Nevin Manimala

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

PLoS One. 2022 Oct 21;17(10):e0276638. doi: 10.1371/journal.pone.0276638. eCollection 2022.

ABSTRACT

Gastrointestinal disease (GI) is the most common illness in pre-weaned dairy calves. Therefore, effective strategies to manipulate the microbiome of dairy calves under commercial dairy operations are of great importance to improve animal health and reduce antimicrobial usage. The objective of this study was to develop a farm-specific FMT product and to investigate its effects on clinical outcomes and fecal microbial composition of dairy calves. The FMT product was derived from feces from healthy donors (5-24 days of age) raised in the same calf ranch facility as the FMT recipients. Healthy and diarrheic calves were randomly enrolled to a control (n = 115) or FMT (n = 112) treatment group (~36 g of processed fecal matter once daily for 3 days). Fecal samples were collected at enrollment and again 9 days later after the first FMT dose. Although the FMT product was rich in organisms typically known for their beneficial probiotic properties, the FMT therapy did not prevent or ameliorate GI disease in dairy calves. In fact, calves that received FMT were less likely to recover from GI disease, and more likely to die due to GI disease complications. Fecal microbial community analysis revealed an increase in the alpha-diversity in FMT calves; however, no major differences across treatment groups were observed in the beta-diversity analysis. Calves that received FMT had higher relative abundance of an uncultured organism of the genus Lactobacillus and Lactobacillus reuteri on day 10. Moreover, FMT calves had lower relative abundance of Clostridium nexile and Bacteroides vulgatus on day 10. Our results indicate the need to have an established protocol when developing FMT products, based on rigorous inclusion and exclusion criteria for the selection of FMT donors free of potential pathogens, no history of disease or antibiotic treatment.

PMID:36269743 | DOI:10.1371/journal.pone.0276638

PLoS One. 2022 Oct 21;17(10):e0276375. doi: 10.1371/journal.pone.0276375. eCollection 2022.

ABSTRACT

We investigated the associations between periodontal inflammation (gingivitis and periodontitis) and all-kind malignancies, specifically breast and prostate cancer, in a cohort followed-up for 30 years. The study hypothesis was based on the oral inflammation vs. systemic health paradigm. A sample of 2,168 subjects from an original cohort of 105,718 individuals from the greater Stockholm area in Sweden that had been followed since 1985 was investigated. Swedish national health registers were used in the study. Chi-square tests and logistic multiple regression analyses were conducted. The results showed that periodontitis was significantly associated with any cancer after adjusting for gender, age, income, and education (p = 0.015). The probability of getting cancer increased on average by 38% if the patient had periodontitis vs. had not; the odds ratio was 1.380 (95% confidence interval l.066-1.786). No significant association was observed between periodontitis and breast cancer (p = 0.608), while the association between periodontitis and prostate cancer tended towards significance (p = 0.082). However, no statistically significant difference was found between the observed and the calculated distribution of any cancer in gingivitis groups (p = 0.079). Thus, the study hypothesis was partly confirmed by showing a statistically significant association between periodontitis and any cancer.

PMID:36269741 | DOI:10.1371/journal.pone.0276375

PLoS One. 2022 Oct 21;17(10):e0276181. doi: 10.1371/journal.pone.0276181. eCollection 2022.

ABSTRACT

Since the spread of COVID-19 pandemic in early 2020, modeling the related factors became mandatory, requiring new families of statistical distributions to be formulated. In the present paper we are interested in modeling the vaccination rate in some African countries. The recorded data in these countries show less vaccination rate, which will affect the spread of new active cases and will increase the mortality rate. A new extension of the inverted Nadarajah-Haghighi distribution is considered, which has four parameters and is obtained by combining the inverted Nadarajah-Haghighi distribution and the odd Lomax-G family. The proposed distribution is called the odd Lomax inverted Nadarajah-Haghighi (OLINH) distribution. This distribution owns many virtuous characteristics and attractive statistical properties, such as, the simple linear representation of density function, the flexibility of the hazard rate curve and the odd ratio of failure, in addition to other properties related to quantile, the rth-moment, moment generating function, Rényi entropy, and the function of ordered statistics. In this paper we address the problem of parameter estimation from frequentest and Bayesian approach, accordingly a comparison between the performance of the two estimation methods is implemented using simulation analysis and some numerical techniques. Finally different goodness of fit measures are used for modeling the COVID-19 vaccination rate, which proves the suitability of the OLINH distribution over other competitive distributions.

PMID:36269740 | DOI:10.1371/journal.pone.0276181

PLoS One. 2022 Oct 21;17(10):e0276438. doi: 10.1371/journal.pone.0276438. eCollection 2022.

ABSTRACT

BACKGROUND: Human Papillomaviruses (HPV) are highly prevalent in the sexually active populations, with a significant burden in terms of health and psychological cost in all class ages. High-risk (HR) HPV genotypes are associated with anogenital dysplasia and cancers, and anal HPV-induced cancer is increasingly observed in women. The interactions of HPV genotype’s between the anus and the cervix, and the subsequent occurrence of dysplasia remains unclear. This clinical study set out to test the hypothesis that risk factors for anal HR-HPV and dysplasia may differ in women with or without cervical dysplasia or in HIV-positive women.

METHODS: Cervical and anal HPV genotypes and cytology testing will be performed prospectively in a cohort of women recruited in a tertiary university hospital in Switzerland. Women will be allocated to three groups: 1) normal previous cervical smear; 2) high-grade cervical dysplasia (H-SIL) at previous cervical smear; 3) HIV+, independently of previous cervical smear result. General inclusion criteria comprised the followings: Female-Age > = 18 years; Satisfactory understanding of French; No objection to HIV testing. Specific inclusion criteria are: Group 1, no past or current gynecological dysplasia and HIV negative; Group 2, Gynecological dysplasia (H-SIL) or carcinoma in situ demonstrated by histology (vulvar, vaginal or cervical) and HIV negative; Group 3: HIV-positive (regardless of viremia or CD4 count) with or without gynecological dysplasia. General exclusion criteria are: Pregnancy; History of anal dysplasia/cancer; Status after pelvic radiotherapy; Absence of anus and anal canal. Estimated prevalences of anal dysplasia are: in group 1, 1% (0-2%); in group 2, 15% (5-27%), and in group 3, 30% (19-45%). With a 10% margin error, a sample size of 120 women per group is required to reach 90% power for detecting statistical significance (unilateral α error of 5%).

DISCUSSION: The primary endpoint is the prevalence of anal and cervical dysplasia, and description of the respective HPV genotypes in each group. The results of this study could improve the standard of screening of cervical and anal dysplasia in women through evidence of concomitant presence of HPV’s and/or dysplasia in anus or cervix to support vaccination for instance. Beginning of recruitment started in September 2016. Results should be presented in end of 2022. Preliminary analysis for first 100 patients reveals that the mean age of the population is 39.6 (± 10.9) years with mean age of first sexual intercourse of 18.5 (± 3.9) years. In this cohort, 12% are vaccinated and 38% having had anal intercourse. Overall, 43% of the studied population had cervical HR-HPV in the studied population, and 53% had normal cytology. Anal LR HPV and HR HP were found in 27.6% and 38.4% of all patients respectively. Eighty percent had normal anal cytology. Groups 1,2 and 3 had a significant difference in terms of age, gestity, parity, age of first sexual intercourse, systematic use of condom, number of cervical LR HPV and HR HPV and abnormal cervical cytologies.

TRIAL REGISTRATION: The study was approved by the institutional review board-CER-VD#2015-00200-on the 29th of June 2016 and is registered on the Swiss National Clinical Trials Portal (SNCTP), SNCTP000002567, Registered 29 June 2016, https://www.kofam.ch/en/snctp-portal/study/40742/.

PMID:36269726 | DOI:10.1371/journal.pone.0276438