bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost drivers in the pharmacological treatment of interstitial lung disease
Authors: Maqhuzu Phillen Nozibuyiso , Kreuter Michael , Bahmer Thomas , Kahn Nicolas , Claussen Martin , Holle Rolf , Schwarzkopf Larissa
Published: August 2021

Introduction

Treatments of interstitial lung diseases (ILDs) mainly focus on disease stabilization and relief of symptoms by managing inflammation or suppressing fibrosis by (in part costly) drugs. To highlight economic burden of drug treatment in different ILD-subtypes we assessed cost trends and therewith-associated drivers.

Methods

Using data from the German, observational HILDA study we estimated adjusted mean medication costs over 36-month intervals using one- and two-part Generalized Estimating Equation (GEE) regression models with a gamma distribution and log link. Next, we determined factors associated with costs.

Results

In Idiopathic pulmonary fibrosis (IPF) mean per capita medication costs increased from €1442 before to €11,000€ at the end of study. In non-IPF subtypes, the increase took place at much lower level. Mean per capita ILD-specific medication costs at the end of the study ranged between €487 (other ILD) and €9142 (IPF). At baseline, higher FVC %predicted values were associated with lower medication costs in IPF (−9%) and sarcoidosis (−1%). During follow up higher comorbidity burden escalated costs in progressive fibrosing ILD (PF-ILD) (+52%), sarcoidosis (+60%) and other ILDs (+24%). The effect of disease duration was not uniform, with cost savings in PF-ILD (−8%) and sarcoidosis (−6%), but increased spending in IPF (+11%).

Conclusion

Pharmacological management of ILD, in particular of IPF imposes a substantial economic burden on the healthcare system. Strategies to reduce comorbidity burden and early treatment may reduce the impact of ILDs on the healthcare system.
The N-terminus of Lactobacillus amylovorus feruloyl esterase plays an important role in its secretion by Lactobacillus plantarum and Escherichia coli
Authors: Xu Zhenshang , Zhang Rongling , Wang Ting , Kong Jian
Published: August 2021

Background

Feruloyl esterase is a multifunctional esterase with potential industrial applications. In the present study, we found the Lactobacillus amylovorus feruloyl esterase (FaeLam) could be secreted by L. plantarum and Escherichia coli. However, no signal peptide was detected in this protein as predicted by SignalP-5.0. Therefore, experiments were carried out to propose an explanation for the extracellular release of FaeLam.

Results

Here, we identified that the FaeLam could be secreted to the culture medium of L. plantarum CGMCC6888 and E. coli DH5α, respectively. To exclude the possibility that FaeLam secretion was caused by its hydrolytic activity on the cell membrane, the inactive FaeLamS106A was constructed and it could still be secreted out of L. plantarum and E. coli cells. Furthermore, the truncated version of the FaeLam without the N-terminal residues was constructed and demonstrated the importance of the 20 amino acids of N-terminus (N20) on FaeLam secretion. In addition, fusion of heterologous proteins with N20 or FaeLam could carry the target protein out of the cells. These results indicated the N-terminus of FaeLam played the key role in the export process.

Conclusions

We proved the N-terminus of L. amylovorus FaeLam plays an important role in its secretion by L. plantarum and E. coli. To our best knowledge, this is the first reported protein which can be secreted out of the cells of both Gram-positive and Gram-negative bacteria. Furthermore, the results of this study may provide a new method for protein secretion in L. plantarum and E. coli through fusion the target protein to N20 of FaeLam.
Short report: Performance evaluation of the Idylla™ KRAS and EGFR mutation tests on paraffin-embedded cytological NSCLC samples
Authors: Offerman Saskia , Prinsen Clemens F. , Knol Ageeth , Methorst Natalie , Kamphorst Jeanette , Niemantsverdriet Maarten
Published: August 2021

Background

Quick and reliable testing of EGFR and KRAS is needed in non-small cell lung cancer (NSCLC) to ensure optimal decision-making for targeted therapy. The Idylla™ platform was designed for Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections but recently several studies were published that evaluated its potential for cytological specimens. This study aimed to validate the Idylla™ platform for the detection of EGFR/KRAS mutations in cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding.

Material and methods

The KRAS Idylla™ test were performed on 11 specimens with a known KRAS mutation. The EGFR Idylla™ test was performed on 18 specimens with a known primary EGFR mutation and 7 specimens with a primary EGFR-EGFR T790M resistance mutation combination.

Results

Concordant KRAS and primary EGFR mutations were detected for both KRAS and primary EGFR mutations. Samples with a total CQ value of < 26 could be considered negative. Samples with a total CQ value of > 26 could not be assessed (probability of false-negative). In specimens with a primary EGFR-EGFR T790M resistance mutation combination, 5/7 cases were not concordant.

Conclusion

Our results confirm the conclusion of recent reports that the Idylla™EGFR assay is not suitable in a resistance to EGFR TKI setting, also not in our cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. KRAS and primary EGFR mutations were detected using the Idylla™ assays in virtually all cytological NSCLC samples. This analysis was rapid and time-saving compared to other mutation detection assays and may be useful if the amount of material is insufficient to perform a full set of molecular tests.
How does urbanization affect perceptions and traditional knowledge of medicinal plants?
Authors: Arjona-García Cecilia , Blancas José , Beltrán-Rodríguez Leonardo , López Binnqüist Citlalli , Colín Bahena Hortensia , Moreno-Calles Ana Isabel , Sierra-Huelsz José Antonio , López-Medellín Xavier
Published: August 2021

Background

The use and knowledge of medicinal plants play an essential role in community health in rural Mexico. Medicinal plants are part of the local heritage and provide a source of economic income. Nevertheless, knowledge of their use has declined due to factors like accelerated urbanization. Some authors have proposed that by reducing natural spaces, urbanization generates changes that impact the recognition, use, and management of natural resources. Here, we evaluate how urbanization affects the knowledge, use, and perception of medicinal plants in a Biosphere Reserve in Mexico.

Methods

Using a mixed methodology including quantitative and qualitative analyses, we generated a list of medicinal plants, methods of preparation, prevalence of illness, and use in two communities with different degrees of urbanization.

Results

A total of 217 medicinal plants were identified. The more urbanized community had greater knowledge of, and used, a larger number of introduced plant species, while the less urbanized community used and had more knowledge about wild plants. One of the factors explaining these differences was occupation, with people who work outdoors showing greater knowledge of wild plants.

Conclusions

Urbanization can lead to a loss of knowledge of the use and management of local wild species, with implications for the conservation of biocultural heritage. Substitution of native medicinal plants by introduced species shows disinterest and disuse in the local medicinal flora, which could be reflected in their ecosystems.
Collaboration between emergency physicians and citizen responders in out-of-hospital cardiac arrest resuscitation
Authors: Jellestad Anne-Sofie Linde , Folke Fredrik , Molin Rune , Lyngby Rasmus Meyer , Hansen Carolina Malta , Andelius Linn
Published: August 2021

Background

Citizen responder programmes dispatch volunteer citizens to initiate resuscitation in nearby out-of-hospital cardiac arrests (OHCA) before the Emergency Medical Services (EMS) arrival. Little is known about the interaction between citizen responders and EMS personnel during the resuscitation attempt. In the Capital Region of Denmark, emergency physicians are dispatched to all suspected OHCAs. The aim of this study was to evaluate how emergency physicians perceived the collaboration with citizen responders during resuscitation attempts.

Method

This cross-sectional study was conducted through an online questionnaire. It included all 65 emergency physicians at Copenhagen EMS between June 9 and December 13, 2019 (catchment area 1.8 million). The questionnaire examined how emergency physicians perceived the interaction with citizen responders at the scene of OHCA (use of citizen responders before and after EMS arrival, citizen responders’ skills in cardiopulmonary resuscitation (CPR), and challenges in this setting).

Results

The response rate was 87.7% (57/65). Nearly all emergency physicians (93.0%) had interacted with a citizen responder at least once. Of those 92.5%(n = 49) considered it relevant to activate citizen responders to OHCA resuscitation, and 67.9%(n = 36) reported the collaboration as helpful. When citizen responders arrived before EMS, 75.5%(n = 40) of the physicians continued to use citizen responders to assist with CPR or to carry equipment. Most (84.9%,n = 45) stated that citizen responders had the necessary skills to perform CPR. Challenges in the collaboration were described by 20.7%(n = 11) of the emergency physicians and included citizen responders being mistaken for relatives, time-consuming communication, or crowding problems during resuscitation.

Conclusion

Emergency physicians perceived the collaboration with citizen responders as valuable, not only for delivery of CPR, but were also considered an extra helpful resource providing non-CPR related tasks such as directing the EMS to the arrest location, carrying equipment and taking care of relatives.
Progesterone receptor antagonists reverse stem cell expansion and the paracrine effectors of progesterone action in the mouse mammary gland
Authors: Ranjan Manish , Lee Oukseub , Cottone Gannon , Mirzaei Mehrabad Elnaz , Spike Benjamin T. , Zeng Zexian , Yadav Shivangi , Chatterton Robert , Kim J. Julie , Clare Susan E. , Khan Seema A.
Published: August 2021

Background

The ovarian hormones estrogen and progesterone (EP) are implicated in breast cancer causation. A specific consequence of progesterone exposure is the expansion of the mammary stem cell (MSC) and luminal progenitor (LP) compartments. We hypothesized that this effect, and its molecular facilitators, could be abrogated by progesterone receptor (PR) antagonists administered in a mouse model.

Methods

Ovariectomized FVB mice were randomized to 14 days of treatment: sham, EP, EP + telapristone (EP + TPA), EP + mifepristone (EP + MFP). Mice were then sacrificed, mammary glands harvested, and mammary epithelial cell lineages separated by flow cytometry using cell surface markers. RNA from each lineage was sequenced and differential gene expression was analyzed using DESeq. Quantitative PCR was performed to confirm the candidate genes discovered in RNA seq. ANOVA with Tukey post hoc analysis was performed to compare relative expression. Alternative splicing events were examined using the rMATs multivariate analysis tool.

Results

Significant increases in the MSC and luminal mature (LM) cell fractions were observed following EP treatment compared to control (p < 0.01 and p < 0.05, respectively), whereas the LP fraction was significantly reduced (p < 0.05). These hormone-induced effects were reversed upon exposure to TPA and MFP (p < 0.01 for both). Gene Ontology analysis of RNA-sequencing data showed EP-induced enrichment of several pathways, with the largest effect on Wnt signaling in MSC, significantly repressed by PR inhibitors. In LP cells, significant induction of Wnt4 and Rankl, and Wnt pathway intermediates Lrp2 and Axin2 (confirmed by qRTPCR) were reversed by TPA and MFP (p < 0.0001). Downstream signaling intermediates of these pathways (Lrp5, Mmp7) showed similar effects. Expression of markers of epithelial-mesenchymal transition (Cdh1, Cdh3) and the induction of EMT regulators (Zeb1, Zeb2, Gli3, Snai1, and Ptch2) were significantly responsive to progesterone. EP treatment was associated with large-scale alternative splicing events, with an enrichment of motifs associated with Srsf, Esrp, and Rbfox families. Exon skipping was observed in Cdh1, Enah, and Brd4.

Conclusions

PR inhibition reverses known tumorigenic pathways in the mammary gland and suppresses a previously unknown effect of progesterone on RNA splicing events. In total, our results strengthen the case for reconsideration of PR inhibitors for breast cancer prevention.
The diversity of unique 1,4,5,6-Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid coding common genes and Universal stress protein in Ectoine TRAP cluster (UspA) in 32 Halomonas species
Authors: Rekadwad Bhagwan Narayan , Li Wen-Jun , Rekha P. D.
Published: August 2021

Objectives

To decipher the diversity of unique ectoine-coding housekeeping genes in the genus Halomonas.

Results

In Halomonas, 1,4,5,6-Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid has a crucial role as a stress-tolerant chaperone, a compatible solute, a cell membrane stabilizer, and a reduction in cell damage under stressful conditions. Apart from the current 16S rRNA biomarker, it serves as a blueprint for identifying Halomonas species. Halomonas elongata 1H9 was found to have 11 ectoine-coding genes. The presence of a superfamily of conserved ectoine-coding among members of the genus Halomonas was discovered after genome annotations of 93 Halomonas spp. As a result of the inclusion of 11 single copy ectoine coding genes in 32 Halomonas spp., genome-wide evaluations of ectoine coding genes indicate that 32 Halomonas spp. have a very strong association with H. elongata 1H9, which has been proven evidence-based approach to elucidate phylogenetic relatedness of ectoine-coding child taxa in the genus Halomonas. Total 32 Halomonas species have a single copy number of 11 distinct ectoine-coding genes that help Halomonas spp., produce ectoine under stressful conditions. Furthermore, the existence of the Universal stress protein (UspA) gene suggests that Halomonas species developed directly from primitive bacteria, highlighting its role during the progression of microbial evolution.
Small extracellular vesicles from menstrual blood-derived mesenchymal stem cells (MenSCs) as a novel therapeutic impetus in regenerative medicine
Authors: Chen Lijun , Qu Jingjing , Mei Quanhui , Chen Xin , Fang Yangxin , Chen Lu , Li Yifei , Xiang Charlie
Published: August 2021

Menstrual blood-derived mesenchymal stem cells (MenSCs) have great potential in regenerative medicine. MenSC has received increasing attention owing to its impressive therapeutic effects in both preclinical and clinical trials. However, the study of MenSC-derived small extracellular vesicles (EVs) is still in its initial stages, in contrast to some common MSC sources (e.g., bone marrow, umbilical cord, and adipose tissue). We describe the basic characteristics and biological functions of MenSC-derived small EVs. We also demonstrate the therapeutic potential of small EVs in fulminant hepatic failure, myocardial infarction, pulmonary fibrosis, prostate cancer, cutaneous wound, type-1 diabetes mellitus, aged fertility, and potential diseases. Subsequently, novel hotspots with respect to MenSC EV-based therapy are proposed to overcome current challenges. While complexities regarding the therapeutic potential of MenSC EVs continue to be unraveled, advances are rapidly emerging in both basic science and clinical medicine. MenSC EV-based treatment has great potential for treating a series of diseases as a novel therapeutic strategy in regenerative medicine.
An explicit unconditionally stable scheme: application to diffusive Covid-19 epidemic model
Authors: Nawaz Yasir , Arif Muhammad Shoaib , Abodayeh Kamaleldin , Shatanawi Wasfi
Published: August 2021

An explicit unconditionally stable scheme is proposed for solving time-dependent partial differential equations. The application of the proposed scheme is given to solve the COVID-19 epidemic model. This scheme is first-order accurate in time and second-order accurate in space and provides the conditions to get a positive solution for the considered type of epidemic model. Furthermore, the scheme’s stability for the general type of parabolic equation with source term is proved by employing von Neumann stability analysis. Furthermore, the consistency of the scheme is verified for the category of susceptible individuals. In addition to this, the convergence of the proposed scheme is discussed for the considered mathematical model.
Exploring the effectiveness of in ovo feeding of vitamin C based on the embryonic vitamin C synthesis and absorption in broiler chickens
Authors: Zhu Yufei , Zhao Jianfei , Wang Chenxu , Zhang Fei , Huang Xinhuo , Ren Zhouzheng , Yang Xin , Liu Yanli , Yang Xiaojun
Published: August 2021

Background

Many researches about in ovo feeding (IOF) of vitamin C (VC) are gradually carried out to explore physiological development in chicken, but little studies focus on VC synthesis capacity of the embryo itself, the selection of injection site and the effectiveness of IOF of VC. This study aims to explore the above problems.

Results

Kidney and yolk sac were the main organs for VC synthesis and L-gulonolactone oxidase (GLO) expression was lower during pre-hatch development than that during post-hatch development. Sodium-dependent vitamin C transporter 1 (SVCT1) expression was increased continuously in yolk sac from embryonic age 19 (E19) to post-hatch day 1 (D1) and in intestine (duodenum, jejunum and ileum) from E17 to D1. Plasma VC content was higher at D1 than that at D21 and D42. IOF of VC significantly reduced GLO expression in liver, kidney and yolk sac as well as SVCT1 expression in duodenum, jejunum and ileum, but increased the VC content in plasma, brain, kidney and liver. In addition, IOF of VC obviously reduced the embryonic morality and increased the hatchability under heat stress.

Conclusions

This study suggested that IOF of VC at E11 in yolk was effective for embryonic VC supplementation. These findings provide a theoretical reference about the method of embryonic VC supplementation and effective methodology on embryonic VC nutrition in broiler chickens.
Predictive analytics using Big Data for the real estate market during the COVID-19 pandemic
Authors: Grybauskas Andrius , Pilinkienė Vaida , Stundžienė Alina
Published: August 2021

As the COVID-19 pandemic came unexpectedly, many real estate experts claimed that the property values would fall like the 2007 crash. However, this study raises the question of what attributes of an apartment are most likely to influence a price revision during the pandemic. The findings in prior studies have lacked consensus, especially regarding the time-on-the-market variable, which exhibits an omnidirectional effect. However, with the rise of Big Data, this study used a web-scraping algorithm and collected a total of 18,992 property listings in the city of Vilnius during the first wave of the COVID-19 pandemic. Afterwards, 15 different machine learning models were applied to forecast apartment revisions, and the SHAP values for interpretability were used. The findings in this study coincide with the previous literature results, affirming that real estate is quite resilient to pandemics, as the price drops were not as dramatic as first believed. Out of the 15 different models tested, extreme gradient boosting was the most accurate, although the difference was negligible. The retrieved SHAP values conclude that the time-on-the-market variable was by far the most dominant and consistent variable for price revision forecasting. Additionally, the time-on-the-market variable exhibited an inverse U-shaped behaviour.
Implementing CT tumor volume and CT pleural thickness into future staging systems for malignant pleural mesothelioma
Authors: Lauk Olivia , Patella Miriam , Neuer Thomas , Battilana Bianca , Frauenfelder Thomas , Nguyen-Kim Thi Dan Linh , Weder Walter , Caviezel Claudio , Hillinger Sven , Inci Ilhan , Opitz Isabelle
Published: August 2021

Objectives

Tumor thickness and tumor volume measured by computed tomography (CT) were suggested as valuable prognosticator for patients’ survival diagnosed with malignant pleural mesothelioma (MPM). The purpose was to assess the accuracy of CT scan based preoperatively measured tumor volume and thickness compared to actual tumor weight of resected MPM specimen and pathologically assessed tumor thickness, as well as an analysis of their impact on overall survival (OS).

Methods

Between 09/2013–08/2018, 74 patients were treated with induction chemotherapy followed by (extended) pleurectomy/decortication ((E)PD). In 53 patients, correlations were made between CT-measured volume and -tumor thickness (cTV and cTT) and actual tumor weight (pTW) based on the available values. Further cTV and pT/IMIG stage were correlated using Pearson correlation. Overall survival (OS) was calculated with Kaplan Meier analysis and tested with log rank test. For correlation with OS Kaplan-Meier curves were made and log rank test was performed for all measurements dichotomized at the median.

Results

Median pathological tumor volume (pTV) and pTW were 530 ml [130 ml – 1000 ml] and 485 mg [95 g – 982 g] respectively. Median (IQR) cTV was 77.2 ml (35.0–238.0), median cTT was 9.0 mm (6.2–13.7). Significant association was found between cTV and pTV (R = 0.47, p < 0.001) and between cTT and IMIG stage (p = 0,001) at univariate analysis. Multivariate regression analysis revealed, that only cTV correlates with pTV. Median follow-up time was 36.3 months with 30 patients dead at the time of the analysis. Median OS was 23.7 months. 1-year and 3-year survival were 90 and 26% respectively and only the cTV remained statistically associated with OS.

Conclusion

Preoperatively assessed CT tumor volume and actual tumor volume showed a significant correlation. CT tumor volume may predict pathological tumor volume as a reflection of tumor burden, which supports the integration of CT tumor volume into future staging systems.
Callose: a multifunctional (1, 3)-β–d-glucan involved in morphogenesis and function of angiosperm stomata
Authors: Apostolakos Panagiotis , Giannoutsou Eleni , Galatis Basil
Published: August 2021

Background

Although the cellulose microfibril organization in guard cell (GC) walls play a crucial role in the mechanism of the stomatal function, recent work showed that matrix cell wall materials are also involved. Especially in the kidney-shaped stomata of the fern Asplenium nidus, callose actively participates in the mechanism of opening and closure of the stomatal pore.

Scope

The present review briefly presents and discusses recent findings concerning the distribution and role of callose in the kidney-shaped stomata of the dicotyledon Vigna sinensis as well as in the dumbbell-shaped stomata of the monocotyledon Zea mays.

Conclusion

The discussed data support that, in both categories of angiosperm stomata, callose is implicated in the mechanism of stomatal pore formation and stomata function by locally affecting the mechanical properties of the GC cell walls.
Comparison of demineralized bone matrix and hydroxyapatite as carriers of
Escherichia coli
recombinant human BMP-2
Authors: Jin Yuan-Zhe , Zheng Guang-Bin , Lee Jae Hyup , Han Shi-Huan
Published: August 2021

Background

Autograft has been widely used in various orthopedic and dental surgery for its superior osteogenicity, osteoinductivity and osteoconductivity. But the available volume of the autograft is limited and the efficacy of it is highly affected by the condition of the patients. Therefore, growth factors such as
Escherichia coli
bone morphogenetic protein-2 (ErhBMP-2) has been widely used in some countries and regions with various carriers that could affect the effects of the growth factors. Demineralized bone matrix (DBM) has been widely used as a bone graft substitute and growth factor carrier, but its effect as a carrier of ErhBMP-2 was less investigated.

Materials and methods

Rat calvaria defect model was used in this study. We implanted ErhBMP-2 with DBM or hydroxyapatite (HA) as a carrier in 8 mm calvaria defect and compared their bone regeneration effect in 4th week and 8th week after implantation with micro-CT and histology. The data was analyzed with one-way ANOVA method with Bonferroni post-hoc analysis.

Result

The group with DBM as the carrier showed significantly higher bone volume and bone thickness than the groups with HA as the carrier in both weeks. And the histology sections showed less adipose tissue formed in the groups with DBM as the carrier.

Conclusion

DBM could be a better carrier for ErhBMP-2 than HA.
Exploring attitudes toward taxation of sugar-sweetened beverages in rural Michigan
Authors: Bombak Andrea E. , Colotti Taylor E. , Raji Dolapo , Riediger Natalie D.
Published: August 2021

Background

While policies to address “obesity” have existed for decades, they have commonly focused on behavioral interventions. More recently, the taxation of sugar-sweetened beverages is gaining traction globally. This study sought to explore individuals’ attitudes and beliefs about sugar-sweetened beverages being taxed in a rural Michigan setting.

Methods

This qualitative study was conducted using critical policy analysis. Data were collected in 25 semi-structured, audio-recorded interviews with adult Michiganders. Following data collection, transcripts were coded into themes using NVivo software.

Results

Four themes emerged in participants’ perspectives regarding sugar-sweetened beverages being taxed:resistance,unfamiliarity, tax effects, andneed for education.While some participants were unfamiliar with sugar-sweetened beverage taxes, many viewed taxation as a “slippery slope” of government intervention, which invoked feelings of mistrust. In addition, participants predicted a sugar-sweetened beverage tax would be ineffective at reducing intake, particularly among regular consumers, who were frequently perceived as mostly low income and/or of higher weight.

Conclusions

Further research is needed to explore perceptions of sugar-sweetened beverage taxes in different geographic areas in the USA to examine how perceptions vary. Policymakers should be aware of the potential implications of this health policy with respect to government trust and stigma towards lower income and higher-weight individuals.
Predictors of catastrophic out-of-pocket health expenditure in rural Egypt: application of the heteroskedastic probit model
Authors: Abdel-Rahman Suzan , Shoaeb Farouk , Fattah Mohamed Naguib Abdel , Abonazel Mohamed R.
Published: August 2021

Background

Out-of-pocket (OOP) health expenditure is a pressing issue in Egypt and far exceeds half of Egypt’s total health spending, threatening the economic viability, and long-term sustainability of Egyptian households. Targeting households at risk of catastrophic health payments based on their characteristics is an obvious pathway to mitigate the impoverishing impacts of OOP health payments on livelihoods. This study was conducted to identify the risk factors of incurring catastrophic health payments hoping to formulate appropriate policies to protect households against financial catastrophes.

Methods

Using data derived from the Egyptian Household Income, Expenditure, and Consumption Survey (HIECS), a multiplicative heteroskedastic probit model is applied to account for heteroskedasticity and avoid biased and inconsistent estimates.

Results

Accounting for heteroskedasticity induces notable differences in marginal effects and demonstrates that the impact of some core variables is underestimated and insignificant and in the opposite direction in the homoscedastic probit model. Moreover, our results demonstrate the principal factors besides health status and socioeconomic characteristics responsible for incurring catastrophic health expenditure, such as the use of health services provided by the private sector, which has a dramatic effect on encountering catastrophic health payments.

Conclusions

The marked differences between estimates of probit and heteroskedastic probit models emphasize the importance of investigating homoscedasticity assumption to avoid policies based on incorrect evidence. Many policies can be built upon our findings, such as enhancing the role of social health insurances in rural areas, expanding health coverage for poor households and chronically ill household heads, and providing adequate financial coverage for households with a high proportion of elderly, sick members, and females. Also, there is an urgent need to limit OOP health payments absorbed by private sector to achieve an acceptable level of fair financing.
In prostatic transition zone lesions (PI-RADS v2.1): which subgroup should be biopsied?
Authors: An Jihae , Kim Young Joong , Seo Jae Young , Hwang Cheol Mog , Oh Dong Hyun , Lee Mu-Sik , Kim Keum Won
Published: August 2021

Background

The study aimed to compare the diagnostic performance of T2-weighted imaging (T2WI) score 3 transition zone (TZ) lesions between Prostate Imaging and Reporting Data System (PI-RADS) v2.1 and modified PI-RADS v2.1-B.

Results

Among TZ lesions (n = 78), 47 (60.0%) had T2WI score of 3, and 16 of the 47 (34.0%) were malignant. The rate of malignancy was 8.8% in PI-RADS category 3A, 100% in PI-RADS category 3B, and 100% in PI-RADS category 4. The apparent diffusion coefficient value of PI-RADS category 3B (0.934 ± 0.158 × 10−3 mm2/s) showed significant difference with that of PI-RADS category 3A (1.098 ± 0.146 × 10−3 mm2/s) but none with PI-RADS category 4 (0.821 ± 0.091 × 10−3 mm2/s). There was no significant difference in the sensitivity and negative predictive value of PI-RADS v2.1 and PI-RADS v2.1-B. Specificity and positive predictive value of modified PI-RADS v2.1-B were much higher than those of PI-RADS v2.1 for both readers (p < .001). The area under the receiver operating characteristic curve tended to be higher with PI-RADS v2.1-B than with PI-RADS v2.1.

Conclusion

Biopsy for PI-RADS 3B lesion is necessary due to its superior malignancy potential than that of PI-RADS 3A lesion.
Insulin Secretion Predicts the Response to Antidiabetic Therapy in Patients With New-onset Diabetes
Authors: Abdelgani S , Puckett C , Adams J , Triplitt C , DeFronzo R A , Abdul-Ghani M
Published: August 2021

Context

The results of the present study demonstrate that beta cell function in newly diagnosed T2DM patients is the key predictor of response to glucose lowering medications and provides a practical tool (C-Pep120 /C-Pep0) to guide the choice of glucose lowering agent.

Objective

This work aims to identify predictors for individualization of antidiabetic therapy in patients with new-onset type 2 diabetes mellitus (T2DM).

Methods

A total of 261 drug-naive participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study, with new-onset diabetes, were randomly assigned in a single-center study to receive 1) metformin followed by glipizide and then insulin glargine on failure to achieve glycated hemoglobin A1c (HbA1c) less than 6.5%, or 2) initial triple therapy with metformin/pioglitazone/exenatide. Each patient received a 75-g oral glucose tolerance test (OGTT) prior to start of therapy. Factors that predicted response to therapy were identified using the area under the receiver operating characteristic curve method.

Results

Thirty-nine patients started and maintained the treatment goal (HbA1c < 6.5%) on metformin only, and did not require intensification of antihyperglycemic therapy; 54 patients required addition of glipizide to metformin; and 47 patients required insulin addition to metformin plus glipizide for glucose control. The plasma C-peptide concentration (C-Pep)120/C-Pep0 ratio during the OGTT was the strongest predictor of response to therapy. Patients with a ratio less than 1.78 were more likely to require insulin for glucose control, whereas patients with a ratio greater than 2.65 were more likely to achieve glucose control with metformin monotherapy. In patients started on initial triple therapy, the HbA1c decreased independently of the C-Pep120/C-Pep0 ratio.

Conclusion

The increase in C-Pep above fasting following glucose load predicts the response to antihyperglycemic therapy in patients with new-onset diabetes. C-Pep120/C-Pep0 provides a useful tool for the individualization of antihyperglycemic therapy in patients with new-onset T2DM.
Timing of Pubertal Development and Midlife Blood Pressure in Men and Women: A Mendelian Randomization Study
Authors: Chan Io Ieong , Kwok Man Ki , Schooling C Mary
Published: August 2021

Introduction

Observational studies suggest earlier puberty is associated with higher adulthood blood pressure (BP), but these findings have not been replicated using Mendelian randomization (MR). We examined this question sex-specifically using larger genome-wide association studies (GWAS) with more extensive measures of pubertal timing.

Methods

We obtained genetic instruments proxying pubertal maturation (age at menarche [AAM] or voice breaking [AVB]) from the largest published GWAS. We applied them to summary sex-specific genetic associations with systolic and diastolic BP z-scores, and self-reported hypertension in women (n = 194 174) and men (n = 167 020) from the UK Biobank, using inverse-variance weighted meta-analysis. We conducted sensitivity analyses using other MR methods, including multivariable MR adjusted for childhood obesity proxied by body mass index (BMI). We used late pubertal growth as a validation outcome.

Results

AAM (beta per 1-year later = -0.030 [95% confidence interval, -0.055 to -0.005] and AVB (beta -0.058 [95% CI, -0.100 to -0.015]) were inversely associated with systolic BP independent of childhood BMI, as were diastolic BP (-0.035 [95% CI, -0.060 to -0.009] for AAM and -0.046 [95% CI, -0.089 to -0.004] for AVB) and self-reported hypertension (odds ratio 0.89 [95% CI, 0.84-0.95] for AAM and 0.87 [95% CI, 0.79-0.96] for AVB). AAM and AVB were positively associated with late pubertal growth, as expected. The results were robust to sensitivity analysis using other MR methods.

Conclusion

Timing of pubertal maturation was associated with adulthood BP independent of childhood BMI, highlighting the role of pubertal maturation timing in midlife BP.
Challenges and Opportunities for Osteoporosis Care During the COVID-19 Pandemic
Authors: Cromer Sara J , Yu Elaine W
Published: August 2021

Purpose

The coronavirus disease 2019 (COVID-19) has both directly and indirectly affected osteoporosis diagnosis and treatment throughout the world.

Methods

This mini-review summarizes the available evidence regarding the effects of COVID-19, its treatment, and the consequences of the pandemic itself on bone health. Additionally, we review evidence and expert recommendations regarding putative effects of osteoporosis medications on COVID-19 outcomes and vaccine efficacy and summarize recommendations for continuation of osteoporosis treatment during the pandemic.

Results

The use of standard screening procedures to assess for osteoporosis and fracture risk declined dramatically early in the pandemic, while rates of fragility fractures were largely unchanged. COVID-19, its treatments, and public health measures to prevent viral spread are each likely to negatively affect bone health. Osteoporosis treatments are not known to increase risk of adverse events from COVID-19, and preclinical data suggest possible beneficial effects of some therapies. Vitamin D deficiency is clearly associated with adverse outcomes from COVID-19, but it remains unclear whether vitamin D supplementation may improve outcomes. Osteoporosis treatment should be continued whenever possible, and recommendations for substituting therapies, if required, are available.

Conclusion

The COVID-19 pandemic has decreased screening and disrupted treatment for osteoporosis. Osteoporosis medications are safe and effective during the pandemic and should be continued whenever possible. Further studies are needed to fully understand the impact of the COVID-19 pandemic on long-term bone health.
High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve Risk Prediction for Type 1 Diabetes
Authors: Jia Xiaofan , He Ling , Miao Dongmei , Waugh Kathleen , Rasmussen Cristy Geno , Dong Fran , Steck Andrea K , Rewers Marian , Yu Liping
Published: August 2021

Context

Single ZnT8 autoantibody (ZnT8A) positivity by standard radiobinding assay (RBA) is commonly seen in nondiabetes population-based screening and the risk of progression to type 1 diabetes (T1D) in subjects with single ZnT8A is unknown.

Objective

Identify the risk of progression to T1D in individuals positive only for ZnT8A.

Methods

We developed an electrochemiluminescence (ECL) assay to detect high-affinity ZnT8A and validated it in 3 populations: 302 patients newly diagnosed with T1D, 135 nondiabetic children positive for ZnT8A by RBA among 23 400 children screened by the Autoimmunity Screening for Kids (ASK) study, and 123 nondiabetic children multiple autoantibody positive or single ZnT8A positive by RBA participating in the Diabetes Autoimmunity Study in the Young (DAISY).

Results

In 302 patients with T1D at diagnosis, the positivity for ZnT8A was 62% both in RBA and ECL. Among ASK 135 participants positive for RBA-ZnT8A, 64 were detected ZnT8A as the only islet autoantibody. Of these 64, only 9 were confirmed by ECL-ZnT8A, found to be of high affinity with increased T1D risk. The overall positive predictive value of ECL-ZnT8A for T1D risk was 87.1%, significantly higher than that of RBA-ZnT8A (53.5%, P < .001). In DAISY, 11 of 2547 children who had no positivity previously detected for other islet autoantibodies were identified as single ZnT8A by RBA; of these, 3 were confirmed positive by ECL-ZnT8A and all 3 progressed to clinical T1D.

Conclusion

A large proportion of ZnT8A by RBA are single ZnT8A with low T1D risk, whereas ZnT8A by ECL was of high affinity and high prediction for T1D development.
Spontaneity of nuclear fusion: a qualitative analysis via classical thermodynamics
Authors: Tosti Silvano
Published: August 2021

Background: So far the feasibility of nuclear reactions has been studied only through the evaluation of the reaction rate, which gives us information about the kinetics, while the thermodynamic analysis has been limited to evaluations of the change in enthalpy without any consideration of the change in entropy.

Methods: This work examines the thermodynamics of nuclear fusion reactions through a simplified approach. The analysis introduces the thermodynamic study of fission and fusion reactions through their comparison with a chemical process.

Results: The main result is that fission reactions are always spontaneous (ΔG < 0) since a lot of energy is released in the form of heat and the system moves spontaneously towards a more disordered state. In contrast, fusion reactions are spontaneous only when the enthalpic contribution of the change in Gibbs free energy overcomes the entropic contribution. This condition is verified when the temperature of the process is below a characteristic value T*, calculated as the ratio between the energy corresponding to the mass defect and the change of entropy of the fusion reaction.

Conclusions: Due to the unavailability of data related to entropy changes in fusion reactions, only a qualitative thermodynamic analysis has been carried out. Through such analysis, the influence of the operating conditions over the spontaneity of fusion processes has been discussed. The final considerations emphasize the role of the thermodynamics analysis that should be implemented in the current studies that, so far, have been mainly based on the assessment of the reaction rate and exothermicity of fusion reactions.
STOCHASTIC ANALYSIS AND OPTIMAL MANAGEMENT OF STAFF INCENTIVES IN A COMMERCIAL ORGANIZATION
Authors: Kondrat'ev Dmitriy , Ostaev Gamlet , Klychova Guzaliya , Valiev Ayrat , Ziganshin Bulat
Published: August 2021

The article discusses the issues of research and assessment of the impact of quantitative parameters of material and social incentives for personnel on the financial results of the activities of commercial organizations, as well as issues of optimal management of these parameters. Stimulation of personnel acts as a tool that guides employees of the organization to achieve specific productive indicators of its activity that have value for the organization by strengthening the desired motives and reinforcing the required motivational structure in the team. Studying the influence of individual incentives on the motivation and performance of an organization is an important management task that provides information necessary for making decisions on improving the incentive system. Therefore, the paper substantiates the methodological tools for stochastic analysis, forecasting and programming the dependence of financial results of work on the quantitative values of individual stimulating factors based on the methods of regression and economic analysis, the index forecasting method. Also, a methodological toolkit for mathematical modeling and optimal decision-making on the prospective structure of quantitative parameters of the organization's personnel incentive system was developed on the basis of the obtained stochastic dependencies and linear programming methods. The article presents an example of mathematical formalization, practical implementation and economic interpretation of tools for stochastic analysis and optimal management of staff incentives based on the proceedings of an agricultural organization. The methods and tools for managing staff incentives described in the work can be used by business entities of various industries and spheres of activity when justifying the directions of restructuring the systems of motivation and incentives for personnel
ADAPTABILITY OF WINTER WHEAT FROM THE INSTITUTE OF PLANT INDUSTRY (VIR) COLLECTION IN THE CIS-MIDDLE URALS
Authors: Torbina Irina , Fardeeva Il'vira
Published: August 2021

The purpose of the research is to identify sources of economically valuable properties for creating a genetic collection of winter wheat in the Cis-middle Urals. The material for research was 30 varieties of winter wheat from the VIR collection for adaptability. The study was carried out in 2016-2019 at the experimental field of the UdmFIC Ural Branch of the Russian Academy of Sciences (Pervomaysky village, Zavyalovsky district of Udmurtia). The soil of the experimental site is well cultivated sod-podzolic medium loamy. According to method of L.A. Zhivotkova, Z.N. Morozova, L.I. Sekatueva (1994) 15 varieties were more adapted to local conditions. These varieties, on average for 3 years of research, formed higher yields (by 2-107 %) than the average for all varieties. The indicator of the level of stability of the variety (ILSV), calculated by the method of E.D. Nettevich (1985) identified only three of the most valuable varieties - Sarlota (ILSV 283 %), Venistar (ILSV 238 %) and Alauda (ILSV 124 %). Overwintering of varieties on average for 2017-2019 was 32 ... 68 %, for the standard-60 %. The best winter hardiness was obtained in the samples Sarlota (68 %) and Vanda (63 %). The sources of high grain content of the spike (33.6...50.8 pcs.) were identified – variety samples Markola, Sarlota, Veldana, Venistar. Large grain (mass of 1000 grains 42.6...52.3 g) formed varieties Charodijka Bilotserkivsʹka, Gonoveva, Stanislava, Sarlota, Vanda. Warm and humid weather in the summer of 2019 led to the massive development of powdery mildew. The varieties Charodijka BilotserkivskaKa, KhmelnNychanka, Zluka, Komertsijna, Markola, Gonoveva were highly stable (7...9 points) for this disease. The increased air temperature and the presence of a drip liquid were the reasons for the intensive development of brown rust in 2017. High stability (7...9 points) this year the varieties Gordovyta, Lasurna, Zluka, Gonoveva, Sarlota, Veldana and Venistar showed signs of illness
INFLUENCE OF FUNGICIDAL TREATMENT ON YIELD AND GRAIN QUALITY OF WINTER WHEAT
Authors: Fadeeva Irina , Gazizov Ilyas , Kurmakaev Fail' , Ignat'eva Irina
Published: August 2021

In 2017-2019, studies were carried out in the Republic of Tatarstan to study the effect of fungicidal treatment on the yield and grain quality of new varieties of winter wheat. The experiment scheme provided for the study of the following options: variety (factor A) - Darina, Nadezhda, Universiade; fungicidal treatment with Titul Duo at a dose of 0.25 l / ha in the heading phase (factor B), years (factor C). The predecessor is pure steam. The soil in the experiment was gray forest, medium loamy. Content in the arable layer: humus (according to Tyurin) - 3.1-3.4%; pHsal. - 5.2-5.5; K2O (according to Kirsanov) - 122-145 mg / kg of soil, P2O5 (according to Kirsanov) - 262-271 mg / kg of soil. Plot area - 25 m2. The yield and quality of grain largely depend on the phytosanitary state of winter wheat crops, in particular, on the development of diseases. The prevalence and harmfulness of leaf-stem diseases in wheat largely depends on the temperature conditions during the growing season of the crop and on the moisture conditions. As a result of the development of diseases, there is a significant decrease not only in yield, but also a deterioration in the quality characteristics of wheat grain. The highest percentage of prevalence (85%) and intensity of development (45.7%) of powdery mildew was observed in the Universiade variety. Evaluation of plants showed a low lesion of the leaf surface by leaf rust: from 18.6% in the Nadezhda variety to 24.6% in the Universiade variety. The biological effectiveness of protective measures in winter wheat crops when treated with a fungicide has been calculated. On average for varieties for three years, the biological effectiveness of the use of the drug Title Duo was more than 90%. The fungicide treatment increased the yield on average for the studied varieties by 0.55 t / ha. The maximum increase in grain yield was obtained for the Universiade variety - 0.68 t / ha. Indicators of technological quality of grain with an average for varieties increased after treatment with fungicide sowing: weight of 1000 grains per 2.2 grams; grain nature by 5.4 g / l; glassiness by 2.6%; evenness by 1.4%; the wet gluten content is 1.6%. According to the results of analysis of variance, a significant influence of the conditions of the year on the indicators of the technological quality of grain was established: on the nature of the grain (56.8%), the total glassiness of the grain (51.43%), the mass of 1000 grains (51.4%) and the gluten deformation index (52.37%). To a lesser extent, environmental conditions influenced the evenness of the grain (22.0%) and the mass fraction of gluten in the grain (21.66%). At the same time, the contribution of the fungicide to the formation of indicators of the technological quality of grain varied from 7.69% (grain evenness) to 32.43% (gluten content). The grain nature by 14.99% was determined by the fungicidal treatment of crops and only by 10.61% depended on the genotype