bluuebunny/crossref_metadata_2025 huggingface dataset:
Microvascular endothelial dysfunction in skin is associated with higher risk of heart failure with preserved ejection fraction in women with type 2 diabetes: the Hoorn Diabetes Care System Cohort
Authors: Canto Elisa Dal , van Deursen L. , Hoek A. G. , Elders P. J. M. , den Ruijter H. M. , van der Velden J. , van Empel V. , Serné E. H. , Eringa E. C. , Beulens J. W.J.
Published: September 2023

Background

Microvascular dysfunction plays a crucial role in complications of type 2 diabetes and might contribute to heart failure with preserved ejection fraction (HFpEF), a disease that disproportionally affects women. We aimed to investigate if presence and degree of microvascular dysfunction (MVD) in skin relates to markers of left ventricular diastolic dysfunction (LVDD) and HFpEF risk in adults with type 2 diabetes, and whether sex modifies this association.

Methods

We recruited 154 participants (50% women) from the Hoorn Diabetes Care System Cohort, a prospective cohort study, for in vivo evaluation of skin MVD, echocardiography and blood sampling. MVD was assessed by laser speckle contrast analysis combined with iontophoresis of insulin, acetylcholine and sodium nitroprusside (SNP). We performed a cross-sectional analysis of the association between perfusion responses and echocardiographic and clinical markers of LVDD and the H2FPEF score by multivariable linear regression analysis adjusted for confounders. Sex was evaluated as a potential effect modifier and the analysis was stratified.

Results

Mean age was 67 ± 6y, mean HbA1c 7.6 ± 1.3%. Women were more frequently obese (54.5 vs. 35.1%), had higher NT-proBNP plasma levels (80, IQR:34–165 vs. 46, 27–117 pg/ml) and E/E’(13.3 ± 4.3 vs. 11.4 ± 3.0) than men. Eleven women and three men were diagnosed with HFpEF, and showed lower perfusion response to insulin than those without HFpEF. A lower perfusion response to insulin and acetylcholine was associated with higher HFpEF risk in women, but not men (10% decreased perfusion response was associated with 5.8% [95%CI: 2.3;9.4%] and 5.9% [1.7;10.1%] increase of the H2FPEF score, respectively). A lower perfusion response to SNP was associated with higher pulmonary arterial systolic pressure in men while a lower perfusion response to acetylcholine associated with higher LV mass index in women and with worse LV longitudinal strain in the total population. No significant associations were found between perfusion responses and conventional LVDD markers.

Conclusions

Impaired microvascular responses to insulin and acetylcholine in skin confers a higher risk of HFpEF in women with type 2 diabetes. In vivo measures of systemic MVD could represent novel risk markers for HFpEF, opening new avenues for the prevention of HFpEF in type 2 diabetes.
Data-driven decision-making for precision diagnosis of digestive diseases
Authors: Jiang Song , Wang Ting , Zhang Kun-He
Published: September 2023

Modern omics technologies can generate massive amounts of biomedical data, providing unprecedented opportunities for individualized precision medicine. However, traditional statistical methods cannot effectively process and utilize such big data. To meet this new challenge, machine learning algorithms have been developed and applied rapidly in recent years, which are capable of reducing dimensionality, extracting features, organizing data and forming automatable data-driven clinical decision systems. Data-driven clinical decision-making have promising applications in precision medicine and has been studied in digestive diseases, including early diagnosis and screening, molecular typing, staging and stratification of digestive malignancies, as well as precise diagnosis of Crohn's disease, auxiliary diagnosis of imaging and endoscopy, differential diagnosis of cystic lesions, etiology discrimination of acute abdominal pain, stratification of upper gastrointestinal bleeding (UGIB), and real-time diagnosis of esophageal motility function, showing good application prospects. Herein, we reviewed the recent progress of data-driven clinical decision making in precision diagnosis of digestive diseases and discussed the limitations of data-driven decision making after a brief introduction of methods for data-driven decision making.
Exploring equity in cancer treatment, survivorship, and service utilisation for culturally and linguistically diverse migrant populations living in Queensland, Australia: a retrospective cohort study
Authors: Scanlon Brighid , Durham Jo , Wyld David , Roberts Natasha , Toloo Ghasem Sam
Published: September 2023

Background

There is strong international evidence documenting inequities in cancer care for migrant populations. In Australia, there is limited information regarding cancer equity for Culturally and Linguistically Diverse (CALD) migrant populations, defined in this study as migrants born in a country or region where English is not the primary language. This study sought to quantify and compare cancer treatment, survivorship, and service utilisation measures between CALD migrant and Australian born cancer populations.

Methods

A retrospective cohort study was conducted utilising electronic medical records at a major, tertiary hospital. Inpatient and outpatient encounters were assessed for all individuals diagnosed with a solid tumour malignancy in the year 2016 and followed for a total of five years. Individuals were screened for inclusion in the CALD migrant or Australian born cohort. Bivariate analysis and multivariate logistic regression were used to compare treatment, survivorship, and service utilisation measures. Sociodemographic measures included age, sex, post code, employment, region of birth and marital status.

Results

A total of 523 individuals were included, with 117 (22%) in the CALD migrant cohort and 406 (78%) in the Australian-born cohort. CALD migrants displayed a statistically significant difference in time from diagnosis to commencement of first treatment for radiation (P = 0.03) and surgery (P = 0.02) and had 16.6 times higher odds of declining recommended chemotherapy than those born in Australia (P = 0.00). Survivorship indicators favoured CALD migrants in mean time from diagnosis to death, however their odds of experiencing disease progression during the study period were 1.6 times higher than those born in Australia (P = 0.04). Service utilisation measures displayed that CALD migrants exhibited higher numbers of unplanned admissions (P = < 0.00), longer cumulative length of those admissions (P = < 0.00) and higher failure to attend scheduled appointments (P = < 0.00).

Conclusion

This novel study has produced valuable findings in the areas of treatment, survivorship, and service utilisation for a neglected population in cancer research. The differences identified suggest potential issues of institutional inaccessibility. Future research is needed to examine the clinical impacts of these health differences in the field of cancer care, including the social and institutional determinants of influence.
Interplay of chronic obstructive pulmonary disease and colorectal cancer development: unravelling the mediating role of fatty acids through a comprehensive multi-omics analysis
Authors: Zhou Youtao , Lin Zikai , Xie Shuojia , Gao Yuan , Zhou Haobin , Chen Fengzhen , Fu Yuewu , Yang Cuiyan , Ke Chuanfeng
Published: September 2023

Background

Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination.

Methods

In this study, we collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases.

Results

In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI 1.01–1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable Mendelian randomization suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data.

Conclusions

This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.
Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors
Authors: Yang Dong , Duan Mei-Han , Yuan Qiu-Er , Li Zhi-Ling , Luo Chuang-Hua , Cui Lan-Yue , Li Li-Chao , Xiao Ying , Zhu Xian-Ying , Zhang Hai-Liang , Feng Gong-Kan , Liu Guo-Chen , Deng Rong , Li Jun-Dong , Zhu Xiao-Feng
Published: September 2023

Background

As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy.

Methods

The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature.

Results

The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs’ marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer.

Conclusions

The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.
Production of a chimeric flavivirus that contains the major structural glycoprotein genes of T’Ho virus in the genetic background of Zika virus
Authors: Tangudu Chandra S. , Hargett Alissa M. , Mitrisin Brooke C. , Laredo-Tiscareño S. Viridiana , Blitvich Bradley J.
Published: September 2023

T’Ho virus is a poorly characterized orthoflavivirus most closely related to Rocio virus and Ilheus virus, two orthoflaviviruses associated with human disease, suggesting that T’Ho virus could also be a human pathogen. The genome of T’Ho virus has been sequenced but an isolate has never been recovered, impeding its phenotypic characterization. In an attempt to generate recombinant T’Ho virus, the entire viral genome was synthesized as three overlapping DNA fragments, joined by Gibson assembly, and transfected into mosquito cells. Several cell culture passages were performed, but virus was not recovered. Subsequent experiments focused on the development of a chimeric orthoflavivirus that contains the premembrane and envelope protein genes of T’Ho virus in the genetic background of Zika virus. The chimeric virus replicated in mosquito (C6/36) and vertebrate (Vero) cells, demonstrating that the major structural glycoproteins of T’Ho virus permit entry into both cell types. The chimeric virus produced plaques in Vero cells that were significantly smaller than those produced by Zika virus. The chimeric virus can potentially be used as a surrogate diagnostic reagent in place of T’Ho virus in plaque reduction neutralization tests, allowing T’Ho virus to be considered in the differential diagnosis.
Ethnobotany for food security and ecological transition: wild food plant gathering and consumption among four cultural groups in Kurram District, NW Pakistan
Authors: Hussain Sayed Taufiq , Muhammad Sayed , Khan Sheharyar , Hussain Wahid , Pieroni Andrea
Published: September 2023

Background

In traditional food systems, especially those of rural populations around the world, wild food plants remain crucial. These resources need to be urgently documented to lay the foundations for sustainable livelihoods and food security.

Methods

In the present field study, we gathered information about wild food plants and mushrooms consumed by four ethnic groups (Turis, Khushis, Hazaras, and Christians) living in Kurram District, NW Pakistan, by conducting semi-structured interviews and holding group discussions.

Results

A total of 57 wild edible plants and mushrooms were reported, with the documented taxa belonging to 50 genera and 34 families. Turis reported the highest number of wild food plants (41), followed by Hazaras (37), Khushis (35), and then Christians, who reported only 11 plants. The most dominant families were Rosaceae, followed by Polygonaceae, Brassicaceae, Fabaceae, Lamiaceae, Moraceae, and Plantaginaceae. The comparative analysis we conducted with the pre-existing Pakistani ethnobotanical studies revealed that 23 wild edible plants have not been previously reported as food items in the area under study, which included Fragaria nubicola, Lepidium draba, Pinus wallichiana, Podophyllum emodi, Prunus jacquemontii, Sambucus nigra, Sideroxylon mascatense, and Thymus linearis. Four wild edible mushrooms are also reported for the area for the first time: Calvatia gigantea, Morchella esculenta, Pisolithus albus, and Tulostoma squamosum. The cross-cultural analysis of wild edible plants and their uses revealed remarkable similarity between Khushis and Hazaras. The overlapping pattern of wild edible plant use among these two groups, as well as Turis, confirms the existence of cross-cultural interactions among these communities, which have shared the same environmental and socio-cultural space for several decades. Food heritage and some unique dishes are linked to wild edible plants in the area, such as Zamda, prepared by Turis, and Saba, famous among Khushis and Hazaras.

Conclusion

This study suggests that some wild edible plants could be cultivated to protect a few threatened species from overexploitation, while the overall wild food plant heritage should be promoted and revitalized; for example, within educational platforms aimed at improving the wellbeing of local communities and the global ecological transition we must deal with.
Drugs involved in Kentucky drug poisoning deaths and relation with antecedent controlled substance prescription dispensing
Authors: Freeman Patricia R. , McAninch Jana , Dasgupta Nabarun , Oyler Douglas R. , Slavov Krassimir , Collins Candice , Hargrove Sarah , Freeman Edward , Miracle Dustin , Slavova Svetla
Published: September 2023

Background

The shift from prescription to illicit drugs involved in drug poisoning deaths raises questions about the current utility of prescription drug monitoring program (PDMP) data to inform drug poisoning (overdose) prevention efforts. In this study, we describe relations between specific drugs involved in Kentucky drug poisoning deaths and antecedent controlled substance (CS) dispensing.

Methods

The study used linked death certificates and PDMP data for 2,248 Kentucky resident drug poisoning deaths in 2021. Death certificate literal text analysis identified drugs mentioned with involvement (DMI) in drug poisoning deaths. We characterized the concordance between each DMI and the CS dispensing history for this drug at varying timepoints since 2008.

Results

Overall, 25.5% of all decedents had dispensed CS in the month before fatal drug poisoning. Over 80% of decedents were dispensed opioid(s) since 2008; the percentage was similar regardless of opioid involvement in the poisoning death. One-third of decedents had dispensed buprenorphine for treatment of opioid use disorder since 2008, but only 6.1% had dispensed buprenorphine in the month preceding death. Fentanyl/fentanyl analogs were DMI in 1,568 (69.8%) deaths, yet only 3% had received a fentanyl prescription since 2008. The highest concordance in the month preceding death was observed for clonazepam (43.6%).

Conclusion

Overall, concordance between CS dispensing history and the drugs involved in poisoning deaths was low, suggesting a need to reevaluate the complex relationships between prescription medication exposure and overdose death and to expand harm reduction interventions both within and outside the healthcare system to reduce drug poisoning mortality.
Composite endpoints, including patient reported outcomes, in rare diseases
Authors: Verbeeck Johan , Dirani Maya , Bauer Johann W. , Hilgers Ralf-Dieter , Molenberghs Geert , Nabbout Rima
Published: September 2023

Background

When assessing the efficacy of a treatment in any clinical trial, it is recommended by the International Conference on Harmonisation to select a single meaningful endpoint. However, a single endpoint is often not sufficient to reflect the full clinical benefit of a treatment in multifaceted diseases, which is often the case in rare diseases. Therefore, the use of a combination of several clinically meaningful outcomes is preferred. Many methodologies that allow for combining outcomes in a so-called composite endpoint are however limited in a number of ways, not in the least in the number and type of outcomes that can be combined and in the poor small-sample properties. Moreover, patient reported outcomes, such as quality of life, often cannot be integrated in a composite analysis, in spite of their intrinsic value.

Results

Recently, a class of non-parametric generalized pairwise comparisons tests have been proposed, which members do allow for any number and type of outcomes, including patient reported outcomes. The class enjoys good small-sample properties. Moreover, this very flexible class of methods allows for prioritizing the outcomes by clinical severity, allows for matched designs and for adding a threshold of clinical relevance. Our aim is to introduce the generalized pairwise comparison ideas and concepts for rare disease clinical trial analysis, and demonstrate their benefit in a post-hoc analysis of a small-sample trial in epidermolysis bullosa. More precisely, we will include a patient relevant outcome (Quality of life), in a composite endpoint. This publication is part of the European Joint Programme on Rare Diseases (EJP RD) series on innovative methodologies for rare diseases clinical trials, which is based on the webinars presented within the educational activity of EJP RD. This publication covers the webinar topic on composite endpoints in rare diseases and includes participants’ response to a questionnaire on this topic.

Conclusions

Generalized pairwise comparisons is a promising statistical methodology for evaluating any type of composite endpoints in rare disease trials and may allow a better evaluation of therapy efficacy including patients reported outcomes in addition to outcomes related to the diseases signs and symptoms.
Infant and Young Child Feeding practices up to 23 months in Namuno District, Cabo Delgado, Mozambique
Authors: Marroda Kodak Raúl , Berti Cristiana , La Vecchia Adriano , Agostoni Carlo , Baroni Bruno Nazim , Bettocchi Silvia , Baglioni Mattia
Published: September 2023

Background

Inadequate breastfeeding and complementary feeding practices are key determinants of child malnutrition and impact one-third of the under-five mortality rate worldwide. The district of Namuno in Cabo Delgado (Mozambique) has been long registering a high prevalence of acute malnutrition. To date, no data exists about Infant and Young Child Feeding (IYCF) practices in the area. The current pilot study explores the feeding practices among children aged 0–23 months in Namuno and sets out its main drivers.

Methods

This cross-sectional study was realized between August and September 2019 and drew on questionnaires for mothers/caregivers of children aged 0 to 23 months. We computed IYCF indicators and correlated them with mothers’/caregivers' school attendance, delivery setting, and distance between home and the place where livelihood activities took place (workplace), using univariate and multivariate (age-adjusted) logistic regression analysis.

Results

The survey was data derived from a sample of 632 mothers/caregivers. 62% of 0–23-month-old children received colostrum whilst only 31% of 0–5 months babies were on exclusive breastfeeding (EBF). Among 6–23 months old children, 17% consumed foods and beverages from at least five out of eight defined food groups, 31% received a minimum frequency of meals, and 23% had a minimum acceptable diet. Data revealed a positive correlation between early initiation of breastfeeding and delivery in a maternity ward (OR 6.9, CI 3.2–16.1, p-value < 0.001). No difference in the IYCF indicators between female and male babies was detected.

Conclusions

In the Namuno district, IYCF practices did not fulfill WHO/UNICEF’s indicators and recommendations. This suggests that efforts should be focused on EBF-enabling interventions to improve children’s dietary consumption patterns.
Effectiveness and safety of mesenchymal stem/stromal cell for radiation-induced hyposalivation and xerostomia in previous head and neck cancer patients (MESRIX-III): a study protocol for a single-centre, double-blinded, randomised, placebo-controlled, phase II study
Authors: Jakobsen Kathrine Kronberg , Carlander Amanda-Louise Fenger , Grønhøj Christian , Todsen Tobias , Melchiors Jacob , Paaske Natasja , Madsen Anne Kathrine Østergaard , Kastrup Jens , Ekblond Annette , Haack-Sørensen Mandana , Farhadi Mohammad , Maare Christian , Friborg Jeppe , Lynggard Charlotte Duch , von Buchwald Christian
Published: September 2023

Background

A predominant side effect of radiotherapy for head and neck cancer is salivary gland hypofunction and xerostomia leading to debilitating oral disorders and impaired quality of life (QoL). Intraglandular mesenchymal stem cell therapy has shown promising results as a treatment for xerostomia.

Methods

This is a randomised, double-blinded, placebo-controlled, parallel-group, prospective, single-centre trial investigating the safety, tolerability, and effectiveness of allogeneic stem cells as a treatment for radiation-induced hyposalivation and xerostomia for previous head and neck cancer patients.

We will include a total of 120 patients who previously have been treated with radiotherapy for a head and neck cancer in Denmark. Participants will be randomly assigned using block randomisation to one of two parallel groups in a 1:1 ratio to receive ultrasound-guided injection of allogeneic adipose-derived mesenchymal stem cell (ASC) (n = 60) or placebo (n = 60) into the submandibular glands. Placebo will consist of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 10% dimethyl sulfoxide (DMSO). The primary endpoint is change in unstimulated whole saliva flow rate. The secondary endpoints are change in stimulated whole saliva flow rate, QoL, and composition of saliva. Further secondary endpoints are safety and immune response (human leukocyte antigen (HLA) response) to the stem cells will be assessed. Patients are evaluated at baseline (before treatment), after 4 months, and after 12 months. All study personnel, except study personnel thawing and preparing the treatment for injection, and participants will be blinded to group assignment. Unblinded study personnel will not participate in the outcome assessment.

Discussion

The trials will investigate the efficacy and safety of ASC injection to the submandibular gland as a potential new treatment for post-radiation xerostomia. We hope the results will pave the way for a clinically relevant treatment to ameliorate patients with xerostomia, a severely hampering condition.

Trial registration

The study is approved by the Danish Data Protection Agency (protocol number P-2020-1164), the National Ethics Committee protocol number: (Protocol number: 1802872), and the Danish Medical Agency (2018-000348-24). The protocol was registered at the ClinicalTrials.gov database (NCT04776538).
Effects of the source of information and knowledge of dengue fever on the mosquito control behavior of residents of border areas of Yunnan, China
Authors: Lun Xinchang , Yang Rui , Lin Linghong , Wang Yiguan , Wang Jun , Guo Yuhong , Xiu Pengcheng , Zhu Caiying , Liu Qiyong , Xu Lei , Meng Fengxia
Published: September 2023

Background

Strengthening the mosquito control measures undertaken by residents of an area where dengue fever is present can significantly decrease the spread of this disease. The aim of this study was to explore the effects of the source of information and knowledge of dengue fever on the mosquito control behavior of residents of areas at high risk of this disease to determine effective ways of enhancing this behavior.

Methods

A survey was conducted via face-to-face interviews or questionnaires between March and May 2021 in three regions of the province of Yunnan, China. The survey included basic information about the respondents, the source(s) of their dengue fever information, the level of their dengue fever knowledge, and the measures they had implemented to control mosquitoes. Principal component analysis was used to extract the main components of the sources of information. Correlation analysis and structural equation analysis were used to explore the impact of the sources of information and residents’ dengue fever knowledge on their mosquito control behavior.

Results

Publicity achieved through mass media, including official WeChat accounts, magazines/newspapers, poster leaflets, television/radio and the Internet, had a direct effect on dengue fever knowledge and mosquito control behavior, and indirectly affected mosquito control behavior through dengue fever knowledge. Organized publicity campaigns, including information provided by medical staff and through community publicity, had a direct effect on dengue fever knowledge and indirectly affected mosquito control behavior through dengue fever knowledge. The residents’ level of dengue fever knowledge had a significant, positive, direct effect on their mosquito control behavior.

Conclusions

Mosquito control is an important measure for the prevention and control of outbreaks of dengue fever. An effective source of information can improve the level of dengue fever knowledge among residents and thus enhance their mosquito control behavior.

Graphical Abstract
Dietary oregano aqueous extract improves growth performance and intestinal health of broilers through modulating gut microbial compositions
Authors: Zhang Fan , Yang Jiantao , Zhan Qinyi , Shi Hao , Li Yanhe , Li Dinggang , Li Yingge , Yang Xiaojun
Published: September 2023

Background

Intestinal health plays a pivotal role in broiler chicken growth. Oregano aqueous extract (OAE) effectively exerts anti-inflammatory and antibacterial effects. However, the protective effects of OAE on intestinal health in broilers and the underlying mechanism remain unclear. This study aimed to investigate the potential effects of OAE on growth performance, the gut microbiota and intestinal health. A total of 840 1-d-old male and female broilers (Arbor Acres) were randomly allocated into 6 groups as follows: basal diet (Con), Con + antibiotics (Anti, colistin sulfate 7 g/kg, roxarsone 35 g/kg), Con + 400, 500, 600 and 700 mg/kg OAE (OAE400, OAE500, OAE600 and OAE700). Subsequently, fermentation in vitro together with oral administration trials were carried out to further assess the function of OAE on intestinal health of broilers.

Results

Dietary 700 mg/kg OAE supplementation resulted in an increase (P < 0.05) in body weight and a decrease (P < 0.05) in feed conversion ratio when compared with the control during d 22 to 42 of the trial. OAE addition resulted in lower (P < 0.05) jejunal crypt depth and mRNA expression of IL-4 and IL-10 at d 42. In addition, dietary OAE addition increased the abundance of Firmicutes (P = 0.087) and Lactobacillus (P < 0.05) in the cecum, and increased (P < 0.05) the content of acetic acid and butyric acid. In the in vitro fermentation test, OAE significantly increased (P < 0.05) the abundance of Lactobacillus, decreased (P < 0.05) the abundance of unspecified_Enterobacteriaceae, and increased the content of acetic acid (P < 0.05). In the oral administration trial, higher (P < 0.05) IL-4 expression was found in broilers when oral inoculation with oregano fermentation microorganisms at d 42. And SIgA content in the ileum was significantly increased (P = 0.073) when giving OAE fermentation supernatant.

Conclusions

Dietary OAE addition could maintain intestinal health and improve growth performance through enhancing intestinal mucosal immunity and barrier function mediated by gut microbiota changes.
CRISPR/Cas9 mediated gene editing of transcription factor ACE1 for enhanced cellulase production in thermophilic fungus Rasamsonia emersonii
Authors: Singh Varinder , Raheja Yashika , Basotra Neha , Sharma Gaurav , Tsang Adrian , Chadha Bhupinder Singh
Published: September 2023

Background

The filamentous fungus Rasamsonia emersonii has immense potential to produce biorefinery relevant thermostable cellulase and hemicellulase enzymes using lignocellulosic biomass. Previously in our lab, a hyper-cellulase producing strain of R. emersonii was developed through classical breeding and system biology approaches. ACE1, a pivotal transcription factor in fungi, plays a crucial role in negatively regulating the expression of cellulase genes. In order to identify the role of ACE1 in cellulase production and to further improve the lignocellulolytic enzyme production in R. emersonii, CRISPR/Cas9 mediated disruption of ACE1 gene was employed.

Results

A gene-edited ∆ACE1 strain (GN11) was created, that showed 21.97, 20.70 and 24.63, 9.42, 18.12%, improved endoglucanase, cellobiohydrolase (CBHI), β-glucosidase, FPase, and xylanase, activities, respectively, as compared to parental strain M36. The transcriptional profiling showed that the expression of global regulator (XlnR) and different CAZymes genes including endoglucanases, cellobiohydrolase, β-xylosidase, xylanase, β-glucosidase and lytic polysaccharide mono-oxygenases (LPMOs) were significantly enhanced, suggesting critical roles of ACE1 in negatively regulating the expression of various key genes associated with cellulase production in R. emersonii. Whereas, the disruption of ACE1 significantly down-regulated the expression of CreA repressor gene as also evidenced by 2-deoxyglucose (2-DG) resistance phenotype exhibited by edited strain GN11 as well as appreciably higher constitutive production of cellulases in the presence of glucose and mixture of glucose and disaccharide (MGDs) both in batch and flask fed batch mode of culturing. Furthermore, ∆ACE1 strains were evaluated for the hydrolysis of biorefinery relevant steam/acid pretreated unwashed rice straw slurry (Praj Industries Ltd; 15% substrate loading rate) and were found to be significantly superior when compared to the benchmark enzymes produced by parent strain M36 and Cellic Ctec3.

Conclusions

Current work uncovers the crucial role of ACE1 in regulating the expression of the various cellulase genes and carbon catabolite repression mechanism in R. emersonii. This study represents the first successful report of utilizing CRISPR/Cas9 genome editing technology to disrupt the ACE1 gene in the thermophlic fungus R. emersonii. The improved methodologies presented in this work might be applied to other commercially important fungal strains for which genetic manipulation tools are limited.
Rural–urban and socio-demographic differentials in perceived health state among aging population in Ghana
Authors: Boateng Richard , Yawson Alfred Edwin , Adoma Prince Owusu
Published: September 2023

Background

The variations in health between rural and urban population have become an increasingly significant public health concern in developing countries including Ghana where urbanization is occurring. Whereas urbanization results in improved access to healthcare services, the concomitant negative consequences of urbanization coupled with unfavorable compositional and contextual attributes can affect the health of populations. The study sought to examine the effect of rural–urban residence and selected socio-demographic factors on perceived health state among aging population by employing a nationally representative data collected by the WHO from 2014 to 2015.

Methods

The data were derived from the WHO Study on Aging wave 2 released in 2019. A total of 4511 individuals, made up of 1018 adults between 18 and 49 years and 3493 respondents within the ages of 50 years and above, were involved in this study. The study examined the Spearman’s rho correlations between perceived health, rural–urban residence, age, sex, marital status, ever schooled, current work state, religion, and regional location. Subsequently, the study employed a multivariable ordinal logistic regression model to test the effect of the selected biosocial and contextual variables on perceived health state.

Results

The selected socio-demographic variables significantly correlated with health state, except for rural–urban residence. However, the predictive ability of rural–urban residence and the socio-demographic variables on perceived health state were strongly ascertained. It was observed that age, sex, rural–urban residence, and current state of work among aging populations were significant predictors of perceived health state as demonstrated by odds ratios and significant p values. The contextual factor of regional location was the most significant variable that increases the perceived health state of respondents in the study.

Conclusions

Continues engagement in work-related activities, an individual’s age within the aging continuum and regional location coupled with its environmental and ecological attributes, may significantly influence the development of positive perception toward health state, which forms a vital constituent of an individual health seeking behavior.
The association of polyunsaturated fatty acids and asthma: a cross-sectional study
Authors: Liu Gangtie , Ye Hengbo , Cheng Qian , Zhao Jian , Ma Congcong , Jie Huichao
Published: September 2023

Background

To examine the relationships between polyunsaturated fatty acids (PUFAs) dietary intake and asthma in children.

Methods

In this cross-sectional study, a total of 14,727 participants from the United States National Health and Nutrition Examination Survey (NHANES) database in 1999–2018 were included, and the baseline characteristics of all participants were gathered. The description analysis was used to explore the possible covariates. Weighted multivariate logistic regression models were adopted to assessed the association between PUFAs dietary intake and asthma in children. In addition, we also performed subgroup analysis based on gender, age, and maternal smoking during pregnancy to investigate this relationship.

Results

The prevalence of asthma approximately was 15.38% in the present study. The result of weighted multivariate logistic regression indicated that, docosahexaenoic [weighted odds ratio (OR) = 0.37, 95% confidence interval (CI) 0.19–0.74], total n − 3 PUFAs (weighted OR = 0.63, 95%CI 0.43–0.91), and eicosapentaenoic (weighted OR = 0.35, 95%CI 0.13–0.95) dietary intake were negatively associated with asthma in children. The subgroup analysis described that when children were male (weighted OR = 0.28, 95%CI 0.10–0.84), or were 5–7 years (weighted OR = 0.04, 95%CI 0.01–0.37), were 7–12 years (weighted OR = 0.46, 95%CI 0.24–0.90), or their maternal smoking during pregnancy (weighted OR = 0.16, 95%CI 0.03–0.90), docosahexaenoic dietary intake was negatively related to childhood asthma.

Conclusion

Docosahexaenoic dietary intake was negatively associated with the asthma in children, especially if children were male, or were 5–12 years, or their maternal smoking during pregnancy.
Optimal monitoring and attack detection of networks modeled by Bayesian attack graphs
Authors: Kazeminajafabadi Armita , Imani Mahdi
Published: September 2023

Early attack detection is essential to ensure the security of complex networks, especially those in critical infrastructures. This is particularly crucial in networks with multi-stage attacks, where multiple nodes are connected to external sources, through which attacks could enter and quickly spread to other network elements. Bayesian attack graphs (BAGs) are powerful models for security risk assessment and mitigation in complex networks, which provide the probabilistic model of attackers’ behavior and attack progression in the network. Most attack detection techniques developed for BAGs rely on the assumption that network compromises will be detected through routine monitoring, which is unrealistic given the ever-growing complexity of threats. This paper derives the optimal minimum mean square error (MMSE) attack detection and monitoring policy for the most general form of BAGs. By exploiting the structure of BAGs and their partial and imperfect monitoring capacity, the proposed detection policy achieves the MMSE optimality possible only for linear-Gaussian state space models using Kalman filtering. An adaptive resource monitoring policy is also introduced for monitoring nodes if the expected predictive error exceeds a user-defined value. Exact and efficient matrix-form computations of the proposed policies are provided, and their high performance is demonstrated in terms of the accuracy of attack detection and the most efficient use of available resources using synthetic Bayesian attack graphs with different topologies.
Clinical outcomes of DAA and related techniques in hip arthroplasty
Authors: Driesman Adam , Yang Charlie C.
Published: September 2023

Total hip arthroplasty (THA) has been one of the most successful surgical interventions in recent memory and is nicknamed by some the “Surgery of the Century”. Over the past decade, there has been a drastic change in THA management with the rise of the direct anterior approach both globally and in the USA market. While many would remark that this has been driven by false marketing, it is clear that the direct anterior approach can be an effective and safe way to perform a THA.

It is the goal of this review to highlight evidence of its outcomes and clinical advantages, in particular, how it can decrease dislocation, even in high-risk individuals, and result in faster recovery in the early postoperative period with decreased muscular inflammation. We will also highlight its major disadvantages, including but not limited to increased wound complications and risk for periprosthetic fracture. Hopefully, this review will provide up-to-date information on the current state of the direct anterior approach and provide recommendations on patients that would be optimal candidates for this technique.
Dyspnoea in liver cirrhosis: beyond the ordinary cardiopulmonary cause
Authors: Yong Yun Xiu , Lim Lee Yee , Lim Kuan Yee
Published: September 2023

Background

Dyspnoea is a common presentation to the casualties, attributed mostly to cardiopulmonary diseases. Approach to dyspnoea consists of initial acute management to ensure airway patency, respiratory support, and hemodynamic stability, followed by identification of the underlying disease for a definite management to reduce short-term inpatient morbidity and mortality, and rehospitalization in long term. Awareness of the patient’s pre-existing medical conditions is a crucial clue to guide the attending doctor to the primary cause. Dyspnea in chronic liver disease can be due to concomitant cardiopulmonary diseases as well as pulmonary vascular congestion or abnormality associated with portal hypertension such as hepatopulmonary syndrome.

Case presentation

A 59-year-old man presented with a syncopal attack associated with breathlessness after physical exertion. He had alcohol associated liver cirrhosis for 2 years with a 6-month duration of platypnea and reduced effort tolerance. His physical examination revealed a cyanosed man with normal blood pressure and heart rate, without evidence of systemic and pulmonary fluid congestions. Chest radiography and computed tomography showed no evidence of pulmonary embolism and parenchymal disease and a normal echocardiography ruled out any cardiogenic cause. A diagnosis of hepatopulmonary syndrome was made after the appearance of microbubbles over left atrium at fourth to fifth cardiac cycle demonstrated by a transthoracic contrast-enhanced echocardiography to suggest an extracardiac intrapulmonary shunt.

Conclusions

HPS is not an uncommon complication of chronic liver disease. Usual manifestation of HPS is platypnea which needs to be differentiated from orthopnoea associated with cardiopulmonary disease. Nevertheless, there is no effective therapeutic approach of HPS besides liver transplantation.
President's Page: Applying geophysical methods to medical ultrasound imaging
Authors: Peng Chuck
Published: September 2023

The similarities and crossovers between geophysical and medical imaging are well known and documented (see President's Pages by D. Lumley and J. Zhang in the March 2021 and June 2022 issues, respectively, for two recent examples from this journal). Each of the two industries has introduced technology of tremendous value to the other, and one can only imagine what future advancements in medical imaging may bring to exploration geophysics — and vice versa. Welcome to the wonderland of the intersection of geophysical imaging and medical imaging.
Seismic Soundoff: How to unlock the power of networking
Authors: Geary Andrew
Published: September 2023

Lia Martinez shares critical skills that are necessary to network successfully. She explains why seven follow-ups is the magic number, the importance of establishing credibility early, and how to use note-taking to your advantage.
Telepsychiatry versus face-to-face treatment: systematic review and meta-analysis of randomised controlled trials
Authors: Hagi Katsuhiko , Kurokawa Shunya , Takamiya Akihiro , Fujikawa Mayu , Kinoshita Shotaro , Iizuka Mari , Furukawa Shota , Eguchi Yoko , Kishimoto Taishiro
Published: September 2023

Background

The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries.

Aims

To compare the efficacy of telepsychiatry and face-to-face treatment.

Method

A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability.

Results

We identified 32 studies (n = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders (k = 6 studies, n = 561; standardised mean difference s.m.d. = −0.325, 95% CI −0.640 to −0.011, P = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder (k = 1, n = 128; s.m.d. = 0.368, 95% CI 0.018–0.717, P = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 26, n = 2290; P = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment (k = 1, n = 61; risk ratio RR = 0.552, 95% CI 0.312–0.975, P = 0.040), whereas the opposite was seen for substance misuse (k = 1, n = 85; RR = 37.41, 95% CI 2.356–594.1, P = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 27, n = 3341; P = 0.564).

Conclusions

Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.
Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study
Authors: Sanft Tara , Harrigan Maura , McGowan Courtney , Cartmel Brenda , Zupa Michelle , Li Fang-Yong , Ferrucci Leah M. , Puklin Leah , Cao Anlan , Nguyen Thai Hien , Neuhouser Marian L. , Hershman Dawn L. , Basen-Engquist Karen , Jones Beth A. , Knobf Tish , Chagpar Anees B. , Silber Andrea , Tanasijevic Anna , Ligibel Jennifer A. , Irwin Melinda L.
Published: September 2023

PURPOSE

Successful completion of chemotherapy is critical to improve breast cancer outcomes. Relative dose intensity (RDI), defined as the ratio of chemotherapy delivered to prescribed, is a measure of chemotherapy completion and is associated with cancer mortality. The effect of exercise and eating a healthy diet on RDI is unknown. We conducted a randomized trial of an exercise and nutrition intervention on RDI and pathologic complete response (pCR) in women diagnosed with breast cancer initiating chemotherapy.

METHODS

One hundred seventy-three women with stage I-III breast cancer were randomly assigned to usual care (UC; n = 86) or a home-based exercise and nutrition intervention with counseling sessions delivered by oncology-certified registered dietitians (n = 87). Chemotherapy dose adjustments and delays and pCR were abstracted from electronic medical records. T-tests and chi-square tests were used to examine the effect of the intervention versus UC on RDI and pCR.

RESULTS

Participants randomly assigned to intervention had greater improvements in exercise and diet quality compared with UC ( P < .05). RDI was 92.9% ± 12.1% and 93.6% ± 11.1% for intervention and UC, respectively ( P = .69); the proportion of patients in the intervention versus UC who achieved ≥85% RDI was 81% and 85%, respectively ( P = .44). The proportion of patients who had at least one dose reduction and/or delay was 38% intervention and 36% UC ( P = .80). Among 72 women who received neoadjuvant chemotherapy, women randomly assigned to intervention were more likely to have a pCR than those randomly assigned to UC (53% v 28%; P = .037).

CONCLUSION

Although a diet and exercise intervention did not affect RDI, the intervention was associated with a higher pCR in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy.