Tag: nevin manimala

Comput Biol Chem. 2024 Apr 24;110:108083. doi: 10.1016/j.compbiolchem.2024.108083. Online ahead of print.

ABSTRACT

Amino acid propensities for protein secondary structures are vital for protein structure prediction, understanding folding, and design, and have been studied using various theoretical and experimental methods. Traditional assessments of average propensities using statistical methods have been done on relatively smaller dataset for only a few secondary structures. They also involve averaging out the environmental factors and lack insights into consistency of preferences across diverse protein structures. While a few studies have explored variations in propensities across protein structural classes and folds, exploration of such variations across protein structures remains to be carried out. In this work, we have revised the average propensities for all six different secondary structures, namely α-helix, β-strand, 3₁₀-helix, π-helix, turn and coil, analyzing the most exhaustive dataset available till date using two robust secondary structure assignment algorithms, DSSP and STRIDE. The propensities evaluated here can serve as a standard reference. Moreover, we present here, for the first time, the propensities within individual protein structures and investigated how the preferences of residues and more interestingly, of their groups formed based on their structural features, vary across different unique structures. We devised a novel approach- the minimal set analysis, based on the propensity distribution of residues, which along with the group propensities led us to the conclusion that a residue’s preference for a specific secondary structure is primarily dictated by its side chain’s structural features. The findings in this study provide a more insightful picture of residues propensities and can be useful in protein folding and design studies.

PMID:38691894 | DOI:10.1016/j.compbiolchem.2024.108083

Comp Immunol Microbiol Infect Dis. 2024 Apr 18;109:102184. doi: 10.1016/j.cimid.2024.102184. Online ahead of print.

ABSTRACT

BACKGROUND: Toxoplasma gondii is an apicomplexan protozoan parasite that infects one-third of the population of the world, including humans, animals, birds, and other vertebrates. The present investigation is the first molecular attempt in the Malakand Division of Pakistan to determine the epidemiology and phylogenetic study of Toxoplasma gondii infecting small ruminants.

METHODOLOGY: A total of (N = 450) blood samples of sheep were randomly collected during the study period (December 2020 to November 2021), and DNA detection was done using PCR by amplifying ITS-1 genes. SPSS.20 and MEGA-11 software were used for statistical significance and phylogenetic analysis.

RESULTS: The overall prevalence of T. gondii infection among sheep was 14.44 % (65/450). A high infection rate was found in more than five-year-olds at 18.33 % (11/60). Sequencing and BLAST analysis of PCR-positive samples confirmed the presence of T. gondii. Randomly, three isolates were sequenced and submitted to GenBank under accession numbers (PP028089-PP028091), respectively. The BLAST analysis of the obtained sequences based on the ITS-1 gene showed 99 % similarities with reported genotypes found in goats of Malakand, Pakistan (PP028089) and dogs of Brazil (MF766454). The study concludes that T. gondii is notably prevalent among the sheep population in the region, emphasizing the significant role of risk factors in disease transmission across animals and potentially to humans. Further research, zoonotic potential analysis, and targeted control measures are warranted to address and manage this parasitic infection effectively.

PMID:38691874 | DOI:10.1016/j.cimid.2024.102184

Neurosurg Focus. 2024 May;56(5):E11. doi: 10.3171/2024.2.FOCUS2413.

ABSTRACT

OBJECTIVE: In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor’s location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC.

METHODS: Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05.

RESULTS: A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively.

CONCLUSIONS: The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

PMID:38691862 | DOI:10.3171/2024.2.FOCUS2413

Neurosurg Focus. 2024 May;56(5):E16. doi: 10.3171/2024.2.FOCUS2421.

ABSTRACT

OBJECTIVE: Numerous studies have investigated the impact of inflammatory factors in cancer, yet few attempts have been made to investigate these markers in skull base chordoma (SBC). Inflammatory values including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) can serve as prognostic markers in various cancers. This study aimed to determine whether these inflammatory factors influence overall survival (OS) or progression-free survival (PFS) in patients with primary SBC.

METHODS: The electronic medical records of patients with primary SBC who underwent resection from 2001 to 2020 were retrospectively reviewed for the associations of sex, age at diagnosis, preoperative steroid use, tumor volume, extent of resection, adjuvant radiation after surgery, tumor metastasis, Ki-67 index, percent homozygous deletion of 9p23 and percent 1p36 loss, and potential prognostic inflammatory markers of NLR, PLR, LMR, SII, and SIRI with the primary outcome measures of OS and PFS. Maximum log-rank statistical tests were used to determine inflammatory marker thresholds for grouping prior to Kaplan-Meier and Cox proportional hazards analysis for OS and PFS of the elucidated groups.

RESULTS: The cohort included 115 primary SBC patients. The mean ± SD tumor volume was 23.0 ± 28.0 cm3, 73% of patients received gross-total resection, 40% received postoperative radiation, 25% had local recurrence, and 6% had subsequent metastatic disease (mean follow-up 47.2 months). Univariable Cox analysis revealed that NLR (p < 0.01), PLR (p = 0.04), LMR (p = 0.04), SII (p < 0.01), and SIRI (p < 0.01) were independently associated with PFS. Additionally, NLR (p = 0.05) and SII (p = 0.03) were significant in multivariable Cox analysis of PFS. However, both univariable and multivariable Cox analysis revealed no correlations with OS.

CONCLUSIONS: The routine assessment of inflammatory biomarkers such as NLR and SIRI could have prognostic value in postresection SBC patients.

PMID:38691858 | DOI:10.3171/2024.2.FOCUS2421

Ocul Immunol Inflamm. 2024 May 1:1-8. doi: 10.1080/09273948.2024.2345289. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the choroidal vascularity index and choroidal thickness in patients with rheumatoid arthritis.

METHOD: This study is a case control study. Our study consists of a total of two groups, with 32 individuals diagnosed with rheumatoid arthritis (RA) and 32 healthy volunteers. The thickness of the subfoveal choroid was measured from the 500 micron (µm), 1000 µm, 1500 µm nasal aspect of the fovea, and 500µm, 1000µm, 1500 µm temporal and subfoveal thickness of the fovea. ImageJ version 1.53i (National Institutes of Health, Bethesda, MD, USA) from open access was used for choroidal vascular index calculation.

RESULTS: The mean age (p = 0.064) and gender distribution (p = 0.522) were not statistically different between these two groups. There was no difference between the groups in terms of visual acuity (p = 0.060), intraocular pressures (p=0.056), refractive errors (p = 0.418), and axial lengths (p = 0.280). Temporal 500 µm CT (p = 0.038), temporal 1000 µm CT (p = 0.010), and temporal 1500 µm CT (p = 0.005) differed significantly between the groups. The luminal area was significantly different between the RA group (842.71 ± 192.77) and the control group (957.78 ± 230.83) (p = 0.034). The choroidal vascularity index showed a significant difference between the RA group (64.99 ± 4.71) and the control group (67.34 ± 3.40) (p = 0.026). A significant difference was observed between the seronegative RA and the control group with temporal 1500 µm CT (p = 0.030), temporal 1000 µm CT (p = 0.023), and luminal area (p = 0.034).

CONCLUSION: We demonstrated thinning in CT and decreased CVI for the first time in RA patients by comparing it with the control group.

PMID:38691844 | DOI:10.1080/09273948.2024.2345289

Ocul Immunol Inflamm. 2024 May 1:1-7. doi: 10.1080/09273948.2024.2344712. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the efficacy and safety of adalimumab for the treatment of non-infectious uveitis (NIU) in four Uveitis Units from tertiary Spanish hospitals.

METHODS: Multicenter and retrospective clinical cohort study including all patients with NIU treated with adalimumab from January 2012 to October 2022 in four uveitis units was performed. Efficacy was measured with the number of relapses, ocular inflammation and reduction in immunosuppression and corticosteroid dosage before and after adalimumab use. We collected data regarding adverse effects and examined the immunogenicity of adalimumab.

RESULTS: One hundred and twenty-two patients (59% females), with a mean age of 48.6 years (SD = 14.8) accounting for 217 eyes were included. The majority (92.6%) were Caucasian. Uveitis analyzed were predominantly panuveitis (34.7%), bilateral (77.9%), acute (41.5%), and non-granulomatous (90%). Most of them were immune mediated (42.6%), and the main reason to initiate adalimumab was refractory disease (96.7%). The analysis was statistically significant due to the reduction in the number of immunosuppressive drugs as well as the dose of oral corticosteroids and the number of relapses during follow-up (p < 0.001). The decrease in ocular inflammation parameters and the improvement in visual acuity (p < 0.05) were also significant. There were no deaths due to the drug and only one reported case of serious infection. In total, 10.9% of 73 patients tested developed anti-adalimumab antibodies and 4.1% lupus-like.

CONCLUSIONS: We consider adalimumab as a leading drug in the treatment of NIU with high safety and efficacy.

PMID:38691840 | DOI:10.1080/09273948.2024.2344712

Neurology. 2024 May;102(10):e209389. doi: 10.1212/WNL.0000000000209389. Epub 2024 May 1.

ABSTRACT

BACKGROUND AND OBJECTIVES: Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents.

METHODS: This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants’ initial diagnosis and management.

RESULTS: A total of 83 adolescents were enrolled between 12 and 18 years. Fifty-eight (70%) presented to an ED before diagnosis of epilepsy. Although most ED presentations were for motor seizures (n = 52; 90%), many patients had a history of nonmotor seizures (20/52 or 38%). Adolescents with initial nonmotor seizures were less likely to present to EDs (26/44 or 59% vs 32/39 or 82%, p = 0.02), and nonmotor seizures were less likely to be correctly identified (2/6 or 33% vs 42/52 or 81%, p = 0.008). A history of initial nonmotor seizures was not recognized in any adolescent who presented for a first-lifetime motor seizure. As a result, initiation of treatment and admission from the ED was not more likely for these adolescents who met the definition of epilepsy compared with those with no seizure history. This lack of nonmotor seizure history recognition in the ED was greater than that observed in the adult group (0% vs 23%, p = 0.03) and occurred in both pediatric and nonpediatric ED settings.

DISCUSSION: Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.

PMID:38691824 | DOI:10.1212/WNL.0000000000209389

J Clin Oncol. 2024 May 1:JCO2302394. doi: 10.1200/JCO.23.02394. Online ahead of print.

ABSTRACT

PURPOSE: Although a contemporary randomized clinical trial has led to the use of whole-pelvic radiation therapy (WPRT), long-term data evaluating a potential reduction in mortality are lacking and are addressed in the current study.

MATERIALS AND METHODS: From 2005 to 2015, 350 men with localized, unfavorable-risk prostate cancer (PC) were randomly assigned to receive androgen deprivation therapy (ADT) and RT plus docetaxel versus ADT and RT. Treatment of the pelvic lymph nodes was at the discretion of the treating physician. Multivariable Cox and Fine and Grays regression analyses were performed to assess whether a significant association existed between radiation treatment volume and all-cause mortality (ACM) and PC-specific mortality (PCSM), respectively, adjusting for known PC prognostic factors and comorbidity. An interaction term between age (categorized by dichotomization at 65 years to enable clinical interpretation and applicability of the results and which approximates the median (66 years [IQR, 61-70]) and radiation treatment volume was included in the analysis.

RESULTS: After a median follow-up of 10.20 years (IQR, 7.96-11.41), 89 men died (25.43%); of these, 42 died of PC (47.19%). Of the 350 randomly assigned patients, 88 (25.14%) received WPRT. In men younger than 65 years, WPRT was associated with a significantly lower ACM risk (adjusted hazard ratio [AHR], 0.33 [95% CI, 0.11 to 0.97]; P = .04) and lower PCSM risk (AHR, 0.17 [95% CI, 0.02 to 1.35]; P = .09) after adjusting for covariates, whereas this was not the case for men 65 years or older.

CONCLUSION: WPRT has the potential to reduce mortality in younger men with unfavorable-risk PC.

PMID:38691823 | DOI:10.1200/JCO.23.02394

J Clin Oncol. 2024 May 1:JCO2301951. doi: 10.1200/JCO.23.01951. Online ahead of print.

ABSTRACT

PURPOSE: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.

METHODS: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared with 15 existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection).

RESULTS: ORN was identified in 219 of 2,732 (8%) consecutive patients with HNC. Factors associated with high risk of ORN were oral cavity or oropharyngeal primaries, received IMRT dose ≥60 Gy, current/ex-smokers, and/or stage III to IV periodontal condition. The ORN rate for high-risk versus low-risk patients was 12.7% versus 3.1% (P < .001) with an AUC of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, ClinRad, was proposed on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems.

CONCLUSION: We identified risk factors for ORN and proposed a novel ORN classification system on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN and may facilitate clinical care and clinical trials.

PMID:38691822 | DOI:10.1200/JCO.23.01951

Wiad Lek. 2024;77(3):557-565. doi: 10.36740/WLek202403126.

ABSTRACT

OBJECTIVE: Aim: To research how the future dentists’ professional self-determination (reflects the cognitive-reflexive component of higher medical education applicants’ readiness to use digital technologies in their professional activities) develops within the formation of information technology competence in the modern realities of Ukraine.

PATIENTS AND METHODS: Materials and Methods: The author’s questionnaire consisted of 15 questions. The questionnaire surveys covered 98 future dentists who studied ‘Medical Informatics’ and ‘Information Technology in Dentistry’ at the Ivano-Frankivsk National Medical University in the September-December 2017-2018 and September- December 2022-2023 academic years. The research results were assessed according to the algorithm described. The research used such methods as analysis, synthesis, comparison, concretisation, systematisation, and generalisation, as well as methods of mathematical statistics for evaluating data, namely correlation analysis, Kolmogorov-Smirnov test, Cronbach’s alpha, Fisher’s test (F-test of equality of variances), Student’s t-test and ranking.

RESULTS: Results: The research found positive dynamics of the professional self-determination levels (in 2022 compared to 2017, the low level decreased by 20.5%, the satisfactory level – by 19.0%, the average level increased by 20.6%, the high level – by 18.9%) and their quality, which within the research increased by 39.5%.

CONCLUSION: Conclusions: By forming information technology competence, future dentists changing the priorities of professional self-determination in the modern realities of Ukraine and acquiring readiness (within the cognitive-reflexive component) to use digital technologies in professional activities.

PMID:38691800 | DOI:10.36740/WLek202403126