bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the content validity of the Manchester–Oxford Foot Questionnaire in surgically treated ankle fracture patients: a qualitative study
Authors: Nguyen Michael Q. , Broström Anders , Iversen Marjolein M. , Harboe Knut , Paulsen Aksel
Published: December 2023

Background

Roughly 10% of fractures in adults are ankle fractures. These injuries are found in both sexes and present with different fracture characteristics. The treatment varies with the patients’ biology and fracture type, and the goals are to restore stability, prevent pain and maintain ankle function. Clinicians generally use outcomes like assessment of radiography, pain level, or function. The use of patient-reported outcome measures is increasing, and the Manchester–Oxford Foot Questionnaire (MOXFQ) has been shown to have good measurement properties when validated in patients with foot and ankle disorders. However, the instrument has not been validated for ankle fracture patients. This study aims to assess the content validity of the items in MOXFQ in surgically treated ankle fracture patients.

Methods

A qualitative deductive design was used to investigate patients’ response process of the MOXFQ. Individual interviews were conducted using cognitive interviewing based on the theoretical framework of the 4-step model by Tourangeau. Adult patients that were surgically treated for an ankle fracture between four weeks and 18 months were purposively sampled, and interviews followed a semi-structured interview guide. The predetermined categories were comprehension, retrieval, judgement, and response.

Results

Seventeen respondents (65% females) were interviewed. Respondents’ age ranged from 27 to 76 years. Some of the respondents in the early recovery phase were limited by post-operative restrictions and did not find the items in the walking/standing domain relevant. Respondents that were allowed weight-bearing as tolerated (WBAT) were able to recall relevant information for most items. Respondents with time since surgery more than 12 months had less pain and remembered fewer relevant episodes in the recall period. Items in the social interaction domain contained ambiguous questions and were generally considered less important by respondents. The summary index score lacked important concepts in measuring overall quality of life.

Conclusions

Pain was a central concept in the post-operative recovery of ankle fracture patients. The MOXFQ-subscales for pain and walking/standing had acceptable content validity in patients that were allowed WBAT. The social interaction-subscale and the summary index score had insufficient content validity for this patient population.
Attacks on Ukrainian healthcare facilities during the first year of the full-scale Russian invasion of Ukraine
Authors: Barten Dennis G. , Tin Derrick , Granholm Fredrik , Rusnak Diana , van Osch Frits , Ciottone Gregory
Published: December 2023

Background

Although the Geneva Conventions and Rome Statute demand protections for healthcare facilities during war, breaches of these protections are frequently reported. The ongoing war in Ukraine is no exception, with several healthcare attacks eliciting widespread condemnation. The Ukrainian Healthcare Center (UHC) has been collecting, verifying and documenting attacks on health infrastructure since the Russia–Ukraine War was launched. The aim of this study was to assess UHC documented healthcare facility attacks during the first year (24 February 2022 to 25 February 2023) of the full-scale Russian invasion of Ukraine.

Methods

The Berkeley Protocol on Digital Open Source Investigations was used to document healthcare attacks. Data collection included temporal factors, location, facility type, attack and weapon type, number of killed and injured healthcare personnel and civilians, and whether facilities were damaged, destroyed or attacked more than once.

Results

There were 334 documented attacks on 267 Ukrainian healthcare facilities, with 230 facilities being damaged and 37 destroyed. General hospitals, primary care clinics, emergency departments and children’s hospitals were most frequently targeted. The majority of attacks took place during the first three months and in eastern Ukrainian oblasts. Heavy weaponry was employed in almost all attacks. The total number of casualties included 97 fatalities and 114 injuries.

Conclusions

During the first year of the full-scale Russian invasion of Ukraine, there were 334 attacks on 267 Ukrainian healthcare facilities documented by the UHC. Heavy weaponry was commonly used, and the direct impact of attacks was considerable in terms of facility damage and casualty tolls.
Predictors of time until return to work and duration of sickness absence in sick-listed precarious workers with common mental disorders: a secondary data-analysis of two trials and one cohort study
Authors: Suijkerbuijk Yvonne B. , Schaafsma Frederieke G. , Jansen Lyanne P. , Audhoe Selwin S. , Lammerts Lieke , Anema Johannes R. , Nieuwenhuijsen Karen
Published: December 2023

Background

Common mental disorders (CMD) are highly prevalent among sick-listed precarious workers and often lead to long-term sickness-absence, work disability and unemployment. This study aimed to identify predictors of a longer time until return to work (RTW) and prolonged duration of sickness absence in sick-listed precarious workers with CMD.

Methods

We conducted a secondary Cox regression analysis using existing data from two Dutch randomized controlled trials and one cohort study among sick-listed precarious workers with CMD (N = 681). Age, gender, baseline employment status, study allocation, severity of psychological symptoms and RTW self-efficacy were evaluated for their predictive value on time until sustainable (≥ 28 days) RTW and duration of sickness absence during 12-month follow-up. In this study, time until sustainable RTW and duration of sickness absence are distinct dependent variables, because they are not mutually exclusive.

Results

Age above 50 years (HR 0.57, 95% CI 0.39–0.82), severe psychological symptoms (HR 0.64, 95% CI 0.43–0.93), unemployment (HR 0.19 95% CI 0.11–0.33) and loss of employment contract during sickness absence (HR 0.25, 95% CI 0.14–0.47) were predictive of a longer time until RTW. Male gender (HR 0.77, 95% CI 0.62–0.97), severe psychological symptoms (HR 0.64, 95% CI 0.46–0.87), unemployment (HR 0.47, 95% CI 0.27–0.84) and loss of employment contract (HR 0.48, 95% CI 0.26–0.90) predicted a prolonged duration of sickness absence.

Conclusions

Unemployment at the moment of sick-listing, loss of employment contract during sickness absence, and severe psychological symptoms are predictors of both a longer time until RTW and prolonged duration of sickness absence among sick-listed precarious workers with CMD. This knowledge assists occupational health and mental health professionals in the early identification of workers at risk of long-term sickness absence, enabling them to arrange targeted occupational rehabilitation support and mental health care.

Trial registration

The included randomized controlled trials were prospectively registered in the Dutch national trial register under NTR4190 (September 27, 2013) and NTR3563 (August 7, 2012).
Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study
Authors: Hung Shih-Kai , Yang Hsuan-Ju , Lee Moon-Sing , Liu Dai-Wei , Chen Liang-Cheng , Chew Chia-Hui , Lin Chun-Hung , Lee Cheng-Hung , Li Szu-Chin , Hong Chung-Lin , Yu Chih-Chia , Yu Ben-Hui , Hsu Feng-Chun , Chiou Wen-Yen , Lin Hon-Yi
Published: December 2023

Background

Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge.

Methods

From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).

Results

After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02).

Conclusion

In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor’s hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.
Turnover of strain-level diversity modulates functional traits in the honeybee gut microbiome between nurses and foragers
Authors: Baud Gilles L. C. , Prasad Aiswarya , Ellegaard Kirsten M. , Engel Philipp
Published: December 2023

Background

Strain-level diversity is widespread among bacterial species and can expand the functional potential of natural microbial communities. However, to what extent communities undergo consistent shifts in strain composition in response to environmental/host changes is less well understood.

Results

Here, we used shotgun metagenomics to compare the gut microbiota of two behavioral states of the Western honeybee (Apis mellifera), namely nurse and forager bees. While their gut microbiota is composed of the same bacterial species, we detect consistent changes in strain-level composition between nurses and foragers. Single nucleotide variant profiles of predominant bacterial species cluster by behavioral state. Moreover, we identify strain-specific gene content related to nutrient utilization, vitamin biosynthesis, and cell–cell interactions specifically associated with the two behavioral states.

Conclusions

Our findings show that strain-level diversity in host-associated communities can undergo consistent changes in response to host behavioral changes modulating the functional potential of the community.
Loss of the centrosomal protein ALMS1 alters lipid metabolism and the regulation of extracellular matrix-related processes
Authors: Bea-Mascato Brais , Gómez-Castañeda Eduardo , Sánchez-Corrales Yara E. , Castellano Sergi , Valverde Diana
Published: December 2023

Background

Alström syndrome (ALMS) is a rare autosomal recessive disease that is associated with mutations in ALMS1 gene. The main clinical manifestations of ALMS are retinal dystrophy, obesity, type 2 diabetes mellitus, dilated cardiomyopathy and multi-organ fibrosis, characteristic in kidneys and liver. Depletion of the protein encoded by ALMS1 has been associated with the alteration of different processes regulated via the primary cilium, such as the NOTCH or TGF-β signalling pathways. However, the cellular impact of these deregulated pathways in the absence of ALMS1 remains unknown.

Methods

In this study, we integrated RNA-seq and proteomic analysis to determine the gene expression profile of hTERT-BJ-5ta ALMS1 knockout fibroblasts after TGF-β stimulation. In addition, we studied alterations in cross-signalling between the TGF-β pathway and the AKT pathway in this cell line.

Results

We found that ALMS1 depletion affects the TGF-β pathway and its cross-signalling with other pathways such as PI3K/AKT, EGFR1 or p53. In addition, alterations associated with ALMS1 depletion clustered around the processes of extracellular matrix regulation and lipid metabolism in both the transcriptome and proteome. By studying the enriched pathways of common genes differentially expressed in the transcriptome and proteome, collagen fibril organisation, β-oxidation of fatty acids and eicosanoid metabolism emerged as key processes altered by the absence of ALMS1. Finally, an overactivation of the AKT pathway was determined in the absence of ALMS1 that could be explained by a decrease in PTEN gene expression.

Conclusion

ALMS1 deficiency disrupts cross-signalling between the TGF-β pathway and other dependent pathways in hTERT-BJ-5ta cells. Furthermore, altered cross-signalling impacts the regulation of extracellular matrix-related processes and fatty acid metabolism, and leads to over-activation of the AKT pathway.
Effect of Elaeagnus Angustifolia extract on in vitro wound healing of human dermal fibroblast cells
Authors: Azaryan Ehsaneh , Sarfi Sepideh , Hosseini Seyede Fatemeh , Saharkhiz Mansoore , vazifeshenas-Darmiyan Khadijeh , Naseri Mohsen
Published: December 2023

Aim

The purpose of this study was to determine the impact of Elaeagnus Angustifolia extract (EA) on human dermal fibroblast (HDF) survival, migration, and wound healing-related genes.

Methods

After preparing the hydroalcoholic extract of EA, MTT and scratch tests were used to determine the effect of EA on the viability and migration of HDFs. In addition, the quantitative polymerase chain reaction (q-PCR) was conducted to evaluate the impact of EA on the expression of wound healing-related genes in HDFs.

Result

According to the MTT test, a nontoxic concentration of EA (100 µg/ml) was obtained for further investigations. The scratch test results demonstrated that EA improved HDFs’ capacity to migrate when compared to the control group. Additionally, q-PCR results revealed that EA could significantly increase wound healing-related genes (VEGF-A, HLA-G5, and IL-6) in comparison with the control group.

Conclusions

The EA could have a significant impact on the viability and migration of HDFs. Also, EA increased the expression of wound healing-related genes.
On the 3D point clouds–palm and coconut trees data set extraction and their usages
Authors: Chantrapornchai Chantana , Srijan Phisit
Published: December 2023

Objective

Drone image data set can be utilized for field surveying and image data collection which can be useful for analytics. With the current drone mapping software, useful 3D object reconstruction is possible. This research aims to learn the 3D data set construction process for trees with open-source software along with their usage. Thus, we research the tools used for 3D data set construction, especially in the agriculture field. Due to the growing open-source community, we demonstrate the case study of our palm and coconut data sets against the open-source ones.

Results

The methodology for achieving the point cloud data set was based on the tools: OpenDroneMap, CloudCompare, and Open3D. As a result, 40 palm trees and 40 coconut tree point clouds were extracted. Examples of the usages are provided in the area of volume estimation and graph analytics.
Biologic use and treatment patterns in patients with chronic rhinosinusitis with nasal polyps: a US real-world study
Authors: Silver Jared , Packnett Elizabeth , Park Julie , Deb Arijita
Published: December 2023

Background

Several biologics are now approved in the US as add-on treatments for chronic rhinosinusitus with nasal polyps (CRSwNP). This cross-sectional, retrospective, real-world study aimed to characterize treatment patterns and identify predictors of biologic use among patients with CRSwNP.

Methods

Adults in the Merative MarketScan Commercial and Medicare Supplemental Databases with medical claims for CRSwNP were identified June 2018–June 2019 (identification period [IP]). Patient characteristics were collated in the IP and treatment pattern data during the IP plus the following year (July 2019–June 2020; observation period [OP]). Data were stratified by sinus surgery and biologic use.

Results

Of the 5997 eligible patients identified (58% male, mean age 48.1 years), 10.7% (n = 642) used biologics during the OP. More biologic users had common respiratory conditions than non-users, particularly asthma (89.1% vs 35.0%; P < 0.001). Biologic users had fewer diagnostic services but more drug-related services than non-users. Only 11.6% of patients who had sinus surgery used biologics, with most (56.1%) having their first biologic dose before sinus surgery and 12.5% ≤ 30 days after. Oral corticosteroid (OCS) use was higher in biologic users than non-users (all patients: 68.8% vs 42.5%; P < 0.001) and in those with/without sinus surgery. Comorbidities, prior OCS/doxycycline use, and age (< 65 years) increased the odds of biologic use, with asthma increasing the odds 5.46 times (P < 0.001).

Conclusions

Biologic use was more common before first/next sinus surgery and in patients with high unmet need, elucidating predictors of biologic use that could be used in clinical practice.
Molecular characteristics and pathogenicity of a novel chicken astrovirus variant
Authors: Bi Xiaoqing , Song Zhenrui , Meng Fanrun , Sun Shiwei , Du Xusheng , Yang Mengzan , Zhou Defang , Cheng Xiangyu , Ding Longying , Shi Hengyang , Lang Feng , Luan Huaibiao , Deng Bing , Yang Liangyu , Cheng Ziqiang
Published: December 2023

It is well-established that the genetic diversity, regional prevalence, and broad host range of astroviruses significantly impact the poultry industry. In July 2022, a small-scale commercial broiler farm in China reported cases of growth retardation and a 3% mortality rate. From chickens displaying proventriculitis and pancreatitis, three chicken astroviruses (CAstV) isolates were obtained and named SDAU2022-1-3. Complete genomic sequencing and analysis revealed the unique characteristics of these isolates from known CAstV strains in ORF1a, ORF1b, and ORF2 genes, characterized by an unusually high variability. Analysis of amino acid mutations in ORF1a, ORF1b, and ORF2 indicated that the accumulation of these mutations played a pivotal role in the emergence of the variant strain. Inoculation experiments demonstrated that affected chickens exhibited liver and kidney enlargement, localized proventricular hemorrhage, and a dark reddish-brown appearance in about two-thirds of the pancreas. Histopathological examination unveiled hepatic lymphocytic infiltration, renal tubular epithelial cell swelling, along with lymphocytic proventriculitis and pancreatitis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis indicated viremia and viral shedding at 3 days post-infection (dpi). The proventriculus displayed the highest viral loads, followed by the liver, kidney, duodenum, and pancreas. Liver parameters (AST and ALT) and kidney parameters (UA and UN) demonstrated mild damage consistent with earlier findings. While the possibility of new mutations in the ORF2 gene of CAstV causing proventriculitis and pancreatitis warrants further investigation, these findings deepen our comprehension of CAstV’s pathogenicity in chickens. Additionally, they serve as valuable references for subsequent research endeavors.
Convergence results on the general inertial Mann–Halpern and general inertial Mann algorithms
Authors: Gebregiorgis Solomon , Kumam Poom
Published: December 2023

In this paper, we prove strong convergence theorem of the general inertial Mann–Halpern algorithm for nonexpansive mappings in the setting of Hilbert spaces. We also prove weak convergence theorem of the general inertial Mann algorithm for k-strict pseudo-contractive mappings in the setting of Hilbert spaces. These convergence results extend and generalize some existing results in the literature. Finally, we provide examples to verify our main results.
Perioperative Quality Initiative (POQI) consensus statement on perioperative assessment of right ventricular function
Authors: O. Ibekwe Stephanie , Deschamps Jean , Grocott Michael P W , Liang Yafen , Shaw Andrew , E. Perry Tjorvi ,   POQI IX Collaborators
Published: December 2023

Background

The right ventricle (RV) plays a central  role in the maintenance of effective cardiac pump function. Despite overwhelming evidence that perioperative RV dysfunction (RVD) and failure (RVF) are associated with poor clinical outcomes, there are very few published recommendations or guidelines for comprehensive, evidence-based RV assessment on the risk of developing either during the perioperative period.

Main text

To address this gap, the Perioperative Quality Initiative-IX (POQI-IX) investigators group, comprised of clinical experts in anesthesiology, cardiovascular surgery, internal medicine, critical care medicine, and advanced practice nursing, has developed a consensus statement based on current literature, published society recommendations, and the clinical expertise of the group. Herein, the group provides recommendations and evidence-based tools related to perioperative RV assessment, functional screening, staging, and the clinical implications of each. These assessment tools are based on comprehensive patient evaluation consisting of physical examination, biomarker data, imaging, and hemodynamic assessment.

Conclusion

This review presents a comprehensive tool for assessing perioperative RV function. We hope that this simple, intuitive tool can be applied to all phases of perioperative care and thereby improve patient outcomes.
Initiation and rapid titration of methadone and slow-release oral morphine (SROM) in an acute care, inpatient setting: a case series
Authors: Rodger Laura , Nader Maya , Turner Suzanne , Lurie Erin
Published: December 2023

Background

Methadone titration in an outpatient setting typically involves initiation with subtherapeutic doses with slow titration to mitigate the risks of respiratory depression and overdose. In pregnancy, and generally, subtherapeutic doses of methadone and slow titrations are associated with poorer outcomes in terms of treatment retention and ongoing illicit opioid use. We aim to describe rapid titration of OAT in an inpatient setting for pregnant injection opioid users with high opioid tolerance secondary to a fentanyl-based illicit drug supply.

Methods

Retrospective case series of patients admitted to a tertiary center with a primary indication of opioid withdrawal and treatment for severe opioid use disorder in pregnancy.

Results

Twelve women received rapid methadone titrations with or without slow-release oral morphine for opioid use disorder during a total of fifteen hospital admissions. All women included in the study were active fentanyl users (12/12). Methadone dosing was increased rapidly with no adverse events with a median dose at day 7 of 65 mg (IQR 60–70 mg) and median discharge dose of 85 mg (IQR 70–92.5 mg) during their admission for titration. Slow-release oral morphine was used in half of the titration admissions (8/15) with a median dose of 340 mg (IQR 187.5–425 mg) at discharge. The median length of admission was 12 days (IQR 9.5–15).

Conclusions

A rapid titration of methadone was completed in an inpatient setting with or without slow-release oral morphine, without adverse events showing feasibility of this protocol for a pregnant population in an inpatient setting. Patients achieved therapeutic doses of methadone (and/or SROM) faster than outpatient counterparts with no known adverse events.
FTO and MC4R polymorphisms, and selected pre-, peri- and postnatal factors as determinants of body mass index and fatness in children: a thorough analysis of the associations
Authors: Bryl Ewa , Szcześniewska Paula , Dutkiewicz Agata , Słopień Agnieszka , Dmitrzak-Węglarz Monika , Hanć Tomasz
Published: December 2023

Background

Overweight and obesity among children have become significant global health concerns. Previous studies have highlighted the potential role of genetic factors, particularly polymorphisms in the FTO and MC4R genes, as well as environmental factors in the development of childhood obesity. This study aimed to investigate the relationships between genetic, socioeconomic and perinatal factors, adverse childhood events (ACEs), and lifestyle, and their impact on overweight, obesity and body composition parameters in children. Additionally, we explored potential interactions between genetic factors and ACEs.

Methods

Four hundred fifty-six children aged 6–12 years participated in our study. Information on the socioeconomic status, perinatal factors, ACEs and lifestyle of the children was collected with a questionnaire completed by their parents/guardians. We examined the children’s body weight and conducted an electrical bioimpedance analysis. Overweight and obesity were diagnosed based on the International Obesity Task Force and McCarthy criteria. We genotyped two selected polymorphisms in the FTO and MC4R genes using the TaqMan SNP allelic discrimination method.

Results

Higher BMI (Body Mass Index) z scores were related to higher paternal BMI and lower maternal age at the child’s birth. Higher FMI (Fat Mass Index) z scores were associated with higher paternal BMI, increased gestational weight, lower maternal education and the presence of the FTO risk allele. Higher FatM (fat mass in kg) z scores were linked to lower maternal education, lower maternal age at the child’s birth, higher maternal body weight gain, paternal BMI and the presence of the FTO risk allele. Moreover, interaction effects were observed on BMI z scores between ACE and FTO AA, and on FMI z scores and FatM z scored between ACE and MC4R CC.

Conclusions

The contribution of environmental factors is more strongly related to changes in body composition than genetic ones. Additionally, the presence of the risk allele combined with unfavourable environmental factors like ACEs leads to visible interaction effects, resulting in increased BMI z scores and FMI z scores in children.
A HIF-1α inhibitor combined with palmitic acid and L-carnitine treatment can prevent the fat metabolic reprogramming under hypoxia and induce apoptosis in hepatocellular carcinoma cells
Authors: Matsufuji Shohei , Kitajima Yoshihiko , Higure Kazuki , Kimura Naoya , Maeda Sachiko , Yamada Kohei , Ito Kotaro , Tanaka Tomokazu , Kai Keita , Noshiro Hirokazu
Published: December 2023

Background

A hypoxic environment often persists within solid tumors, including hepatocellular carcinoma (HCC). Hypoxia-inducible factor-1α (HIF-1α) can accelerate cancer malignancy by inducing hypoxia-dependent expression of various genes. Tumor hypoxia can also induce metabolic reprogramming of fatty acid (FA) metabolism, through which HIF-1α plays an essential role in diminishing fatty acid β-oxidation (FAO) in hypoxic cancer cells.

Methods

We aimed to investigate potential new drug therapy options for targeting hypoxic cancer cells within HCC tumors, specifically through combining HIF-1α inhibition with palmitic acid (PA) + L-carnitine (LC) treatment to effectively induce apoptosis in hypoxic HCC cells. To test this hypothesis, in vitro and in vivo studies were performed.

Results

We first demonstrated that hypoxia-dependent apoptosis was induced by an overload of PA in two HCC cell lines (HepG2 and Hep3B) via excessive production of reactive oxygen species (ROS). Moreover, this observed PA-induced apoptosis was enhanced by HIF-1α knockdown (KD) in these cells under hypoxia. In addition, the combination of PA with FAO activator LC increased FAO activity and led to stronger cell death than PA alone in hypoxic HIF-1α KD cells, specifically through further ROS generation. To clarify the mechanism of hypoxia-induced FA metabolism reprogramming, expression levels of the genes encoding FAO enzymes CPT1A, ACSL1, MCAD, and LCAD, FA transporter CD36, and FA esterification enzymes DGAT and APGAT were analyzed using HIF-1α KD and scramble control (SC) cells. The results suggested that HIF-1α could repress mRNA expression of the FAO-related enzymes and CD36, while it upregulated FA esterification gene expression. This suggested a central role for HIF-1α in hypoxia-induced reprogramming of FA metabolism in HCC cells. Using a nude mouse model, PA administration was found to induce apoptosis from ROS overproduction in HIF-1α KD tumors compared with SC tumors. Additional LC treatment synergistically enhanced the PA-induced apoptosis in HIF-1α KD tumors. Finally, in vivo therapy composed of HIF-1α inhibitor YC-1 with PA + LC could induce ROS-mediated apoptosis in HepG2 tumors without significant toxicity.

Conclusions

A combination therapy of YC-1 with PA + LC may be a unique anti-tumor therapy for targeting hypoxic HCC cells, specifically by ROS overproduction leading to forced FAO activation.
The effects of intermittent fasting diet in comparison with low-calorie diet on lipid profile, glycemic status, and liver fibrosis in patients with non-alcoholic fatty liver (NAFLD): a study protocol for a randomized controlled clinical trial
Authors: Karimi Mehdi , Nejad Maryam Mofidi , Akhgarjand Camellia , Sohrabpour Amir Ali , Poustchi Hossein , Imani Hossein , Mohammadi Hamed
Published: December 2023

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by an increase in fat in liver cells. The outbreak of NAFLD is estimated to be 32.4% worldwide, with higher rates in Asia and Iran. Nutritional factors such as excessive calorie intake, high fructose intake, copper deficiency, and increased iron intake play an important role in NAFLD. Since there is no specific treatment for NAFLD, intermittent fasting (IF) diet has been suggested as an alternative treatment for obesity and related complications. Previous studies showed the potential positive effects of IF on metabolic health and the reduction of oxidative stress in NAFLD. This randomized controlled trial (RCT) will be aimed to examine the effect of the IF diet in comparison with a low-calorie diet (LCD) on lipid profile, glycemic status, and liver fibrosis in patients with NAFLD.

Methods and analysis

This is a parallel randomized clinical trial conducted on 52 overweight and obese patients with NAFLD. Participants will be randomly assigned to receive either 16:8 IF (fasting from 8 P.M. to 12 P.M. the next day) or a low-calorie (55% carbohydrate- 30% fat, 15% protein) diet for 12 weeks. Anthropometric measurements, liver assessments, and metabolic evaluations will be assessed before and after the intervention. Primary outcomes include liver steatosis and fibrosis, while secondary outcomes include liver function enzymes, insulin resistance, lipid profile, and anthropometric measurements.

Discussion

Since obesity and insulin resistance are the most important risk factors of NAFLD, and there is no treatment for it, it seems that lifestyle changes such as low caloric diet like IF and exercise can improve lipid metabolism and liver enzymes.

Trial registration

Iranian registry of clinical trials (IRCT20170202032367N5).
Improved postprocessing of dynamic glucose-enhanced CEST MRI for imaging brain metastases at 3 T
Authors: Wu Yulun , Derks Sophie H. A. E. , Wood Tobias C. , de Blois Erik , van der Veldt Astrid A. M. , Smits Marion , Warnert Esther A. H.
Published: December 2023

Background

Dynamic glucose-enhanced (DGE) chemical exchange saturation transfer (CEST) has the potential to characterize glucose metabolism in brain metastases. Since the effect size of DGE CEST is small at 3 T (< 1%), measurements of signal-to-noise ratios are challenging. To improve DGE detection, we developed an acquisition pipeline and extended image analysis for DGE CEST on a hybrid 3-T positron emission tomography/magnetic resonance imaging system.

Methods

This cross-sectional study was conducted after local ethical approval. Static Z-spectra (from -100 to 100 ppm) were acquired to compare the use of 1.2 versus 2 ppm to calculate static glucose-enhanced (glucoCEST) maps in 10 healthy volunteers before and after glucose infusion. Dynamic CEST images were acquired during glucose infusion. Image analysis was optimized using motion correction, dynamic B0 correction, and principal component analysis (PCA) to improve the detection of DGE CEST in the sagittal sinus, cerebrospinal fluid, and grey and white matter. The developed DGE CEST pipeline was applied to four patients diagnosed with brain metastases.

Results

GlucoCEST was strongest in healthy tissues at 2 ppm. Correcting for motion, B0, and use of PCA locally improved DGE maps. A larger contrast between healthy tissues and enhancing regions in brain metastases was found when dynamic B0 correction and PCA denoising were applied.

Conclusion

We demonstrated the feasibility of DGE CEST with our developed acquisition and analysis pipeline at 3 T in patients with brain metastases. This work enables a direct comparison of DGE CEST to 18F-fluoro-deoxy-D-glucose positron emission tomography of glucose metabolism in patients with brain metastases.

Relevance statement

Contrast between brain metastasis and healthy brain tissue in DGE CEST MR images is improved by including principle component analysis and dynamic magnetic field correction during postprocessing. This approach enables the detection of increased DGE CEST signal in brain metastasis, if present.

Key points

• Despite the low signal-to-noise ratio, dynamic glucose-enhanced CEST MRI is feasible at 3 T.

• Principal component analyses and dynamic magnetic field correction improve DGE CEST MRI.

• DGE CEST MRI does not consequently show changes in brain metastases compared to healthy brain tissue.

• Increased DGE CEST MRI in brain metastases, if present, shows overlap with contrast enhancement on T1-weighted images.

Graphical Abstract
WAS: improved white-box cryptographic algorithm over AS iteration
Authors: Yang Yatao , Zhai Yuying , Dong Hui , Zhang Yanshuo
Published: December 2023

The attacker in white-box model has full access to software implementation of a cryptographic algorithm and full control over its execution environment. In order to solve the issues of high storage cost and inadequate security about most current white-box cryptographic schemes, WAS, an improved white-box cryptographic algorithm over AS iteration is proposed. This scheme utilizes the AS iterative structure to construct a lookup table with a five-layer ASASA structure, and the maximum distance separable matrix is used as a linear layer to achieve complete diffusion in a small number of rounds. Attackers can be prevented from recovering the key under black-box model. The length of nonlinear layer S and affine layer A in lookup table is 16 bits, which effectively avoids decomposition attack against the ASASA structure and makes the algorithm possess anti-key extraction security under the white-box model, while WAS possesses weak white-box (32 KB, 112)-space hardness to satisfy anti-code lifting security. WAS has provable security and better storage cost than existing schemes, with the same anti-key extraction security and anti-code lifting security, only 128 KB of memory space is required in WAS, which is only 14% of SPACE-16 algorithm and 33% of Yoroi-16 algorithm.
The impact of controlling diseases of significant global importance on greenhouse gas emissions from livestock production
Authors: Capper Judith L.
Published: December 2023

Background

A considerable body of evidence has reported the beneficial effects of improving productivity on reducing environmental impacts from livestock production. However, despite the negative impacts of animal diseases on reproduction, growth and milk production, there is little information available upon the impacts of animal disease on greenhouse gas emissions (GHGe). This study aimed to partially address this knowledge gap by investigating the effects of globally important vaccine-preventable diseases on GHGe from various livestock systems, namely: intensive dairy, extensive beef, commercial swine and backyard poultry production.

Methods

Simple deterministic models were developed within Microsoft Excel to quantify the impacts of livestock disease on productivity (defined as total milk and/or meat yield, MMY) adjusted for disease prevalence both at the population level (high or low), and at the herd or flock level. Disease-induced changes in MMY were applied to the GHGe per kg of milk or meat according to the consequent changes in livestock populations required to maintain milk or meat production. Diseases investigated comprised foot and mouth, brucellosis, anthrax, lumpy skin disease, classical swine fever, porcine reproductive and respiratory syndrome (PRRS), low and high pathogenicity avian influenza (LPAI and HPAI), avian infectious bronchitis and Newcastle disease.

Results

All diseases investigated had multifactorial impacts on total MMY, yet diseases that increased mortality in breeding or growing livestock (e.g. anthrax, classical swine fever and HPAI) showed greater impacts on GHGe per unit of milk or meat produced than those that primarily affecting yields or reproduction (e.g. brucellosis or LPAI). Prevalence also had considerable effects on potential GHGe. For example, maintaining backyard poultry meat production from a 100,000 hen population with 70% prevalence of HPAI increased GHGe by 11,255 MT CO2eq compared to a 30% prevalence at 3475 MT CO2eq above the baseline (0% prevalence). Effective reduction of the prevalence of PRRS in swine from 60 to 10%, FMD in beef cattle from 45 to 5% prevalence, or AIB in poultry from 75 to 20% prevalence would reduce GHGe intensities (CO2eq/kg CW) by 22.5%, 9.11% and 11.3% respectively.

Conclusions

Controlling livestock disease can reduce MMY losses at the farm level, which improves food security, reduces GHGe and enhances livestock system sustainability.
Reduced graphene oxide/TiO2/NiFe2O4 nanocomposite as a stable photocatalyst and strong antibacterial agent
Authors: Jihad Kamal Mohammed , Roknabadi Mahmood Rezaee , Mohammadi Mojtaba , Goharshadi Elaheh K.
Published: December 2023

In this study, we prepared reduced graphene oxide (rGO)/titanium dioxide (TiO2)/nickel ferrite (NiFe2O4) nanocomposites with different mass ratios of rGO, TiO2, and NiFe2O4 by a simple hydrothermal method. These nanocomposites were found to exhibit enhanced visible light harvesting, reduced electron–hole recombination, and improved magnetic properties compared to rGO, TiO2, and NiFe2O4. The study evaluated the photocatalytic and antibacterial activity of the nanocomposites, with particular emphasis on the GTN211 (with a mass ratio of 2:1:1 for rGO:TiO2:NiFe2O4) nanocomposite. The results showed that the GTN211 nanocomposite exhibited the best photocatalytic performance under both UV and visible light irradiation, achieving 95 and 89% degradation of Methylene Blue dye in 15 min, respectively. The study also investigated the photodegradation mechanism using various scavengers and found that holes were the main active species in the process. In addition to photocatalytic activity, the GTN211 nanocomposite also showed good antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria, with the minimum inhibitory concentration of 1 mg mL−1 for both bacteria and a minimum bactericidal concentration of 0.8 and 1 mg mL−1, respectively. Hence, the GTN211 nanocomposite has potential as a material for environmental remediation and biomedical applications. The combination of photocatalytic and antibacterial activity makes this material a promising candidate for a wide range of applications.
Diagnostic accuracy of the different pulse sequences of multi-parametric prostate MRI in the diagnosis of prostate cancer in the peripheral and transitional zones
Authors: Gadalla Amr A. Elfattah Hassan , Sabet Marianne Abdallah , Edesa Wael Abdelgawwad , Wahba Manal Halim , Abolyazid Sherif M.
Published: December 2023

Background

One of the most prevalent malignancies among males is prostate carcinoma (PCa). For the diagnosis of PCa, multiparametric magnetic resonance imaging (mpMRI) constitutes by far the most accurate imaging technique. The PI-RADS v2.1 indications for dynamic contrast enhanced (DCE) sequence include identifying PI-RADS score 3 lesions, as clinically significant prostate carcinoma, aiding evaluation of examinations having poor quality of T2 as well as diffusion weighted imaging (DWI), and helping readers having relatively reduced expertise. Most articles don't provide outcomes pertaining to these indications, which weakens their conclusions. All MRI scans, even those with low quality T2 or DWI, were included in our study. Additionally, special emphasis on assessing peripheral zone lesions was made. Our objective was to assess the diagnostic accuracy of the various mpMRI pulse sequences, including the T2 sequence, diffusion and apparent diffusion coefficient (ADC) sequences, both T2 and diffusion sequences (biparametric (bp) MRI), DCE sequence, and the entire examination (mpMRI), in the diagnosis of PCa in the peripheral as well as the transitional zone using PI-RADS version 2.1 scoring system, once when malignant lesions are considered as those having PI-RADS scores 4 and 5 and once when PI-RADS categories 3, 4 and 5 were regarded as malignant.

Results

In the assessment of peripheral zone lesions, when PI-RADS categories 3, 4, and 5 were considered malignant, both bpMRI and mpMRI showed similar sensitivity (94.29%) and diagnostic accuracy (77.78%) while when considering scores 4 and 5 malignant, mpMRI demonstrated increased diagnostic accuracy and sensitivity but lower specificity (sensitivity was 82.86%/60%, specificity was 80%/100%, and diagnostic accuracy was 82.22%/68.89% for mpMRI/bpMRI test comparaison). Both bpMRI and mpMRI had similar sensitivity (95.83%) and diagnostic accuracy (71.05%) when PI-RADS categories 3, 4, and 5 were regarded as malignant; however, mpMRI demonstrated better diagnostic accuracy and sensitivity considering scores 4 and 5 malignant (sensitivity was 77.08% for mpMRI compared to 60.42% for bpMRI and diagnostic accuracy was 82.89% for mpMRI compared to 75% for bpMRI).

Conclusions

Both bpMRI and mpMRI demonstrated similar diagnostic accuracy when PI-RADS categories 3, 4, and 5 were taken into account as malignant while mpMRI had higher diagnostic accuracy considering categories 4 and 5 malignant.
Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome
Authors: Zhang Yulin , Cheng Ziwei , Hong Liyu , Liu Jia , Ma Xinyue , Wang Wenjing , Pan Ran , Lu Wenjie , Luo Qichao , Gao Shan , Kong Qin
Published: December 2023

Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1β production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.
Image-domain seismic inversion by deblurring with invertible recurrent inference machines
Authors: Peng Haorui , Vasconcelos Ivan , Ravasi Matteo
Published: December 2023

In complex geologic settings and in the presence of sparse acquisition systems, seismic migration images manifest as nonstationary blurred versions of the unknown subsurface model. Thus, image-domain deblurring is an important step to produce interpretable and high-resolution models of the subsurface. Most deblurring methods focus on inverting seismic images for their underlying reflectivity by iterative least-squares inversion of a local Hessian approximation; this is obtained by either direct modeling of the so-called point-spread functions (PSFs) or by a migration-demigration process. In this work, we adopt a novel deep-learning (DL) framework, based on invertible recurrent inference machines (i-RIMs), which allows approaching any inverse problem as a supervised learning task informed by the known modeling operator (convolution with PSFs in our case): our algorithm can directly invert migrated images for impedance perturbation models, assisted with the prior information of a smooth velocity model and the modeling operator. Because i-RIMs are constrained by the forward operator, they implicitly learn to shape/regularize output models in a training-data-driven fashion. As such, the resulting deblurred images indicate great robustness to noise in the data and spectral deficiencies (e.g., due to limited acquisition). The key role played by the i-RIM network design and the inclusion of the forward operator in the training process is supported by several synthetic examples. Finally, using field data, we find that i-RIM-based deblurring has great potential in yielding robust, high-quality relative impedance estimates from migrated seismic images. Our approach could be of importance toward future DL-based quantitative reservoir characterization and monitoring.