Category: Nevin Manimala

J Clin Oncol. 2022 Oct 21:JCO2200947. doi: 10.1200/JCO.22.00947. Online ahead of print.

ABSTRACT

PURPOSE: Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease.

METHODS: Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation.

RESULTS: Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04).

CONCLUSION: Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.

PMID:36269899 | DOI:10.1200/JCO.22.00947

Appl Neuropsychol Adult. 2022 Oct 21:1-6. doi: 10.1080/23279095.2022.2133606. Online ahead of print.

ABSTRACT

OBJECTIVE: Epilepsy is a severe disease in which seizures play the leading role. Striking clinical manifestations of the attacks take most of the attention of healthcare professionals. Apart from epilepsy itself, it is well known that epilepsy patients may also have psychiatric comorbidities. These disorders, such as anxiety and depression, are mostly thought to be related to epileptic seizures or antiepileptic medications. In clinical practice, cognitive impairment is another disrupted area of interest in epileptic patients. Our study aimed to detect this deterioration and its correlations with mood disorders and epileptic disease features such as seizure frequency and illness duration.

MATERIALS AND METHODS: After obtaining verbal and written consent, we enrolled 52 epilepsy patients in our study. A short demographic form indicating their gender, epileptic disease features, and medication usage information was completed for each patient. The Quick Mild Cognitive Impairment Screen (QMCI) test, the Hamilton Anxiety Rating Scale (Ham-A), and the Hospital Anxiety and Depression Scale (HADS) were applied by an experienced psychologist. Abnormal brain magnetic resonance imaging findings (e.g., encephalomalacia, large arachnoid cysts, a considerable amount of white matter gliotic lesions, neoplastic or vascular space-occupying lesions, hippocampal malformations), vitamin and electrolyte imbalances, other chronic diseases as well as thyroid dysfunction were considered as exclusion criteria since they might interfere with cognition. We excluded abnormalities to this extent because we wanted to acquire a homogenous sampling population without structural disadvantages. Thus, we could be able to determine slight changes in cognition properly.

RESULTS: We found decreased cognitive scores directly proportional to lower education level, higher seizure frequency, longer disease duration, generalized tonic-clonic (GTC) type of seizure, and antiepileptic polytherapy. Also, complying with the literature, a high frequency of depression was found in our study group. Interestingly, decreased anxiety levels of the patients were statistically related to higher seizure frequency, which may indicate adaptive mechanisms to frequent seizures. Finally, a multivariate regression analysis revealed a significant negative impact of GTC type of seizure on cognition.

CONCLUSION: Epilepsy and epileptic seizures affect cognition negatively. Thus, newly diagnosed epilepsy patients should be assessed for cognitive status as soon as possible. This assessment will allow epileptologists to understand future deteriorations in their patients’ cognition. In our study, it is shown that QMCI is an effective and practical way to assess the cognitive statuses of epilepsy patients.

PMID:36269892 | DOI:10.1080/23279095.2022.2133606

Environ Sci Technol. 2022 Oct 21. doi: 10.1021/acs.est.2c02287. Online ahead of print.

ABSTRACT

Increasing evidence indicates that exposure to microcystin-LR (MC-LR) can cause kidney damage. However, the association between MC-LR exposure and chronic kidney disease (CKD) risk in humans has not been studied. Therefore, we conducted a population-based case-control study involving 135 CKD cases and 135 matched controls in central China and analyzed the effects of MC-LR alone as well as combined with the known risk factor cadmium (Cd). Compared to the lowest quartile of MC-LR exposure, the highest quartile had a 2.82-fold (95% confidence interval [CI]: 1.37, 5.83) significantly increased risk for CKD, displaying a dose-response relationship (p_trend < 0.05). Our animal study also showed that MC-LR exposure induced kidney injury via the PI3K/AKT/mTOR signaling pathway. Comparing the highest Cd quartile to the lowest, the adjusted odds ratio for CKD was 3.43 (95% CI: 1.42, 8.27), exhibiting a dose-response relationship (p_trend < 0.05). Furthermore, a positive additive interaction was observed between MC-LR and Cd (relative excess risk due to interaction = 2.34, 95% CI: 0.30, 4.39; attributable proportion of interaction = 0.68, 95% CI: 0.37, 0.99). Our study firstly revealed that MC-LR exposure is an independent risk factor for CKD and has a synergistic relationship with Cd. MC-LR and Cd exposures are associated with CKD risk in a dose-response manner.

PMID:36269891 | DOI:10.1021/acs.est.2c02287

Acta Biochim Pol. 2022 Oct 21. doi: 10.18388/abp.2020_6388. Online ahead of print.

ABSTRACT

Much research has shown how important role leptin – a hormone secreted by adipose tissue – plays in the regulation of human body weight, mainly due to its appetite-decreasing effects. Under the conditions of energy balance, leptin is an indicator of the amount of triglycerides stored in adipose tissue. In contrast, in a state of hunger or overeating, it acts as an energy balance sensor, and when its level is too high, it fails to reduce food intake, disturbing maintenance of the proper body mass. Recent studies indicate that there is a relationship between a vegetarian diet and the decreased incidence of cardiovascular diseases, certain types of cancer and obesity. It has been noted that people on plant-based diets have lower body weight and percentage of body fat than omnivores. The aim of the study was to analyze the relationship between serum leptin concentrations and the type of diet. The 143 female volunteers on a vegetarian, vegan or omnivore diet were enrolled in the study. All participants had normal body weight (BMI≥18.5<24.9kg/m2). There were statistically significant differences in the serum leptin concentrations of the studied women. Both in the group of vegetarians and vegans circulating leptin was significantly lower (p<0.001) than in the group of omnivores, with the lack of differences in neither BMI nor in body fat content. This suggests that leptin levels are affected not only by the amount of stored fat, but also by the consumed food. This observation indicates the health-promoting properties of plant diets, by influencing circulating leptin.

PMID:36269890 | DOI:10.18388/abp.2020_6388

Tex Heart Inst J. 2022 Sep 1;49(5):e217650. doi: 10.14503/THIJ-21-7650.

ABSTRACT

BACKGROUND: Vascular complications (VCs) after transfemoral transcatheter aortic valve implantation (TAVI) have an increased mortality risk, and vascular closure device (VCD) use is mandatory. The percutaneous MANTA VCD (Teleflex) is a novel collagen-based technology for closure of large-bore arteriotomies. We compared the MANTA VCD with the suture-based ProGlide VCD (Abbott Vascular).

METHODS: A retrospective review was performed on all consecutive patients who underwent transfemoral TAVI in our center from January 1, 2015, to February 28, 2021, and 30-day outcomes were recorded. Major adverse cardiovascular events (MACE) were cardiac death, disabling stroke, and/or major VCs. Access site-related VCs were VCs related to the access site vessel from which the transcatheter valve was introduced and advanced.

RESULTS: The MANTA VCD was used in 99 patients and the ProGlide in 224. There was 4.0% MACE in the MANTA group and 4.9% in the ProGlide group (P = .999). Overall VCs were 10.1% vs 7.6%, major VCs were 3.0% vs 2.2%, and minor VCs 7.1% vs 5.4%(P = .753). Access site-related VCs were 5.1% vs 5.8% in the (P = .999), and periprocedural vascular surgical intervention was needed in 6.1% of the MANTA group vs 2.2% of the ProGlide group (P = .099).

CONCLUSION: There was no significant difference in MACE, mortality, cardiovascular mortality, VCs, access site-related VCs, periprocedural vascular surgical interventions, bleeding, or transfusion rate between the 2 groups. The MANTA VCD group had more periprocedural vascular surgical interventions which did not reach statistical significance.

PMID:36269884 | DOI:10.14503/THIJ-21-7650

Blood Adv. 2022 Oct 21:bloodadvances.2022007791. doi: 10.1182/bloodadvances.2022007791. Online ahead of print.

ABSTRACT

Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to inferior outcomes in children with ALL. However, similar correlation in adults is lacking. Here, we studied the prevalence and risk factors associated with pegylated (PEG)-asparaginase discontinuation in young adults with ALL treated on the US intergroup CALGB 10403 study and examined the prognostic impact of early discontinuation (ED) (defined as <4 of 5 or 6 planned doses) on survival outcomes. The analysis included 176 patients who achieved complete remission and initiated the delayed intensification (DI) cycle. The median number of PEG-asparaginase doses administered before DI was 5 (range: 1-6), with 57 (32%) patients with early discontinuation. The ED patients were older (median=26 vs. 23 years; P=0.023). Survival was apparently lower for ED patients compared with those receiving =/> 4 doses, but this finding was not statistically significant (HR=1.82; 95%CI: 0.97-3.43, P=0.06), with corresponding 5-year OS rates of 66% and 80%, respectively. In patients with standard-risk ALL, the early discontinuation of PEG-asparaginase adversely influenced OS (HR=2.3; 95%CI: 1.02-5.22, P=0.04) with a trend toward inferior EFS (HR=1.84; 95%CI: 0.92-3.67, P=0.08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P=0.64) or EFS (P=0.32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high WBC at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.

PMID:36269846 | DOI:10.1182/bloodadvances.2022007791

PLoS One. 2022 Oct 21;17(10):e0276489. doi: 10.1371/journal.pone.0276489. eCollection 2022.

ABSTRACT

The amplitude and frequency of the mechanical bearing fault vibration signals vary with time, and which are non-stationary and non-Gaussian process. The fault signals belong to α stable distribution, and the characteristic index 1 < α < 2, even the noises are α stable distribution in extreme cases. The existing linear chirplet transform (LCT) degenerates, even fails under α stable distribution environment. A fractional low order linear chirplet transform (FLOLCT) which takes advantage of fractional p order moment is presented for α stable distribution noise environment, and the corresponding FLOLCT time-frequency representation (FLOLCTTFR) is developed in this paper. By employing a series of polynomial chirp rate parameters instead of a single chirp rate of the FLOLCT method, a fractional low order polynomial linear chirplet transform (FLOPLCT) is developed to improve time frequency concentration of the signals. The improved FLOLCT and FLOPLCT methods are used to compare with the existing LCT and PLCT methods based on second order statistics, the results reveal performance advantages of the proposed methods. Finally, the FLOLCT and FLOPLCT methods are applied to analyze the fault signature of the bearing ball fault data in the position of DE (Drive end accelerometer) and extract their fault signature, the result illustrates their performances.

PMID:36269776 | DOI:10.1371/journal.pone.0276489

PLoS Biol. 2022 Oct 21;20(10):e3001803. doi: 10.1371/journal.pbio.3001803. Online ahead of print.

ABSTRACT

Brain asymmetry in the sensitivity to spectrotemporal modulation is an established functional feature that underlies the perception of speech and music. The left auditory cortex (ACx) is believed to specialize in processing fast temporal components of speech sounds, and the right ACx slower components. However, the circuit features and neural computations behind these lateralized spectrotemporal processes are poorly understood. To answer these mechanistic questions, we use mice, an animal model that captures some relevant features of human communication systems. In this study, we screened for circuit features that could subserve temporal integration differences between the left and right ACx. We mapped excitatory input to principal neurons in all cortical layers and found significantly stronger recurrent connections in the superficial layers of the right ACx compared to the left. We hypothesized that the underlying recurrent neural dynamics would exhibit differential characteristic timescales corresponding to their hemispheric specialization. To investigate, we recorded spike trains from awake mice and estimated the network time constants using a statistical method to combine evidence from multiple weak signal-to-noise ratio neurons. We found longer temporal integration windows in the superficial layers of the right ACx compared to the left as predicted by stronger recurrent excitation. Our study shows substantial evidence linking stronger recurrent synaptic connections to longer network timescales. These findings support speech processing theories that purport asymmetry in temporal integration is a crucial feature of lateralization in auditory processing.

PMID:36269764 | DOI:10.1371/journal.pbio.3001803

PLoS One. 2022 Oct 21;17(10):e0276497. doi: 10.1371/journal.pone.0276497. eCollection 2022.

ABSTRACT

Skin rash is a well-known predictive marker of the response to cetuximab (Cmab) in metastatic colorectal cancer (mCRC). However, the mechanism of skin rash development is not well understood. Following exposure to EGFR-targeted therapies, changes in IL-8 levels have been reported. The aim of this study was to evaluate the association between skin rash and inflammatory cytokine levels, including IL-8. Between 2014 and 2017, we prospectively enrolled 38 mCRC patients who underwent chemotherapy with either Cmab or bevacizumab (Bmab) at two hospitals. We performed multiplex cytokine ELISA with 20 inflammatory cytokines including E-selectin, GM-CSF, IFN-alpha, IFN-γ, IL-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IP-10, MCP-1, MIP-1 alpha, MIP-1 beta, P-selectin, sICAM-1, and TNF-alpha at baseline before cycle 1, 24 h after cycle 1, before cycle 2 (= 14 d), and before cycle 3 (= 28 d). Cytokine levels were compared using ANOVA after log-transformation. IL-8 genotypes in 30 patients treated with Cmab were determined using the polymerase chain reaction restriction fragment length polymorphism technique. Depending on the RAS mutational status, 30 and eight patients were treated with Cmab and Bmab-based chemotherapy, respectively. Skin rash developed in 23 (76.6%) of the 30 patients treated with Cmab plus FOLFIRI, after cycle 1. Only the mean log-transformed serum IL-8 level in patients with skin toxicity was statistically lower (2.83 ± 0.15) than in patients who did not experience skin toxicity (3.65 ± 0.27) and received Bmab (3.10 ± 0.26) (ANOVA test, p value = 0.0341). In addition, IL-8 polymorphism did not affect IL-8 levels, skin toxicity, or tumor response in Cmab treated patients. This study suggests that the inflammatory cytokine levels might be affected by Cmab exposure and are associated with the development of skin rash in mCRC patients. Further studies are warranted to evaluate this interaction in Cmab treated patients.

PMID:36269747 | DOI:10.1371/journal.pone.0276497

PLoS One. 2022 Oct 21;17(10):e0276401. doi: 10.1371/journal.pone.0276401. eCollection 2022.

ABSTRACT

In bottom-up proteomics, proteins are enzymatically digested into peptides before measurement with mass spectrometry. The relationship between proteins and their corresponding peptides can be represented by bipartite graphs. We conduct a comprehensive analysis of bipartite graphs using quantified peptides from measured data sets as well as theoretical peptides from an in silico digestion of the corresponding complete taxonomic protein sequence databases. The aim of this study is to characterize and structure the different types of graphs that occur and to compare them between data sets. We observed a large influence of the accepted minimum peptide length during in silico digestion. When changing from theoretical peptides to measured ones, the graph structures are subject to two opposite effects. On the one hand, the graphs based on measured peptides are on average smaller and less complex compared to graphs using theoretical peptides. On the other hand, the proportion of protein nodes without unique peptides, which are a complicated case for protein inference and quantification, is considerably larger for measured data. Additionally, the proportion of graphs containing at least one protein node without unique peptides rises when going from database to quantitative level. The fraction of shared peptides and proteins without unique peptides as well as the complexity and size of the graphs highly depends on the data set and organism. Large differences between the structures of bipartite peptide-protein graphs have been observed between database and quantitative level as well as between analyzed species. In the analyzed measured data sets, the proportion of protein nodes without unique peptides ranged from 6.4% to 55.0%. This highlights the need for novel methods that can quantify proteins without unique peptides. The knowledge about the structure of the bipartite peptide-protein graphs gained in this study will be useful for the development of such algorithms.

PMID:36269744 | DOI:10.1371/journal.pone.0276401