bluuebunny/crossref_metadata_2025 huggingface dataset:
Permethrin-treated baby wraps for the prevention of malaria: results of a randomized controlled pilot study in rural Uganda
Authors: Boyce Ross M. , Muhindo Enid , Baguma Emmanuel , Muhindo Rabbison , Shem Bwambale , François Ruthly , Hawke Sam , Shook-Sa Bonnie E. , Ntaro Moses , Nalusaji Aisha , Nyehangane Dan , Reyes Raquel , Juliano Jonathan J. , Siedner Mark J. , Staedke Sarah G. , Mulogo Edgar M.
Published: February 2022

Background

Progress against malaria has stalled and may even be slipping backwards in high-burden countries. This is due to a range of factors including insecticide resistance and mosquito feeding behaviours that limit contact with widely-employed interventions including long-lasting insecticidal nets and indoor-residual spraying. Thus, further innovations in malaria control are urgently needed.

Methods

The pilot was a randomized, placebo-controlled pilot study of permethrin-treated baby wraps—known locally as lesus—in children 6–18 months of age at a single site in rural western Uganda. Fifty mother–infant pairs were assigned to permethrin-treated or untreated lesus in a 1:1 allocation. Participants and clinical staff were blinded to group assignments through use of sham treatment and re-treatment of lesus. Participants attended scheduled clinic visits every 2 weeks for a total 12 weeks. The primary outcome of interest was the safety of the intervention, assessed as changes in the frequency of use, rates of discontinuation, and incidence of adverse events, such as skin rash. Secondary outcomes included acceptability and feasibility of the intervention as measured through participant satisfaction and completion of study activities, respectively.

Results

Overall, rates of retention and participation were relatively high with 86.0% (43 of 50) of participants completing all scheduled visits, including 18 (75.0%) and 25 (96.2%) in the intervention and control arms respectively. By the conclusion of the 12-week follow-up period, one adverse event (0.35 events per 100 person-weeks, one-sided 95% CI 0.0–1.65) was reported. Satisfaction with the lesu was high in both groups. In each study arm, there were five incident RDT positive results, but the only PCR-positive results were observed in the control group (n = 2).

Conclusions

Permethrin-treated baby wraps were well-tolerated and broadly acceptable. Adverse events were infrequent and mild. These findings support future trials seeking to determine the efficacy of treated wraps to prevent P. falciparum malaria infection in young children as a complementary tool to existing household-based interventions.

Trial registration: ClinicalTrials.gov Identifier: NCT04102592, Registered 25 September 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT04102592
The durability, functionality and acceptability of novel screened doors and windows after 4 years of use in a Gambian village: a cross-sectional survey
Authors: Shenton Fiona C. , Jawara Musa , Carrasco-Tenezaca Majo , Knudsen Jakob , D’Alessandro Umberto , Lindsay Steve W.
Published: February 2022

Background

The World Health Organization recommends house screening as a tool for malaria control, yet evidence of the long-term durability, functionality and acceptability of this intervention is lacking. In this study, the sustainability and use of novel types of screened doors and windows was examined 4 years after installation in a Gambian village.

Methods

A survey of 31 houses, each with two screened doors and two screened windows, was conducted in the rainy season. There were four types of screened door and two types of screened window. Trained staff carried out the survey and interviews of room owners were conducted in the local language before translation into English.

Results

Structurally, the manufactured doors and windows were highly durable and in excellent condition. Most doors shut smoothly 50/61 (82%), although only 25/61 (41%) shut fully automatically with the latch slotting into the hole on the frame and holding fast. Door locks were less robust, with only (24/61) 39% present and working. Blinds proved especially flimsy, with only 4/109 (4%) of door blinds and 10/56 (18%) of window blinds present and in working order. Householders hung curtains inside most doors 50/61 (82%) and in 26/61 (43%) of the windows. Front doors were commonly found propped open 21/31 (68%) and 23/27 (85%) of those with a front door curtain, put their curtains down at night. Doors and windows were well liked, 19/31 (61%) of respondents were happy with them because they kept mosquitoes out 14/31 (45%) and provided security 12/31 (39%). The main reason given for the use of curtains was to provide privacy 26/28 (93% of those with curtains), especially while the door was open or had ‘see-through’ panels.

Conclusions

Overall, the screened doors and windows were in full-working order and undamaged after 4 years of use. The doors and windows were well liked, especially for their ability to reduce the entry of mosquitoes and for the security they afforded. Improvements to the lock design are needed before scale-up. Most householders hung curtains behind their doors for privacy. Installation of screening in buildings should be accompanied with recommendations that at night, when doors and windows are closed, curtains be lifted or drawn to one side—to improve ventilation and keep the house cool.
Reducing the equity gap in child health care and health system reforms in Latin America
Authors: Maceira Daniel , Brumana Luisa , Aleman Joaquín González
Published: February 2022

Background

During the first decade of the current century, Latin American countries have shown high and consistent economic growth rates, increasing per capita GDP and reducing poverty. Social indicators improved in even the poorest and least equitable countries in the region. In terms of health care results, marked advances were made in infant mortality rates.

Objective

The aim of this paper is to identify if decreasing poverty rates in Latin America and the Caribbean during the first decade of the century have had an effect on health inequality, specifically by reducing the health care equity gap and, if so, whether that trend and its effects were distributed evenly at the sub-national level.

Methods

Basic statistical tools were applied to national and sub-national administrative data for eleven Latin American countries (Argentina, Belize, Bolivia, Brazil, Colombia, Dominican Republic, El Salvador, Mexico, Nicaragua, Peru, and Uruguay) to compare the evolution of a set of social determinants with a classic health care outcome, such infant mortality) during the period 1995–2012. This document proposes a set of indicators to analyze relative evolution of results and convergence to equity, and to discuss general trends in health care reforms across the region.

Results

The document shows a correspondence between poverty reduction, and improvement of health care indicators at a regional level, though national differences persist. In some cases, like Brazil and Peru, the reduction in infant mortality rates is coupled with significant movements towards health equity. This trend is different in Bolivia, where the drop in poverty is not followed by better outcomes in poor departments. At the same, results are not necessarily linked to health systems organization and/or specific reforms. For instance, both Brazil and Peru pursue in applying decentralized solutions, although the incentive mechanisms are quite different: the former has a supply side structure at the public provision level while the latter has implemented mixed payment systems.

Conclusion

While some of the same instruments and measures of effectiveness in health care reforms appear across the region, specific impact evaluations should be performed. To reduce the equity gap in Latin America requires not only major improvements in social determinants but also the design and implementation of sound institutional policy and more robust regulatory frameworks (institutional determinants) so that more resources yield better practices.
The impact of body mass index (BMI) on MRI diagnostic performance and surgical management for axillary lymph node in breast cancer
Authors: Chen Shu-Tian , Lai Hung-Wen , Wu Wen-Pei , Chen Shou-Tung , Liao Chiung-Ying , Wu Hwa-Koon , Chen Dar-Ren , Mok Chi Wei
Published: February 2022

Background

We hypothesized that different BMI might have different impact on pre-operative MRI axillary lymph node (ALN) prediction accuracy and thereby subsequent surgical lymph node management. The aim of this study is to evaluate the effect of BMI on presentation, surgical treatment, and MRI performance characteristics of breast cancer with the main focus on ALN metastasis evaluation.

Methods

The medical records of patients with primary invasive breast cancer who had pre-operative breast MRI and underwent surgical resection were retrospectively reviewed. They were categorized into 3 groups in this study: underweight (BMI < 18.5), normal (BMI of 18.5 to 24), and overweight (BMI > 24). Patients’ characteristics, surgical management, and MRI performance for axillary evaluation between the 3 groups were compared.

Results

A total of 2084 invasive breast cancer patients with a mean age of 53.4 ± 11.2 years were included. Overweight women had a higher rate of breast conserving surgery (56.7% vs. 54.5% and 52.1%) and initial axillary lymph node dissection (15.9% vs. 12.2% and 8.5%) if compared to normal and underweight women. Although the post-operative ALN positive rates were similar between the 3 groups, overweight women were significantly found to have more axillary metastasis on MRI compared with normal and underweight women (50.2% vs 37.7% and 18.3%). There was lower accuracy in terms of MRI prediction in overweight women (65.1%) than in normal and underweight women (67.8% and 76.1%).

Conclusion

Our findings suggest that BMI may influence the diagnostic performance on MRI on ALN involvement and the surgical management of the axilla in overweight to obese women with breast cancer.
Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency
Authors: Li Yanan , Steinberg Jeffrey , Coleman Zane , Wang Shubo , Subramanian Chitra , Li Yimei , Patay Zoltan , Akers Walter , Rock Charles O. , Jackowski Suzanne , Bagga Puneet
Published: February 2022

Background

Pantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden–Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency. A reliable technique to identify the neurometabolic effects of PANK dysfunction and to monitor therapeutic responses is needed.

Methods

We applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671.

Results

1H MRS reliably quantified changes in cerebral metabolites, including glutamate/glutamine, lactate, and N-acetyl aspartate in a neuronal Pank1 and Pank2 double-knockout (SynCre+Pank1,2 dKO) mouse model of brain CoA deficiency. The neuronal SynCre+Pank1,2 dKO mice had distinct decreases in Glx/tCr, NAA/tCr, and lactate/tCr ratios compared to the wildtype matched control mice that increased in response to BBP-671 treatment.

Conclusions

BBP-671 treatment completely restored glutamate/glutamine levels in the brains of the mouse model, suggesting that these metabolites are promising clinically translatable biomarkers for future therapeutic trials.
Modulation of the tumor microenvironment by armed vesicular stomatitis virus in a syngeneic pancreatic cancer model
Authors: Tang Sijia , Shi Lei , Luker Breona T. , Mickler Channen , Suresh Bhavana , Lesinski Gregory B. , Fan Daping , Liu Yuan , Luo Ming
Published: February 2022

Background

The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma is a major factor that limits the benefits of immunotherapy, especially immune checkpoint blockade. One viable strategy for reverting the immunosuppressive conditions is the use of an oncolytic virus (OV) in combination with other immunotherapy approaches. Infection of PDAC cells with a robust OV can change the tumor microenvironment and increase tumor antigen release by its lytic activities. These changes in the tumor may improve responses to immunotherapy, including immune checkpoint blockade. However, a more potent OV may be required for efficiently infecting pancreatic tumors that may be resistant to OV.

Methods

Vesicular stomatitis virus, a rapid replicating OV, was armed to express the Smac protein during virus infection (VSV-S). Adaptation by limited dilution largely increased the selective infection of pancreatic cancer cells by VSV-S. The engineered OV was propagated to a large quantity and evaluated for their antitumor activities in an animal model.

Results

In a syngeneic KPC model, intratumoral injection of VSV-S inhibited tumor growth, and induced increasing tumor infiltration of neutrophils and elimination of myeloid derived suppressor cells and macrophages in the tumor. More importantly, M2-like macrophages were eliminated preferentially over those with an M1 phenotype. Reduced levels of arginase 1, TGF-β and IL-10 in the tumor also provided evidence for reversion of the immunosuppressive conditions by VSV-S infection. In several cases, tumors were completely cleared by VSV-S treatment, especially when combined with anti-PD-1 therapy. A long-term survival of 44% was achieved.

Conclusions

The improved OV, VSV-S, was shown to drastically alter the immune suppressive tumor microenvironment when intratumorally injected. Our results suggest that the combination of potent OV treatment with immune checkpoint blockade may be a promising strategy to treat pancreatic cancer more effectively.
Identification of immune-infiltrated hub genes as potential biomarkers of Moyamoya disease by bioinformatics analysis
Authors: Jin Fa , Duan Chuanzhi
Published: February 2022

Background

Moyamoya disease (MMD) is a rare chronic progressive cerebrovascular disease. Recent studies have shown that autoimmune inflammation may also be an important pathology in MMD but the molecular mechanisms of inflammation in this disease are still large unknown. This study was designed to identify key biomarkers and the immune infiltration in vessel tissue of MMD using bioinformatics analysis.

Methods

Raw gene expression profiles (GSE157628, GSE141024) were downloaded from the Gene Expression Omnibus (GEO) database, identified differentially expressed genes (DEGs) and performed functional enrichment analysis. The CIBERSORT deconvolution algorithm was used to analyze the proportion of immune cells between MMD and an MMD-negative control group. We screened for neutrophil-associated DEGs, constructed a protein–protein interaction network (PPI) using STRING, and clarified the gene cluster using the Cytoscape plugin MCODE analysis. The receiver operating characteristic (ROC) curve was applied to test and filter the best gene signature.

Results

A total of 570 DEGs were detected, including 212 downregulated and 358 up-regulated genes. Reactome and KEGG enrichment revealed that DEGs were involved in the cell cycle, molecular transport, and metabolic pathways. The immune infiltration profile demonstrated that MMD cerebrovascular tissues contained a higher proportion of neutrophils, monocytes, and natural killer cells in MMD than in controls. The PPI network and MCODE cluster identified nine DEGs (UNC13D, AZU1, PYCARD, ELANE, SDCBP, CCL11, CCL15, CCL20, and CXCL5) associated with neutrophil infiltration. ROC results showed that UNC13D has good specificity and sensitivity (AUC = 0.7846).

Conclusions

The characteristics of immune infiltration in the cerebrovascular tissues of MMD patients and abnormal expression of hub genes provide new insights for understanding MMD progression. UNC13D is shows promise as a candidate molecule to determine neutrophil infiltration characteristics in MMD.
Concordance between the schedule for the evaluation of individual quality of life-direct weighting (SEIQoL-DW) and the EuroQoL-5D (EQ-5D) measures of quality of life outcomes in adults with X-linked hypophosphatemia
Authors: Jandhyala Ravi
Published: February 2022

Background

Accurate measurement of any constructs in clinical studies is of critical importance, especially if the adoption of an intervention relies on detecting a significant treatment effect where one exists. Under Neutral theory, the amount of relevant and irrelevant indicators selected to operationalise the construct contribute equally to the accuracy of the observation. The Neutral or accurate observation is achieved by observing all relevant indicators only. Generic QoL instruments such as EQ-5D are increasingly being accepted as imprecise, especially in rare diseases, based on the relevance of their indicators. QoL is a construct that embodies a patient's subjectivity, individuality, and local circumstances at measurement. SEIQoL-DW is an instrument designed to respect these characteristics of QoL through eliciting indicators or cues directly from the subject along with the proportion of the overall QoL they contribute. EQ-5D and SEIQoL can therefore be considered as being at opposing ends of accuracy in QoL measurement. XLH is a hereditary, progressive, rare disease characterised by phosphate wasting, affecting both children and adults and impacting their QoL. The purpose of this study was to observe if any change in QoL of adult XLH patients were detectable using EQ-5D, SEIQoL eliciting new cues at each visit, and SEIQoL administering baseline cues overall visits (thereby silencing its time-dependency) versus baseline over 12 months. In addition, any association between the three sets of observations was explored.

Results

All quality of life scores were observed to decrease from baseline by 13.36%, 7.32% and 2.7% based on SEIQoLvisit_cues, SEIQoLbaseline_cues, and EQ-5D assessments, respectively. The decrease in the quality of life scores was only statistically significant (p = 0.037) for SEIQoLvisit_cues. Beyond the baseline visit, the only highly positive and statistically significant pairwise association was between SEIQoLvisit_cues and SEIQoLbaseline_cues at M6 (ρ = 0.782, P value < 0.05) and M9 (ρ = 0.879, P value < 0.05).

Conclusions

EQ-5D and SEIQoLbaseline_cues failed to detect the same statistically significant decrease in QoL observed by SEIQoLvisit_cues. Both sets of SEIQoL observations were more closely associated with each other than with EQ-5D. Observing constructs such as QoL in rare diseases benefit from a Neutrality in indicator selection and respecting variation in dominance of various indicators over time.
Construction and immune effect of an HPV16/18/58 trivalent therapeutic adenovirus vector vaccine
Authors: Wan Bing , Qin Lu , Ma Weihong , Wang He
Published: February 2022

Objective

This study aims to prepare candidate vaccines for cervical cancer immunotherapy by inserting the fused genes of human papillomavirus (HPV)16/18/58 mE6E7 lacking transforming activity into an adenovirus vector and to verify its efficiency in model mice with tumor expressing the associated HPV genes.

Methods

The E6/E7 genes of HPV16/18/58 were point-mutated to abolish their transforming activity, and adenovirus (AD)-HPV16/18/58 mE6E7 adenovirus vaccine was constructed. The immune effect of the adenovirus vaccine against HPV16/18/58-type tumors was analyzed by tumor morphology, enzyme linked immunosorbent assay, enzyme-linked immunospot and specific cytotoxic T lymphocyte (CTL) and T lymphocyte subsets.

Results

The HPV16/18/58 mE6E7 plasmid containing point mutations was verified by quantitative real-time polymerase chain reaction (qRT-PCR), enzyme digestion and electrophoresis, and gene sequencing. qRT-PCR and Western blots verified that AD-HPV16/18/58 mE6E7 could express the HPV16 mE6E7, HPV18 mE6E7 and HPV58 mE6E7 fusion genes and proteins in cells. The results of animal experiments were as follows: In the vaccine group, the tumors formed later, the incubation period was longer, the growth was slower, growth was inhibited, and the survival period was significantly prolonged. The immunological results all showed that the vaccine could induce effective humoral and cellular immunity in mice with three types of tumors, compared with the phosphate buffered saline (PBS) group and the adenovirus-negative control (AD-NC) group, the differences were statistically significant (P < 0.05).

Conclusion

We successfully constructed the HPV16/18/58 trivalent therapeutic adenovirus vaccine AD-HPV16/18/58 mE6E7. The AD-HPV16/18/58 mE6E7 adenovirus vaccine can protect immunized mice to a certain extent from TC-1, U14/LV-HPV18 E6E7 and U14/LV-HPV58 E6E7 cells, which contain HPV16, 18 and 58 E6 and/or E7 genes, respectively.
SARS-CoV-2 infection as possible downstream disease precipitator in autoantibody-positive insulin-dependent diabetes mellitus: a case report
Authors: Schiaffini Riccardo , Campana Andrea , Deodati Annalisa , Peschiaroli Emanuela , Lanzillotta Maria Francesca , Fierabracci Alessandra
Published: February 2022

Background

SARS-CoV-2 causes lesions, in addition to lung, in endocrine organs such as the pancreas through ACE2 receptor. Recently the relationship between SARS-CoV-2 exposition and the incidence or evolution of clinical autoimmune diabetes has attracted the attention of diabetologists.

Case presentation

We report the analysis of the clinical history of a child diagnosed for insulin-dependent diabetes mellitus (Type 1 diabetes) at the time a paucisymptomatic COVID-19 infection occurred, followed by well-controlled metabolic status. As opposite to previous findings SARS-CoV2 did not cause ketosis and ketoacidosis. Polydipsia was reported a few months and weight loss 4 weeks before SARS- CoV-2 infection suggesting that SARS-CoV-2 could not be the trigger of Type 1 diabetes in this patient.

Conclusions

SARS-CoV-2 in this patient was an unexpected event in the course of disease. We advance the hypothesis that the SARS-CoV-2 infection, even if paucisymptomatic could have acted in the present case report as a hypothetical downstream precipitating factor; whilst the inciting triggering event of the autoimmune disease, as confirmed by the presence of circulating autoantibodies, could have occurred even before, as generally assumed for this category of disorders. The precipitating mechanism could have been the acute interaction between virus and the ACE receptor on the beta cells, at the time that hyperglycemia and glycosuria were ascertained, and HbA1c levels confirmed a metabolic dysregulation over the previous 3 months in absence of ketoacidosis.
A novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys), in a Chinese son and his father with lipoprotein glomerulopathy: two case reports
Authors: Wang Runxiu , Zhao Chengbo , Chen Wen , Liu Zhiping , Xie Fuhua
Published: February 2022

Background

Lipoprotein glomerulopathy is a rare and newly recognized glomerular disease that can lead to kidney failure. Its pathological features include the presence of lipoprotein embolus in the loop cavity of glomerular capillaries. It is believed that apolipoprotein E gene mutation is the initiator of the disease. Since the discovery of lipoprotein glomerulopathy, 16 different apolipoprotein E mutations have been reported worldwide, but most of these cases are sporadic. Here we report two cases of lipoprotein glomerulopathy, a Chinese son and his father, with a novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys).

Case presentation

Case 1, a 33-year-old Chinese man, was hospitalized on 3 March 2014 owing to edema and weakness of facial and lower limbs for 1 month. Laboratory data showed urine protein 3+, hematuria 2+, serum creatinine 203 μmol/L, uric acid 670 μmol/L, total cholesterol 12.91 mmol/L, triglyceride 5.61 mmol/L, high-density lipoprotein 1.3 mmol/L, low-density lipoprotein 7.24 mmol/L, apolipoprotein B 2.48 g/L, and lipid protein (a) 571 mg/L. Renal tissue examined by immunofluorescence and electron microscopy indicated lipoprotein glomerulopathy. Case 2, 55-year-old father of case 1, was hospitalized on 12 January 2016 owing to edema of his lower extremities for 6 months. Laboratory data showed urine protein 2+, hematuria 2+, serum creatinine 95 μmol/L, uric acid 440 μmol/L, total cholesterol 4.97 mmol/L, triglyceride 1.91 mmol/L, high-density lipoprotein 1.18 mmol/L, low-density lipoprotein 3.12 mmol/L, apolipoprotein B 2.48 g/L, and lipid protein (a) 196 mg/L. Renal tissue examined by immunofluorescence and electron microscopy indicated lipoprotein glomerulopathy. Apolipoprotein E mutation test showed that they had the same gene mutation, a novel type of apolipoprotein E mutation.

Based on their clinical presentation and examination findings, they were diagnosed with lipoprotein glomerulopathy. Case 1 was treated with prednisone and dual plasma replacement, followed by simvastatin, nifedipine, triptolide, and angiotensin II receptor blocker drug therapy. After 1 month, the edema symptoms of the patient were alleviated, and urinary protein, serum creatinine, and uric acid were quantitatively reduced. Case 2 was treated with Tripterygium wilfordii and angiotensin II receptor blocker drugs for 3 weeks, and his edema symptoms were alleviated, and urinary protein, serum creatinine, and uric acid were quantitatively reduced.

Conclusions

The apolipoprotein E mutation in the two cases we reported was a familial aggregation phenomenon, and the mutation is a novel type, which we named ApoE Ganzhou (Arg43Cys). The location of the gene mutation is close to the most common mutation type of lipoprotein glomerulopathy, ApoE Kyoto (Arg25Cys), so we speculate that its pathogenic role might be the similar to that of ApoE Kyoto (Arg25Cys).
Note on difference equations with the right-hand side function nonincreasing in each variable
Authors: Stević Stevo , Iričanin Bratislav , Kosmala Witold , Šmarda Zdeněk
Published: February 2022

We present an example of a difference equation of arbitrary order, possessing the right-hand side function that is homogeneous to a certain degree and nonincreasing in each variable, which has a unique positive equilibrium, as well as solutions that do not converge to the equilibrium. The example shows that the main result in the paper: O. Moaaz, Dynamics of difference equation $x_{n+1}=f(x_{n-l}, x_{n-k})$

x

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+
1

=
f
(

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−
l

,

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n
−
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(Adv. Differ. Equ. 2018:447, 2018), is incorrect.
Approximation by bivariate Chlodowsky type Szász–Durrmeyer operators and associated GBS operators on weighted spaces
Authors: Aslan Reşat , Mursaleen M.
Published: February 2022

In this article, we consider a bivariate Chlodowsky type Szász–Durrmeyer operators on weighted spaces. We obtain the rate of approximation in connection with the partial and complete modulus of continuity and also for the elements of the Lipschitz type class. Moreover, we examine the degree of convergence with regard to the weighted modulus of continuity and Peetre’sK-functional. Further, we construct the associated GBS type of these operators and estimate the degree of approximation using the mixed modulus of continuity and a class of the Lipschitz of Bögel type continuous functions. Finally, with the help of Maple software, we present the comparisons of the convergence of the bivariate Chlodowsky type Szász–Durrmeyer operators and associated GBS type operators to certain functions with some graphs and error estimation tables.
What drives internationalization of new ventures? Evidence from India
Authors: Arafat Mohd. Yasir , Khan Ahmed Musa , Ansari Mohd Shamim , Saleem Imran
Published: February 2022

The researchers have already recognized the importance of entrepreneurship, but the role of new venture internationalization is still a matter of research. This study is measuring the influence of education, age, technology, fear of failure, and competition on new venture internationalization. It based on the interviews of 3413 respondents from India done by the Global Entrepreneurship Monitor. The influence of various factors on new venture internationalization has been measured through logistic regression. The technology, fear of failure, and competition have a significantly positive influence on new venture internationalization. This is one of the inceptive studies to measure the impact of education, age, technology, fear of failure and competition on new venture internationalization.
Progression patterns in monoclonal gammopathy of undetermined significance and multiple myeloma outcome: a cohort study in 42 patients
Authors: Tahiru Widad , Izarra Santamaria Antonio , Hultdin Johan , Wu Wendy Yi-Ying , Späth Florentin
Published: February 2022

Follow-up of low-risk monoclonal gammopathy of undetermined significance (MGUS) is debated as multiple myeloma (MM) progression risk is low. Worse MM outcome was reported for patients followed for low-risk MGUS, possibly due to less optimal follow-up. However, it is unknown whether progressing low-risk MGUS is associated with aggressive tumor behavior. Understanding these patterns is crucial for MGUS management. Here, we investigated whether progression from low-risk MGUS is associated with worse MM outcome in patients who had no MGUS follow-up before myeloma diagnosis. We retrospectively determined the MGUS status in repeated pre-diagnostic blood samples prospectively collected from 42 myeloma patients in median 11.6 years (first sample) and 3.3 years (repeated sample) before myeloma diagnosis. At first pre-diagnostic blood draw, 12 had low-risk (defined by an immunoglobulin [Ig] G monoclonal [M] spike < 15 g/L and a normal free light-chain ratio) and 30 had MGUS of other risk. MM bone disease was more common in patients with low-risk MGUS at first blood draw (67% vs. 30%, P = 0.041). Median survival since myeloma diagnosis was worse in low-risk than other MGUS at first blood draw (2.3 vs. 7.5 years, P = 0.004). Modest progression was observed between first and repeated blood draw for the majority of low-risk MGUS as 67% remained as low- or low-intermediate-risk MGUS at repeated blood draw. Our study, albeit limited by its small size, indicates that progression from low-risk MGUS is associated with worse MM outcome regardless of MGUS follow-up. Although further investigation is needed, progressing low-risk MGUS could belong to a group of aggressive tumors with progression that is difficult to predict.
HOXA13 promotes gastric cancer progression partially via the FN1-mediated FAK/Src axis
Authors: Qin Zhiwei , Zhou Chongzhi
Published: February 2022

Background

Gastric cancer (GC) is one of the most common cancers causing a poor prognosis worldwide. HOXA13, as a member of the homeobox (HOX) family, is involved in the regulation of cancer progression and has attracted increasing attention, as a potential novel target for anticancer strategies. However, the significance of HOXA13 in GC remains unclear. This article aims to explore the potential mechanism of HOXA13 in GC progression.

Methods

Quantitative real-time PCR was carried out to detect the expression of HOXA13 and FN1 and the correlation between HOXA13 and FN1 in GC tissues. In vitro assays were conducted to investigate the role of HOXA13 and FN1 in the malignant phenotypes of GC cells and the function of HOXA13 in the activation of the FAK/Src axis in GC cells. Coimmunoprecipitation was performed to reveal the relationship between ITGA5, ITGB1 and FN1 in GC cells. A dual luciferase assay was performed to assess miR-449a-targeted regulation of HOXA13 expression.

Results

Quantitative real-time PCR verified that HOXA13 was elevated and positively correlated with FN1 in GC. In vitro and in vivo assays demonstrated that high expression of HOXA13 promoted GC progression, especially metastasis. Mechanistically, rescue experiments, chromatin immunoprecipitation and dual luciferase assays revealed that HOXA13 directly bound to the FN1 promoter region to enhance the activation of the FAK/Src axis, leading to GC cell proliferation and metastasis. Furthermore, the result of a dual luciferase assay suggested that HOXA13 was directly targeted by miR-449a.

Conclusions

Our results show that HOXA13 is a positive regulator of the FAK/Src axis mediated by FN1 in GC and promotes GC progression. Thus, targeting HOXA13, together with FN1, may provide a novel prospective anticancer strategy.
Effect of arbuscular mycorrhizal fungi on the accumulation of secondary metabolites in roots and reproductive organs of Solanum nigrum, Digitaria sanguinalis and Ipomoea purpurea
Authors: Rashidi Sakineh , Yousefi Ali Reza , Pouryousef Majid , Goicoechea Nieves
Published: February 2022

Background

The application of arbuscular mycorrhizal fungi (AMF) can induce the synthesis and accumulation of secondary metabolites in the tissues of host plants, thus impacting their allelopathic potential.

Materials and methods

The objective of this study was to determine the effect of three AMF species (Rhizoglomus intraradices, Funneliformis mosseae, Rhizoglomus fasciculatum) on photosynthetic pigments and secondary metabolites content in roots and reproductive organs ofIpomoea purpureaL.,Digitaria sanguinalisL., andSolanum nigrumL. as a problematic weed species.

Results

Among compared weeds, the roots ofD. sanguinalisassociated with AMF accumulated the highest level of phenols. Higher content of flavonoids was obtained in roots ofS. nigrum (7.46 mg g−1FW)following colonization withR. intraradices.Berries ofS. nigruminoculated withR. intraradiceshad a higher concentration of terpenoids (21.45 mg 100 mL−1of extract) than reproductive organs ofD. sanguinalisandI. purpurea.Colonization withR. intraradicesimproved total phenolics in seeds ofD. sanguinaliscompared to the reproductive organs of other weeds. These compounds released from seeds help defend against pathogen infection, consequently increasing seed production. In addition, phenylalanine ammonia lyase enzyme activity in leaves ofD. sanguinaliscolonized byR. fasciculatumandF. mosseaewas 55% and 67%, respectively, higher thanI. purpureaplants, grown in the same condition.

Conclusions

Results suggest that AMF can play a crucial role in enhancing of secondary metabolites in these three weeds, thereby improving their allelopathic potential and competitive ability.

Graphic Abstract
Identifying potential barriers and solutions to patient partner compensation (payment) in research
Authors: Richards Dawn P. , Cobey Kelly D. , Proulx Laurie , Dawson Shoba , de Wit Maarten , Toupin-April Karine
Published: February 2022

Research that engages patients on the research team is often supported by grant funding from different organizations and, in some cases, principal investigators (who control the grant funding) provide patient partners with compensation (or payment) for their contributions. However, we have noted a gap in resources that identify and address barriers to compensating patient partners (no matter the size, degree or length of their engagement). In this paper, we present thoughts and experiences related to barriers to compensating patient partners with the goal of helping individuals identify and find solutions to these obstacles. Based on our experiences as individuals who live with chronic conditions and are patient partners, and those who are researchers who engage patient partners, we have identified eight barriers to compensating patient partners. We discuss each of these barriers: lack of awareness about patient partnership, institutional inflexibility, policy guidance from funders, compensation not prioritized in research budgets, leadership hesitancy to create a new system, culture of research teams, preconceived beliefs about the skills and abilities of patient partners, and expectations placed on patient partners. We demonstrate these barriers with real life examples and we offer some solutions. To further demonstrate these barriers, we ask readers to reflect on some scenarios that present realistic parallel situations to those that patient partners face. The intention is to illustrate, through empathy or putting yourself in someone else’s shoes, how we might all do better with respect to institutional barriers related to patient partner compensation. Last, we issue a call to action to share resources and identify actions to overcome these barriers from which we will create an online resource repository.
CHA2DS2 VASc score and brachial artery flow-mediated dilation as predictors for no-reflow phenomenon in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Rashed Mohamed Ismail , Saleh Mohamed Ayman , Elfekky Ehab Mohamed , Elmahmoudy Ahmed Mohamed
Published: February 2022

Background

Following primary percutaneous coronary intervention (PCI), no-reflow is associated with a high rate of long-term unfavorable clinical outcomes. Despite the importance of early no-reflow prediction in cardiovascular medicine, noninvasive assessment is lacking. This study aimed to evaluate the preprocedural CHA2DS2 VASc score and the brachial artery flow-mediated dilation percentage (FMD%) as predictors of the no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.

Results

This study included 150 patients who presented with acute STEMI, underwent primary PCI, and were divided into two groups according to the flow result, reflow group and a no-reflow group. The CHA2DS2 VASc score was calculated and evaluation of endothelial function by measuring the brachial artery FDM% was done for each patient before the procedure. There were 39 (26%) patients in the no-reflow group and 111 (74%) in the reflow group. The no-reflow patients were older and had significantly higher body mass index (BMI), higher frequency of diabetes mellitus, hypertension, history of heart failure, dyslipidemia, Killip class IV on admission, thrombus grade V, multiple affected vessels, conventional stenting, and multiple stents placement, longer ischemic times, higher CHA2DS VASc score, and lower brachial artery FMD% (p-values of < 0.05 for all). Moreover, there was a significant negative correlation between CHA2DS VAS score and preprocedural FMD%, with the higher the score indicating lower FMD among cases (p-value = 0.000).

Conclusions

Preprocedural CHA2DS2 VASc score and the brachial artery FMD can be used as predictors for the no-reflow phenomenon in patients with STEMI, undergoing primary PCI.
Role of ultrasound and Doppler findings as a predictor of thyroid hormonal levels in cases of Hashimoto thyroiditis
Authors: Mahmoud Rasha , Azeem Khaled Mohammed , Sayed Ahmed Safaa Ahmed , Ali Faten Mohamed
Published: February 2022

Background

Chronic lymphocytic thyroiditis or Hashimoto’s thyroiditis (HT) is a common form of organ specific autoimmune disease mediated by anti-thyroid autoantibodies. Ultrasound including Doppler is helpful diagnostic tool in the diagnosis of Hashimoto’s thyroiditis. This study aimed to evaluate the ultrasound and Doppler characters of Hashimoto thyroiditis and to analyze the relationship between these ultrasound, Doppler features and thyroid hormones level.

Results

Thyroid gland sonographic parenchymal abnormalities (septations, undulation, micronodularity, gland hyper vascularity, hypoechogenicity, sizable nodules as well as enlarged para-tracheal lymph nodes) were significantly higher in Hashimoto cases compared to control group (P value is < 0.001). Undulation of thyroid gland margin was the most sensitive sonographic sign seen in about 72% of studied cases. Thyroid stimulating hormone (TSH) level was significantly high in cases with grade 2 echogenicity compared to cases with grade 0 and grade 1 echogenicity and was significantly high in cases with para-tracheal abnormal enlarged lymph nodes (p < 0.05). TSH & thyroxine (T4) levels were significantly high in cases with high gland vascularity in Doppler study (p < 0.05).

Conclusions

Ultrasound is a very good diagnostic tool in HT with established signs. It can suggest hypothyroidism (high TSH) in cases of grade 2 parenchymal echogenicity, high vascularity and para-tracheal lymph nodes enlargement. These finding could be helpful in patient management and can contribute in better understanding the disease progression.
Effectiveness of mometasone furoate nasal spray on tympanometric results and hearing loss in children with otitis media with effusion
Authors: Ahmed Mohamed Rifaat , Eldeeb Wael Elshahat
Published: February 2022

Background

Otitis media with effusion (OME) is one of the commonest causes of hearing loss in children. Oral and nasal topical steroids alone or combined with antibiotics lead to its quicker resolution. The aim of this study was the assessment of the efficacy of mometasone furoate nasal spray in conjunction with oral antibiotics for management of OME in children. One hundred sixty-eight children aged (4–12 years old) diagnosed with bilateral OME for at least 3 months were randomly allocated into two equal groups: the 1st group received mometasone furoate aqueous nasal spray plus oral amoxicillin–clavulanate for 4 weeks, and the 2nd group received amoxicillin–clavulanate alone for the same period.

Results

The tympanometric results after 1 month of medical treatment was much better in the 1st group compared to the 2nd group with 60% of patients of the 1st group having type A tympanogram versus 16% of patients of the 2nd group having this type (p = 0.0001). However, the average air-bone gap was not statistically different between the two groups.

Conclusion

Mometasone furoate nasal spray is effective in OME as adjunctive treatment when combined with antibiotics as it helps to normalize the Eustachian tube function and middle ear status.
Minority Enrollment in Phase II and III Clinical Trials in Urologic Oncology
Authors: Owens-Walton Jeunice , Williams Cheyenne , Rompré-Brodeur Alexis , Pinto Peter A. , Ball Mark W.
Published: February 2022

PURPOSE

Proportionate minority representation in clinical trials is an important step toward addressing health care inequities. Given the paucity of data on this topic in urologic oncology, we sought to quantify the enrollment of minority patients in clinical trials studying prostate, kidney, and bladder/urothelial cancers.

METHODS

The ClincialTrials.gov database was queried for completed phase II and III interventional trials in prostate, kidney, and bladder cancers. The SEER database was used to calculate the US prevalence of these genitourinary cancers. Representation quotients (RQ) were calculated to describe the relative proportion of each racial/ethnic group enrolled in clinical trials over the proportion of persons from each group among national cancer cases by cancer type.

RESULTS

Of 341 trials that met initial eligibility criteria, only 169 (49.7%) reported data on race or ethnicity. Aggregate RQs from 2000 to 2017 showed that White patients were continually over-represented in trials for all cancer types. Black and Asian patients were poorly represented across all cancer types. When stratified by 3-year increments, the RQs remained stable for all races, from 2000 to 2017. When stratified by ethnicity, Hispanic patients were under-represented across all cancer types in the study period. When examining representation by funding source, we found that US government–funded clinical trials proportionally enroll the most diverse patient populations over those funded by academic institutions and industry. Interestingly, more than 50% of the trials examined did not report race nor ethnicity, highlighting a crucial flaw in investigator compliance with federal clinical trial mandates.

CONCLUSION

Clinical trials targeting prostate, kidney, and bladder cancers continue to under-represent racial/ethnic minority patients. On the basis of the incidence of these cancers within minority populations, efforts should focus on creating racially and ethnically inclusive cancer research.
Insulin Pump–related Inpatient Admissions in a National Sample of Youth With Type 1 Diabetes
Authors: Everett Estelle M , Copeland Timothy P , Moin Tannaz , Wisk Lauren E
Published: February 2022

Background

Insulin pump use in type 1 diabetes management has significantly increased in recent years, but we have few data on its impact on inpatient admissions for acute diabetes complications.

Methods

We used the 2006, 2009, 2012, and 2019 Kids’ Inpatient Database to identify all-cause type 1 diabetes hospital admissions in those with and without documented insulin pump use and insulin pump failure. We described differences in (1) prevalence of acute diabetes complications, (2) severity of illness during hospitalization and disposition after discharge, and (3) length of stay (LOS) and inpatient costs.

Results

We identified 228 474 all-cause admissions. Insulin pump use was documented in 7% of admissions, of which 20% were due to pump failure. The prevalence of diabetic ketoacidosis (DKA) was 47% in pump nonusers, 39% in pump users, and 60% in those with pump failure. Admissions for hyperglycemia without DKA, hypoglycemia, sepsis, and soft tissue infections were rare and similar across all groups. Admissions with pump failure had a higher proportion of admissions classified as major severity of illness (14.7%) but had the lowest LOS (1.60 days, 95% CI 1.55-1.65) and healthcare costs ($13 078, 95% CI $12 549-$13 608).

Conclusions

Despite the increased prevalence of insulin pump in the United States, a minority of pediatric admissions documented insulin pump use, which may represent undercoding. DKA admission rates were lower among insulin pump users compared to pump nonusers. Improved accuracy in coding practices and other approaches to identify insulin pump users in administrative data are needed, as are interventions to mitigate risk for DKA.
The Doctor Who Would Be King
Authors: Lachenal Guillaume
Published: February 2022

In The Doctor Who Would Be King Guillaume Lachenal tells the extraordinary story of Dr. Jean Joseph David, a French colonial army doctor who governed an entire region of French Cameroon during World War II. Dr. David—whom locals called “emperor”—dreamed of establishing a medical utopia. Through unchecked power, he imagined realizing the colonialist fantasy of emancipating colonized subjects from misery, ignorance, and sickness. Drawing on archives, oral histories, and ethnographic fieldwork, Lachenal traces Dr. David’s earlier attempts at a similar project on a Polynesian island and the ongoing legacies of his failed experiment in Cameroon. Lachenal does not merely recount a Conradian tale of imperial hubris, he brings the past into the present, exploring the memories and remains of Dr. David’s rule to reveal a global history of violence, desire, and failure in which hope for the future gets lost in the tragic comedy of power.