bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor deposits in thyroid carcinomas
Authors: Guray Durak Merih , Gokcay Deniz , Emecen Serra Begum , Ozdogan Ozhan , Sevinc Ali Ibrahim , Ikiz Ahmet Omer , Dogan Ersoy , Karabay Nuri , Ellidokuz Hulya , Sarioglu Sulen
Published: July 2024

Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; P = .006). TDs were more common in women (P = .045), and in multifocal tumors (P = .017). In addition, cases with TDs had larger tumor size (P = .002), more lymphatic invasion (P = .009), extrathyroidal extension (P < .001), and distant metastasis (P < .001). The mean follow-up period of the patients was 120.1 months (range, 4–341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; P = .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (P = .002). Sex (P = .001), tumor type (P = .002), pT classification of the tumor (P < .001), perineural invasion (P = .002) and TDs (P = .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (P = .001) and TDs (P = .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (P = .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.
Mapping the landscape: A bibliometric perspective on autophagy in spinal cord injury
Authors: Wang Fei , Zhang Songou , Xu Yangjun , He Wei , Wang Xiang , He Zhongwei , Shang Jinxiang , Zhenyu Zhang
Published: July 2024

Background:

Spinal cord injury (SCI) is a severe condition that often leads to persistent damage of nerve cells and motor dysfunction. Autophagy is an intracellular system that regulates the recycling and degradation of proteins and lipids, primarily through lysosomal-dependent organelle degradation. Numerous publications have highlighted the involvement of autophagy in the secondary injury of SCI. Therefore, gaining a comprehensive understanding of autophagy research is crucial for designing effective therapies for SCI.

Methods:

Dates were obtained from Web of Science, including articles and article reviews published from its inception to October 2023. VOSviewer, Citespace, and SCImago were used to visualized analysis. Bibliometric analysis was conducted using the Web of Science data, focusing on various categories such as publications, authors, journals, countries, organizations, and keywords. This analysis was aimed to summarize the knowledge map of autophagy and SCI.

Results:

From 2009 to 2023, the number of annual publications in this field exhibited wave-like growth, with the highest number of publications recorded in 2020 (44 publications). Our analysis identified Mei Xifan as the most prolific author, while Kanno H emerged as the most influential author based on co-citations. Neuroscience Letters was found to have published the largest number of papers in this field. China was the most productive country, contributing 232 publications, and Wenzhou Medical University was the most active organization, publishing 39 papers.

Conclusion:

We demonstrated a comprehensive overview of the relationship between autophagy and SCI utilizing bibliometric tools. This article could help to enhance the understanding of the field about autophagy and SCI, foster collaboration among researchers and organizations, and identify potential therapeutic targets for treatment.
Association between cardiovascular health and pelvic inflammatory disease: Analyses of the NHANES 2015 to 2018
Authors: Yang Yang , Chen Kewei , Li Huaifang , Tong Xiaowen
Published: July 2024

While the link between female reproductive function and cardiovascular health (CVH) is well-established, the association between pelvic inflammatory disease (PID) and CVH remains largely unexplored. This study, therefore, sets out to fill this gap in knowledge by investigating the potential relationship between PID and CVH. To ensure the reliability and validity of our findings, data for this cross-sectional study were meticulously collected from the 2015–2018 National Health and Nutrition Examination Survey (NHANES). After applying stringent exclusion criteria, a total of 2442 women were included in the study. The Life Essential 8 (LE8) scoring system, a robust tool developed by the American Heart Association (AHA), was employed to assess the CVH. Logistic regression with multiple variables and smooth curve fitting were utilized to analyze the association. Subgroup and interaction analyses were performed to determine the strength of this association across different demographic groups. The study included 2442 women, with an average CVH score of 66.29 ± 16.27. After accounting for all covariates, each unit increase in CVH score was associated with 2% lower odds of PID prevalence (OR = 0.98, 95% CI: 0.97–0.99). Notably, participants with high CVH had a striking 71% lower odds of PID prevalence compared to those with low CVH. Stratified analyses further revealed a consistent inverse association between CVH score and PID across various subgroups, underscoring the robustness of our findings. The research has uncovered a significant inverse association between CVH and PID. This suggests that improving the CVH level could be a promising strategy for reducing the odds of PID.
The relationship between exercise atmosphere, flow experience, and subjective well-being in middle school students: A cross-sectional study
Authors: Zou Na , Shang Yao , Wang Qingran
Published: July 2024

The aim of this research was to explore the effect of exercise atmosphere (EA) on the flow experience (FE) and subjective well-being (SWB) of middle school students and further analyze the mediating effect of FE between EA and SWB, and to provide theoretical references for improving middle school students’ SWB. A cross-sectional design was used. 1056 middle school students from 6 middle schools in Sichuan, China, voluntarily completed the Exercise Atmosphere Scale (EAS), Short (9-item) Dispositional Flow Scales (SDFS-2), Positive and Negative Affect Scale (PANAS), and Satisfaction with Life Scale (SLS). The data collected for this investigation were processed using SPSS 19.0 and Process 3.0. EA could positively predict FE and SWB. FE could positively predict SWB. FE partially mediated the relationship between EA and SWB. The study demonstrated the mediating effect of FE between EA and middle school students’ SWB. It was proposed that the positive EA contributes to the emergence of FE during physical exercise in middle school students, which leads to a better sense of SWB.
Health literacy as a predictor of cardiovascular disease risk factor knowledge level among women in Turkey: A community-based cross-sectional study
Authors: Yardimci Gürel Tuğba , Güner Özlem
Published: July 2024

While more common in men globally, heart diseases also rank as the leading cause of death among women. This study aimed to examine the relationship between Turkish women’s level of knowledge about cardiovascular disease (CVD) risk factors and their health literacy. Data for this descriptive and cross-sectional study were collected online by using Health Literacy Scale and CVD risk factor knowledge level scale from October 2022, to May 2023. The study sample consisted of 409 women. It was found that the total score average of the women on the CVD risk factor knowledge level was 20.65 ± 4.72 and the Health Literacy Scale was 107.06 ± 16.01. There was a moderate, significantly positive correlation between CVD knowledge levels and health literacy (r = .548, P = .000). It was found that women with high health literacy also had increased knowledge levels. Furthermore, all health literacy dimensions of access to information (P < .001), understanding information (P < .001), appraisal/evaluation (P < .001), and implementation (P < .001) were detected as the predictors of CVD risk factor knowledge levels. Factors such as educational level and economic status significantly influenced scores on both scales (P < .05). The study’s findings highlight the challenges encountered by women with low socioeconomic status in accessing accurate information. It may be recommended that nurses provide health education and consultancy services to these women on the prevention and management of cardiovascular diseases. Also, public education programs should consider socioeconomic and educational levels, focusing on women who encounter difficulties accessing information.
Integrative analysis of gene and microRNA expression profiles reveals candidate biomarkers and regulatory networks in psoriasis
Authors: Chen Lu , Wang Xiaochen , Liu Chang , Chen Xiaoqing , Li Peng , Qiu Wenhong , Guo Kaiwen
Published: July 2024

Psoriasis (PS) is a chronic inflammatory skin disease with a long course and tendency to recur, the pathogenesis of which is not fully understood. This article aims to identify the key differentially expressed genes (DEGs) and microRNA (miRNAs) of PS, construct the core miRNA-mRNA regulatory network, and investigate the underlying molecular mechanism through integrated bioinformatics approaches. Two gene expression profile datasets and 2 miRNA expression profile datasets were downloaded from the gene expression omnibus (GEO) database and analyzed by GEO2R. Intersection DEGs and intersection differentially expressed miRNAs (DEMs) were each screened. The Metascape database and R software were used to perform enrichment analysis of intersecting DEGs and study their functions. Target genes of DEMs were predicted from the online database miRNet. The protein-protein interaction files of the overlapping target genes were obtained from string and the miRNA-mRNA network was constructed by Cytoscape software. In addition, the online web tool CIBERSORT was used to analyze the immune infiltration of dataset GSE166388, and the relative abundance of 22 immune cells in the diseased and normal control tissues was calculated and assessed. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the relative expression of the screened miRNAs and mRNAs to assess the applicability of DEMs and DEGs as biomarkers in PS. A total of 205 mating DEGs and 6 mating DEMs were screened. 103 dysregulated crossover genes from 205 crossover DEGs and 7878 miRNA target genes were identified. The miRNA-mRNA regulatory network was constructed and the top 10 elements were obtained from CytoHubba, including hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2. QRT-PCR revealed significant differences in miRNA and gene expression between inflammatory and normal states. In this study, the miRNA-mRNA core regulator pairs hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2 may be involved in the course of PS. This study provides new insights to discover new potential targets and biomarkers to further investigate the molecular mechanism of PS.
Adapting to the shifting landscape: Implications of climate change for malaria control: A review
Authors: Obeagu Emmanuel Ifeanyi , Obeagu Getrude Uzoma
Published: July 2024

Malaria, a global public health challenge, continues to affect millions of lives, particularly in regions where its transmission is endemic. The interplay between climate change and malaria dynamics has emerged as a critical concern, reshaping the landscape of this vector-borne disease. This review publication, titled “Adapting to the shifting landscape: Implications of climate change for malaria control,” explores the multifaceted relationship between climate change and the control of malaria. The paper begins by dissecting the influence of climate change on malaria dynamics, including alterations in temperature, precipitation, and other climatic factors that impact the habitat and life cycle of malaria vectors. It delves into the evolving ecology and behavior of malaria vectors in response to changing climatic conditions, emphasizing the importance of understanding these adaptations. As a response to this shifting landscape, the review discusses adaptive strategies for malaria control, ranging from vector control measures to the utilization of climate data in early warning systems. Community engagement and education are highlighted as essential components of these strategies, recognizing the vital role of local communities in effective malaria control efforts. The paper also identifies future directions and research needs, underscoring the importance of staying ahead of the evolving climate–malaria relationship. This review underscores the urgency of adapting to the changing landscape of malaria transmission driven by climate change. It emphasizes the significance of proactively addressing climate-related challenges to enhance malaria control and protect the health and well-being of vulnerable populations.
Hemophagocytic lymphohistiocytosis secondary to rifampin treatment: A case report
Authors: Wang Caihong , Qiu Junke , Huang Xiaoqing , Xu Jiekun , Pan Lei
Published: July 2024

Rationale:

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening systemic inflammatory syndrome characterized by an overactive immune response. This hyperactivation can arise from genetic mutations, infections, malignancies, or autoimmune disorders. Medication-induced HLH is extremely rare and requires special attention.

Patient concerns:

A 53-year-old female diagnosed with pulmonary and urinary tract tuberculosis. She underwent quadruple therapy, including isoniazid, rifampin, ethambutol, and pyrazinamide. Subsequently, she developed fever, hepatosplenomegaly, pancytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, increased soluble CD25 levels, decreased natural killer cell activity, and hemophagocytosis, notably without eosinophilia. Her clinical symptoms were exacerbated by rifampin intake.

Diagnoses:

Pulmonary and left kidney tuberculosis, multiple organ failure, and rifampin-induced HLH.

Interventions:

Anti-tuberculosis regimen (isoniazid, pyrazinamide, ethambutol, and levofloxacin, excluding rifampin) combined with glucocorticoid therapy.

Outcomes:

Satisfactory recovery with improved clinical symptoms, laboratory tests, and chest imaging studies.

Lessons:

Early correct diagnosis and appropriate management of HLH are essential to save the lives of affected patients. The potential severe side effects of rifampin should not be ignored.
Multiple brain abscesses caused by Nocardia farcinica infection after hand injury: A case report and literature review
Authors: Xue Kun , Zhang Anling , Liu Shuyu , Chen Dawei
Published: July 2024

Rationale:

Nocardia infection is commonly regarded as an opportunistic pulmonary pathogen affecting debilitated or immunocompromised individuals. Brain abscesses caused by Nocardia farcinica are rare and pose a diagnostic challenge. Traditional diagnostic techniques for identifying Nocardia species, such as blood culture, microscopy, and pathology, have shown inadequate performance. In the reported case, we applied metagenomic next-generation sequencing (mNGS) to diagnose a case of brain abscess due to N. farcinica.

Patient concerns:

A 66-year-old female developed a brain abscess after sustaining a hand injury. The patient exhibited a gradual change in personality and experienced tremors in her right upper limb for a duration of 1 month.

Diagnoses:

The pathogen responsible for the multiple brain abscesses was identified in the cerebrospinal fluid as N. farcinica through mNGS.

Interventions:

Antibiotic treatment included trimethoprim-sulfamethoxazole, linezolid, amikacin, meropenem, and moxifloxacin.

Outcomes:

The patient’s symptoms and signs improved significantly after administration of antibiotics to which the pathogen is known to be sensitive. After 5 months of follow-up, magnetic resonance imaging of the head showed that the abscess was basically cured. The patient lived a normal life with no adverse drug reactions.

Lessons:

Nocardia brain infection is characterized by an insidious onset and lacks distinctive clinical and imaging features. mNGS was advantageous for the timely identification and management of Nocardia-associated brain abscess in the present case and obviated the need for invasive brain surgery. Expeditious and precise diagnosis coupled with prompt antibiotic therapy can significantly reduce the mortality rate associated with this condition.
Retinopathy risk factors in patients with type 2 diabetes on liraglutide
Authors: Mahzari Moeber M. , Alanazy Abdulmalik M. , Feroz Zeeshan , Almani Khalid M. , Alghamdi Meshari A. , Almadani Abdulaziz S. , Alzahrani Majed K. , Alibrahim Ahmed R. , Badri Motasim
Published: July 2024

Liraglutide, a glucagon-like peptide 1 receptor agonist, effectively treats type 2 diabetes(T2D) by lowering glucose levels, suppressing glucagon release, and promoting insulin secretion. Liraglutide has been shown to reduce body weight and glycated hemoglobin (HbA1c) levels and improve cardiovascular outcomes. However, evidence regarding the association between liraglutide and diabetic retinopathy in the Middle East is insufficient. Therefore, this study aimed to investigate the characteristics and risk factors of diabetic retinopathy in patients with T2D treated with liraglutide in Saudi Arabia. This retrospective cohort study was conducted on patients (≥14 years) with T2D treated with liraglutide between 2015 and 2021, who had a documented retinopathy assessment at baseline before liraglutide initiation and during follow-up, at King Abdulaziz Medical City (KAMC), Riyadh. Data collection included demographic information, retinopathy status, body mass index (BMI), and HbA1c level at baseline and follow-up after liraglutide use. The study included 181 patients with a mean age of 58.2 (9.8) years. Of these, 72.9% were females. At baseline, the median weight (interquartile range) was 88 (77–100) kg, diabetes duration was 19 (13–23.5) years, and HbA1c level was 9% (8–10%). Total of 69.6% were on insulin, 22.7% were on oral hypoglycemic agents, and 7.7% were on no other medications in addition to liraglutide. After a median of 2 years follow-up, both HbA1c level and weight decreased significantly (P < .001). Seventy-one of the 87 patients (81.6%) without retinopathy at baseline continued to show no retinopathy. Among patients with retinopathy at baseline, 25.5% showed improvement and 44.7% showed no change. In the multivariate binary mixed effect analysis, factors significantly associated with retinopathy were: use of insulin (odds ratio [OR]:2.68; 95% confidence interval [CI]: 1.18–6.09, P = .019), older age (OR:1.03; 95% CI: 1.00–1.06; P = .022), higher HbA1c level (OR:1.17; 95% CI: 1.02–1.34; P = .024), Hypertension (OR:2.56; 95% CI: 1.13–5.76; P=<.0001) and longer diabetes duration (OR:1.04; 95% CI: 1.00–1.08; P = .024). In conclusion, liraglutide use caused significant reductions in the HbA1c level and weight of patients with T2D. Most patients showed no change in retinopathy status after liraglutide use.
Identification of a novel nonsense SLC16A2 gene mutation in an infant with severe neurologic phenotype: A case report
Authors: Peng Wu , Shi Shuxia , Yang Liqi , Liu Deyun
Published: July 2024

Rationale:

Allan–Herndon–Dudley syndrome (AHDS) results from a pathogenic variant in the hemizygous subunit of the SLC16A2 gene, which encodes monocarboxylate transporter 8 and follows an X-linked recessive pattern. AHDS manifests as neuropsychomotor developmental delay, intellectual disability, movement disorders, and thyroid hormone abnormalities. It is frequently misdiagnosed as cerebral palsy or hypothyroidism.

Patient concerns:

A 9-month-old male infant exhibited poor head control, hypodynamia, motor retardation, hypertonic limbs, and thyroid abnormalities. Despite levothyroxine supplementation and rehabilitation therapy, no improvements were observed. Whole-exome sequencing identified a novel nonsense mutation in SLC16A2 (c.124G > T, p.E42X), which unequivocally established the diagnosis.

Diagnoses:

AHDS was confirmed.

Interventions:

Levothyroxine treatment commenced early in infancy, followed by 3 months of rehabilitation therapy, starting at 5 months of age. The combined administration of levothyroxine and methimazole was initiated at 1 year and 10 months of age, respectively.

Outcomes:

While improvements were noted in thyroid hormone levels, neurological developmental delays persisted.

Lessons:

AHDS should be considered in patients presenting with atypical neurological features and thyroid hormone abnormalities such as elevated triiodothyronine and decreased thyroxine levels. The early utilization of exome sequencing aids in prompt diagnosis. The identified SLC16A2 nonsense mutation correlates with severe neurological phenotypes and adds to the spectrum of genetic variations associated with AHDS.
Diagnosis of suprascapular nerve entrapment syndrome based on the infraspinatus muscle cross-sectional area on shoulder MRI
Authors: Cho Jaeho , Yi Jungmin , Kim Hyunhae , Moon Sunyoung , Choi Woobin , Kang Keum Nae , Shin Hojin , Kim Young Uk
Published: July 2024

Suprascapular nerve entrapment (SNE) syndrome is a commonly overlooked cause of shoulder weakness and pain. It frequently causes weakness over the posterior and lateral and posterior aspects of the shoulder, as well as pain of infraspinatus muscles. Therefore, we considered that the infraspinatus muscle cross-sectional area (IMCSA) might be a new morphological parameter to analyze SNE syndrome. We assumed that the IMCSA is an important morphologic parameter in SNE syndrome diagnosis. We acquired infraspinatus muscle data from 10 patients with SNE syndrome and from 10 healthy subjects who had undergone magnetic resonance imaging of the shoulder and who revealed no evidence of SNE syndrome. We analyzed the infraspinatus muscle thickness (IMT) and IMCSA at the shoulder on the imaging of the shoulder using our image analysis program. The IMCSA was measured as the whole infraspinatus muscle cross-sectional area that was most atrophied in the sagittal S-MR images. The IMT was measured as the thickest level of infraspinatus muscle. The mean IMT was 29.17 ± 2.81 mm in the healthy subjects and 25.22 ± 3.19 mm in the SNE syndrome group. The mean IMCSA was 1321.95 ± 175.91 mm2 in the healthy group and 1048.38 ± 259.94 mm2 in the SNE syndrome group. SNE syndrome patients had significantly lower IMT (P < .001) and IMCSA (P < .001) than the healthy group. The ROC curve shows that the optimal cutoff point of the IMT was 26.74 mm, with 70.0% sensitivity, 70.0% specificity, and an AUC of 0.83 (95% CI, 0.65–1.00). The best cutoff value of the IMCSA was 1151.02 mm2, with 80.0% sensitivity, 80.0% specificity, and AUC of 0.87 (95% CI, 0.69–1.00). The IMT and IMCSA were both significantly associated with SNE syndrome. And the IMCSA was a highly sensitive diagnostic tool.
Physical activity as mediator between back pain and disability
Authors: Karklins Aleksandra E. , Pernaa Katri I. , Saltychev Mikhail , Juhola Juhani E. , Arokoski Jari P.A.
Published: July 2024

The objective was to explore the mediating role of leisure-time physical activity on the correlation between back pain and disability. A mediation analysis was conducted among the cross-sectional sample of 1330 patients in outpatient clinic. The average age was 47.6 years and 64% were women. For the entire sample, the mediating effect of physical activity remained below 10% of the total effect. The mediating effect was significantly greater among women comparing to men – up to 19.0% [95% confidence interval (CI) 10.4–27.6%] versus 2.3% (95% CI 0.0–6.1%). The effect did not significantly differ based on age, BMI, or educational or professional status. Some insignificant trends, however, could be seen – the effect was possibly stronger among patients with higher educational level and those with higher BMI. The results suggested that while physical activity seems to be a weak mediator, its mediating role might vary across different groups of patients with back pain. This variation should be taken into account when planning rehabilitation measures for people with back pain.
Risk Factors of Acute Ischemic Stroke and Mortality Among Adults With Endocardial Fibroelastosis
Authors: Warsi Talal , Ramphul Kamleshun , Dulay Mansimran Singh , Jeelani Saddam , Verma Renuka , Kumar Nomesh , Dhaliwal Jasninder Singh , Carver Caleb , Sakthivel Hemamalini , Gardezi Syed Khurram Mushtaq , Deshpande Saurabh , Sherif Akil A. , Liu Alexander , Ahmed Raheel
Published: July 2024

Objectives:

Endocardial fibroelastosis (EFE) is a rare form of restrictive cardiomyopathy associated with high morbidity and mortality. The literature is sparse on information pertaining to risk stratification. Thus, we sought to highlight the risk factors of acute ischemic stroke (AIS) and mortality in adults with EFE.

Methods:

The National Inpatient Sample (NIS) database was queried from 2001 to 2020 using the International Classification of Diseases 9th Revision (ICD-9) and 10th Revision (ICD-10) codes for adult patients with EFE. Factors associated with AIS and mortality were identified.

Results:

In all, 18495 cases of EFE fit the inclusion criteria, of which 2370 (12.82%) had AIS. The mean ages for patients with and without AIS were 62.37 and 54.24, respectively. Multivariate regression suggested greater odds of AIS in patients with hypertension (aOR 2.329, P<0.01), dyslipidemia (aOR: 1.566, P<0.01), peripheral vascular disease (PVD) (aOR: 1.736, P<0.01), alcohol abuse (aOR: 1.817, P<0.01), age >60 y (aOR: 1.646, P<0.01), females (vs. males, aOR: 1.238, P<0.01), and smokers (aOR: 1.697, P<0.01). Patients with cirrhosis (aOR: 0.174, P<0.01), CKD (aOR: 0.369, P<0.01), COPD (aOR: 0.402, P<0.01), atrial fibrillation (aOR: 0.542, P<0.01) had lower odds of AIS. 3.1% of EFE patients with AIS died. Diabetes (aOR: 11.665, P<0.01) and COPD (aOR: 3.201, P=0.017) were associated with the greatest odds of all-cause mortality. Dyslipidemia (aOR: 0.387, P=0.010) and females (vs. males, aOR: 0.432, P=0.012) had reduced odds of all-cause mortality.

Conclusion:

Several risk factors are associated with AIS in EFE, while diabetes, COPD, and being male are associated with mortality in EFE.
Body Fit With a Pouching System With Concave Contour for People With an Outward Peristomal Body Profile
Authors: Rolfsen Thomas , Vestergaard Martin , Hansen Mads Fuglesang , Boisen Esben Bo , Dambæk Marianne Raff
Published: July 2024

PURPOSE:

The purpose of the study was to investigate the fit of a two-piece pouching system with a concave-shaped skin barrier on people with an outward peristomal body profile and its effect on leakage, wear time, and quality of life (QoL) related to using an ostomy product.

DESIGN:

Randomized, controlled, open-label, cross-over trial.

SUBJECTS AND SETTINGS:

The sample comprised 53 subjects with outward peristomal body profiles and problems with leakage of ostomy effluent from their pouching system. Participants were randomized to the concave two-piece pouching system or a comparator (two-piece pouching system with a flat skin barrier) for 3 weeks. Subjects were then crossed over to the opposite skin barrier for an additional 3 weeks. The study was conducted in Denmark, Norway, Germany, and the Netherlands; data were collected in multiple ambulatory clinics or during home visits.

METHODS:

The primary end point was the ability of the skin barrier to fit body contours; secondary outcomes were leakage of effluent from the pouching system, wear time, and QoL related to using an ostomy product via the validated Ostomy-Q questionnaire. Primary comparisons between concave and comparator pouching systems were evaluated using proportional odds models and mixed models taking test period into account.

RESULTS:

Analysis included randomized subjects who had been exposed to at least one product and with information on at least one end point (full-analysis-set, n = 52). The concave pouching system provided a better fit to body contours than the comparator (P< .001) and reduced the degree of leakage underneath the skin barrier (LS mean difference = −1.84, 95% CI −3.31 to −0.37; P = .016). Participants experienced fewer episodes of leakage outside the skin barrier when using concave versus comparator pouching system (13.0% vs. 26.7%, respectively). Participants reported significant improvements in QoL (LS mean difference = 14.3; 95% CI 9.4 to 19.2; P < .001). No significant difference in wear time between skin barrier shapes was reported.

CONCLUSIONS:

Study findings indicate that a pouching system with a concave skin barrier achieved a better body fit on people with an outward peristomal body profile and resulted in fewer leakage incidents and higher QoL compared to using a pouching system with a flat skin barrier.
Risk Factors for Incontinence-Associated Dermatitis in Critically Ill Patients with Incontinence
Authors: Wang Guandong , Wang Xueying , Wang Haibo , Wang Liang , Li Wenjuan
Published: July 2024

PURPOSE:

This systematic review analyzed evidence related to risk factors for Incontinence Associated Dermatitis (IAD) in critically ill incontinent patients.

METHOD:

Systematic review and meta-analysis.

SEARCH STRATEGY:

Eight databases, including PubMed, Embase, CINAHL, Cochrane Library, and Web of Science, were searched for studies published in the English language. The China National Knowledge Infrastructure, WanFang Data, and Chinese Scientific Journal Database were also searched for studies evaluating risk of IAD in critically ill incontinent patients published in the Chinese language.

FINDINGS:

Twenty-four studies with moderate-to-high methodological quality were included. Significant risk factors for developing IAD were being older [odds ratio (OR) = 1.06, 95% confidence interval (CI): 1.02–1.10, P = .007], fever (OR = 2.57, 95% CI: 1.87–3.57, P < .00001), diagnosed with consciousness disorder (OR = 5.70, 95% CI: 2.28–14.22, P = .0002), having higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR = 1.71, 95% CI: 1.25–2.35, P = .0009), lower Braden score (OR = 0.73, 95% CI: 0.56–0.96, P = .02), lower oxygen saturation (OR = 2.76, 95% CI: 1.52–5.00, P = .0008), double incontinence (OR = 4.10, 95% CI: 2.34–7.17, P < .00001), liquid stool (OR = 6.55, 95% CI: 4.12–10.41, P < .00001), frequent incontinence (OR = 1.21, 95% CI: 1.03–1.43, P = .02), and higher perineal assessment tool (PAT) score (OR = 3.18, 95% CI: 1.76–5.76, P = .0001).

IMPLICATIONS:

Findings of this systematic review and meta-analysis suggest that healthcare providers should consider risk factors such as older age, fever, consciousness disorder, higher APACHE II score, lower Braden score and double incontinence matter when developing strategies for the prevention and management of IAD in critically ill incontinent patients.
Scavengers in the human-dominated landscape: an experimental study
Authors: Biswas Sourabh , Bhowmik Tathagata , Ghosh Kalyan , Roy Anamitra , Lahiri Aesha , Sarkar Sampita , Bhadra Anindita
Published: July 2024

Rapid urbanization is a major cause of habitat and biodiversity loss and human–animal conflict. While urbanization is inevitable, we need to develop a good understanding of the urban ecosystem and the urban-adapted species, in order to ensure sustainable cities for our future. Scavengers play a major role in urban ecosystems, and often, urban adaptation involves a shift towards scavenging behaviour in wild animals. We experimented at different sites in the state of West Bengal, India, to identify the scavenging guild within urban habitats, in response to human-provided food. Our study found a total of 17 different vertebrate species across 15 sites, over 498 sessions of observations. We carried out network analysis to understand the dynamics of the system and found that the free-ranging dog and common myna were key species within the scavenging networks. This study revealed the complexity of scavenging networks within human-dominated habitats.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Connecting and integrating cooperation within and between species
Authors: Bronstein Judith L. , Sridhar Hari
Published: July 2024

There has long been a fundamental divide in the study of cooperation: researchers focus either on cooperation within species, including but not limited to sociality, or else on cooperation between species, commonly termed mutualism. Here, we explore the ecologically and evolutionarily significant ways in which within- and between-species cooperation interact. We highlight two primary cross-linkages. First, cooperation of one type can change the context in which cooperation of the other type functions, and thus potentially its outcome. We delineate three possibilities: (i) within-species cooperation modulates benefits for a heterospecific partner; (ii) between-species cooperation affects the dynamics of within-species cooperation; and (iii) both processes take place interactively. The second type of cross-linkage emerges when resources or services that cooperation makes available are obtainable either from members of the same species or from different species. This brings cooperation at the two levels into direct interaction, to some extent obscuring the distinction between them. We expand on these intersections between within- and between-species cooperation in a diversity of taxa and interaction types. These interactions have the potential to weave together social networks and trophic dynamics, contributing to the structure and functioning of ecological communities in ways that are just beginning to be explored.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Reclassification of type strains of Rhizobium indigoferae and Sinorhizobium kummerowiae into the species Rhizobium leguminosarum and Sinorhizobium meliloti, respectively
Authors: Menéndez Esther , Flores-Félix José David , Kaur Sabhjeet , diCenzo George C. , Young J. Peter W. , Peix Alvaro , Velázquez Encarna
Published: July 2024

The species Rhizobium indigoferae and Sinorhizobium kummerowiae were isolated from legume nodules and the 16S rRNA sequences of their respective type strains, CCBAU 71042T and CCBAU 71714T, were highly divergent from those of the other species of the genera Rhizobium and Sinorhizobium, respectively. However, the 16S rRNA gene sequences obtained for strains CCBAU 71042T and CCBAU 71714T several years after description, were different from the original ones, showing 100 % similarity to the type strains of Rhizobium leguminosarum and Sinorhizobium meliloti, respectively. Phylogenetic analyses of two housekeeping genes, recA and atpD, confirmed the high phylogenetic closeness of strains CCBAU 71042T and CCBAU 71714T to the respective type strains of R. leguminosarum and S. meliloti. In the present work, we compared the genomes of the type strains of R. indigoferae and S. kummerowiae available in several culture collections with those of the respective type strains of R. leguminosarum and S. meliloti, some of them obtained in this study. The calculated average nucleotide identity–blast and digital DNA–DNA hybridization values in both cases were higher than those recommended for species differentiation, supporting the proposal for the reclassification of the type strains of R. indigoferae and S. kummerowiae into the species R. leguminosarum and S. meliloti, respectively.
FORWARD: A Learning Framework for Logical Network Perturbations to Prioritize Targets for Drug Development
Authors: Sinha Saptarshi , McLaren Ella , Mullick Madhubanti , Singh Siddharth , Boland Brigid S. , Ghosh Pradipta
Published: July 2024

Despite advances in artificial intelligence (AI), target-based drug development remains a costly, complex and imprecise process. We introduce F.O.R.W.A.R.D [Framework for Outcome-based Research and Drug Development], a network-based target prioritization approach and test its utility in the challenging therapeutic area of Inflammatory Bowel Diseases (IBD), which is a chronic condition of multifactorial origin. F.O.R.W.A.R.D leverages real-world outcomes, using a machine-learning classifier trained on transcriptomic data from seven prospective randomized clinical trials involving four drugs. It establishes a molecular signature of remission as the therapeutic goal and computes, by integrating principles of network connectivity, the likelihood that a drug’s action on its target(s) will induce the remission-associated genes. Benchmarking F.O.R.W.A.R.D against 210 completed clinical trials on 52 targets showed a perfect predictive accuracy of 100%. The success of F.O.R.W.A.R.D was achieved despite differences in targets, mechanisms, and trial designs. F.O.R.W.A.R.D-driven in-silico phase ’0’ trials revealed its potential to inform trial design, justify re-trialing failed drugs, and guide early terminations. With its extendable applications to other therapeutic areas and its iterative refinement with emerging trials, F.O.R.W.A.R.D holds the promise to transform drug discovery by generating foresight from hindsight and impacting research and development as well as human-in-the-loop clinical decision-making.
Microphysiological system modeling pericyte-induced temozolomide resistance in glioblastoma
Authors: Maity Surjendu , Jewell Christopher , Yilgor Can , Kawakita Satoru , Sharma Saurabh , Gomez Alejandro , Mecwan Marvin , Falcone Natashya , Ermis Menekse , Monirizad Mahsa , Kouchehbaghi Negar Hosseinzadeh , Zehtabi Fatemeh , Khorsandi Danial , Dokmeci Mehmet Remzi , Moniz-Garcia Diogo , Quiñones-Hinojosa Alfredo , Khademhosseini Ali , Jucaud Vadim
Published: July 2024

Glioblastoma (GBM) is a malignancy with poor survival and high rates of chemoresistance. Temozolomide (TMZ), the standard-of-care chemotherapy for GBM patients, but GBM cells can be resistant to TMZ, resulting in limited clinical efficacy. Elucidating the complex mechanisms of TMZ chemoresistance in GBM requires novelin vitromodels replicating the complex tumor microenvironment (TME). We present an multicellular 3D GBM model recapitulating the biomechanical characteristics of brain tissues and pericyte-mediated TMZ resistance. The composite hydrogel used to encapsulate GBM spheroids (U87, LN229, and PDM140), pericytes, or GBM spheroids with pericytes, mimics the rheological properties of brain tissues (G’∼800Pa and G”∼100Pa). When untreated, the GBM models remain viable and proliferative for 14 days. PDM140 spheroids were most sensitive to TMZ (IC50=73μM), followed by LN229 (IC50=278μM) and U87 (IC50=446μM). With pericytes, the viability of TMZ-treated GBM spheroids significantly increases by 22.7% for PDM140, 32.5% for LN229, and 22.1% for U87, confirming pericyte-induced GBM chemoresistance responses. The upregulation (380-fold) of C-C motif chemokine ligand 5 (CCL5) in pericytes upon TMZ treatment could explain the chemoresistance responses. This innovative brain-mimicking 3D GBM model represents a novelin vitroplatform for testing the efficacy of TMZ and novel drugs targeting CCL5-mediated chemoresistance pathways in GBM.
Design of two-stage multidrug chemotherapy schedules using replicator game dynamics
Authors: Stuckey K. , Newton P.K.
Published: July 2024

We use a replicator evolutionary game in conjunction with control theory to design a two-stage multidrug chemotherapy schedule where each stage has a specific design objective. In the first stage, we use optimal control theory that minimizes a cost function to design atransfer orbitwhich takes any initial tumor-cell frequency composition and steers it to a state-space region of three competing clonal subpopulations in which the three populations co-exist with a relatively equal abundance (high-entropy co-existence region). In the second stage, we use adaptive control with continuous monitoring of the subpopulation balance to design amaintenance orbitwhich keeps the subpopulations trapped in the favorable co-existence region to suppress the competitive release of a resistant cell population in order to avoid the onset of chemoresistance. Our controlled replicator dynamics model consists of a chemo-sensitive cell phenotypeS, which is sensitive to both drugs, and two resistant cell phenotypes,R1andR2, which are sensitive to drugs 1 and 2 respectively, but resistant to drug 2 and 1. The 3 × 3 payoff matrix used to define the fitness function associated with the interactions of the competing populations is a prisoner’s dilemma matrix which ensures that in the absence of chemotherapy, theSpopulation (defectors) has higher fitness (reproductive prowess) than the two resistant cell populations, reflecting an inherent cost of resistance which our chemotherapy design methodology seeks to exploit. In our model, the two drugsC1andC2can act synergistically, additively, or antagonistically on the populations of cells as they compete and evolve under natural and artifical selection dynamics. Our model brings to light the inherent trade-offs between navigating to the maintenance orbit in minimal time vs. arriving there using the least total drug dose and also that the optimal balance of synergystic or antagonistic drug combinations depends the frequency balance of the populations of cells.
Perturbed pediatric serum metabolome in mild and severe dengue disease
Authors: Soma Paul S. , Gullberg Rebekah C. , Graham Barbara , Islam M. Nurul , Balmaseda Angel , Blair Carol D. , Beaty Barry J. , Belisle John T. , Harris Eva , Perera Rushika
Published: July 2024

Dengue viruses (DENVs) are the most prevalent arboviruses affecting humans. Four billion people are at risk of infection and this burden is rapidly increasing due to geographic expansion of the mosquito vector. Infection with any of the four serotypes of DENV can result in a self-limiting disease but debilitating febrile illness (DF), and some infections progress to severe disease with manifestations such as hemorrhage and shock. DENV infection drives the metabolic state of host cells for viral benefit and induces a host-immune response that has metabolic implications that link to disease. In this study, a dynamic metabolic response to DENV infection and disease was measured in 535 pediatric patient sera using liquid chromatography-mass spectrometry. The metabolome was interrogated to discover biochemical pathways and identify key metabolites perturbed in severe dengue disease. A biomarker panel of thirty-two perturbed metabolites was utilized to classify DF, and severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with high sensitivity and specificity equating to a balanced accuracy of 96.9%. Some metabolites that were structurally confirmed here belong to important biochemical pathways of omega-3 and omega-6 fatty acids, sphingolipids, purines, and tryptophan metabolism. A previously reported trend between serotonin and platelets in DHF patients has been expanded upon here to reveal a major depletion of serotonin, but not platelets, in DSS patients. This study differentiated and classified DF and DHF/DSS using a serum metabolic biomarker panel based on perturbed biochemical pathways that have potential implications for severe dengue disease.

One sentence summary:Metabolic biomarkers distinguish dengue hemorrhagic fever and dengue shock syndrome from dengue fever and lend insight to severe disease pathology
SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1
Authors: Dong Fangyuan , He Kang , Zhang Shan , Song Kaiyuan , Jiang Luju , Hu LiPeng , Li Qing , Zhang Xue-Li , Zhang Naiqi , Li Bo-Tai , Zhu Li-Li , Li Jun , Feng Mingxuan , Gao Yunchen , Chen Jie , Hu Xiaona , Wang Jiaofeng , Jiang Chongyi , Zhu Helen He , Da Lin-Tai , Ji Jianguang , Bao Zhijun , Jiang Shu-Heng
Published: July 2024

Although there is growing appreciation for effective repurposing of selective serotonin reuptake inhibitors (SSRIs) for cancer therapy, particularly hepatocellular carcinoma (HCC), efforts are hampered by limited knowledge of their molecular targets and mechanism of action. Global inverse gene-expression profiling method, drug affinity responsive target stability assay, and in silico molecular docking analysis was performed to identify the targets of SSRIs. Murine subcutaneous, orthotopic models, and patient-derived xenograft were employed to explore the therapeutic effects and underlying mechanisms of SSRIs in HCC. The clinical relevance of SSRI use was verified with real world data. SSRIs exhibit significant anti-HCC effects independent of their known target serotonin reuptake transporter. The glucose transporter 1 (GLUT1) is identified as a new target of SSRIs. Citalopram binds to and antagonizes GLUT1, resulting in reduced glycolytic flux and ATP generation. Mutant GLUT1 in the binding site E380 of citalopram compromises the inhibitory effects of citalopram on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth kinetics of GLUT1highliver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis of health records found that SSRIs use is associated with a lower risk of metastasis among HCC patients. Our study reveals an unprecedented role of SSRIs in cancer metabolism, and establishes a rationale for repurposing SSRIs as potential anticancer drugs for HCC.
The first complete mitochondrial genome of tjaku□a (Great Desert Skink,Liopholis kintorei)
Authors: Thuo David , Wallace Jesse , Keogh J. Scott , Macgregor Nicholas A. , Goumas Margarita , Swan Shaeleigh , Guest Tracey , Doerr Erik D. , Paltridge Rachel , Kenny Jeremy , Merson Samuel D. , Joseph Leo
Published: July 2024

The complete mitochondrial genome (mitogenome) of the tjaku□a,Liopholis kintoreiwas obtained using next-generation sequencing, making it the first recorded mitogenome of the genusLiopholisand theTiliquini. The mitogenome is 16,844bp in length with a base composition of A (31.7%), T (24.4%), G (14.6%), and C (29.3%) and a G + C content of 43.9%. The genome contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes (12S and 16S), and three non-coding fragments, consisting of the putative control region and two mitochondrially encoded heavy strand origin of replication region (OriH). The gene order is identical to that of typical skink mitogenomes. This genomic resource will provide valuable information for genetic studies of this genus and contribute to the growing collection of mitogenomes within the family Scincidae.