Nevin Manimala

J Clin Endocrinol Metab. 2022 Apr 16:dgac232. doi: 10.1210/clinem/dgac232. Online ahead of print.

ABSTRACT

CONTEXT: Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in bone density, microstructure and strength.

OBJECTIVE: To define effects of treatment with teriparatide followed by denosumab on Lumbar Spine (LS) volumetric BMD (vBMD) and stiffness by finite element analysis assessed on central QCT (cQCT) scans.

DESIGN, SETTINGS AND PARTICIPANTS: Ancillary analysis of baseline, post-teriparatide and post-denosumab cQCT scans from a randomized trial of 41 women allocated to teriparatide (20 mcg daily; N=28) or placebo (N=11). After 6 months (M), those on teriparatide continued for 18M and those on placebo switched to teriparatide for 24M. After completing teriparatide, 33 enrolled in a phase 2B extension with denosumab (60mg q6M) for 12M.

MAIN OUTCOME MEASURES: Primary outcomes were percent change from baseline in LS trabecular vBMD and stiffness after teriparatide, and between end of teriparatide and completing denosumab. Percent change from baseline in LS trabecular vBMD and stiffness after sequential teriparatide and denosumab were secondary outcomes.

FINDINGS: There were large increases (all p<0.001) in trabecular vBMD (25%), other vBMD parameters, and stiffness (21%) after teriparatide. Statistically significant increases in trabecular vBMD (10%; p<0.001) and other vBMD parameters (p=0.03-0.001) were seen after denosumab, while stiffness increased by 7% (p=0.068). Sequential teriparatide and denosumab led to highly significant (all p<0.001) increases LS trabecular vBMD (43%), other vBMD parameters (15-31%) and stiffness (21%).

CONCLUSIONS: The large and statistically significant increases in volumetric density and stiffness after sequential treatment with teriparatide followed by denosumab are encouraging and support use of this regimen in PreMenIOP.

PMID:35428889 | DOI:10.1210/clinem/dgac232

J Clin Endocrinol Metab. 2022 Apr 16:dgac231. doi: 10.1210/clinem/dgac231. Online ahead of print.

ABSTRACT

CONTEXT: It is still debated whether prolonged use of proton pump inhibitors (PPIs) might affect metabolic health.

OBJECTIVE: To investigate the relationship between prolonged use of PPIs and the risk of developing diabetes.

METHODS: We performed a case-control study nested into a cohort of 777,420 patients newly treated with PPIs between 2010 and 2015 in Lombardy, Italy. A total of 50,535 cases diagnosed with diabetes until 2020 were matched with an equal number of controls that were randomly selected from the cohort members according to age, sex, and clinical status. Exposure to treatment with PPIs was assessed in case-control pairs based on time of therapy. A conditional logistic regression model was fitted to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the exposure-outcome association, after adjusting for several covariates. Sensitivity analyses were performed to evaluate the robustness of our findings.

RESULTS: Compared to patients who used PPIs for <8 weeks, higher odds of diabetes of 19% (95% CI, 15-24%), 43% (38-49%), and 56% (49-64%) were observed among those who used PPIs for between 8 weeks and 6 months, 6 months and 2 years, and >2 years, respectively. The results were consistent when analyses were stratified according to age, sex and clinical profile, with higher ORs being found in younger patients and those with worse clinical complexity. Sensitivity analyses revealed that the association was consistent and robust.

CONCLUSIONS: Regular and prolonged use of PPIs is associated with a higher risk of diabetes. Physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use.

PMID:35428888 | DOI:10.1210/clinem/dgac231

Sci Rep. 2022 Apr 15;12(1):6334. doi: 10.1038/s41598-022-10140-z.

ABSTRACT

In recent years, deep learning techniques have shown impressive performance in the field of identification of diseases of crops using digital images. In this work, a deep learning approach for identification of in-field diseased images of maize crop has been proposed. The images were captured from experimental fields of ICAR-IIMR, Ludhiana, India, targeted to three important diseases viz. Maydis Leaf Blight, Turcicum Leaf Blight and Banded Leaf and Sheath Blight in a non-destructive manner with varied backgrounds using digital cameras and smartphones. In order to solve the problem of class imbalance, artificial images were generated by rotation enhancement and brightness enhancement methods. In this study, three different architectures based on the framework of ‘Inception-v3’ network were trained with the collected diseased images of maize using baseline training approach. The best-performed model achieved an overall classification accuracy of 95.99% with average recall of 95.96% on the separate test dataset. Furthermore, we compared the performance of the best-performing model with some pre-trained state-of-the-art models and presented the comparative results in this manuscript. The results reported that best-performing model performed quite better than the pre-trained models. This demonstrates the applicability of baseline training approach of the proposed model for better feature extraction and learning. Overall performance analysis suggested that the best-performed model is efficient in recognizing diseases of maize from in-field images even with varied backgrounds.

PMID:35428845 | DOI:10.1038/s41598-022-10140-z

Sci Rep. 2022 Apr 15;12(1):6352. doi: 10.1038/s41598-022-09949-5.

ABSTRACT

Disease-free survival (DFS) comprises both breast cancer and non-breast cancer events. DFS has not been validated as a surrogate endpoint for overall survival (OS) in most breast cancer subtypes. We assessed changes to the type of events contributing to DFS over time. We identified adjuvant studies in breast cancer (BC) from 2000 to 2020 where the endpoint was DFS. We examined change in distant DFS events and the BC-related DFS using univariable and multivariable linear regression. Data were reported quantitatively using the Burnand criteria irrespective of statistical significance. We included 84 studies (88 cohorts), comprising 212,191 participants, 41,604 DFS events and 23,205 distant DFS events. The DFS event rate/100 participants/year has declined modestly over time (ß – 0.34, p = 0.001). Start year was negatively associated with distant DFS events (ß – 0.58, p < 0.0001); however, the effect was lost after adjusting for follow-up time (ß – 0.18, p = 0.096). The average number of BC-related events/100 participants/year also declined over time (ß – 0.28, p = 0.009). In multivariable analysis, start year and ER expression were quantitatively associated with distant DFS events and BC-related DFS events. DFS events have declined over time driven by a reduction in BC related events. As DFS events are increasingly defined by non-BC events, there will be limited surrogacy between DFS and OS.

PMID:35428842 | DOI:10.1038/s41598-022-09949-5

Sci Rep. 2022 Apr 15;12(1):6347. doi: 10.1038/s41598-022-09801-w.

ABSTRACT

This study presents findings in the terahertz (THz) frequency spectrum for non-contact cardiac sensing applications. Cardiac pulse information is simultaneously extracted using THz waves based on the established principles in electronics and optics. The first fundamental principle is micro-Doppler motion effect. This motion based method, primarily using coherent phase information from the radar receiver, has been widely exploited in microwave frequency bands and has recently found popularity in millimeter waves (mmWave) for breathe rate and heart rate detection. The second fundamental principle is reflectance based optical measurement using infrared or visible light. The variation in the light reflection is proportional to the volumetric change of the heart, often referred as photoplethysmography (PPG). Herein, we introduce the concept of terahertz-wave-plethysmography (TPG), which detects blood volume changes in the upper dermis tissue layer by measuring the reflectance of THz waves, similar to the existing remote PPG (rPPG) principle. The TPG principle is justified by scientific deduction, electromagnetic wave simulations and carefully designed experimental demonstrations. Additionally, pulse measurements from various peripheral body parts of interest (BOI), palm, inner elbow, temple, fingertip and forehead, are demonstrated using a wideband THz sensing system developed by the Terahertz Electronics Lab at Arizona State University, Tempe. Among the BOIs under test, it is found that the measurements from forehead BOI gives the best accuracy with mean heart rate (HR) estimation error 1.51 beats per minute (BPM) and standard deviation 1.08 BPM. The results validate the feasibility of TPG for direct pulse monitoring. A comparative study on pulse sensitivity is conducted between TPG and rPPG. The results indicate that the TPG contains more pulsatile information from the forehead BOI than that in the rPPG signals in regular office lighting condition and thus generate better heart rate estimation statistic in the form of empirical cumulative distribution function of HR estimation error. Last but not least, TPG penetrability test for covered skin is demonstrated using two types of garment materials commonly used in daily life.

PMID:35428772 | DOI:10.1038/s41598-022-09801-w

Sci Rep. 2022 Apr 15;12(1):6262. doi: 10.1038/s41598-022-10346-1.

ABSTRACT

An accurate prediction of major adverse events after percutaneous coronary intervention (PCI) improves clinical decisions and specific interventions. To determine whether machine learning (ML) techniques predict peri-PCI adverse events [acute kidney injury (AKI), bleeding, and in-hospital mortality] with better discrimination or calibration than the National Cardiovascular Data Registry (NCDR-CathPCI) risk scores, we developed logistic regression and gradient descent boosting (XGBoost) models for each outcome using data from a prospective, all-comer, multicenter registry that enrolled consecutive coronary artery disease patients undergoing PCI in Japan between 2008 and 2020. The NCDR-CathPCI risk scores demonstrated good discrimination for each outcome (C-statistics of 0.82, 0.76, and 0.95 for AKI, bleeding, and in-hospital mortality) with considerable calibration. Compared with the NCDR-CathPCI risk scores, the XGBoost models modestly improved discrimination for AKI and bleeding (C-statistics of 0.84 in AKI, and 0.79 in bleeding) but not for in-hospital mortality (C-statistics of 0.96). The calibration plot demonstrated that the XGBoost model overestimated the risk for in-hospital mortality in low-risk patients. All of the original NCDR-CathPCI risk scores for adverse periprocedural events showed adequate discrimination and calibration within our cohort. When using the ML-based technique, however, the improvement in the overall risk prediction was minimal.

PMID:35428765 | DOI:10.1038/s41598-022-10346-1

Sci Rep. 2022 Apr 15;12(1):6298. doi: 10.1038/s41598-022-10245-5.

ABSTRACT

The static and fatigue tensile properties of high-strength polyacrylonitrile (PAN)-based carbon (IMS60) and electronic (E)-class glass (E-glass) hybrid fiber-reinforced epoxy matrix composites (HFRPs) were investigated. The fiber orientations of the HFRP specimens were set to unidirectional with [(0_(IMS60))/(0_(E-glass))]_S (subscript S means symmetry and [(0_(IMS60))/(0_(E-glass))/(0_(E-glass))/(0_(IMS60))]), [(0_(E-glass))/(0_(IMS60))]_S, [(0_(E-glass))/(0_(IMS60))₂]_S, [(0_(E-glass))/(0_(IMS60))₃]_S, [(0_(E-glass))/(0_(IMS60))₅]_S, [(0_(E-glass))₂/(0_(IMS60))]_S, [(0_(E-glass))₃/(0_(IMS60))]_S, and [(0_(E-glass))₅/(0_(IMS60))]_S. Under static loading for the [(0_(IMS60))/(0_(E-glass))]_S, [(0_(E-glass))/(0_(IMS60))]_S, [(0_(E-glass))/(0_(IMS60))₂]_S, [(0_(E-glass))/(0_(IMS60))₃]_S, and [(0_(E-glass))/(0_(IMS60))₅]_S HFRP specimens, the stress applied to the specimen was almost linearly proportional to the strain until failure. However, the tensile stress-strain curves of the [(0_(E-glass))₂/(0_(IMS60))]_S, [(0_(E-glass))₃/(0_(IMS60))]_S, and [(0_(E-glass))₅/(0_(IMS60))]_S HFRP specimens had a complicated shape (jagged trace). The Weibull statistical distributions of the tensile strength values were also examined. The Weibull moduli for the [(0_(E-glass))/(0_(IMS60))]_S, [(0_(E-glass))/(0_(IMS60))₂]_S, [(0_(E-glass))/(0_(IMS60))₃]_S, [(0_(E-glass))/(0_(IMS60))₅]_S, [(0_(E-glass))₂/(0_(IMS60))]_S, [(0_(E-glass))₃/(0_(IMS60))]_S, and [(0_(E-glass))₅/(0_(IMS60))]_S HFRP specimens were higher than those for the mono carbon fiber-reinforced epoxy (CFRP) and glass fiber-reinforced epoxy (GFRP) specimens. Under fatigue loading, the fatigue properties of the HFRP specimens showed CFRP-dominant behaviour at high stress levels and GFRP-dominant behaviour at low stress levels. The fatigue properties of the HFRP specimens increased with increasing volume fraction of CFRP in the following order: ([(0_(E-glass))/(0_(IMS60))₅]_S > [(0_(E-glass))/(0_(IMS60))₃]_S > [(0_(E-glass))/(0_(IMS60))₂]_S > [(0_(IMS60))/(0_(E-glass))]_S > [(0_(E-glass))/(0_(IMS60))]_S > [(0_(E-glass))₂/(0_(IMS60))]_S > [(0_(E-glass))₃/(0_(IMS60))]_S > [(0_(E-glass))₅/(0_(IMS60))]_S).

PMID:35428749 | DOI:10.1038/s41598-022-10245-5

Postgrad Med J. 2022 Apr 15:postgradmedj-2022-141642. doi: 10.1136/postgradmedj-2022-141642. Online ahead of print.

ABSTRACT

BACKGROUND: Various complications have been reported in patients with COVID-19 including pneumomediastinum.

METHODS: The primary objective of the study was to determine the incidence of pneumomediastinum in COVID-19 positive patients who underwent CT pulmonary angiography (CTPA). The secondary objectives were to analyse if the incidence of pneumomediastinum changed between March and May 2020 (peak of the first wave in the UK) and January 2021 (peak of the second wave in the UK) and to determine the mortality rate in patients with pneumomediastinum. We undertook an observational, retrospective, single-centre, cohort study of patients with COVID-19 admitted to Northwick Park Hospital.

RESULTS: 74 patients in the first wave and 220 patients in the second wave met the study criteria. Two patients during the first wave and eleven patients during the second wave developed pneumomediastinum.

CONCLUSIONS: The incidence of pneumomediastinum changed from 2.7% during the first wave to 5% during the second wave and this change was not statistically significant (p value 0.4057). The difference in mortality rates of patients with pneumomediastinum in both waves of COVID-19 (69.23%) versus patients without pneumomediastinum in both waves of COVID-19 (25.62%) was statistically significant (p value 0.0005). Many patients with pneumomediastinum were ventilated, which could be a confounding factor. When controlling for ventilation, there was no statistically significant difference in the mortality rates of ventilated patients with pneumomediastinum (81.81%) versus ventilated patients without pneumomediastinum (59.30%) (p value 0.14).

PMID:35428734 | DOI:10.1136/postgradmedj-2022-141642

Neurology. 2022 Apr 15:10.1212/WNL.0000000000200349. doi: 10.1212/WNL.0000000000200349. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Individuals with cerebellar ataxia (CA) can develop impulsive behavioral symptoms, often resulting in negative interpersonal consequences, detrimentally impacting their quality of life. Limited evidence exists concerning impulsivity in CA and its associated behavioral changes. We assessed impulsive traits in CA using the Barratt impulsivity scale (BIS-11) and compared them with those of Parkinson disease (PD), in order to investigate the differences in the impulsive trait profiles between CA and PD.

METHODS: We conducted a dual-center cross-sectional study with CA and PD subjects enrolled through consecutive sampling from movement disorders clinics at Columbia University Medical Center and Vanderbilt University Medical Center, respectively. Age-matched controls were recruited at the respective institutions. Participants were excluded if they had prior or comorbid neurological and psychiatric diseases known to be associated with impulsivity. All subjects completed the BIS-11 questionnaire as a measure of impulsive traits. We used a general linear model and a least absolute shrinkage and selection operation regression to compare the total, subscale, and individual items of the BIS-11 scores between groups. Subgroup analyses were performed to isolate cerebellar contributions to impulsivity from potential effects of extracerebellar pathology and dopaminergic dysfunction or medications.

RESULTS: A total of 190 participants: 90 age-matched controls, 50 CA, and 50 PD participants completed the assessments. Persons with CA reported 9.7% greater BIS-11 scores than controls (p < 0.001), while persons with PD participants reported 24.9% higher than controls (p < 0.001). In CA, the most impacted domain of impulsivity was non-planning. In contrast, persons with PD noted greater impulsivity across the non-planning, attentional, and motor domains.

DISCUSSION: Impulsivity in CA is uniquely driven by the non-planning trait, unlike in PD. This suggests that the cerebellum and basal ganglia may differentially govern impulsive behaviors with the cerebellum contributing to the brain circuitry of impulsivity in a domain-specific manner.

PMID:35428731 | DOI:10.1212/WNL.0000000000200349

Horm Mol Biol Clin Investig. 2022 Apr 15. doi: 10.1515/hmbci-2021-0090. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to evaluate the levels of serum lipoprotein a, LP (a), in Jordanian patients with type 2 diabetes mellitus (DM); and to examine its relation to glycemic control, metabolic syndrome (MS) and duration of DM. The LP (a) is considered one of the independent risk factors for coronary artery disease (CAD) in the general population.

METHODS: Fasting blood samples were drawn from 51 diabetic patients with type 2 DM and 31 non-diabetic age and sex control subjects. Serum LP (a) was measured along with other parameters, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and glycosylated haemoglobin (HbA_1c). Correlation analyses were performed between LP (a) and the various variables measured.

RESULTS: LP (a) measurement showed a skewed distribution towards the lower levels in both groups. Mean LP (a) levels showed a statistically insignificant difference between the two groups. No correlations of LP (a) were observed with age, sex or body mass index (BMI). No correlations of LP (a) with LDL-c, HDL-c, TG, TC, MS, DM duration or HbA_1c were observed. The LP (a) serum levels were significantly higher in type 2 diabetic patients with retinopathy.

CONCLUSIONS: LP (a) serum levels are not increased in type 2 diabetic patients; so, LP (a) may not be a reliable marker for early therapeutic interventions in DM patients, even in high-risk for thrombosis groups.

PMID:35427448 | DOI:10.1515/hmbci-2021-0090