bluuebunny/crossref_metadata_2025 huggingface dataset:
Model-based standardization using multiple imputation
Authors: Remiro-Azócar Antonio , Heath Anna , Baio Gianluca
Published: February 2024

Background

When studying the association between treatment and a clinical outcome, a parametric multivariable model of the conditional outcome expectation is often used to adjust for covariates. The treatment coefficient of the outcome model targets a conditional treatment effect. Model-based standardization is typically applied to average the model predictions over the target covariate distribution, and generate a covariate-adjusted estimate of the marginal treatment effect.

Methods

The standard approach to model-based standardization involves maximum-likelihood estimation and use of the non-parametric bootstrap. We introduce a novel, general-purpose, model-based standardization method based on multiple imputation that is easily applicable when the outcome model is a generalized linear model. We term our proposed approach multiple imputation marginalization (MIM). MIM consists of two main stages: the generation of synthetic datasets and their analysis. MIM accommodates a Bayesian statistical framework, which naturally allows for the principled propagation of uncertainty, integrates the analysis into a probabilistic framework, and allows for the incorporation of prior evidence.

Results

We conduct a simulation study to benchmark the finite-sample performance of MIM in conjunction with a parametric outcome model. The simulations provide proof-of-principle in scenarios with binary outcomes, continuous-valued covariates, a logistic outcome model and the marginal log odds ratio as the target effect measure. When parametric modeling assumptions hold, MIM yields unbiased estimation in the target covariate distribution, valid coverage rates, and similar precision and efficiency than the standard approach to model-based standardization.

Conclusion

We demonstrate that multiple imputation can be used to marginalize over a target covariate distribution, providing appropriate inference with a correctly specified parametric outcome model and offering statistical performance comparable to that of the standard approach to model-based standardization.
Ethnoracial disparities in childhood growth trajectories in Brazil: a longitudinal nationwide study of four million children
Authors: Benes Matos da Silva Helena , Ribeiro-Silva Rita de Cássia , Freitas de Mello e Silva Juliana , Chis Ster Irina , Rebouças Poliana , Goes Emanuelle , Ichihara Maria Yury , Ferreira Andrêa , M. Pescarini Julia , Leovigildo Fiaccone Rosemeire , S. Paixão Enny , L. Barreto Maurício
Published: February 2024

Background

The literature contains scarce data on inequalities in growth trajectories among children born to mothers of diverse ethnoracial background in the first 5 years of life.

Objective

We aimed to investigate child growth according to maternal ethnoracial group using a nationwide Brazilian database.

Methods

A population-based retrospective cohort study employed linked data from the CIDACS Birth Cohort and the Brazilian Food and Nutrition Surveillance System (SISVAN). Children born at term, aged 5 years or younger who presented two or more measurements of length/height (cm) and weight (kg) were followed up between 2008 and 2017. Prevalence of stunting, underweight, wasting, and thinness were estimated. Nonlinear mixed effect models were used to estimate childhood growth trajectories, among different maternal ethnoracial groups (White, Asian descent, Black, Pardo, and Indigenous), using the raw measures of weight (kg) and height (cm) and the length/height-for-age (L/HAZ) and weight-for-age z-scores (WAZ). The analyses were also adjusted for mother’s age, educational level, and marital status.

Results

A total of 4,090,271 children were included in the study. Children of Indigenous mothers exhibited higher rates of stunting (26.74%) and underweight (5.90%). Wasting and thinness were more prevalent among children of Pardo, Asian, Black, and Indigenous mothers than those of White mothers. Regarding children’s weight (kg) and length/height (cm), those of Indigenous, Pardo, Black, and Asian descent mothers were on average shorter and weighted less than White ones. Regarding WAZ and L/HAZ growth trajectories, a sharp decline in average z-scores was evidenced in the first weeks of life, followed by a period of recovery. Over time, z-scores for most of the subgroups analyzed trended below zero. Children of mother in greater social vulnerability showed less favorable growth.

Conclusion

We observed racial disparities in nutritional status and childhood growth trajectories, with children of Indigenous mothers presenting less favorable outcomes compared to their White counterparts. The strengthening of policies aimed at protecting Indigenous children should be urgently undertaken to address systematic ethnoracial health inequalities.
Efficient administration of a combination of
nifedipine and sildenafil citrate versus only nifedipine on clinical outcomes in women
with threatened preterm labor: a systematic review and meta-analysis
Authors: Manouchehri Elham , Makvandi Somayeh , Razi Mahdieh , Sahebari Maryam , Larki Mona
Published: February 2024

Background

Preterm labor (PTL) is a common and serious pregnancy disorder that
can cause long-term neurological issues in the infant. There are conflicting
studies concerning whether sildenafil citrate (SC) reduces preterm labor
complications. Therefore, the meta-analysis aimed to examine the clinical
outcomes in women with threatened PTL who received nifedipine plus SC therapy
versus only nifedipine.

Methods

For the original articles, six databases were searched using
relevant keywords without restriction on time or language until January 13,
2024. The Cochrane risk-of-bias tool for randomized trials (RoB) and the Risk of
Bias Assessment Tool for Nonrandomized Studies (RoBANS) were both used to assess
the risk of bias in randomized and non-randomized studies, and GRADE determined
the quality of our evidence. Meta-analysis of all data was carried out using
Review Manager (RevMan) version 5.1.

Results

Seven studies with mixed quality were included in the meta-analysis.
The study found that combining nifedipine and SC resulted in more prolongation
of pregnancy (MD = 6.99, 95% CI: 5.32, 8.65, p < 0.00001), a lower rate of delivery in the 1st to 3rd days
after hospitalization (RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001), a higher birth weight (252.48 g vs. nifedipine
alone, p = 0.02), and the risk ratio of
admission to the neonatal intensive care unit (NICU) was significantly lower
(RR = 0.62, 95% CI: 0.50, 0.76, p < 0.00001) compared to nifidepine alone. The evidence was high
for prolongation of pregnancy, delivery rate 24–72 h after admission, and NICU
admission, but low for newborn birth weight.

Conclusions

Given the effectiveness of SC plus nifedipine in increased
prolongation of pregnancy and birth weight, lower delivery in the 1st to 3rd
days after hospitalization, and NICU admission, Gynecologists and obstetricians
are suggested to consider this strategy for PTL management, although additional
article rigor is required to improve the quality of the evidence.
Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer
Authors: Yang Luchen , Liu Xiaoyang , Peng Zhufeng , Liu Zhenghuan , Song Pan , Zhou Jing , Ma Kai , Yu Yunfei , Dong Qiang
Published: February 2024

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011–2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.
Cost of illness due to respiratory syncytial virus acute lower respiratory tract infection among infants hospitalized in Argentina
Authors: Dvorkin Julia , Sosa Emiliano , Vodicka Elizabeth , Baral Ranju , Sancilio Andrea , Dueñas Karina , Rodriguez Andrea , Rojas-Roque Carlos , Carruitero Patricia B. , Polack Fernando P. , Pecenka Clint , Libster Romina , Caballero Mauricio T.
Published: February 2024

Background

Information is scarce regarding the economic burden of respiratory syncytial virus (RSV) disease in low-resource settings. This study aimed to estimate the cost per episode of hospital admissions due to RSV severe disease in Argentina.

Methods

This is a prospective cohort study that collected information regarding 256 infants under 12 months of age with acute lower respiratory tract infection (ALRTI) due to RSV in two public hospitals of Buenos Aires between 2014 and 2016. Information on healthcare resource use was collected from the patient’s report and its associated costs were estimated based on the financial database and account records of the hospitals. We estimated the total cost per hospitalization due to RSV using the health system perspective. The costs were estimated in US dollars as of December 2022 (1 US dollar = 170 Argentine pesos).

Results

The mean costs per RSV hospitalization in infants was US$587.79 (95% confidence interval [CI] $535.24 – $640.33). The mean costs associated with pediatric intensive care unit (PICU) admission more than doubled from those at regular pediatric wards ($1,556.81 [95% CI $512.21 – $2,601.40] versus $556.53 [95% CI $514.59 – $598.48]).

Conclusions

This study shows the direct economic impact of acute severe RSV infection on the public health system in Argentina. The estimates obtained from this study could be used to inform cost-effectiveness analyses of new preventive RSV interventions being developed.
Deep learning in oral cancer- a systematic review
Authors: Warin Kritsasith , Suebnukarn Siriwan
Published: February 2024

Background

Oral cancer is a life-threatening malignancy, which affects the survival rate and quality of life of patients. The aim of this systematic review was to review deep learning (DL) studies in the diagnosis and prognostic prediction of oral cancer.

Methods

This systematic review was conducted following the PRISMA guidelines. Databases (Medline via PubMed, Google Scholar, Scopus) were searched for relevant studies, from January 2000 to June 2023.

Results

Fifty-four qualified for inclusion, including diagnostic (n = 51), and prognostic prediction (n = 3). Thirteen studies showed a low risk of biases in all domains, and 40 studies low risk for concerns regarding applicability. The performance of DL models was reported of the accuracy of 85.0–100%, F1-score of 79.31 - 89.0%, Dice coefficient index of 76.0 - 96.3% and Concordance index of 0.78–0.95 for classification, object detection, segmentation, and prognostic prediction, respectively. The pooled diagnostic odds ratios were 2549.08 (95% CI 410.77–4687.39) for classification studies.

Conclusions

The number of DL studies in oral cancer is increasing, with a diverse type of architectures. The reported accuracy showed promising DL performance in studies of oral cancer and appeared to have potential utility in improving informed clinical decision-making of oral cancer.
Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program
Authors: Nicholls Stephen J. , Tofé Santiago , le Roux Carel W. , D’Alessio David A. , Wiese Russell J. , Pavo Imre , Brown Katelyn , Weerakkody Govinda J. , Zeytinoglu Meltem , Romera Irene C.
Published: February 2024

Background

Metabolic syndrome is characterized as the co-occurrence of interrelated cardiovascular risk factors, including insulin resistance, hyperinsulinemia, abdominal obesity, dyslipidemia and hypertension. Once weekly tirzepatide is approved in the US and EU for the treatment of type 2 diabetes (T2D) and obesity. In the SURPASS clinical trial program for T2D, tirzepatide demonstrated greater improvements in glycemic control, body weight reduction and other cardiometabolic risk factors versus placebo, subcutaneous semaglutide 1 mg, insulin degludec, and insulin glargine. This post hoc analysis assessed the effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome across SURPASS 1–5.

Methods

Metabolic syndrome was defined as having ≥ 3 of 5 criteria according to the US National Cholesterol Education Program: Adult Treatment Panel III. Analyses were based on on-treatment data at the primary endpoint from patients adherent to treatment (taking ≥ 75% study drug). A logistic regression model with metabolic syndrome status as the response variable, metabolic syndrome status at the baseline visit as an adjustment, and randomized treatment as fixed explanatory effect was used. The effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by categorical weight loss, background medication and gender were assessed.

Results

In SURPASS, the prevalence of patients meeting the criteria for metabolic syndrome at baseline was 67–88% across treatment groups with reductions at the primary endpoint to 38–64% with tirzepatide versus 64–82% with comparators. Reductions in the prevalence of patients meeting the criteria for metabolic syndrome was significantly greater with all tirzepatide doses versus placebo, semaglutide 1 mg, insulin glargine, and insulin degludec (p < 0.001). Individual components of metabolic syndrome were also reduced to a greater extent with tirzepatide vs comparators. Greater reductions in body weight were associated with greater reductions in the prevalence of patients meeting the criteria for metabolic syndrome and its individual components. Background SGLT2i or sulfonylurea use or gender did not impact the change in prevalence of patients meeting the criteria for metabolic syndrome.

Conclusions

In this post hoc analysis, tirzepatide at all doses studied was associated with a greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome compared to placebo, semaglutide 1 mg, insulin degludec, and insulin glargine. Although more evidence is needed, these data would support greater potential improvement in cardiovascular risk factor profile with tirzepatide treatment in people across the continuum of T2D.
Presurgical computed tomography-guided localization of lung ground glass nodules: comparing hook-wire and indocyanine green
Authors: Han Rui , Wang Long-Fei , Teng Fei , Lin Jia , Xian Yu-Tao , Lu Yun , Wu An-Le
Published: February 2024

Background

Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs.

Methods

Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques.

Results

A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000).

Conclusions

Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization.
Hospital infections and health-related quality of life after cardiac surgery: a multicenter survey
Authors: Rijnhart-de Jong Hilda G. , Haenen Jo , Porta Fabiano , Timmermans Marijke , Boerma E. Christiaan , de Jong Kim ,   on behalf of the participating centers of the Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration, Bramer S. , Daeter E. J. , Hoohenkerk G. J. F. , Markou A. L. P. , Speekenbrink R. G. H. , Segers P. , Stooker W. , Li W. W. L. , Bekkers J. A. , Porta F.
Published: February 2024

Background

Recent research suggested that hospital infections are a predictive marker for physical non-recovery one year after cardiothoracic surgery. The purpose of this study was to explore whether this risk factor is etiologic. Additional, the influence of a potential effect modifying factor, diabetes mellitus, was investigated.

Methods

In this multicenter study, patients underwent elective or urgent cardiothoracic surgery between 01-01-2015 and 31-12-2019, and completed pre- and one year post-operative Short Form Health Survey 36/12 quality of life questionnaires. A binary logistic regression model, in which the inverse of the propensity score for infection risk was included as a weight variable, was used. Second, this analysis was stratified for diabetes mellitus status.

Results

8577 patients were included. After weighing for the propensity score, the standardized mean differences of all variables decreased and indicated sufficient balance between the infection and non-infection groups. Hospital infections were found to be a risk factor for non-recovery after cardiothoracic surgery in the original and imputed dataset before weighting. However, after propensity score weighing, hospital infections did not remain significantly associated with recovery (OR for recovery = 0.79; 95% CI [0.60–1.03]; p = 0.077). No significant interaction between diabetes mellitus and hospital infections on recovery was found (p = 0.845).

Conclusions

This study could not convincingly establish hospital infections as an etiologic risk factor for non-improvement of physical recovery in patients who underwent cardiothoracic surgery. In addition, there was no differential effect of hospital infections on non-improvement of physical recovery for patients with and without diabetes mellitus.

Trial registration International Clinical Trials Registry Platform ID NL9818; date of registration, 22-10-2021 (https://trialsearch.who.int/).
Sacubitril/valsartan ameliorates tubulointerstitial fibrosis by restoring mitochondrial homeostasis in diabetic kidney disease
Authors: Zhang Xing-Jian , Liu Cong-Cong , Li Zuo-Lin , Ding Lin , Zhou Yan , Zhang Dong-Jie , Zhang Yao , Hou Shu-Ting , Ma Rui-Xia
Published: February 2024

Background

Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear.

Methods

Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro.

Results

We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor.

Conclusions

Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.
Dendritic cell vaccination in combination with erlotinib in a patient with inoperable lung adenocarcinoma: a case report
Authors: Kosumi Takuya , Kobayashi Masanori , Shimodaira Shigetaka , Sugiyama Haruo , Koido Shigeo
Published: February 2024

Background

Satisfactory treatment for patients with unresectable advanced lung cancer has not yet been established. We report a case of unresectable advanced lung cancer (stage IIIb: T2aN3M0) treated with a total of 15 doses of dendritic cells pulsed with a Wilms’ tumor 1 and mucin 1 vaccine in combination with erlotinib, a small molecule epidermal growth factor receptor tyrosine kinase inhibitor, for more than 699 days without recurrence or metastasis.

Case presentation

A 63-year-old Korean woman was diagnosed with lung adenocarcinoma by pathology and computed tomography. The adenocarcinoma showed an epidermal growth factor receptor (EGFR) mutation, no anaplastic lymphoma kinase expression, and less than 1% expression of programmed death ligand 1. She received erlotinib alone for approximately 1 month. She then received erlotinib and the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine. The diameter of the erythema at the vaccinated sites was 30 mm at 48 hours after the first vaccination. Moreover, it was maintained at more than 20 mm during the periods of vaccination. These results suggested the induction of antitumor immunity by the vaccine. Remarkably, the tumor size decreased significantly to 12 mm, a 65.7% reduction, after combined therapy with eight doses of the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine and erlotinib for 237 days based on fluorodeoxyglucose uptake by positron emission tomography/computed tomography and computed tomography. Interestingly, after 321 days of combination therapy, the clinical findings improved, and no tumor was detected based on computed tomography. Validation of the tumor’s disappearance persisted for at least 587 days after treatment initiation, without any indication of recurrence or metastasis.

Conclusion

Standard anticancer therapy combined with the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine may have therapeutic effects for such patients with unresectable lung adenocarcinoma.
Relaxed fibronectin: a potential novel target for imaging endometriotic lesions
Authors: Trachsel Belinda , Imobersteg Stefan , Valpreda Giulia , Singer Gad , Grabherr Regula , Ormos Mark , Burger Irene A. , Kubik-Huch Rahel A. , Schibli Roger , Vogel Viola , Béhé Martin
Published: February 2024

Background

Endometriosis is characterized by the ectopic occurrence of endometrial tissue. Though considered benign, endometriotic lesions possess tumor-like properties such as tissue invasion and remodeling of the extracellular matrix. One major clinical hurdle concerning endometriosis is its diagnosis. The diagnostic modalities ultrasound and MRI are often unable to detect all lesions, and a clear correlation between imaging and clinical symptoms is still controversial. Therefore, it was our aim to identify a potential target to image active endometriotic lesions.

Results

For our studies, we employed the preclinical radiotracer [111In]In-FnBPA5, which specifically binds to relaxed fibronectin–an extracellular matrix protein with key functions in homeostasis that has been implicated in the pathogenesis of diseases such as cancer and fibrosis. We employed this tracer in biodistribution as well as SPECT/CT studies in mice and conducted immunohistochemical stainings on mouse uterine tissue as well as on patient-derived endometriosis tissue. In biodistribution and SPECT/CT studies using the radiotracer [111In]In-FnBPA5, we found that radiotracer uptake in the myometrium varies with the estrous cycle of the mouse, leading to higher uptake of [111In]In-FnBPA5 during estrogen-dependent phases, which indicates an increased abundance of relaxed fibronectin when estrogen levels are high. Finally, immunohistochemical analysis of patient samples demonstrated that there is preferential relaxation of fibronectin in the proximity of the endometriotic stroma.

Conclusion

Estrous cycle stages characterized by high estrogen levels result in a higher abundance of relaxed fibronectin in the murine myometrium. This finding together with a first proof-of-concept study employing human endometriosis tissues suggests that relaxed fibronectin could be a potential target for the development of a diagnostic radiotracer targeting endometriotic lesions. With [111In]In-FnBPA5, the matching targeting molecule is in preclinical development.
PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies
Authors: Liu Peiyu , Sun Dandan , Zhang Shuchang , Chen Shimei , Wang Xiaoqian , Li Huiming , Wei Fang
Published: February 2024

Background

Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis.

Main body

In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease.

Conclusion

Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.
Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study
Authors: Domizi R. , Damiani E. , Carsetti A. , Graciotti L. , Procopio A. D. , Scorcella C. , Casarotta E. , Giaccaglia P. , Donati A. , Adrario E.
Published: February 2024

Background

Acetaminophen (ACT) has been studied in septic patients with detectable plasmatic levels of cell-free hemoglobin (Hb), where it demonstrated to inhibit the hemoprotein-mediated lipid peroxidation and oxidative injury, with a potential of beneficial effect on the endothelium. On the basis of this background, the aim of this study was to evaluate the sublingual microcirculation and the peripheral tissue perfusion before-and-after administration of ACT on clinical judgment in a cohort of febrile septic and septic shock patients.

Methods

Prospective observational study. 50 adult septic and septic shocks treated with ACT for pyrexia, where the sublingual microcirculation and the peripheral tissue perfusion with Near Infrared Spectroscopy (NIRS) and vascular occlusion test (VOT) were evaluated before ACT (t0), after 30 min (t1) and after 2 h (t2). Cell-free Hb and the markers of oxidative stress and endothelial damage were measured at t0 and t2.

Results

The study showed a significant increase of the density of the perfused small and total vessels of the sublingual microcirculation 30 min after the infusion of ACT; it also showed an increase of the Microvascular Flow Index (MFI) and a decrease in the heterogeneity of the flow.

At a peripheral muscular level, we found an acceleration in the reperfusion curve after VOT at t1, expression of a higher reactivity of the microvasculature.

Conclusions

ACT infusion did not show a clear correlation with cell-free Hb; however, it exhibited protective effect toward the microcirculation that was evident in particular in septic patients. This correlation merits further exploration.
Identity fraud victimization: a critical review of the literature of the past two decades
Authors: Irvin-Erickson Yasemin
Published: February 2024

This study aims to provide an understanding of the nature, extent, and quality of the research evidence on identity fraud victimization in the US. Specifically, this article reviews, summarizes, and comments on the state of empirical research of identity fraud victimization in the US based on a narrative review of 52 published empirical studies. Studies included in this review suggest that the prevalence of identity fraud in the US has increased over the years and existing account frauds is the most prevalent type of identity fraud. There is a pressing need for more research on the prevalence of identity fraud victimization among minors, institutionalized individuals, and individuals from minority groups; long-term prevalence of identity fraud victimization; and emerging forms of identity fraud such as synthetic identity fraud victimization. Studies included in this review further suggest that identity fraud risk factors vary based on the fraud type considered. Identity fraud victims can experience a variety of harms. Longitudinal studies following identity fraud victims are essential for reliably estimating the risk factors for identity fraud victimization and the impact of identity fraud victimization on individual victims. The research on services for identity fraud victims is limited and suggests the positive impact of trauma-informed services for serious identity fraud victims. The overwhelming lack of research on the impact of programs and services for identity fraud victims necessitates more attention from scholars to study the impact of programs, interventions, and services for identity fraud victims on reporting of victimization, prevention of victimization, experiences of victims, and victim-centered cost benefit analysis of services. Policy and practice implications of these findings are discussed.
Online hate speech victimization: consequences for victims’ feelings of insecurity
Authors: Dreißigacker Arne , Müller Philipp , Isenhardt Anna , Schemmel Jonas
Published: February 2024

This paper addresses the question whether and to what extent the experience of online hate speech affects victims’ sense of security. Studies on hate crime in general show that such crimes are associated with a significantly higher feeling of insecurity, but there is little evidence concerning feeling of insecurity due to online hate speech. Based on a secondary data analysis of a representative population survey in Lower Saxony, Germany, on the topic of cybercrime in 2020 (N = 4,102), we tested three hypotheses regarding the effect of offline and online hate speech on feelings of insecurity. As a result, compared to non-victims, victims of online hate speech exhibit a more pronounced feeling of insecurity outside the Internet, while victims of other forms of cybercrime do not differ in this regard from non-victims. We found no effect for offline hate speech when relevant control variables were included in the statistical model. Possible reasons for this finding are assumed to lie in the characteristics of the phenomenon of online hate speech, for example, because the hateful content spreads uncontrollably on the Internet and reaches its victims even in protected private spheres.
An interval constraint-based trading strategy with social sentiment for the stock market
Authors: Li Mingchen , Yang Kun , Lin Wencan , Wei Yunjie , Wang Shouyang
Published: February 2024

Developing effective strategies to earn excess returns in the stock market is a cutting-edge topic in the field of economics. At the same time, stock price forecasting that supports trading strategies is considered one of the most challenging tasks. Therefore, this study analyzes and extracts news media data, expert comments, social opinion data, and pandemic text data using natural language processing, and then combines the data with a deep learning model to forecast future stock price patterns based on historical stock prices. An interval constraint-based trading strategy is constructed. Using data from several typical stocks in the Chinese stock market during the COVID-19 period, the empirical studies and trading simulations show, first, that the sentiment composite index and the deep learning model can improve the accuracy of stock price forecasting. Second, the interval constraint-based trading strategy based on the proposed approach can effectively enhance returns and thus, can assist investors in decision-making.
Molecular phylogenetics of the Ophiocordyceps sinensis-species complex lineage (Ascomycota, Hypocreales), with the discovery of new species and predictions of species distribution
Authors: Dai Yongdong , Chen Siqi , Wang Yuanbing , Wang Yao , Yang Zhuliang , Yu Hong
Published: February 2024

Ophiocordyceps sinensis is a famous traditional Chinese medicine adapted to the alpine environment of the Qinghai-Tibet Plateau and adjacent regions. Clarification of the species diversity of Ophiocordyceps sinensis and its relatives could expand the traditional medicinal resources and provide insights into the speciation and adaptation. The study is prompted by the discovery of a new species, O. megala, described here from a biodiversity hotspot in the Hengduan Mountains, China. Combined morphological, ecological, and phylogenetic evidence supports its distinctiveness from O. sinensis, O. xuefengensis, and O. macroacicularis. Additionally, based on the phylogenetic construction of Ophiocordyceps, a special clade was focused phylogenetically on the more closely related O. sinensis complex, which was defined as the O. sinensis- species complex lineage. A total of 10 species were currently confirmed in this lineage. We made a comprehensive comparison of the sexual/asexual morphological structures among this species complex, distinguishing their common and distinctive features. Furthermore, using the method of species distribution modelling, we studied the species ocurrences in relation to climatic, edaphic, and altitudinal variables for the eight species in the O. sinensis-species complex, and determined that their potential distribution could extend from the southeastern Qinghai-Tibet Plateau to the Xuefeng Mountains without isolating barrier. Thus, the biodiversity corridor hypothesis was proposed around the O. sinensis-species complex. Our study highlights the phylogeny, species diversity, and suitable distribution of the O. sinensis-species complex lineage, which should have a positive implication for the resource discovery and adaptive evolution of this unique and valuable group.
Novel mutation as a cause of anterior segment dysgenesis leading to blindness in progeny: the genetics decoded!
Authors: Pritti Kumari , Mishra Vineet , Aggarwal Somesh , Mistri Mehul , Chhetry Manisha
Published: February 2024

Background

Anterior segment dysgenesis (ASD) disorders comprises of spectrum of developmental conditions affecting the structures of angle of anterior chamber including cornea, iris, and lens. These conditions are characterized by both autosomal dominant and recessive patterns of inheritance often with incomplete penetrance/variable expressivity. A significant overlap among phenotypes attributed to mutations in different ASD genes is well recognized.

Case presentation

We present a case involving a 29-year-old pregnant woman referred for genetic screening and counseling. She had a 7-year-old male child with congenital bilateral corneal opacity, and his elder sister also exhibited similar findings. Exome sequencing identified a novel variant in the CYP1B1 gene in a homozygous state, which was associated with anterior segment dysgenesis. Both parents were found to be carriers of the same variant, while the sister had the same variant in a homozygous state. Genotype–phenotype correlation was performed, and it was concluded that the novel variant could be responsible for the eye changes in both siblings. The parents sought prenatal diagnosis for the current pregnancy, which was deemed possible.

Conclusions

This case underscores the importance of genetic testing in such rare diseases, as it can assist in early diagnosis, management, and prognosis. It also aids clinicians and parents in making decisions regarding the continuation of the pregnancy at the appropriate time.
An infective endocarditis complicated by multiple septic emboli: case report
Authors: Amri Meriam , Tamir El Mehdi , Drighil Abdenasser , Habbal Rachida
Published: February 2024

Background

Owing to challenges associated with heart failure and cardiac embolism, infectious endocarditis emerges as a critical pathology characterized by elevated mortality and morbidity rates. Our case stands out as a rare instance of endocarditis involving multisystem embolization, with a successful outcome.

Case presentation

We present the case of an 81-year-old man whose admission was further complicated by various septic emboli affecting the brain (manifesting as a brain abscess and ischemic stroke), spleen (resulting in splenic infarction), and spinal cord. The patient received a diagnosis of infective endocarditis affecting the native mitral valve. Following prompt medical and surgical intervention, the overall progression was favorable despite encountering several challenges.

Conclusions

This case is notable for its detailed description and analysis of the multiple embolic events. More importantly, it underscores the significance of timely surgical intervention and the collaborative approach of a heart team in the face of complicated endocarditis marked by numerous septic emboli. Despite the typically grim prognosis associated with such cases, the outcomes emphasize the positive impact of timely surgery on prognosis.
Effects of the Cortisol Milieu on Tumor-Infiltrating Immune Cells in Corticotroph Tumors
Authors: Kanzawa Maki , Shichi Hiroki , Kanie Keitaro , Yamamoto Masaaki , Yamamoto Naoki , Tsujimoto Yasutaka , Bando Hironori , Iguchi Genzo , Kitano Shigehisa , Inoshita Naoko , Yamada Shozo , Ogawa Wataru , Itoh Tomoo , Fukuoka Hidenori
Published: February 2024

Context

Corticotrophs are susceptible to lymphocyte cytotoxicity, as seen in hypophysitis, suggesting that an immunological approach may be a potential strategy for corticotroph-derived tumors.

Objective

We aimed to clarify whether corticotroph tumors that induce hypercortisolemia (ACTHomas) could be targets for immunotherapy.

Methods

Tumor-infiltrating immune cells were immunohistochemically analyzed. ACTHomas were compared with other pituitary tumors, and further divided into 3 different cortisol-exposed milieus: Naïve (ACTHomas without preoperative treatment), Met (ACTHomas with preoperative metyrapone), and SCA (silent corticotroph adenomas). A 3-dimensional cell culture of resected tumors was used to analyze the effects of immune checkpoint inhibitors.

Results

The number of tumor-infiltrating lymphocytes (TILs) was low in ACTHomas. Among these, the number of CD8+ cells was lower in ACTHomas than in both somatotroph and gonadotroph tumors (both P < .01). Then we compared the differences in TILs among Naïve, Met, and SCA. The number of CD4+ cells, but not CD8+ cells, was higher in both Met and SCA than in Naïve. Next, we investigated tumor-associated macrophages, which could negatively affect T cell infiltration. The numbers of CD163+ and CD204+ cells were positively associated with cortisol levels. Moreover, tumor size was positively correlated with the number of CD204+ cells.

Conclusion

We found the possibility that ACTHomas were immunologically cold in a cortisol-independent manner. In contrast, the tumor infiltration of CD4+ cells and M2-macrophages were associated with the cortisol milieu. Future studies are needed to validate these results and develop effective immunotherapy while considering the cortisol milieu.
THE PRACTICE OF BROADCASTING THE DIGITAL EDUCATIONAL ENVIRONMENT IN THE CONTEXT OF THE IMPLEMENTATION OF ANDRAGOGICAL SUPPORT OF TEACHERS
Authors: Farus Oksana A. , Yakusheva Galina I. , Ryabtsov Sergey N.
Published: February 2024

Background. The relevance of the study is determined by the need to significantly increase the percentage of the introduction of digital technologies in the educational process.

Purpose. The authors of the article aim to form a model for the implementation of the process of andragogical support of teachers, developed in the context of the digitalization of modern society and aimed at mastering the elements of the digital educational environment by teachers, taking into account new tools and services.

Materials and methods. The achievement of the goals set in the work was carried out on the basis of general scientific research methods within the framework of comparative, theoretical analysis of scientific literature and normative documents on the methodological foundations of the organization of the processes of andragogical support of teachers within the digital educational environment. In the empirical part of the study, the authors visualized the process of organizing additional education for teachers on the basis of the Orenburg State Pedagogical University through the method of practical modeling.

Results. The analysis of scientific literature and normative documents in the field of andragogical support of a teacher allowed the authors to identify and characterize three key components of digitalization of the teacher support process in modern society. The assessment of the content component of these components and the practical experience of broadcasting the digital educational environment in the context of the implementation of andragogical support of teachers allowed the authors to develop a model for organizing additional teacher education. Using the example of this model, the possibilities of using the advantages of digital technologies in the additional education of a teacher are shown.

Practical implications. The results obtained can be applied in the system of additional education of teachers.
OPTIMIZATION OF FOREIGN LANGUAGE TEACHING IN HIGHER EDUCATION: «FLIPPED CLASSROOM» AND PRODUCTIVE METHOD OF TEACHING
Authors: Aksenova Zhanna A. , Aksenova Olga S.
Published: February 2024

The article deals with the topic of implementation of the flipped classroom technology of blended learning in foreign language classes in higher education. This is particularly important in terms of the need to create personalized learning experience for students. The aim of the paper is to identify the main advantages of the flipped classroom technology in foreign language teaching in higher education.

Methodological basis includes theoretical and methodological analysis of literature on the research problem as well as systematization of the studied information.

As a result of the research, the essence of the notion “blended learning” was revealed and the main advantages of the flipped classroom technology in foreign language classes were identified. The special place of productive method of teaching foreign languages was determined as it contributes to the development of students’ grammar-discourse competence.

It was concluded that “flipped classroom”, having a number advantages, in combination with the productive method of teaching can contribute to optimization of foreign language teaching in higher education.
POTENTIAL AND EFFECTIVENESS OF DISTANCE TEACHING A FOREIGN LANGUAGE
Authors: Shageeva Gulnara R.
Published: February 2024

The subject of the article is reflection on the use of e-learning in language education. Based on the opportunities provided by distance learning in language education, a description of an empirical study is given, the main purpose of which was to evaluate the effectiveness and analyze the properties of distance learning in the process of teaching/learning foreign languages. The main goal of the planned study was to evaluate the effectiveness and analyze the properties of distance learning in the glottodidactic process. During the discussion, the conditions and possibilities for introducing e-learning in the context of language education at the academic level were discussed. Our own research was quantitative and qualitative in nature. The effectiveness of distance learning in editing written statements in a foreign language was assessed on the basis of statistical analysis of data obtained as a result of a training experiment. As part of the survey study, observations covered various aspects of distance learning. Based on the above considerations, it is worth emphasizing the need to continue research on the use of e-learning in the glottodidactic process within the framework of various language skills and at various levels of foreign language proficiency. Of course, organizing the process of distance learning, as well as contact learning, requires appropriate actions to individualize learning and, as a result, constant adaptation of the concept of classes conducted in a distance model to the specific educational needs of students, which can lead to a more conscious and effective use of the potential e-learning in language education. The most important results of the study are discussed later in the article.