles of CCT and group B (26 cases) receiving 5-6 cycles of CCT. In group A, the relative IL-V15 (p = 0.014), the relative IL-V50 (p = 0.010) and the absolute LP-V50 (p = 0.011) were negative correlated with the neutrophil nadir. No significant variable was found in group B. No significant variables related to the lymphocyte nadir were found, and the neutrophil-to-lymphocyte ratio (NLR) was analysed. Age (p < 0.05), relative LP-V15 (p = 0.037) and absolute PBM-mean (p < 0.001) were found to be negative related to NLR.

CONCLUSION: The dosimetric parameters of relative irradiated volume of BM have more statistically significant datas on acute HT than absolute irradiated volume. The nadir of haemoglobin and platelets and the vertice of NLR were more affected by the irradiation dose to LP, while neutrophils were more affected by the dose to IL. Acute HT was negative related to both low-dose irradiation (V10-30) and high-dose irradiation (V40, V50). For more than 4 cycles of CCT, the effect of BM irradiation on the neutrophils nadir was masked by chemotherapy.

PMID:37031167 | DOI:10.1186/s13014-023-02248-x

J Chem Phys. 2023 Apr 7;158(13):134103. doi: 10.1063/5.0142248.

ABSTRACT

There are many atomistic simulation methods with very different costs, accuracies, transferabilities, and numbers of empirical parameters. I show how statistical model selection can compare these methods fairly, even when they are very different. These comparisons are also useful for developing new methods that balance cost and accuracy. As an example, I build a semiempirical model for hydrogen clusters.

PMID:37031147 | DOI:10.1063/5.0142248

J Chem Phys. 2023 Apr 7;158(13):135101. doi: 10.1063/5.0139848.

ABSTRACT

The omnipresence and diversity of allosteric regulation in proteins and protein associations complemented by the potential for the design of allosterically acting biologics and drugs call for the development of a new generation of computational models for the analysis of allostery and rational engineering/design of desired signaling and effector molecules determining it. One of the most important challenges is the consideration of the role of amino acid sequence in forming the protein’s allosteric communication, including the mode and strength of the allosteric signal that is communicated to the regulated functional site. Here, we present the network-based model with a sequence dependence added in consideration of allosteric communication by combining the structure-based statistical mechanical model of allostery with the Miyazawa-Jernigan residue-residue potential. Applying the model in the analysis of five classical allosteric proteins, we found that it is necessary to consider the following two major determinants: (i) the free energy exerted by the allosteric site on the regulated one and (ii) the background (average) change in dynamics of the overall structure. We show that working together these two components determine the allosteric modulation, calling one to study their dependence on structures, oligomerization states, and sequence divergence in different proteins.

PMID:37031128 | DOI:10.1063/5.0139848

J Orthop Sci. 2023 Apr 6:S0949-2658(23)00080-5. doi: 10.1016/j.jos.2023.03.010. Online ahead of print.

ABSTRACT

BACKGROUND: Walking is the most affected motor function in children with cerebral palsy (CP). Orthopaedic surgery is regularly used to improve ambulation in children with CP. Selective Percutaneous Myofascial Lengthening (SPML) is considered the state-of-the art technique for surgical lengthening of spastic/contracted muscles in CP. The purpose of this study was to investigate the effect of combined SPML surgery and postoperative functional physiotherapy on gait function and characteristics of children with spastic cerebral palsy (CP).

METHODS: Twenty-six children with spastic CP, aged 5-7 years, Gross Motor Function Classification System (GMFCS) levels II (n = 6), III (n = 12) and IV (n = 8) participated in a quasi-experimental one-group pretest-posttest study with a 9-month follow-up. The Global Motion Graph Deviation Index (MGDI) (including MGDI sub-indices of each joint in each plane of motion) and spatiotemporal parameters of a three-dimensional kinematic gait analysis were used to assess the gait function and characteristics, respectively.

RESULTS: Nine months following SPML and functional physiotherapy, statistically significant improvements (p < 0.05) were noted in the Global MGDI, the MGDIs of sagittal plane knee and ankle motion analysis graphs, and the four most common spatiotemporal measures of gait: walking velocity, stride length, step length, and cadence.

CONCLUSION: Children with spastic CP seem to gain better overall gait function following SPML procedure and functional physiotherapy, by achieving higher walking velocity, longer stride length and step length, and faster cadence. Further studies with control group and longer follow-up three-dimensional gait analyses are warranted to validate these positive results.

PMID:37031098 | DOI:10.1016/j.jos.2023.03.010

Eur Urol Focus. 2023 Apr 6:S2405-4569(23)00079-2. doi: 10.1016/j.euf.2023.03.010. Online ahead of print.

ABSTRACT

BACKGROUND: Studies assessing the stone-free rate (SFR) after ureteroscopy are limited to expert centers with varied definitions of stone free. Real-world data including community practices related to surgeon characteristics and outcomes are lacking.

OBJECTIVE: To evaluate the SFR for ureteroscopy and its predictors across diverse surgeons in Michigan.

DESIGN, SETTING, AND PARTICIPANTS: We assessed the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry for patients with renal or ureteral stones treated with ureteroscopy between 2016 and 2021 who had postoperative imaging.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Stone free was defined as no fragments on imaging reports within 60 d entered by independent data abstractors. Factors associated with being stone free were examined using logistic regression, including annual surgeon volume. We then assessed variation in surgeon-level SFRs adjusted for risk factors.

RESULTS AND LIMITATIONS: We identified 6487 ureteroscopies from 164 surgeons who treated 2091 (32.2%) renal and 4396 (67.8%) ureteral stones. The overall SFRs were 49.6% (renal) and 72.7% (ureteral). Increasing stone size, lower pole, proximal ureteral location, and multiplicity were associated with not being stone free. Female gender, positive urine culture, use of ureteral access sheath, and postoperative stenting were associated with residual fragments when treating ureteral stones. Adjusted surgeon-level SFRs varied for renal (26.1-72.4%; p < 0.001) and ureteral stones (52.2-90.2%; p < 0.001). Surgeon volume was not a predictor of being stone free for renal stones. Limitations include the lack of imaging in all patients and use of different imaging modalities.

CONCLUSIONS: The real-world complete SFR after ureteroscopy is suboptimal with substantial surgeon-level variation. Interventions focused on surgical technique refinement are needed to improve outcomes for patients undergoing ureteroscopy and stone intervention.

PATIENT SUMMARY: Results from a diverse group of community practicing and academic center urologists show that for a large number of patients, it is not possible to be completely stone free after ureteroscopy. There is substantial variation in surgeon outcomes. Quality improvement efforts are needed to address this.

PMID:37031097 | DOI:10.1016/j.euf.2023.03.010

Eur Urol Focus. 2023 Apr 6:S2405-4569(23)00077-9. doi: 10.1016/j.euf.2023.03.011. Online ahead of print.

ABSTRACT

BACKGROUND: The optimal radiological follow-up of prostate lesions negative on magnetic resonance imaging (MRI)-targeted biopsy (MRI-TB) is yet to be optimised.

OBJECTIVE: To present medium-term radiological and clinical follow-up of biopsy-negative lesions.

DESIGN, SETTING, AND PARTICIPANTS: The records for men who underwent multiparametric MRI at the UCLH one-stop clinic for suspected prostate cancer between September 2017 and March 2020 were reviewed (n = 1199). Patients with Likert 4 or 5 lesions were considered (n = 495), and those with a subsequent negative MRI-TB comprised the final study population (n = 91).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline and follow-up MRI and biopsy data (including prostate-specific antigen [PSA], prostate volume, radiological scores, and presence of any noncancerous pathology) were extracted from reports. The last follow-up date was the date of the last test or review in clinic.

RESULTS AND LIMITATIONS: Median follow-up was 1.8 yr (656 d, interquartile range [IQR] 359-1008). At baseline, the median age was 65.4 yr (IQR 60.7-70.0), median PSA was 7.1 ng/ml (IQR 4.7-10.0), median prostate volume was 54 ml (IQR 39.5-75.0), and median PSA density (PSAD) was 0.13 ng/ml² (IQR 0.09-0.18). Eighty-six men (95%) had Likert 4 lesions, while the remaining five (5%) had Likert 5 lesions. Only 21 men (23%) had a single lesion; most had at least two. Atrophy was the most prevalent pathology on MRI-TB, present in 64 men (74%), and followed by acute inflammation in 42 (46%), prostatic intraepithelial neoplasia in 33 (36%), chronic inflammation in 18 (20%), atypia in 13 (14%), and granulomatous inflammation in three (3%). Fifty-eight men had a second MRI study (median 376 d, IQR 361-412). At the second MRI, median PSAD decreased to 0.11 ng/ml² (IQR 0.08-0.18). A Likert 4 or 5 score persisted only in five men (9%); 40 men (69%) were scored Likert 3, while the remaining 13 (22%) were scored Likert 2 (no lesion). Of 45 men with a Likert ≥3 score, most only had one lesion at the second MRI (28 men; 62%). Of six men with repeat MRI-TB during the study period, two were subsequently diagnosed with prostate cancer and both had persistent Likert 4 scores (at baseline and at least one follow-up MRI).

CONCLUSIONS: Most biopsy-negative MRI lesions in the prostate resolve over time, but any persistent lesions should be closely monitored.

PATIENT SUMMARY: Lesions in the prostate detected via magnetic resonance imaging (MRI) scans that are negative for cancer on biopsy usually resolve. Repeat MRI can indicate persistent lesions that might need a second biopsy.

PMID:37031096 | DOI:10.1016/j.euf.2023.03.011

J Adolesc Health. 2023 Apr 6:S1054-139X(23)00110-6. doi: 10.1016/j.jadohealth.2023.02.015. Online ahead of print.

ABSTRACT

PURPOSE: Parents’ attitudes toward contraceptive delivery methods have been shown to impact their adolescents’ use of contraceptive methods. However, little is known about the HIV pre-exposure prophylaxis (PrEP) delivery method attitudes of parents of sexual and gender minority (SGM) adolescents assigned male at birth (AMAB). This exploratory, mixed-method formative study examined the PrEP delivery method preferences among a convenience sample of 33 parents of SGM adolescents AMAB who live in Texas.

METHODS: Participants completed an online survey, where they selected their preferred PrEP method for their SGM adolescent AMAB to use: PrEP as a daily oral pill, a bimonthly injectable, or a yearly implant. Parents answered an open-ended question about their reasons for choosing their preferred method. We analyzed data through descriptive statistics and inductive content analysis.

RESULTS: Findings from this convenience sample suggest that there is not one PrEP delivery method that parents of SGM adolescents AMAB prefer: one third of parents (33.3%) selected PrEP as a daily oral pill, 45.5% selected PrEP as a bimonthly injectable, and 21.2% selected PrEP as an annual implant. Parents cited multiple reasons for selecting a delivery method over another, with the most prevalent reasons being adherence (57.6%), access or cost (21.2%), and generic convenience or ease (21.2%).

DISCUSSION: Findings from this formative exploratory study sets the stage for future research and intervention development in increasing parental knowledge, preferences, and preference motivations for PrEP delivery methods.

PMID:37031089 | DOI:10.1016/j.jadohealth.2023.02.015

J Adolesc Health. 2023 Apr 6:S1054-139X(23)00105-2. doi: 10.1016/j.jadohealth.2023.02.010. Online ahead of print.

ABSTRACT

PURPOSE: Substance use is common among adolescents, and among those with substance use disorders; use often persists into middle age, underlying the importance of early detection and treatment. The goal of this quality improvement project was to increase the electronic substance use screening rate of adolescents presenting for preventative health visits from 0% to 50% between March 2021 and September 2021.

METHODS: This is an ongoing quality improvement project. Participants included patients ≥12 who presented to the Adolescent Medicine Clinic for preventative health visits. We incorporated the Screening to Brief Intervention into the existing Car, Relax, Alone, Forget, Friends, Trouble tool within the electronic health record. We completed a Plan-Do-Study-Act cycle by reviewing every patient’s chart who did not receive screening and identified that a common reason for missed screening was designating the visit as “establishing care” rather than preventative health visit. We modified our eligible patient criteria to include all adolescents presenting to establish primary care.

RESULTS: We achieved a statistically significant center-line shift with a p value (<.001) from approximately 0% at baseline to a new baseline of 85% from June 2021 to June 2022. After broadening our eligibility criteria, our electronic screening rate improved from 78% in November 2021, to 83% in December 2021.

DISCUSSION: Electronic health record integration of the Screening to Brief Intervention/Car, Relax, Alone, Forget, Friends, Trouble is an effective method to systematically and electronically screen adolescents for SUD at preventative health visits. Integration using similar approaches may benefit other institutions interested in providing standardized SUD screening.

PMID:37031088 | DOI:10.1016/j.jadohealth.2023.02.010