bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of information analysis for pandemic response: intensive care unit preparedness at the onset of COVID-19
Authors: Eze Peter U. , Geard Nicholas , Baker Christopher M. , Campbell Patricia T. , Chades Iadine
Published: May 2023

Background

During the early stages of the COVID-19 pandemic, there was considerable uncertainty surrounding epidemiological and clinical aspects of SARS-CoV-2. Governments around the world, starting from varying levels of pandemic preparedness, needed to make decisions about how to respond to SARS-CoV-2 with only limited information about transmission rates, disease severity and the likely effectiveness of public health interventions. In the face of such uncertainties, formal approaches to quantifying the value of information can help decision makers to prioritise research efforts.

Methods

In this study we use Value of Information (VoI) analysis to quantify the likely benefit associated with reducing three key uncertainties present in the early stages of the COVID-19 pandemic: the basic reproduction number ($$R_0$$

R
0

), case severity (CS), and the relative infectiousness of children compared to adults (CI). The specific decision problem we consider is the optimal level of investment in intensive care unit (ICU) beds. Our analysis incorporates mathematical models of disease transmission and clinical pathways in order to estimate ICU demand and disease outcomes across a range of scenarios.

Results

We found that VoI analysis enabled us to estimate the relative benefit of resolving different uncertainties about epidemiological and clinical aspects of SARS-CoV-2. Given the initial beliefs of an expert, obtaining more information about case severity had the highest parameter value of information, followed by the basic reproduction number $$R_0$$

R
0

. Resolving uncertainty about the relative infectiousness of children did not affect the decision about the number of ICU beds to be purchased for any COVID-19 outbreak scenarios defined by these three parameters.

Conclusion

For the scenarios where the value of information was high enough to justify monitoring, if CS and $$R_0$$

R
0

are known, management actions will not change when we learn about child infectiousness. VoI is an important tool for understanding the importance of each disease factor during outbreak preparedness and can help to prioritise the allocation of resources for relevant information.
Diabetes is accompanied by secretion of pro-atherosclerotic exosomes from vascular smooth muscle cells
Authors: Yu Heng , Douglas Hunter F. , Wathieu Donald , Braun Ryan A. , Edomwande Christine , Lightell Daniel J. , Pham Thaidan , Klingenberg Natasha C. , Bishop Shelia Pugh , Khismatullin Damir B. , Woods T. Cooper
Published: May 2023

Background

Atherosclerosis is a common co-morbidity of type 2 diabetes mellitus. Monocyte recruitment by an activated endothelium and the pro-inflammatory activity of the resulting macrophages are critical components of atherosclerosis. Exosomal transfer of microRNAs has emerged as a paracrine signaling mechanism regulating atherosclerotic plaque development. MicroRNAs-221 and -222 (miR-221/222) are elevated in vascular smooth muscle cells (VSMCs) of diabetic patients. We hypothesized that the transfer of miR-221/222 via VSMC-derived exosomes from diabetic sources (DVEs) promotes increased vascular inflammation and atherosclerotic plaque development.

Methods

Exosomes were obtained from VSMCs, following exposure to non-targeting or miR-221/-222 siRNA (-KD), isolated from diabetic (DVEs) and non-diabetic (NVEs) sources and their miR-221/-222 content was measured using droplet digital PCR (ddPCR). Expression of adhesion molecules and the adhesion of monocytes was measured following exposure to DVEs and NVEs. Macrophage phenotype following exposure to DVEs was determined by measuring mRNA markers and secreted cytokines. Age-matched apolipoprotein-E-deficient mice null (ApoE−/−) mice were maintained on Western diet for 6 weeks and received injections of saline, NVEs, NVE-KDs, DVEs or DVE-KDs every other day. Atherosclerotic plaque formation was measured using Oil Red Oil staining.

Results

Exposure of human umbilical vein and coronary artery endothelial cells to DVEs, but not NVEs, NVE-KDs, or DVE-KDs promoted increased intercellular adhesion molecule-1 expression and monocyte adhesion. DVEs but not NVEs, NVE-KDs, or DVE-KDs also promoted pro-inflammatory polarization of human monocytes in a miR-221/222 dependent manner. Finally, intravenous administration of DVEs, but not NVEs, resulted in a significant increase in atherosclerotic plaque development.

Conclusion

These data identify a novel paracrine signaling pathway that promotes the cardiovascular complications of diabetes mellitus.
Population monitoring of trisomy 21: problems and approaches
Authors: Sperling Karl , Scherb Hagen , Neitzel Heidemarie
Published: May 2023

Trisomy 21 (Down syndrome) is the most common autosomal aneuploidy among newborns. About 90% result from meiotic nondisjunction during oogenesis, which occurs around conception, when also the most profound epigenetic modifications take place. Thus, maternal meiosis is an error prone process with an extreme sensitivity to endogenous factors, as exemplified by maternal age. This contrasts with the missing acceptance of causal exogenous factors. The proof of an environmental agent is a great challenge, both with respect to ascertainment bias, determination of time and dosage of exposure, as well as registration of the relevant individual health data affecting the birth prevalence. Based on a few exemplary epidemiological studies the feasibility of trisomy 21 monitoring is illustrated. In the nearer future the methodical premises will be clearly improved, both due to the establishment of electronic health registers and to the introduction of non-invasive prenatal tests. Down syndrome is a sentinel phenotype, presumably also with regard to other congenital anomalies. Thus, monitoring of trisomy 21 offers new chances for risk avoidance and preventive measures, but also for basic research concerning identification of relevant genomic variants involved in chromosomal nondisjunction.
Objective and subjective cognition in survivors of COVID-19 one year after ICU discharge: the role of demographic, clinical, and emotional factors
Authors: Godoy-González Marta , Navarra-Ventura Guillem , Gomà Gemma , de Haro Candelaria , Espinal Cristina , Fortià Cristina , Ridao Natalia , Miguel Rebanal Nuria , Oliveras-Furriols Laia , Subirà Carles , Jodar Mercè , Santos-Pulpón Verónica , Sarlabous Leonardo , Fernández Rafael , Ochagavía Ana , Blanch Lluís , Roca Oriol , López-Aguilar Josefina , Fernández-Gonzalo Sol
Published: May 2023

Background

Intensive Care Unit (ICU) COVID-19 survivors may present long-term cognitive and emotional difficulties after hospital discharge. This study aims to characterize the neuropsychological dysfunction of COVID-19 survivors 12 months after ICU discharge, and to study whether the use of a measure of perceived cognitive deficit allows the detection of objective cognitive impairment. We also explore the relationship between demographic, clinical and emotional factors, and both objective and subjective cognitive deficits.

Methods

Critically ill COVID-19 survivors from two medical ICUs underwent cognitive and emotional assessment one year after discharge. The perception of cognitive deficit and emotional state was screened through self-rated questionnaires (Perceived Deficits Questionnaire, Hospital Anxiety and Depression Scale and Davidson Trauma Scale), and a comprehensive neuropsychological evaluation was carried out. Demographic and clinical data from ICU admission were collected retrospectively.

Results

Out of eighty participants included in the final analysis, 31.3% were women, 61.3% received mechanical ventilation and the median age of patients was 60.73 years. Objective cognitive impairment was observed in 30% of COVID-19 survivors. The worst performance was detected in executive functions, processing speed and recognition memory. Almost one in three patients manifested cognitive complaints, and 22.5%, 26.3% and 27.5% reported anxiety, depression and post-traumatic stress disorder (PTSD) symptoms, respectively. No significant differences were found in the perception of cognitive deficit between patients with and without objective cognitive impairment. Gender and PTSD symptomatology were significantly associated with perceived cognitive deficit, and cognitive reserve with objective cognitive impairment.

Conclusions

One-third of COVID-19 survivors suffered objective cognitive impairment with a frontal-subcortical dysfunction 12 months after ICU discharge. Emotional disturbances and perceived cognitive deficits were common. Female gender and PTSD symptoms emerged as predictive factors for perceiving worse cognitive performance. Cognitive reserve emerged as a protective factor for objective cognitive functioning.

Trial registration: ClinicalTrials.gov Identifier: NCT04422444; June 9, 2021.
Univariate versus multivariate spectrophotometric data analysis of triamterene and xipamide; a quantitative and qualitative greenly profiled comparative study
Authors: Abd El-Hadi Heidi R. , Eissa Maya S. , Zaazaa Hala E. , Eltanany Basma M.
Published: May 2023

Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The purpose of this research is the quantitative and qualitative analysis of this binary mixture by green univariate and multivariate spectrophotometric methods. Univariate methods were zero order absorption spectra method (D0) and Fourier self-deconvolution (FSD), as TRI was directly determined by D0 at 367.0 nm in the range (2.00–10.00 µg/mL), where XIP show no interference. While XIP was determined by FSD at 261.0 nm in the range (2.00–8.00 µg/mL), where TRI show zero crossing. Multivariate methods were Partial Least Squares, Principal Component Regression, Artificial Neural Networks, and Multivariate Curve Resolution-Alternating Least Squares. A training set of 25 mixtures with different quantities of the tested components was used to construct and evaluate them, 3 latent variables were displayed using an experimental design. A set of 18 synthetic mixtures with concentrations ranging from (3.00–7.00 µg/mL) for TRI and (2.00–6.00 µg/mL) for XIP, were used to construct the calibration models. A collection of seven synthetic mixtures with various quantities was applied to build the validation models. All the proposed approaches quantitative analyses were evaluated using recoveries as a percentage, root mean square error of prediction, and standard error of prediction. Strong multivariate statistical tools were presented by these models, and they were used to analyze the combined dosage form available on the Egyptian market. The proposed techniques were evaluated in accordance with ICH recommendations, where they are capable of overcoming challenges including spectral overlaps and collinearity. When the suggested approaches and the published one were statistically compared, there was no discernible difference between them. The green analytical method index and eco-scale tools were applied for assessment of the established models greenness. The suggested techniques can be used in product testing laboratories for standard pharmaceutical analysis of the substances being studied.
Efficient integrated production of bioethanol and antiviral glycerolysis lignin from sugarcane trash
Authors: Khattab Sadat Mohamed Rezk , Okano Hiroyuki , Kimura Chihiro , Fujita Takashi , Watanabe Takashi
Published: May 2023

Background

Sugarcane trash (SCT) represents up to 18% of the aboveground biomass of sugarcane, surpassing 28 million tons globally per year. The majority of SCT is burning in the fields. Hence, efficient use of SCT is necessary to reduce carbon dioxide emissions and global warming and establish agro-industrial biorefineries. Apart from its low costs, conversion of whole biomass with high production efficiency and titer yield is mandatory for effective biorefinery systems. Therefore, in this study, we developed a simple, integrated method involving a single step of glycerolysis pretreatment to produce antiviral glycerolysis lignin (AGL). Subsequently, we co-fermented glycerol with hydrolyzed glucose and xylose to yield high titers of bioethanol.

Results

SCT was subjected to pretreatment with microwave acidic glycerolysis with 50% aqueous (aq.) glycerol (MAG50); this pretreatment was optimized across different temperature ranges, acid concentrations, and reaction times. The optimized MAG50 (opMAG50) of SCT at 1:15 (w/v) in 1% H2SO4, 360 µM AlK(SO4)2 at 140 °C for 30 min (opMAG50) recovered the highest amount of total sugars and the lowest amount of furfural byproducts. Following opMAG50, the soluble fraction, i.e., glycerol xylose-rich solution (GXRS), was separated by filtration. A residual pulp was then washed with acetone, recovering 7.9% of the dry weight (27% of lignin) as an AGL. AGL strongly inhibited the replication of encephalomyocarditis virus (EMCV) in L929 cells without cytotoxicity. The pulp was then saccharified in yeast peptone medium by cellulase to produce a glucose concentration similar to the theoretical yield. The total xylose and arabinose recoveries were 69% and 93%, respectively. GXRS and saccharified sugars were combined and co-fermented through mixed cultures of two metabolically engineered Saccharomyces cerevisiae strains: glycerol-fermenting yeast (SK-FGG4) and xylose-fermenting yeast (SK-N2). By co-fermenting glycerol and xylose with glucose, the ethanol titer yield increased to 78.7 g/L (10% v/v ethanol), with a 96% conversion efficiency.

Conclusion

The integration of AGL production with the co-fermentation of glycerol, hydrolyzed glucose, and xylose to produce a high titer of bioethanol paves an avenue for the use of surplus glycerol from the biodiesel industry for the efficient utilization of SCT and other lignocellulosic biomasses.
Benign breast disease with malignant imaging features: a case report
Authors: Zhong Yuanyuan , Cheng Yiqin , Chen Ling , Yin Yulian
Published: May 2023

Background

Diabetic mastopathy is a rare breast condition that occurs in women with poorly controlled diabetes and is characterized by hardening of the breast tissue. The purpose of this case report is to provide an overview of the clinical characteristics and therapeutic principles of this rare disease to support front-line physicians in their crucial activity of case identification.

Case presentation

A 64-year-old Asian female patient with a history of type II diabetes mellitus was referred to our clinic for an evaluation of a newly discovered breast mass. The patient had been diagnosed with diabetes more than 20 years prior and was being managed with oral hypoglycemic agents. Her past medical history was otherwise unremarkable. Physical examination of the breast revealed a palpable, mobile, and firm mass measuring 6 × 4 cm in the upper quadrant of the right breast. Ultrasound images showed an uneven hypoechoic nodule, BI-RADS 4B. Mammography showed the compact and flaky nature of the two breasts and the heterogeneity of the substantive density increases. The patient’s clinical manifestations and imaging findings suggest the possibility of breast cancer. The patient opted for surgical excision of the mass. Through surgery, the mass was completely excised with negative margins. Pathological examination of the mass revealed a proliferation of fibroblastic cells, with an increased nuclear/cytoplasmic ratio, consistent with a diagnosis of diabetic mastopathy.

Conclusions

This case report serves to highlight the importance of recognizing diabetic mastopathy as a possible differential diagnosis of a breast mass in patients with diabetes mellitus. In our patient, early diagnosis and treatment with lumpectomy resulted in a favorable outcome, emphasizing the importance of prompt medical and surgical management. In addition, more research is needed to mine the diagnostic marker of diabetic mastopathy and provide data related to its prognosis.
Endophytic actinobacteria from wild medicinal plants are a natural source of insecticide to control the African cotton leafworm (Spodoptera littoralis)
Authors: Diab Mohamed K. , Mead Hala M. , Khedr Mohamad A. , Nafie Mohamed S. , Abu-Elsaoud Abdelghafar M. , Hanora Amro , El-Shatoury Sahar A.
Published: May 2023

Insecticide resistance in agricultural pests has prompted the need to discover novel compounds with new modes of action. We investigated the potency of secondary metabolites from seventy endophytic actinobacteria against laboratory and field strains of Spodoptera littoralis (fourth instar), comparable to the bioinsecticide spinetoram (Radiant SC 12%). Endophytes from Artemisia herba-alba and A. judaica were highly effective. Chemical profiling of the most potent metabolite of the strain Streptomyces sp. ES2 was investigated using LC-QTOF-MS-MS technique, and the activity was validated through molecular docking studies. Metabolic extracts from actinobacteria belonging to Streptomyces, Nocardioides, and Pseudonocardia showed immediate and latent death to the Spodoptera littoralis fourth instar larvae. The metabolite from strain ES2 has shown the most promising and significant histopathological and inhibitory effects on the fourth instar larvae. ES2 metabolite caused lesions in the body wall cuticle, indicating a different mode of action than that of Radiant. Chemical profiling of ES2 showed the presence of cyromazine (molt inhibitor), 4-nitrophenol, and diazinon as key constituents. In conclusion, these findings suggest that secondary metabolites from endophytic actinobacteria inhabiting wild medicinal plants can be a sustainable source for promising natural biocontrol agents. This is the first illustration of the insecticidal activity of Artemisia spp. microbiome, and natural cyromazine synthesis by actinobacteria.
Some properties of branching processes with random control functions and affected by viral infectivity in random environments
Authors: Ren Min , Zhang Guanghui
Published: May 2023

In this paper, a model of branching processes with random control functions and affected by viral infectivity in independent and identically distributed random environments is established, and the Markov property of the model and a sufficient condition for the model to be certainly extinct under some conditions are discussed. Then, the limit properties of the model are studied. Under the normalization factor $\{S_{n}:n\in N\}$
{

S
n

:
n
∈
N
}
, the normalization processes $\{\hat{W}_{n}:n\in N\}$
{

W
ˆ

n

:
n
∈
N
}
are studied, and the sufficient conditions of $\{\hat{W}_{n}:n\in N\}$
{

W
ˆ

n

:
n
∈
N
}
a.s., $L^{1}$

L
1

and $L^{2}$

L
2

convergence are given; A sufficient condition and a necessary condition for convergence to a nondegenerate at zero random variable are obtained. Under the normalization factor $\{I_{n}:n\in N\}$
{

I
n

:
n
∈
N
}
, the normalization processes $\{\bar{W}_{n}:n\in N\}$
{

W
¯

n

:
n
∈
N
}
are studied, and the sufficient conditions of $\{\bar{W}_{n}:n\in N\}$
{

W
¯

n

:
n
∈
N
}
a.s., and $L^{1}$

L
1

convergence are obtained.
Exploring energy citizenship in the urban heating system with the ‘Walking with Energy’ methodology
Authors: Palm Jenny , Ambrose Aimee
Published: May 2023

Background

Energy citizenship has emerged as a concept which attempts to capture the new role envisaged for urban citizens as engaged and active in the energy transition. However, exactly how to successfully engage energy citizens requires more research and this article aims to contribute to this knowledge gap. The article presents a new methodology, ‘Walking with Energy’, which seeks to (re)connect citizens with where their energy is coming from. By experimenting with the application of this method in the UK and Sweden, we consider how viewing and talking about heating provision, while in the energy landscape, can encourage participants to reflect upon their local, mundane energy experiences and foster a greater sense of energy citizenship and greater motivation to engage with debates around heating transition.

Results

The article presents four different events: (1) a physical walk to an energy recovery facility, (2) a walk to view a building’s heat exchanger, (3) a round-table discussion using pictures to communicate in a language café, and (4) a virtual tour around an Energy Recovery Facility. The way we conducted the events influenced who engaged, for example: the walk through a heat facility and the walk to visit a heat exchanger in the basement of a University building tended to attract white middle-class people, while the virtual tour attracted a more mixed audience in terms of age and background, but most had a strong environmental interest. The language café targeted immigrants. The different events resulted in many similar reflections, but there was also variation. For example, the walk through the heat facility generated the most focused and least diverse reflections, while the event focussed on the heat exchanger opened up a wide range of issues for discussion.

Conclusions

We find that the method encouraged the sharing of personal experiences, storytelling, and deepened the engagement of participants with debates about energy. The method can help promote energy democracy and boost a deliberative dialogue about present and future energy systems among citizens. We also learnt that promotion of energy citizenship requires not only active citizens but also active facilitation to create opportunities for citizens to engage and reflect.
Autosomal recessive congenital cataract is associated with a novel 4-bp splicing deletion mutation in a novel C10orf71 human gene
Authors: Chograni M. , Alahdal H. M. , Rejili M.
Published: May 2023

Congenital cataract is one of the most genetically heterogeneous ocular conditions with different genes involved in its etiology. Here, we describe the analysis of a new candidate gene of a congenital bilateral cataract associated with polymalformative syndrome, moderate global developmental delay, microcephaly, axial hypotonia, intrauterine growth restriction and facial dysmorphism for two affected siblings. Molecular analysis included exome sequencing and genome wide homozygosity mapping revealed a region of homozygosity shared by the two affected siblings at 10q11.23. The new C10orf71 gene was included in this interval and direct sequencing of this gene revealed an already described homozygous c. 2123T > G mutation (p. L708R) for the two affected subjects. Interestingly, we revealed in contrast a 4-bp deletion on the 3'-splicing acceptor site of intron 3-exon 4, namely defined as IVS3-5delGCAA. The C10Orf71 gene expression analysis using RT-PCR showed an expression pattern in different fetal organs and tissues as well as in leukocytes and confirmed that the IVS3-5delGCAA deletion of the C10orf71 gene is a splicing mutation responsible for the shortening of the C10orf71 protein in the two related patients. The C10orf71 gene has not been described to date as associated to the autosomal recessive phenotype.
How to study a predator that only eats a few meals a year: high-frequency accelerometry to quantify feeding behaviours of rattlesnakes (Crotalus spp.)
Authors: Hanscom Ryan J. , DeSantis Dominic L. , Hill Jessica L. , Marbach Tyler , Sukumaran Jeet , Tipton Anna F. , Thompson Morgan L. , Higham Timothy E. , Clark Rulon W.
Published: May 2023

Background

Many snakes are low-energy predators that use crypsis to ambush their prey. Most of these species feed very infrequently, are sensitive to the presence of larger vertebrates, such as humans, and spend large portions of their lifetime hidden. This makes direct observation of feeding behaviour challenging, and previous methodologies developed for documenting predation behaviours of free-ranging snakes have critical limitations. Animal-borne accelerometers have been increasingly used by ecologists to quantify activity and moment-to-moment behaviour of free ranging animals, but their application in snakes has been limited to documenting basic behavioural states (e.g., active vs. non-active). High-frequency accelerometry can provide new insight into the behaviour of this important group of predators, and here we propose a new method to quantify key aspects of the feeding behaviour of three species of viperid snakes (Crotalusspp.) and assess the transferability of classification models across those species.

Results

We used open-source software to create species-specific models that classified locomotion, stillness, predatory striking, and prey swallowing with high precision, accuracy, and recall. In addition, we identified a low cost, reliable, non-invasive attachment method for accelerometry devices to be placed anteriorly on snakes, as is likely necessary for accurately classifying distinct behaviours in these species. However, species-specific models had low transferability in our cross-species comparison.

Conclusions

Overall, our study demonstrates the strong potential for using accelerometry to document critical feeding behaviours in snakes that are difficult to observe directly. Furthermore, we provide an ‘end-to-end’ template for identifying important behaviours involved in the foraging ecology of viperids using high-frequency accelerometry. We highlight a method of attachment of accelerometers, a technique to simulate feeding events in captivity, and a model selection procedure using biologically relevant window sizes in an open-access software for analyzing acceleration data (AcceleRater). Although we were unable to obtain a generalized model across species, if more data are incorporated from snakes across different body sizes and different contexts (i.e., moving through natural habitat), general models could potentially be developed that have higher transferability.
A multi-level intervention to reduce the stigma of substance use and criminal involvement: a pilot feasibility trial protocol
Authors: Moore Kelly E. , Johnson Jennifer E. , Luoma Jason B. , Taxman Faye , Pack Robert , Corrigan Patrick , Hart Jim , Slone Judge Duane
Published: May 2023

Background

Stigma associated with substance use and criminal involvement is pervasive and creates a barrier to evidence-based addiction care within the criminal legal system. Research has yet to examine a multi-level stigma intervention which targets the intersection of these stigmas among both criminal legal staff and legally-involved clients.

Methods

This paper presents the protocol for a non-randomized trial of a multi-level stigma intervention called Combatting Stigma to Aid Reentry and Recovery (CSTARR) that involves two interventions: (1) training for criminal legal staff to address public stigma and (2) group-based acceptance and commitment therapy to address self-stigma among legally-involved adults enrolled in substance use treatment. Staff and client participants are engaged with a program called the Tennessee Recovery Oriented Compliance Strategy in 6 East Tennessee counties. This study examines the feasibility, acceptability, and preliminary effectiveness of CSTARR using a type 1 hybrid implementation/effectiveness trial with pre to post follow-up.

Discussion

Stigma must be addressed in the criminal legal system to facilitate the uptake of evidence-based addiction care. This study is the first to evaluate a stigma intervention designed for the criminal legal setting and results will be used to inform a larger, randomized controlled trial. The rationale for this study, research design and measures, as well as potential implications for the field are described.

Trial registration

This clinical trial is registered at clinicaltrials.gov with the identifier NCT05152342. Registered 11/5/2021 athttps://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BIN8&selectaction=Edit&uid=U0005X4C&ts=2&cx=-u3wsbx.
Methodological concerns about “concordance-statistic for benefit” as a measure of discrimination in predicting treatment benefit
Authors: Xia Yuan , Gustafson Paul , Sadatsafavi Mohsen
Published: May 2023

Prediction algorithms that quantify the expected benefit of a given treatment conditional on patient characteristics can critically inform medical decisions. Quantifying the performance of treatment benefit prediction algorithms is an active area of research. A recently proposed metric, the concordance statistic for benefit (cfb), evaluates the discriminative ability of a treatment benefit predictor by directly extending the concept of the concordance statistic from a risk model with a binary outcome to a model for treatment benefit. In this work, we scrutinize cfb on multiple fronts. Through numerical examples and theoretical developments, we show that cfb is not a proper scoring rule. We also show that it is sensitive to the unestimable correlation between counterfactual outcomes and to the definition of matched pairs. We argue that measures of statistical dispersion applied to predicted benefits do not suffer from these issues and can be an alternative metric for the discriminatory performance of treatment benefit predictors.
Longitudinal assessment of cardiac parameters through MRI in breast cancer patients treated with anti-HER2 therapy
Authors: Cheng Sainan , Wang Jianwei , Wang Yawen , Qi Linlin , Li Fenglan , Liu Jianing , Chen Jiaqi , Fan Yang , Xie Lizhi
Published: May 2023

Background

We evaluated the early changes in left ventricular (LV) volumetric, functional, and tissue characteristics in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with trastuzumab and/or pertuzumab at cardiac magnetic resonance imaging (MRI).

Methods

HER2-positive breast cancer patients undergoing planned anti-HER2 therapy and nonanthracycline-based chemotherapy were enrolled and subdivided into dual anti-HER2 (trastuzumab plus pertuzumab) group and trastuzumab group. Cardiac MRI was performed before treatment and three months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, and T1 and T2 relaxation times. Cardiac dysfunction was primarily defined as a > 10% reduction in LV ejection fraction (LVEF) to < 55% and/or a > 15% global longitudinal strain (GLS) change at the follow-up MRI examination.

Results

Twenty-four HER2-positive patients were evaluated (16 in the dual anti-HER2 group, 8 in the trastuzumab group). Six patients developed cardiac dysfunction at follow-up, five of them in the dual anti-HER2 group. One patient developed symptomatic heart failure, and five patients developed asymptomatic cardiac dysfunction. Patients displayed significantly decreased systolic function and increased T1 and T2 relaxation time at follow-up (p ≤ 0.031). Systolic dysfunction remained significant in the dual anti-HER2 group. The decrease in GLS in the trastuzumab group was not significant (p = 0.169). T1 and T2 relaxation times tended to increase, but this was not significant at subgroup analysis.

Conclusions

Cardiac MRI scans showed frequent signs of subclinical cardiotoxicity after short-term anti-HER2 therapy and nonanthracycline-based chemotherapy; the effect was slightly stronger in patients treated with dual therapy.

Key points

• A frequent subclinical cardiotoxicity was detected by cardiac magnetic resonance imaging after short-term anti-human epidermal growth factor receptor 2 (HER2) therapy.

• The change in myocardial strain was more marked in patients treated with dual (trastuzumab plus pertuzumab) than with trastuzumab only anti-HER2 therapy.

• Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy.
Biocontrol potential of two deep-sea microorganisms against gray blight disease of tea
Authors: Xu Guangxin , Ying Feng , Wu Huangming , Tang Xixiang
Published: May 2023

Background

Gray blight is among the most destructive diseases that affect tea plants worldwide. In this study, microorganisms from deep-sea sediment samples for those with antagonistic effects were screened against gray blight caused by Pestalotiopsis theae.

Results

Thirty-two and twenty-eight morphologically different deep-sea bacteria and fungi were isolated, respectively. Isolates B5 and A65 clearly inhibited the pathogens in vitro and were prepared as wettable agent powders for evaluation in micro-plot field trials. Foliar application of the 48-h culture of B5 (1 × 108, 2 × 107, 1 × 107 colony-forming units (CFU)/ml) significantly reduced the incidence of gray blight disease. Compared to the untreated control, spraying with B5 inhibited gray blight disease by 78.57%. Isolate B5 was identified as Bacillus subtilis B5 in morphological and 16S rDNA sequence analyses. The foliar application of 7-day cultures of A65 (1 × 108, 2 × 107, 1 × 107 CFU/ml) significantly reduced the incidence of gray blight disease. A65 (108 CFU/ml) inhibited gray blight disease by 75.46% and was identified as Paecilomyces lilacinus A65 in morphologically and internally transcribed spacer sequence analyses.

Conclusions

These candidate microbial pesticides may inhibit gray wilt in tea, replace chemical pesticides’ use without causing environmental pollution, and promote the development of green agriculture.
Prescribing habits of Moroccan psychiatrists toward patients with schizophrenia: about 72 practitioners
Authors: Benallel Khadija , Mansouri Wafaa , Salim Jalal , Benjelloun Roukaya , Kadiri Mohamed
Published: May 2023

Background

The therapeutic decision toward patients with schizophrenia is very different from one psychiatrist to another when faced with potentially similar clinical symptoms. It depends on many factors that are related to the patient’s and the doctor’s profiles, and the drug’s characteristics. To date, no study has been conducted in Morocco on the prescribing habits of psychiatrists toward patients with schizophrenia. The objectives of our survey are to identify the molecules most prescribed by psychiatrists in Morocco for patients with schizophrenia and to determine the most common therapeutic strategies.

Results

Our survey recruited 72 Moroccan psychiatrists. The median age was 36.5 years. 72.2% were women, and 37.5% had between 5 and 10 years of practice. More than two-thirds were practicing in the public sector in big cities. Olanzapine was an antipsychotic prescribed as first-line treatment for a patient with schizophrenia. For the majority, the most frequent combination was atypical antipsychotics with conventional neuroleptics. On the one hand, most psychiatrists reported prescribing neuroleptics long-acting injectable (neuroleptic LAIs). In the other hand, almost half of the participants had never prescribed second-generation antipsychotic long-acting injectables (SGA-LAIs). The high cost (77.8%), lack of availability of the product in certain sectors (33.3%), lack of therapeutic choice (26.4%), and lack of patient profile that could use the drug (23.6%), were among the strong reasons given for not prescribing SGA-LAIs.

Conclusions

The treatment decision for patients with schizophrenia differs from one clinician to the other. It depends on various factors that may be related to the psychiatrist, the patient, and to the drug.
Bioactivity assays and phytochemical analysis upon Achillea filipendulina, focusing on xanthine oxidase inhibitory and antimalarial properties
Authors: Asnaashari Solmaz , Marefat Sahar , Vatankhah Amir Mansour , Bamdad Moghaddam Sedigheh , Delazar Abbas , Hamedeyazdan Sanaz
Published: May 2023

Background

Achillea filipendulina (L.) is an important medicinal plant and an Asian species of the Asteraceae family. A. filipendulina that grows in Central and Southwest Asia. It was chosen for study with the aim of screening biologically active compounds in the essential oil of the aerial parts and the antioxidant, antimalarial and xanthine oxidase inhibitory activities of its extract. Essential oil was extracted by using Clevenger apparatus. Extraction was done by Soxhlet apparatus with solvents of n-hexane, DCM (dichloromethane) and MeOH (methanol), and then, fractionation of extracts was accomplished through various chromatographic techniques including VLC (vacuum liquid chromatography) approach and SPE (solid phase extraction) technique.

Results

Approximately 79% of A. filipendulina essential oil components were recognized by the gas chromatography mass spectrometry (GC–MS), of which monoterpenes were 63.2% the most abundant components, except for terpenes, other compounds such as fatty acids, phenols, aromatic compounds and ketones were identified, as well antimalarial activity test was done by β-hematin formation assay and xanthine oxidase inhibitory activity was accomplished by Ransod kit, then antioxidant activity was performed by DPPH (2,2-diphenyl 1-picrylhydrzyl) free radical scavenging technique. Preliminary phytochemical screening of MeOH and DCM extracts was done by TLC (thin layer chromatography) and total phenol assay. Monoterpenoids were the main component of the aerial part’s essential oil. Among different extracts, MeOH extract had significant antioxidant and xanthine oxidase inhibitory activities with RC50 (mg/mL) = 0.0707 and IC50 = 12.8741 µg/mL, respectively. Moreover DCM extract had significant antimalarial activities with IC50 (mg/mL) = 0.2511. Among the fractions, 40% and 60% Sep-Pak fraction of MeOH extract had stronger xanthine oxidase inhibitory and antioxidant activities. The 40% fraction of MeOH extract showed the strongest antioxidant and xanthine oxidase inhibitory activities, which might be related to the presence of phenolic compounds. The 80% VLC fraction of DCM extract also indicated the strong antimalarial activities.

Conclusion

As this plant revealed a high content of phenols along with high antioxidant, antimalarial and xanthine oxidase inhibitory activities, it could have great medicinal value. Our results suggested the possible use of A. filipendulina in development of highly potent new pure medicinal compounds.
Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases
Authors: Mahmud Aar Rafi , Ema Tanzila Ismail , Siddiquee Mohd. Faijanur - Rob , Shahriar Asif , Ahmed Hossain , Mosfeq-Ul-Hasan Md. , Rahman Nova , Islam Rahatul , Uddin Muhammad Ramiz , Mizan Md. Furkanur Rahaman
Published: May 2023

Background

Flavonols are phytoconstituents of biological and medicinal importance. In addition to functioning as antioxidants, flavonols may play a role in antagonizing diabetes, cancer, cardiovascular disease, and viral and bacterial diseases. Quercetin, myricetin, kaempferol, and fisetin are the major dietary flavonols. Quercetin is a potent scavenger of free radicals, providing protection from free radical damage and oxidation-associated diseases.

Main body of the abstract

An extensive literature review of specific databases (e.g., Pubmed, google scholar, science direct) were conducted using the keywords “flavonol,” “quercetin,” “antidiabetic,” “antiviral,” “anticancer,” and “myricetin.” Some studies concluded that quercetin is a promising antioxidant agent while kaempferol could be effective against human gastric cancer. In addition, kaempferol prevents apoptosis of pancreatic beta-cells via boosting the function and survival rate of the beta-cells, leading to increased insulin secretion. Flavonols also show potential as alternatives to conventional antibiotics, restricting viral infection by antagonizing the envelope proteins to block viral entry.

Short conclusion

There is substantial scientific evidence that high consumption of flavonols is associated with reduced risk of cancer and coronary diseases, free radical damage alleviation, tumor growth prevention, and insulin secretion improvement, among other diverse health benefits. Nevertheless, more studies are required to determine the appropriate dietary concentration, dose, and type of flavonol for a particular condition to prevent any adverse side effects.
Signaling pathways involved in the biological functions of dendritic cells and their implications for disease treatment
Authors: Cheng Hao , Chen Wenjing , Lin Yubin , Zhang Jianan , Song Xiaoshuang , Zhang Dunfang
Published: May 2023

The ability of dendritic cells (DCs) to initiate and regulate adaptive immune responses is fundamental for maintaining immune homeostasis upon exposure to self or foreign antigens. The immune regulatory function of DCs is strictly controlled by their distribution as well as by cytokines, chemokines, and transcriptional programming. These factors work in conjunction to determine whether DCs exert an immunosuppressive or immune-activating function. Therefore, understanding the molecular signals involved in DC-dependent immunoregulation is crucial in providing insight into the generation of organismal immunity and revealing potential clinical applications of DCs. Considering the many breakthroughs in DC research in recent years, in this review we focused on three basic lines of research directly related to the biological functions of DCs and summarized new immunotherapeutic strategies involving DCs. First, we reviewed recent findings on DC subsets and identified lineage-restricted transcription factors that guide the development of different DC subsets. Second, we discussed the recognition and processing of antigens by DCs through pattern recognition receptors, endogenous/exogenous pathways, and the presentation of antigens through peptide/major histocompatibility complexes. Third, we reviewed how interactions between DCs and T cells coordinate immune homeostasis in vivo via multiple pathways. Finally, we summarized the application of DC-based immunotherapy for autoimmune diseases and tumors and highlighted potential research prospects for immunotherapy that targets DCs. This review provides a useful resource to better understand the immunomodulatory signals involved in different subsets of DCs and the manipulation of these immune signals can facilitate DC-based immunotherapy.
A tutorial of image-domain least-squares reverse time migration through point-spread functions
Authors: Zhang Wei , Gao Jinghuai
Published: May 2023

Least-squares reverse time migration (LSRTM) has shown great potential to improve the amplitude fidelity and spatial resolution of a reverse time migration (RTM) image. However, the main disadvantage is that it requires significant computational resources for the iterative solution. To ameliorate this problem, the image-domain LSRTM (IDLSRTM) approach through point-spread functions (PSFs) has been proven to be a viable and alternative technique to deconvolve the standard RTM image. In this paper, we develop a tutorial for the numerical implementation of IDLSRTM through PSFs. The Hessian matrix in the standard IDLSRTM approach is estimated through the spatial interpolation of precomputed PSFs on the fly, where the PSFs are computed by one-round forward modeling and migration. However, the resulting IDLSRTM scheme is highly ill-conditioned because of the incomplete acquisition condition, irregular subsurface illumination, and band-limited data. To stabilize inversion and improve the inverted image, we suggest that the PSFs and RTM images should be deblurred by applying a deblurring filter. The deblurring PSFs can reduce the condition number of the standard Hessian matrix and make the inverse problem more well conditioned, thus improving imaging quality and accelerating convergence. Furthermore, the regularization operators should be imposed to produce a reasonable inverted image and avoid the overfitting of the image-matching term. Based on several examples with synthetic and field data, we can conclude two significant points. The first point is that the standard IDLSRTM approach through the conventional PSFs can only recover a reflectivity image similar to the deblurring RTM and nonstationary matching filter (NMF) approaches. The second point is that the deblurring IDLSRTM approach through the deblurring PSFs can retrieve the reflectivity image with higher resolution and better amplitude fidelity than the standard IDLSRTM approach and the standard RTM approach with the deblurring filter or NMF.
Factors Associated With Practice of Multimodal Care for Cancer Cachexia Among Physicians and Nurses Engaging in Cancer Care
Authors: Amano Koji , Arakawa Sayaka , Hopkinson Jane B. , Baracos Vickie E. , Oyamada Shunsuke , Koshimoto Saori , Mori Naoharu , Ishiki Hiroto , Morita Tatsuya , Takeuchi Takashi , Satomi Eriko
Published: May 2023

PURPOSE

Multimodal care for cancer cachexia is needed. This study examined factors associated with practicing multimodal cachexia care among physicians and nurses engaging in cancer care.

METHODS

This was a preplanned secondary analysis of a survey investigating clinicians' perspectives on cancer cachexia. Data of physicians and nurses were used. Data on knowledge, skills, and confidence in multimodal cachexia care were obtained. Nine items on practicing multimodal cachexia care were evaluated. Participants were divided into two groups as practicing multimodal cachexia care (above median value for the nine items) or not. Comparisons were made using the Mann-Whitney U test or chi-square test. Multiple regression analysis was performed to identify the factors of practicing the multimodal care.

RESULTS

Total of 233 physicians and 245 nurses were included. Significant differences were observed between the groups: female sex ( P = .025), palliative care versus oncology specialization ( P < .001), the number of clinical guidelines used ( P < .001), the number of symptoms used ( P = .005), training for cancer cachexia ( P = .008), knowledge on cancer cachexia ( P < .001), and confidence in cancer cachexia management ( P < .001). Palliative care specialization (partial regression coefficient [ B] = 0.85; P < .001), the number of clinical guidelines used ( B = 0.44; P < .001), knowledge on cancer cachexia ( B, 0.94; P < .001), and confidence in cancer cachexia management ( B = 1.59; P < .001) were statistically significant in multiple regression analysis.

CONCLUSION

Specialization in palliative care, specific knowledge, and confidence were associated with the practice of multimodal care for cancer cachexia.
Transportation-related Environmental Mixtures and Diabetes Prevalence and Control in Urban/Metropolitan Counties in the United States
Authors: Weiss Margaret C , Adusumilli Sneha , Jagai Jyotsna S , Sargis Robert M
Published: May 2023

Diabetes rates in the United States are staggering and climbing. Importantly, traditional risk factors fail to completely account for the magnitude of the diabetes epidemic. Environmental exposures, including urban and metropolitan transportation quality, are implicated as contributors to disease. Using data from the county-level Environmental Quality Index (EQI) developed for the United States, we analyzed associations between transportation and air quality environmental metrics with overall diabetes prevalence and control within urban/metropolitan counties in the United States from 2006 to 2012. Additionally, we examined effect modification by race/ethnicity through stratification based on the county-level proportion of minority residents. Last, we applied mixture methods to evaluate the effect of simultaneous poor transportation factors and worse air quality on the same outcomes. We found that increased county-level particulate matter air pollution and nitrogen dioxide along with reduced public transportation usage and lower walkability were all associated with increased diabetes prevalence. The minority proportion of the population influences some of these relationships as some of the effects of air pollution and the transportation-related environment are worse among counties with more minority residents. Furthermore, the transportation and air quality mixtures were found to be associated with increased diabetes prevalence and reduced diabetes control. These data further support the burgeoning evidence that poor environments amplify diabetes risk. Future cohort studies should explore the utility of environmental policies and urban planning as tools for improving metabolic health.