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AnteayerPLOS ONE Medicine&Health

Comparison of methods for texture analysis of QUS parametric images in the characterization of breast lesions

by Laurentius O. Osapoetra, William Chan, William Tran, Michael C. Kolios, Gregory J. Czarnota

Purpose

Accurate and timely diagnosis of breast carcinoma is very crucial because of its high incidence and high morbidity. Screening can improve overall prognosis by detecting the disease early. Biopsy remains as the gold standard for pathological confirmation of malignancy and tumour grading. The development of diagnostic imaging techniques as an alternative for the rapid and accurate characterization of breast masses is necessitated. Quantitative ultrasound (QUS) spectroscopy is a modality well suited for this purpose. This study was carried out to evaluate different texture analysis methods applied on QUS spectral parametric images for the characterization of breast lesions.

Methods

Parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average scatterer diameter (ASD), and average acoustic concentration (AAC) were determined using QUS spectroscopy from 193 patients with breast lesions. Texture methods were used to quantify heterogeneities of the parametric images. Three statistical-based approaches for texture analysis that include Gray Level Co-occurrence Matrix (GLCM), Gray Level Run-length Matrix (GRLM), and Gray Level Size Zone Matrix (GLSZM) methods were evaluated. QUS and texture-parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis in order to classify breast lesions as either benign or malignant. We developed a diagnostic model using different classification algorithms including linear discriminant analysis (LDA), k-nearest neighbours (KNN), support vector machine with radial basis function kernel (SVM-RBF), and an artificial neural network (ANN). Model performance was evaluated using leave-one-out cross-validation (LOOCV) and hold-out validation.

Results

Classifier performances ranged from 73% to 91% in terms of accuracy dependent on tumour margin inclusion and classifier methodology. Utilizing information from tumour core alone, the ANN achieved the best classification performance of 93% sensitivity, 88% specificity, 91% accuracy, 0.95 AUC using QUS parameters and their GLSZM texture features.

Conclusions

A QUS-based framework and texture analysis methods enabled classification of breast lesions with >90% accuracy. The results suggest that optimizing method for extracting discriminative textural features from QUS spectral parametric images can improve classification performance. Evaluation of the proposed technique on a larger cohort of patients with proper validation technique demonstrated the robustness and generalization of the approach.

Intestinal parasitic infections and associated factors among people living with HIV/AIDS in Ethiopia: A systematic review and meta-analysis

by Adam Wondmieneh, Getnet Gedefaw, Birhan Alemnew, Addisu Getie, Melaku Bimerew, Asmamaw Demis

Background

Intestinal parasitic infections are major public health problems throughout the world, particularly in people living with HIV/AIDS. People living with HIV/AIDS are vulnerable groups for a variety of diseases, hence they are easily affected by opportunistic and non-opportunistic intestinal parasites due to the weakening of their immunity. Therefore, this study aimed to estimate the pooled prevalence and factors associated with intestinal parasitic infections among people living with HIV/AIDS in Ethiopia.

Methods

Articles were identified through search engines in the online electronic databases PubMed/MEDLINE, EMBASE, HINARI, CINAHL, Cochrane Library, Google Scholar, and reference lists of previous studies following the PRISMA Protocol. Studies conducted between 2003 and 2020 with English language were included in this study. This review included papers with having high-quality NOS scores. Meta-analysis was computed using STATA version 11 software. Heterogeneity was assessed using the Cochrane Q-test and I2 test statistics. Subgroup and sensitivity analysis was employed with evidence of heterogeneity. Publication bias was determined using the funnel plot and Egger’s regression test statistic.

Results

This study included a total of twenty-two cross-sectional studies with 5,833 study participants. The mean age of the study participants was 35 years old. The pooled prevalence of intestinal parasitic infection among people living with HIV/AIDS in Ethiopia was 39.15% (95%CI: 32.34, 45.95). The pooled prevalence of intestinal parasitic infections among people living with HIV/AIDS who had taking ART and who had not to start ART was found to be 28.27% (95%CI 22.47, 34.06) and 41.63% (95%CI: 28.75, 54.52) respectively. Unavailability of latrine (AOR: 4.87, (95% CI: 2.39, 9.92)), CD4+ T cell count Conclusion

In this study, the overall pooled prevalence of intestinal parasitic infections among HIV/AIDS patients in Ethiopia was relatively high. CD4+ T-cell count

Optimizing direct RT-LAMP to detect transmissible SARS-CoV-2 from primary nasopharyngeal swab samples

by Dawn M. Dudley, Christina M. Newman, Andrea M. Weiler, Mitchell D. Ramuta, Cecilia G. Shortreed, Anna S. Heffron, Molly A. Accola, William M. Rehrauer, Thomas C. Friedrich, David H. O’Connor

SARS-CoV-2 testing is crucial to controlling the spread of this virus, yet shortages of nucleic acid extraction supplies and other key reagents have hindered the response to COVID-19 in the US. Several groups have described loop-mediated isothermal amplification (LAMP) assays for SARS-CoV-2, including testing directly from nasopharyngeal swabs and eliminating the need for reagents in short supply. Frequent surveillance of individuals attending work or school is currently unavailable to most people but will likely be necessary to reduce the ~50% of transmission that occurs when individuals are nonsymptomatic. Here we describe a fluorescence-based RT-LAMP test using direct nasopharyngeal swab samples and show consistent detection in clinically confirmed primary samples with a limit of detection (LOD) of ~625 copies/μl, approximately 100-fold lower sensitivity than qRT-PCR. While less sensitive than extraction-based molecular methods, RT-LAMP without RNA extraction is fast and inexpensive. Here we also demonstrate that adding a lysis buffer directly into the RT-LAMP reaction improves the sensitivity of some samples by approximately 10-fold. Furthermore, purified RNA in this assay achieves a similar LOD to qRT-PCR. These results indicate that high-throughput RT-LAMP testing could augment qRT-PCR in SARS-CoV-2 surveillance programs, especially while the availability of qRT-PCR testing and RNA extraction reagents is constrained.

The role of CPAP as a potential bridge to invasive ventilation and as a ceiling-of-care for patients hospitalized with Covid-19—An observational study

by Jonathan Walker, Shaman Dolly, Liji Ng, Melissa Prior-Ong, Kalpana Sabapathy

Background

Continuous positive airway pressure (CPAP) ventilation may be used as a potential bridge to invasive mechanical ventilation (IMV), or as a ceiling-of-care for persistent hypoxaemia despite standard oxygen therapy, according to UK guidelines. We examined the association of mode of respiratory support and ceiling-of-care on mortality.

Methods

We conducted a retrospective cohort analysis of routinely collected de-identified data of adults with nasal/throat SARs-CoV-2 swab-positive results, at the Calderdale and Huddersfield NHS Foundation Trust between 10th March-19th April 2020 (outcomes determined on 22nd May).

Findings

Of 347 patients with SARs-CoV-2 swab-positive results, 294 (84.7%) patients admitted for Covid-19 were included in the study. Sixty-nine patients were trialled on CPAP, mostly delivered by face mask, either as an early ceiling of care instituted within 24 hours of admission (N = 19), or as a potential bridge to IMV (N = 44). Patients receiving a ceiling of care more than 24 hours after admission (N = 6) were excluded from the analysis. Two hundred and fifteen patients (73.1%) maximally received air/standard oxygen therapy, and 45 (15.3%) patients maximally received CPAP. Thirty-four patients (11.6%) required IMV, of which 24 had received prior CPAP. There were 138 patients with an early ceiling-of-care plan (pre-admission/within 24h). Overall, 103(35.0%) patients died and 191(65.0%) were alive at study end. Among all patients trialled on CPAP either as a potential bridge to IMV (N = 44) or as a ceiling-of-care (N = 19) mortality was 25% and 84%, respectively. Overall, there was strong evidence for higher mortality among patients who required CPAP or IMV, compared to those who required only air/oxygen (aOR 5.24 95%CI: 1.38, 19.81 and aOR 46.47 95%CI: 7.52, 287.08, respectively; p Conclusion

Our data suggest that among patients with no ceiling-of-care, an initial trial of CPAP as a potential bridge to IMV offers a favourable therapeutic alternative to early intubation. In contrast, among patients with a ceiling-of care, CPAP seems to offer little additional survival benefit beyond oxygen therapy alone. Information on ceilings of respiratory support is vital to interpreting mortality from Covid-19.

Strengths and limitations of this study

Prevalence and determinants of the place of delivery among reproductive age women in sub–Saharan Africa

by Kenneth Setorwu Adde, Kwamena Sekyi Dickson, Hubert Amu

Introduction

Maternal mortality is an issue of global public health concern with over 300,000 women dying globally each year. In sub-Saharan Africa (SSA), these deaths mainly occur around childbirth and the first 24hours after delivery. The place of delivery is, therefore, important in reducing maternal deaths and accelerating progress towards attaining the 2030 sustainable development goals (SDGs) related to maternal health. In this study, we examined the prevalence and determinants of the place of delivery among reproductive age women in SSA.

Materials and methods

This was a cross-sectional study among women in their reproductive age using data from the most recent demographic and health surveys of 28 SSA countries. Frequency, percentage, chi-square, and logistic regression were used in analysing the data. All analyses were done using STATA.

Results

The overall prevalence of health facility delivery was 66%. This ranged from 23% in Chad to 94% in Gabon. More than half of the countries recorded a less than 70% prevalence of health facility delivery. The adjusted odds of health facility delivery were lowest in Chad. The probability of giving birth at a health facility also declined with increasing age but increased with the level of education and wealth status. Women from rural areas had a lower likelihood (AOR = 0.59, 95%CI = 0.57–0.61) of delivering at a health facility compared with urban women.

Conclusions

Our findings point to the inability of many SSA countries to meet the SDG targets concerning reductions in maternal mortality and improving the health of reproductive age women. The findings thus justify the need for peer learning among SSA countries for the adaption and integration into local contexts, of interventions that have proven to be successful in improving health facility delivery among reproductive age women.

Economic impact of the first wave of the COVID-19 pandemic on acute care hospitals in Japan

by Jung-ho Shin, Daisuke Takada, Tetsuji Morishita, Hueiru Lin, Seiko Bun, Emi Teraoka, Takuya Okuno, Hisashi Itoshima, Hiroyuki Nagano, Kenji Kishimoto, Hiromi Segawa, Yuka Asami, Takuya Higuchi, Kenta Minato, Susumu Kunisawa, Yuichi Imanaka

Background

In response to the coronavirus diseases 2019 (COVID-19) pandemic, the Japanese government declared a state of emergency on April 7, 2020. Six days earlier, the Japan Surgical Society had recommended postponing elective surgical procedures. Along with the growing public fear of COVID-19, hospital visits in Japan decreased.

Methods

Using claims data from the Quality Indicator/Improvement Project (QIP) database, this study aimed to clarify the impact of the first wave of the pandemic, considered to be from March to May 2020, on case volume and claimed hospital charges in acute care hospitals during this period. To make year-over-year comparisons, we considered cases from July 2018 to June 2020.

Results

A total of 2,739,878 inpatient and 53,479,658 outpatient cases from 195 hospitals were included. In the year-over-year comparisons, total claimed hospital charges decreased in April, May, June 2020 by 7%, 14%, and 5%, respectively, compared to the same months in 2019. Our results also showed that per-case hospital charges increased during this period, possibly to compensate for the reduced case volumes. Regression results indicated that the hospital charges in April and May 2020 decreased by 6.3% for hospitals without COVID-19 patients. For hospitals with COVID-19 patients, there was an additional decrease in proportion with the length of hospital stay of COVID-19 patients including suspected cases. The mean additional decrease per COVID-19 patient was estimated to 5.5 million JPY.

Conclusion

It is suggested that the hospitals treating COVID-19 patients were negatively incentivized.

Biology of a putative male aggregation-sex pheromone in <i>Sirex noctilio</i> (Hymenoptera: Siricidae)

by Quentin Guignard, Marc Bouwer, Bernard Slippers, Jeremy Allison

A putative male-produced pheromone has recently been described for the global pest of pines, Sirex noctilio, but field-activity has not been demonstrated. This study aimed to investigate the pheromone biology of S. noctilio in more detail. Specifically, we i) analysed effluvia and extracts for additional compounds by gas chromatography coupled with electro-antennographic detection (GC-EAD), mass spectrometry (GC-MS) and two dimensional time of flight mass spectrometry (GC X GC TOF MS), ii) conducted dose-response experiments for putative pheromone components, iii) determined the site of synthesis/ storage of the putative pheromone and iv) determined the release rate of the putative pheromone from males and three types of lures. A blend of four compounds was identified, including the previously described (Z)-3-decenol and (Z)-4-decenol, and two new compounds (Z)-3-octenol and (Z)-3-dodecenol. All compounds elicited a response from both male and female antennae, but the strength of the response varied according to sex, compound and dose tested. (Z)-3-Decenol and (Z)-3-octenol at lower and higher doses, respectively, elicited larger responses in males and females than the other two compounds. (Z)-3-Octenol and (Z)-4-decenol generally elicited larger female than male antennal responses. The site of synthesis and/or storage in males was determined to be the hind legs, likely in the leg-tendon gland. The relative release rate of the major compound by male wasps was shown to be 90 ± 12.4 ng/min, which is between 4 and 15 times greater than that observed from typical lures used previously. These observations are consistent with the hypothesis that these compounds may mediate lek formation in S. noctilio males and lek location in females.

Effectiveness of COVID-19 shelter-in-place orders varied by state

by Yevgeniy Feyman, Jacob Bor, Julia Raifman, Kevin N. Griffith

State “shelter-in-place” (SIP) orders limited the spread of COVID-19 in the U.S. However, impacts may have varied by state, creating opportunities to learn from states where SIPs have been effective. Using a novel dataset of state-level SIP order enactment and county-level mobility data form Google, we use a stratified regression discontinuity study design to examine the effect of SIPs in all states that implemented them. We find that SIP orders reduced mobility nationally by 12 percentage points (95% CI: -13.1 to -10.9), however the effects varied substantially across states, from -35 percentage points to +11 percentage points. Larger reductions were observed in states with higher incomes, higher population density, lower Black resident share, and lower 2016 vote shares for Donald J. Trump. This suggests that optimal public policies during a pandemic will vary by state and there is unlikely to be a “one-size fits all” approach that works best.

Reevaluating the true diagnostic accuracy of dipstick tests to diagnose urinary tract infection using Bayesian latent class analysis

by Prashant Bafna, Surendran Deepanjali, Jharna Mandal, Nathan Balamurugan, Rathinam P. Swaminathan, Tamilarasu Kadhiravan

Objective

Previous studies on diagnostic accuracy of dipstick testing for leukocyte esterase (LE) and nitrite to diagnose urinary tract infection (UTI) had used urine culture, which is an imperfect gold standard. Estimates of diagnostic accuracy obtained using the classical gold standard framework might not reflect the true diagnostic accuracy of dipstick tests.

Methods

We used the dataset from a prospective, observational study conducted in the emergency department of a teaching hospital in southern India. Patients with a clinical suspicion of UTI underwent dipstick testing for LE and nitrite, urine microscopy, and urine culture. Based on the results of urine microscopy and culture, UTI was classified into definite, probable, and possible. Patients with microscopic pyuria and a positive urine culture were adjudicated as definite UTI. Unequivocal imaging evidence of emphysematous pyelonephritis or perinephric collections was also considered definite UTI. We estimated the diagnostic accuracy of LE and nitrite tests using the classical analysis (assuming definite UTI as gold standard) and two different Bayesian latent class models (LCMs; 3-tests in 1-population and 2-tests in 2-populations models).

Results

We studied 149 patients. Overall, 64 (43%) patients had definite, 76 (51%) had probable, and 2 (1.3%) had possible UTI; 7 (4.6%) had alternate diagnoses. In classical analysis, LE was more sensitive than nitrite (87.5% versus 70.5%), while nitrite was more specific (24% versus 58%). The 3-tests in 1-population Bayesian LCM indicated a substantially better sensitivity and specificity for LE (98.1% and 47.6%) and nitrite (88.2% and 97.7%). True sensitivity and specificity of urine culture as estimated by the model was 48.7% and 73.0%. Estimates of the 2-tests in 2-populations model were in agreement with the 3-tests in 1-population model.

Conclusions

Bayesian LCMs indicate a clinically important improvement in the true diagnostic accuracy of urine dipstick testing for LE and nitrite. Given this, a negative dipstick LE would rule-out UTI, while a positive dipstick nitrite would rule-in UTI in our study setting. True diagnostic accuracy of urine dipstick testing for UTI in various practice settings needs reevaluation using Bayesian LCMs.

Psychological responses during the COVID-19 outbreak among university students in Bangladesh

by Md. Saiful Islam, Md. Safaet Hossain Sujan, Rafia Tasnim, Md. Tajuddin Sikder, Marc N. Potenza, Jim van Os

Mental health problems in students are considered a public health challenge. We assessed the prevalence of depression, anxiety, and stress (DAS) with the DASS-21, as well as associated factors, among university students in Bangladesh early in the COVID-19 outbreak. We hypothesized high levels of DAS and their associations with previously reported factors (e.g., poor sleep, lack of exercise, heavy internet use) and those linked to disadvantage (e.g., low monthly family income). We also enquired about participants’ satisfaction with their pursuit of their academic studies while living under COVID-19 restrictions. An internet-based survey was conducted during the month of April 2020, involving 3,122 Bangladeshi university students aged 18 to 29 years (59.5% males; mean age 21.4±2 years). Prevalence estimates of depression, anxiety and stress were, respectively, 76.1%, 71.5% and 70.1% for at least mild symptoms, 62.9%, 63.6% and 58.6% for at least moderate symptoms, 35.2%, 40.3%, and 37.7% for at least severe symptoms and 19.7%, 27.5% and 16.5% for at least very severe symptoms. The present estimates of DAS were more prevalent than in previous pre-COVID-19 studies among Bangladeshi university students. Regression analyses with DASS-21-score as a dependent variable revealed associations with factors mostly as hypothesized. The largest effect size on DAS symptoms was related to students’ satisfaction with their academic studies during the pandemic. As this survey used cross-sectional and self-reported methods, causality cannot be inferred. Mental health monitoring of students attempting to cope with the impacts of the COVID-19 outbreak may be useful and feasible.

On the molecular relationship between Hounsfield Unit (HU), mass density, and electron density in computed tomography (CT)

by Atchar Sudhyadhom

Accurate determination of physical/mass and electron densities are critical to accurate spatial and dosimetric delivery of radiotherapy for photon and charged particles. In this manuscript, the biology, chemistry, and physics that underly the relationship between computed tomography (CT) Hounsfield Unit (HU), mass density, and electron density was explored. In standard radiation physics practice, quantities such as mass and electron density are typically calculated based off a single kilovoltage CT (kVCT) scan assuming a one-to-one relationship between HU and density. It is shown that, in absence of mass density assumptions on tissues, the relationship between HU and density is not one-to-one with uncertainties as large as 7%. To mitigate this uncertainty, a novel multi-dimensional theoretical approach is defined between molecular (water, lipid, protein, and mineral) composition, HU, mass density, and electron density. Empirical parameters defining this relationship are x-ray beam energy/spectrum dependent and, in this study, two methods are proposed to solve for them including through a tissue mimicking phantom calibration process. As a proof of concept, this methodology was implemented in a separate in-house created tissue mimicking phantom and it is shown that sub 1% accuracy is possible for both mass and electron density. As molecular composition is not always known, the sensitivity of this model to uncertainties in molecular composition was investigated and it was found that, for soft tissue, sub 1% accuracy is achievable assuming nominal organ/tissue compositions. For boney tissues, the uncertainty in mineral content may lead to larger errors in mass and electron density compared with soft tissue. In this manuscript, a novel methodology to directly determine mass and electron density based off CT HU and knowledge of molecular compositions is presented. If used in conjunction with a methodology to determine molecular compositions, mass and electron density can be accurately calculated from CT HU.

Risk factors of papillary thyroid microcarcinoma that predispose patients to local recurrence

by Krzysztof Kaliszewski, Dorota Diakowska, Marta Rzeszutko, Łukasz Nowak, Michał Aporowicz, Beata Wojtczak, Krzysztof Sutkowski, Jerzy Rudnicki

Background

Currently, less aggressive treatment or even active surveillance of papillary thyroid microcarcinoma (PTMC) is widely accepted and recommended as a therapeutic management option. However, there are some concerns about these approaches. We investigated whether there are any demographic, clinical and ultrasound characteristics of PTMC patients that are easy to obtain and clinically available before surgery to help clinicians make proper therapeutic decisions.

Methods

We performed a retrospective chart review of 5,021 patients with thyroid tumors surgically treated in one center in 2008–2018. Finally, 182 (3.62%) PTMC patients were selected (158 (86.8%) females and 24 (13.2%) males, mean age 48.8±15.4 years). We analyzed the disease-free survival (DFS) time of the PTMC patients according to demographic and histopathological parameters. Univariate and multivariate logistic regression analyses were used to assess the relationships of demographic, clinical and ultrasound characteristics with aggressive histopathological features.

Results

Age ≥55 years, hypoechogenicity, microcalcifications, irregular tumor shape, smooth margins and high vascularity significantly increased the risk for minimal extrathyroidal extension (minETE), lymph node metastasis (LNM), and capsular and vascular invasion (p5 mm (p = 0.021), and patients with LNM (p = 0.002).

Conclusions

The absence of microcalcifications, irregular tumor shape, blunt margins, hypoechogenicity and high vascularity in PTMC patients below 55 years and with tumor diameters below 5 mm may allow clinicians to select individuals with a low risk of local recurrence so that they can receive less aggressive management.

Application of machine learning in the diagnosis of gastric cancer based on noninvasive characteristics

by Shuang-Li Zhu, Jie Dong, Chenjing Zhang, Yao-Bo Huang, Wensheng Pan

Background

The diagnosis of gastric cancer mainly relies on endoscopy, which is invasive and costly. The aim of this study is to develop a predictive model for the diagnosis of gastric cancer based on noninvasive characteristics.

Aims

To construct a predictive model for the diagnosis of gastric cancer with high accuracy based on noninvasive characteristics.

Methods

A retrospective study of 709 patients at Zhejiang Provincial People's Hospital was conducted. Variables of age, gender, blood cell count, liver function, kidney function, blood lipids, tumor markers and pathological results were analyzed. We used gradient boosting decision tree (GBDT), a type of machine learning method, to construct a predictive model for the diagnosis of gastric cancer and evaluate the accuracy of the model.

Results

Of the 709 patients, 398 were diagnosed with gastric cancer; 311 were health people or diagnosed with benign gastric disease. Multivariate analysis showed that gender, age, neutrophil lymphocyte ratio, hemoglobin, albumin, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were independent characteristics associated with gastric cancer. We constructed a predictive model using GBDT, and the area under the receiver operating characteristic curve (AUC) of the model was 91%. For the test dataset, sensitivity was 87.0% and specificity 84.1% at the optimal threshold value of 0.56. The overall accuracy was 83.0%. Positive and negative predictive values were 83.0% and 87.8%, respectively.

Conclusion

We construct a predictive model to diagnose gastric cancer with high sensitivity and specificity. The model is noninvasive and may reduce the medical cost.

Exploring the determinants of synergetic development of social organizations participating in home-based elderly care service: An SEM method

by Qiuhu Shao, Jingfeng Yuan, Junwei Ma, Hongxing Ding, Wei Huang

The current aging service industry has problems in meeting the ever-increasing demand for the home-based elderly care service (HECS). Social organizations participating in HECS seems to be a promising way to address these problems but also raises new challenges, like uncoordinated cooperation among stakeholders, which could lead to low management efficiency and low service quality. However, Synergetic development can be promising to enhance the participation of social organizations and to improve social welfare. This study introduces a conceptual model to explore relationships between five determinants and synergetic development of social organizations participating in HECS. A structural equation model (SEM) based on questionnaire survey is used as a test methodology. The results indicated that stakeholder engagement plays a critical role in synergetic development in HECS, resource allocation can only be improved by institutional climate, and supervision capacity cannot facilitate information sharing. This study provides effective strategies and directions for the improvement of home-based elderly care services.

Validation of a simplified risk prediction model using a cloud based critical care registry in a lower-middle income country

by Bharath Kumar Tirupakuzhi Vijayaraghavan, Dilanthi Priyadarshini, Aasiyah Rashan, Abi Beane, Ramesh Venkataraman, Nagarajan Ramakrishnan, Rashan Haniffa, the Indian Registry of IntenSive care(IRIS) collaborators

Background

The use of severity of illness scoring systems such as the Acute Physiology and Chronic Health Evaluation in lower-middle income settings comes with important limitations, primarily due to data burden, missingness of key variables and lack of resources. To overcome these challenges, in Asia, a simplified model, designated as e-TropICS was previously developed. We sought to externally validate this model using data from a multi-centre critical care registry in India.

Methods

Seven ICUs from the Indian Registry of IntenSive care(IRIS) contributed data to this study. Patients > 18 years of age with an ICU length of stay > 6 hours were included. Data including age, gender, co-morbidity, diagnostic category, type of admission, vital signs, laboratory measurements and outcomes were collected for all admissions. e-TropICS was calculated as per original methods. The area under the receiver operator characteristic curve was used to express the model’s power to discriminate between survivors and non-survivors. For all tests of significance, a 2-sided P less than or equal to 0.05 was considered to be significant. AUROC values were considered poor when ≤ to 0.70, adequate between 0.71 to 0.80, good between 0.81 to 0.90, and excellent at 0.91 or higher. Calibration was assessed using Hosmer-Lemeshow C -statistic.

Results

We included data from 2062 consecutive patient episodes. The median age of the cohort was 60 and predominantly male (n = 1350, 65.47%). Mechanical Ventilation and vasopressors were administered at admission in 504 (24.44%) and 423 (20.51%) patients respectively. Overall, mortality at ICU discharge was 10.28% (n = 212). Discrimination (AUC) for the e-TropICS model was 0.83 (95% CI 0.812–0.839) with an HL C statistic p value of Conclusion

e-TropICS has utility in the care of critically unwell patients in the South Asia region with good discriminative capacity. Further refinement of calibration in larger datasets from India and across the South-East Asia region will help in improving model performance.

Association of <i>PARP1</i>-specific polymorphisms and haplotypes with non-small cell lung cancer subtypes

by Jing Jin, Heather Robeson, Pebbles Fagan, Mohammed S. Orloff

Objective

The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer.

Materials and methods

DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed.

Results

SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12–3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19–6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61–6.75; 95%CI from 1.82 to 19.9; P-value Conclusion

PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.

Dose-dependent effects of necrostatin-1 supplementation to tissue culture media of young porcine islets

by Hien Lau, Nicole Corrales, Samuel Rodriguez, Colleen Luong, Mohammadreza Mohammadi, Veria Khosrawipour, Shiri Li, Michael Alexander, Paul de Vos, Jonathan R. T. Lakey

Previous studies have shown that necrostatin-1 (Nec-1) supplementation improved the viability of murine islets following exposure to nitric oxide, increased the survival of human islets during hypoxic culture, and augmented the maturation of pre-weaned porcine islets (PPIs) after 7 days of tissue culture. A limitation of these studies is that only one concentration of Nec-1 was used, and no studies have determined the optimal dose of Nec-1 for PPIs. Thus, the present study examined the effects of Nec-1 on PPIs at four different doses—0, 25, 50, 100, and 200 μM—after 7 days of tissue culture when supplemented on day 3. PPIs were isolated from pancreata of pre-weaned Yorkshire piglets (8–15 days old) and cultured in a specific islet maturation media added with Nec-1 on day 3 of tissue culture at 4 different doses—0, 25, 50, 100, and 200 μM (n = 6 for each dose). After 7 days of tissue culture, islets were assessed for recovery, viability, endocrine cellular content, GLUT2 expression in beta cells, and insulin secretion after glucose challenge. Nec-1 did not affect the viability of both intact islets and dissociated islets cells during tissue culture regardless of doses. Islets cultured in media supplemented with Nec-1 at 100 μM, but not 25, 50, or 200 μM, had a significantly higher recovery, composition of endocrine cells, GLUT2 expression in beta cells, and insulin secretion capacity than control islets cultured in media without Nec-1 supplementation. Moreover, culturing islets in 200 μM Nec-1 supplemented media not only failed to improve the insulin release but resulted in a lower glucose-induced insulin stimulation index compared to islets cultured in media added with 100 μM Nec-1. Xenotransplantation using porcine islets continues to demonstrate scientific advances to justify this area of research. Our findings indicate that Nec-1 supplementation at 100 μM was most effective to enhance the in vitro maturation of PPIs during tissue culture.

Effects of cooperative games on enjoyment in physical education—How to increase positive experiences in students?

by Eliane Stephanie Engels, Philipp Alexander Freund

Enjoyment is one of the most important factors for the maintenance of regular physical activity. The present study investigated if cooperative games in physical education classes (grades 6–9) can increase students’ enjoyment of physical activity. Data were collected in a quasi-experimental study employing a two-group design with repeated measures and randomization of classes to conditions. The total sample consisted of N = 285 students from regular schools in Germany aged 10 to 16 years (Mage = 12.67 years, SD = 1.10; 48.4% female). We found that cooperative games led to a higher perceived enjoyment in physical education classes (F(1) = 3.49, p = .063, ηp2 = .012), increased the feeling of how strong students felt related to each other (F(1) = 4.38, p = .037, ηp2 = .016), and facilitated feelings of perceived competence in physical education class (F(1) = 6.31, p = .013, ηp2 = .022). In addition, social relatedness and perceived competence partly mediated the effect of cooperative games on enjoyment. The findings indicate that systematically designed cooperative games can help foster enjoyment in physical education classes.

Behavioral measures to fight COVID-19: An 8-country study of perceived usefulness, adherence and their predictors

by Jürgen Margraf, Julia Brailovskaia, Silvia Schneider

Behavioral measures, such as the wearing of facemasks and maintaining of distance to other people, have been central in fighting the COVID-19 pandemic and will continue to be important in curbing its spread. We therefore investigated their perceived usefulness, adherence and their predictors in representative online samples in eight countries (France, Germany, Poland, Russia, Spain, Sweden, U.K., U.S.). Of the 7,658 participants, 77.4% rated governmental measures (highest: Germany, lowest: France) as useful and 91.7% reported adherence to them. Adherence was lowest in Russia and Poland, where people felt particularly left alone and not well supported, and in the U.S. and Sweden, where governments showed ambivalent attitudes towards the measures. The highest adherence was reported in countries with very high mortality (U.K., Spain, France) or very positively perceived government communication (Germany). Female gender, higher age, belonging to a risk group, being affected physically and mentally, perception of governmental communication as guided by the interests of people, feeling of being well informed and the level of positive mental health positively predicted both outcomes, while being affected economically negatively predicted both outcomes. Country-specific results are considered in the light of the protection motivation theory and the theory of planned behavior together with potential ways to improve active participation of the population. Overall, we recommend the governments and authorities to stress that each individual can contribute to the control of the COVID-19 situation by adherence to the measures in the public communication. Moreover, they should emphasize the risk of unconscious infection of older individuals by younger people, as well as the importance of physical activity for the protection of mental and physical health especially during the pandemic.

Molecular characterization and drug resistance patterns of <i>Mycobacterium tuberculosis</i> complex in extrapulmonary tuberculosis patients in Addis Ababa, Ethiopia

by Getu Diriba, Abebaw Kebede, Habteyes Hailu Tola, Bazezew Yenew, Shewki Moga, Desalegn Addise, Ayinalem Alemu, Zemedu Mohammed, Muluwork Getahun, Mengistu Fantahun, Mengistu Tadesse, Biniyam Dagne, Misikir Amare, Gebeyehu Assefa, Dessie Abera, Kassu Desta

Background

Molecular characterization of Mycobacterium tuberculosis (MTB) is important to understand the pathogenesis, diagnosis, treatment, and prevention of tuberculosis (TB). However, there is limited information on molecular characteristics and drug-resistant patterns of MTB in patients with extra-pulmonary tuberculosis (EPTB) in Ethiopia. Thus, this study aimed to determine the molecular characteristics and drug resistance patterns of MTB in patients with EPTB in Addis Ababa, Ethiopia.

Methods

This study was conducted on frozen stored isolates of EPTB survey conducted in Addis Ababa, Ethiopia. A drug susceptibility test was performed using BACTEC-MGIT 960. Species and strain identification were performed using the Geno-Type MTBC and spoligotyping technique, respectively. Data were entered into the MIRU-VNTRplus database to assess the spoligotype patterns of MTB. Analysis was performed using SPSS version 23, and participants’ characteristics were presented by numbers and proportions.

Results

Of 151 MTB isolates, 29 (19.2%) were resistant to at least one drug. The highest proportion of isolates was resistant to Isoniazid (14.6%) and Pyrazinamide (14.6%). Nine percent of isolates had multidrug-resistant TB (MDR-TB), and 21.4% of them had pre-extensively drug-resistant TB (pre-XDR-TB). Among the 151 MTB isolates characterized by spoligotyping, 142 (94.6%) had known patterns, while 9 (6.0%) isolates were not matched with the MIRU-VNTRplus spoligotype database. Of the isolates which had known patterns, 2% was M.bovis while 98% M. tuberculosis. Forty-one different spoligotype patterns were identified. The most frequently identified SpolDB4 (SIT) wereSIT149 (21.2%), SIT53 (14.6%) and SIT26 (9.6%). The predominant genotypes identified were T (53.6%), Central Asia Strain (19.2%) and Haarlem (9.9%).

Conclusion

The present study showed a high proportion of MDR-TB and pre-XDR-TB among EPTB patients. The strains were mostly grouped into SIT149, SIT53, and SIT26. The T family lineage was the most prevalent genotype. MDR-TB and pre-XDR-TB prevention is required to combat these strains in EPTB. A large scale study is required to describe the molecular characteristics and drug resistance patterns of MTB isolates in EPTB patients.

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