Nevin Manimala

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Mar 22;256:119731. doi: 10.1016/j.saa.2021.119731. Online ahead of print.

ABSTRACT

Diabetes has become a major public health problem worldwide, and the incidence of diabetes has been increasing progressively. Diabetes is prone to cause various complications, among which diabetic keratopathy (DK) emphasizes the significant impact on the cornea. The current diagnosis of DK lacks biochemical markers that can be used for early and non-invasive screening and detection. In contrast, in this study, Raman spectroscopy, which demonstrates non-destructive, label-free features, especially the unique advantage of providing molecular fingerprint information for target substances, were utilized to interrogate the intrinsic information of the corneal tissues from normal and diabetic mouse models, respectively. Visually, the Raman spectral response derived from the biochemical components and biochemical differences between the two groups were compared. Moreover, multivariate analysis methods such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were carried out for advanced statistical analysis. PCA yields a diagnostic results of 57.4% sensitivity, 89.2% specificity, 74.8% accuracy between the diabetic group and control group; Moreover, PLS-DA was employed to enhance the diagnostic ability, showing 76.1% sensitivity, 86.1% specificity, and 87.6% accuracy between the diabetic group and control group. Our proof-of-concept results show the potential of Raman spectroscopy-based techniques to help explore the underlying pathogenesis of DK disease and thus be further expanded for potential applications in the early screening of diabetic diseases.

PMID:33819764 | DOI:10.1016/j.saa.2021.119731

Res Vet Sci. 2021 Mar 29;136:464-471. doi: 10.1016/j.rvsc.2021.03.018. Online ahead of print.

ABSTRACT

Diarrhea is the most common cause of mortality and morbidity in dairy calves during the first weeks of life. It is responsible for the majority of costs related to animal death and treatments, as well as lower productivity due to reduced weight gain. Therefore, studies that focus on strategies to reduce diarrhea incidence and to improve animal welfare are very important for the dairy industry. For that reason, the beneficial effects of red propolis on the health status of preweaned dairy calves was studied. Animal disease data usually present incomplete observations of interest time, so-called censored observations and one of the statistical techniques for this modeling type is the survival analysis, hence it is a set of methods for analyzing data where the response variable is the time until the occurrence of an event of interest. We propose among some methods of survival data analysis, the long-term models. The motivation to study these models is the fact that part of the population is not susceptible to the event of interest during the period of the study, considered as immune or cured. In this paper, we studied the Weibull distribution in a structure of long-term model, including the covariates in the proportion of cured through the logistic link function. Besides, we used the residual analysis to check the assumptions of the model. The reason for the choice of the Weibull distribution was that this model is very flexibility to model a variety of data sets, among them animal science and long-term survival data. We illustrate its application with a case study from an animal experiment, which examined the time till the occurrence of diarrhea in Holstein calves, where a proportion of the animals were not susceptible to this health condition. This experiment aimed to verify the efficiency of red propolis in disease prevention and the influence of that on the proportion of animals that are not susceptible to diarrhea.

PMID:33819754 | DOI:10.1016/j.rvsc.2021.03.018

ESMO Open. 2021 Apr 2;6(2):100099. doi: 10.1016/j.esmoop.2021.100099. Online ahead of print.

ABSTRACT

BACKGROUND: The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting.

PATIENTS AND METHODS: We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian ‘real-world’ setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients’ characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant.

RESULTS: Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P = 0.095).

CONCLUSIONS: Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials.

PMID:33819752 | DOI:10.1016/j.esmoop.2021.100099

J Affect Disord. 2021 Mar 19;287:354-358. doi: 10.1016/j.jad.2021.03.039. Online ahead of print.

ABSTRACT

BACKGROUND: Metrics of journal’s impact factor may suggest the journal’s influence in a particular field, but they have been used inadvertently as a measure of the journal and individual publications’ scientific quality.

METHODS: We assessed how scientific journals in the field of psychiatry and mental health are ranked (top 20) according to the scores of distinct metrics (Eigenfactor score, Google Scholar Metrics, Journal Citation Reports, Scimago Journal & Country Rank, and Source Normalized Impact per Paper), described their main characteristics and perfomed a spearman’s correlation analyses to investigate to which extent these metrics are associated. We also discussed the limitations of dealing with these metrics and the rankings they provide as a proxy of the journal’s quality.

RESULTS: Only 5 (12.5%) journals appear in all metrics (JAMA Psychiatry, American Journal of Psychiatry, Molecular Psychiatry, Schizophrenia Bulletin, and the Journal of Child Psychology and Psychiatry), more than one-third of the journals show up in only one and less than half (42.5%) appear in three or more. Only JAMA Psychiatry is in one of the first five positions of all metrics. No journal ranked in the same position across the metrics. On the other hand, we found the correlations between all the metrics were statistically significant.

LIMITATIONS: The metrics included are not exhaustive.

CONCLUSIONS: Although each metric provides a particular ranking, they are highly correlated. Rankings also change according to distinct subject categories in which they are assessed. We suggest less emphasis should be given to Journal Metrics to infer journal’s quality.

PMID:33819734 | DOI:10.1016/j.jad.2021.03.039

Appl Radiat Isot. 2021 Mar 31;173:109705. doi: 10.1016/j.apradiso.2021.109705. Online ahead of print.

ABSTRACT

Stream sediment is a useful raw material used for building construction, mostly used in the desert parts of the world. Such sediment is a Naturally Occurring Radioactive Material (NORM), and, hence, it requires a radiological characterization to be used. This work aims to study the natural radioactivity in fifty points distributed in surface of stream sediments in the area of Gabal El Seila region, south-eastern desert of Egypt, since there is a lack of information about the radioactivity levels of the sediment samples from such recent growing interest area. The activity concentration of ²³⁸U, ²³²Th and ⁴ K natural radionuclides using a portable RS-230 γ-ray spectrometer were determined. Mean values are 38.51 ± 10.83, 33.35 ± 8.82, 659.18 ± 110.87 Bq/kg for ²³⁸U, ²³²Th, ⁴ K respectively. Radiological hazard indexes were computed and compared with the UNSCEAR and other worldwide ranges. All the results are statistically presented and discussed. They show that no significant radiation hazard coming from the studied area, with the most values lower than international recommended limits. The achievements of the present study fall within the measurements of natural environmental radiation in an unexplored area of great interest being a desert. The obtained results can be used as database for future research, and as tool for radiological awareness in the use of sediments as raw material.

PMID:33819729 | DOI:10.1016/j.apradiso.2021.109705

J Biomech. 2021 Mar 20;121:110392. doi: 10.1016/j.jbiomech.2021.110392. Online ahead of print.

ABSTRACT

High body mass index (BMI) and obesity have been implicated as risk factors for lumbar degenerative disc disease and low back pain. Despite this, there is limited in vivo data to quantify how obesity influences the mechanical function of intervertebral discs (IVD) in response to activities of daily living. Recently, our lab has developed methodologies to non-invasively measure in vivo IVD deformation resulting from activities of daily living using magnetic resonance (MR) imaging and solid modeling techniques. This pilot study expands on these methodologies to assess how BMI influences IVD deformation following treadmill walking in eight asymptomatic individuals. Ordinary least squares regression analyses revealed a statistically significant relationship between BMI and compressive deformation (strain (%)) in the L5-S1 IVD (R² = 0.61, p < 0.05). This relationship was weaker in the L3-L4 (R² = 0.28, p > 0.05) and L4-L5 IVDs (R² = 0.28, p > 0.05). Importantly, no relationship between pre-exercise disc height and BMI was identified (p > 0.05). Therefore, the results of this study suggest that BMI may alter the mechanical response of lumbar spine IVDs, particularly at the L5-S1 level. Furthermore, the observed relationship between increased BMI and IVD compressive deformation, in the absence of a detected relationship between pre-exercise disc height and BMI, suggests that changes in IVD mechanical function may be more sensitive to alterations in disc health than static clinical imaging alone. This finding highlights the importance of quantifying disc mechanical function when examining the relationship between BMI and IVD degeneration.

PMID:33819699 | DOI:10.1016/j.jbiomech.2021.110392

J Pediatr Endocrinol Metab. 2021 Apr 6. doi: 10.1515/jpem-2020-0512. Online ahead of print.

ABSTRACT

OBJECTIVES: Given their established role in hepatic function and insulin resistance for adults, early screening of type 2 diabetes mellitus (T2DM) in the pediatric population may potentially be improved by the assessment of elevated liver enzymes.

METHODS: Our study enrolled 151 nondiabetic children aged 10-14 years. Patients were assessed for demographics and five risk factors for T2DM. The levels of γ-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were determined in serum samples. The effects of demographics and risk factors on abnormal liver enzyme levels were assessed with univariate chi-square analyses and also with multivariate logistic regression analyses, which were controlled for gender.

RESULTS: Frequencies for abnormal liver enzyme values were as follows: 13 (9%) for GGT, 5 (3%) for ALT, and 20 (13%) for ALP. Across analyses, two results were consistently statistically significant. Females were more likely to have abnormal ALP levels, and patients with BMI percentile ≥95% and with acanthosis nigricans were more likely to have abnormal GGT levels.

CONCLUSIONS: Our study suggests GGT as potential marker for T2DM discovery in children. Subsequent long-term longitudinal studies would help to more clearly delineate GGT’s association with T2DM. Additionally, future studies that elucidate the molecular contribution of GGT elevation to T2DM pathogenesis are needed.

PMID:33819416 | DOI:10.1515/jpem-2020-0512

WMJ. 2021 Mar;120(S1):S6-S9.

ABSTRACT

IMPORTANCE: Wisconsin has the second-highest Black homicide rate in the country, reporting a rate of 37.57 deaths per 100,000 Black non-Hispanic Wisconsinites. Meanwhile, White non-Hispanics experience a homicide rate of 2.0 deaths per 100,000.

OBJECTIVE: This data identifies a public health disparity that deserves further investigation. This study seeks to detail the mortality rate of all-cause homicide, firearm-related homicide, non-firearm-related homicide, and legal intervention firearm-related homicide; leading causes of death; average age of death; and years of potential life lost (YPLL) between White non-Hispanics and Black non-Hispanics in Wisconsin during 2000-2017.

DESIGN: Wisconsin homicide rates, ranked leading causes of death, and average age of death were obtained through the Wisconsin Department of Health Services via the Wisconsin Interactive Statistics on Health (WISH) Query System. National data were obtained through the Centers for Disease Control and Prevention’s Web-based Injury Statistics Query and Reporting System (WISQARS). Homicide rates, ranked leading causes of death, average age of death, and YPLL were compared by mechanism of injury, county of residence, and race and ethnicity.

PARTICIPANTS AND EXPOSURES: The entire population of Black non-Hispanic Americans and White non-Hispanic Americans during 2000-2017 was included. For comparison, this was narrowed to the population of Black non-Hispanic Wisconsinites and White non-Hispanic Wisconsinites during 2000-2017. Exposure groups include all homicide victims during 2000-2017.

MAIN OUTCOMES AND MEASURES: We hypothesized that Black non-Hispanic Wisconsinites would have a significantly worse burden of disease compared to White non-Hispanic Wisconsinites, as well as Black non-Hispanic Americans.

RESULTS: This study found that firearm-related homicide rates for Black non-Hispanics compared to White non-Hispanics were 14.6 times greater in Milwaukee, 29.9 times greater in Wisconsin, and 13.0 times greater in urban counties of the United States. Firearm-related homicide is the second-leading cause of death for Black non-Hispanics in Milwaukee and the fourth-leading cause of death in Wisconsin. YPLL per person for Black non-Hispanic victims of firearm-related homicide are 36.83 years in Milwaukee and 37.04 years in Wisconsin.

CONCLUSION AND RELEVANCE: Our findings strongly suggest that Black non-Hispanic Wisconsinites endure a significantly worse burden of firearm-related homicide compared to White non-Hispanic Wisconsinites and Black non-Hispanic Americans. This study demonstrates a significant disparity in firearm-related homicide that should inspire policy discussion.

PMID:33819395

Ann Clin Transl Neurol. 2021 Apr 5. doi: 10.1002/acn3.51358. Online ahead of print.

ABSTRACT

OBJECTIVE: Despite the need for diagnostics and research, data on fluid biomarkers in hereditary spastic paraplegia (HSP) are scarce. We, therefore, explore Neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of patients with hereditary spastic paraplegia and provide information on the influence of demographic factors.

METHODS: The study recruited 59 HSP cases (33 genetically confirmed) and 59 controls matched in age and sex. Neurofilament light chain levels were assessed by enzyme-linked immunosorbent assay. The statistical analysis included the effects of age, sex, and genetic status (confirmed vs. not confirmed).

RESULTS: Levels of CSF NfL were significantly increased in patients with hereditary spastic paraplegia compared to controls (median 741 pg/mL vs. 387 pg/mL, p < 0.001). Age (1.4% annual increase) and male sex (81% increase) impacted CSF NfL levels in patients. The age-dependent increase of CSF NfL levels was steeper in controls (2.6% annual increase). Thus, the CSF NfL ratio of patients and matched controls-expressing patients’ fold increases in CSF NfL-declined considerably with age.

INTERPRETATION: CSF NfL is a reliable cross-sectional biomarker in hereditary spastic paraplegia. Sex is a relevant factor to consider, as male patients have remarkably higher CSF NfL levels. While levels also increase with age, the gap between patients and controls is narrowing in older subjects. This indicates distinct temporal dynamics of CSF NfL in patients with hereditary spastic paraplegia, with a rise around phenotypic conversion and comparatively static levels afterward.

PMID:33819388 | DOI:10.1002/acn3.51358

Asia Pac J Clin Oncol. 2021 Apr 5. doi: 10.1111/ajco.13570. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has forced rapid system-wide changes to be implemented within cancer care at an alarming pace. Clinical trials are a key element of comprehensive cancer care. Ensuring the continuing safe conduct of cancer clinical trials in the context of a pandemic is challenging.

METHODS: We aimed to describe the COVID-19 pandemic response of a Cancer Care Clinical Research Unit (CRU) of a tertiary hospital in Queensland, Australia. We used a mixed methods approach for this case study. Emailed directives from CRU managers to all CRU staff sharing were qualitatively analysed and mapped against our unit activities over longitudinal time points. Data from patient recruitment and protocol deviations were analysed using descriptive statistics.

RESULTS: Mapping activity from 11 March to 30 September 2020 revealed rapid change during the first 2 weeks. Four key strategies to accommodate change were identified: supporting patients and families, introduction of telehealth, accessing investigational product, and social distancing. Early in the pandemic we recognised that our core key stakeholders were integral to our response. When compared to the previous 12 months, our recruitment numbers dropped markedly in early phases of the response but recovered over time, as we accommodated internal and external impacts.

CONCLUSION: Our experience of agility as a necessity, adapting to support patients, and managing both clinical research activity and sponsors during the height of the pandemic response is presented here in order to inform future disaster response planning by clinical trial organisations.

PMID:33819387 | DOI:10.1111/ajco.13570