bluuebunny/crossref_metadata_2025 huggingface dataset:
A pharmacokinetic and safety study of oral arsenic trioxide in patients with acute promyelocytic leukemia
Authors: Ravandi Farhad , Rangaraju Sravanti , Kantarjian Hagop M , Garcia-Manero Guillermo , Yilmaz Musa , Baker Kristen , Hall Terence , Grabenstein Joy , Roy Pourab , Zamboni Beth Ann , Zamboni William , Warlick Erica , Kelly Michael , Roth David A , Ghiaur Gabriel
Published: February 2025

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). While intravenous (IV) ATO in combination with all trans retinoic acid is highly efficacious in the treatment of acute promyelocytic leukemia (APL) there remains a significant unmet need for patients due to the treatment burden associated with receiving daily ATO infusions over nearly a year of treatment and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-‑2101 and ATO IV following single- and multiple-dose administration, and the impact of food on PK for SY-2101, were evaluated in this Phase 1 study in 15 participants with APL. SY-2101 in the fasted state demonstrated comparable systemic exposure to ATO IV based on the active metabolite arsenious acid [As(III)], with geometric mean ratios (GMRs) of SY-2101 to ATO IV of 1.00 for AUC0-last and AUC0-inf. The GMR of SY-2101 to ATO IV Cmax was 0.76. This difference in Cmax was expected due to the different route of administration. Comparisons of SY-2101 in fed to fasted states also showed similar exposure and no clinically relevant differences with GMRs of AUC0-last, AUC0-inf, and Cmax of 1.08, 1.12, and 0.85, respectively, allowing for administration of SY-2101 with or without food. SY-2101 was well tolerated. The majority of adverse events were low grade. This study provides the first intrapatient PK crossover results directly comparing SY-2101 to ATO IV and supports the likelihood of clinical equivalence between the two formulations if used to treat patients with APL. NCT04996030
Women’s experience of gestational diabetes and healthcare in southern Sweden – a qualitative study
Authors: Björk Javanshiri Amanda , Modig Sara , Nymberg Peter , Calling Susanna
Published: February 2025

Background

Gestational diabetes is one of the most common pregnancy complications, affecting 14% of all pregnancies globally, and its prevalence is increasing. Gestational diabetes is associated with short and long-term complications for both the mother and their offspring, which are possible to prevent by glycemic control mainly facilitated by healthy lifestyle behaviors. Hence, women diagnosed with gestational diabetes have a significant role in disease management which can be perceived as burdensome. Previous research has well documented the psychological implications of diagnosis in the women and the need for support from healthcare. Despite the global burden of disease associated with gestational diabetes, recent qualitative studies exploring women's experiences are scarce, particularly in Sweden. Thus, highlighting a critical gap in understanding the impact of this condition and the women's experiences of diagnosis and prenatal healthcare, which this study aimed to address.

Methods

Purposive sampling was used to recruit women with previous gestational diabetes in southern Sweden. Individual interviews were held with 17 participants according to a semi-structured interview guide. The interviews were audio recorded and transcribed verbatim. Data analysis was conducted according to qualitative content analysis.

Results

The analysis generated 10 subcategories, which were grouped into three categories labeled: “experience of diagnosis”, “a complex relationship with food” and “experience of prenatal healthcare”. One theme emerged: to suddenly become a patient as opposed to an expectant mother. Most women were initially overwhelmed by the diagnosis and its consequences. They felt that healthy eating was important, despite it limiting their everyday lives, which also revealed a complicated relationship with food. Women felt supported during pregnancy but abandoned after labor. They requested additional information and emotional support from healthcare personnel, increased awareness and understanding of the treatment burden of gestational diabetes, improved person-centered care, and collaboration between healthcare providers, particularly to ensure better support in reducing future risk of disease.

Conclusions

This study provides an understanding of women’s experience of gestational diabetes and the care provided in southern Sweden. Their views could improve future care regarding both successful gestational diabetes management and post-pregnancy follow-up to prevent long-term adverse health outcomes.
Blood metabolites reflect the effect of gut microbiota on differentiated thyroid cancer: a Mendelian randomization analysis
Authors: Zhang Hanfei , Li Yuhao , Li Lin
Published: February 2025

Background

Studies have linked gut microbiome and differentiated thyroid cancer (DTC). However, their causal relationships and potential mediating factors have not been well defined. Our study investigated the causal relationships between the gut microbiome, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), as well as the mediating effect of potential blood metabolites, using genetic approaches.

Methods

Leveraging the summary statistics of gut microbial taxa, blood metabolites, PTC and FTC from the largest genome-wide association studies (GWAS) to date, we applied the bidirectional and mediation Mendelian randomization (MR) design. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal taxa. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0.

Results

After sensitivity analyses, we identified 4 taxa, 19 blood metabolites, and 5 gut bacterial pathways were causally associated with PTC. Similarly, 3 taxa, 31 blood metabolites, and 3 gut bacterial pathways were found to be causally associated with FTC, with 2 blood metabolites exhibiting bidirectional causal relationships. Metabolic pathway analysis revealed 8 significant pathways in PTC and FTC. MR-BMA analysis pinpointed species Bifidobacterium longum as the primary causal taxon for PTC and genus Bacteroides for FTC. The mediation MR analysis showed that sphingomyelin (d18:2/23:0, d18:1/23:1, d17:1/24:1) and 2-hydroxysebacate mediated the causal effects of specific gut microbiota on PTC and FTC, respectively.

Conclusion

The study suggested a causal relationship between several gut microbial taxa and DTC, and that specific blood metabolites might mediate this relationship.
Food insecurity and cardiovascular disease risk factors among U.S. adults
Authors: Royer Michael F. , Rosas Lisa G. , King Abby C.
Published: February 2025

Background

Food insecurity is an ongoing public health issue that involves limited or uncertain access to food. National rates of food insecurity among U.S. households have increased from 10.2% (~ 13,500,000 households) in 2021 to 12.8% (~ 17,000,000 households) in 2022 and most recently 13.5% (~ 18,000,000 households) in 2023. Food insecurity is associated with various health conditions and behaviors that raise the risk of cardiovascular disease (CVD). Little is known about whether the associations between food insecurity and CVD risk factors among U.S. adults differ by gender and race/ethnicity.

Methods

The 2017–2018 National Health and Nutrition Examination Survey dataset was accessed for a cross-sectional study on the associations between food insecurity and six CVD risk factors among U.S. adults. Food insecurity was measured with the 10-item Adult Food Security Survey Module. General linear models were used to analyze the associations between food insecurity and high blood pressure, high cholesterol, diabetes, cigarette smoking, sedentary time, and body mass index (BMI). Moderation analyses examined differences in the association between food insecurity and CVD risk factors by gender and race/ethnicity.

Results

Food insecurity was positively associated with high blood pressure (B = 0.104, p = 0.04), diabetes (B = 0.087, p = 0.006), and cigarette smoking (B = 0.239, p = 0.002); and food insecurity was negatively associated with sedentary time (B=-0.765, p = 0.02). Moderation analyses for gender revealed that women who were food insecure had greater BMI than men who were food insecure (B = 2.284, p = 0.02). Moderation analyses for race/ethnicity determined that, compared to White adults with food insecurity, high blood pressure rates were lower among Asian (B=-0.164, p = 0.04) and Black (B=-0.153, p = 0.04) adults with food insecurity, high cholesterol rates were greater among Latino adults with food insecurity (B = 0.168, p = 0.04), and cigarette smoking rates were lower among Black (B=-0.246, p = 0.03) and Latino (B=-0.380, p = 0.006) adults with food insecurity.

Conclusions

This research produced useful insight into how food insecurity relates to conditions and behaviors that increase CVD risk. Evidence from this study can inform both longitudinal and prevention efforts aimed at investigating food insecurity as both a harmful social determinant of health and a potential predictor of CVD risk among U.S. adults.

Trial registration

N/A.
ZEB1 expression in Th17 cells correlated with p-STAT3 in human apical periodontitis
Authors: Sun Xiaoyue , Yang Jingwen , Wang Zijun , Nie Qing , Yang Qian , Zhang Wei , Liu Mingwen , Wang Li , Zhu Lingxin
Published: February 2025

Background

ZEB1, a zinc-finger E homeobox-binding transcription factor most frequently associated with developmental programs linked to epithelial-mesenchymal transition, has been demonstrated to regulate immune cell function. The study aimed to investigate the expression pattern of ZEB1 in Th17 cells and its colocalization with p-STAT3 in human apical periodontitis lesions.

Methods

Thirty-nine human periapical tissues were collected for ex vivo study, including periapical granulomas (PGs, n = 14), radicular cysts (RCs, n = 12), and healthy control tissues (control group, n = 13). Inflammatory infiltration of the lesions was assessed using hematoxylin-eosin staining. The expression of ZEB1 was detected and analyzed by immunohistochemistry. The localization of ZEB1 in Th17 cells and its colocalization with p-STAT3 were assessed using fluorescence colocalization.

Results

ZEB1 expression was significantly higher in PGs and RCs than in the healthy control group; however no significant difference between the two groups was observed. Immunofluorescence analysis revealed that ZEB1 expression was correlated with IL17 and CD4 double-positive cells in human periapical lesions. ZEB1/ p-STAT3 double-positive cells were predominant in RCs and PGs than in the healthy control group.

Conclusions

The expression of ZEB1 was significantly elevated in PGs and RCs, and correlated with Th17 cells and p-STAT3 expression. This study revealed that ZEB1 is a potential player correlated with STAT3 activation and Th17 cells in apical periodontitis pathogenesis.
Moral distress among maternal-fetal medicine fellows: a national survey study
Authors: Ding Jia Jennifer , Vu Thi , Stammler Suzanne , Murray Peter , Epstein Elizabeth , Cross Sarah N.
Published: February 2025

Background

Moral distress, or the inability to carry out what one believes to be ethically appropriate because of constraints or barriers, is understudied in obstetrics and gynecology. We sought to characterize moral distress among Maternal-Fetal Medicine (MFM) fellows using a standardized survey.

Methods

We disseminated a national anonymized survey study of MFM fellows electronically regarding moral distress using a validated questionnaire with supplemental questions pertaining to specific challenges within MFM clinical care. Multivariable linear regression modeling was used to examine the association between abortion restrictions, maternal mortality, and moral distress, controlling for demographic variables. Thematic analysis was performed for the free text responses elaborating upon moral distress and grouped by thematic elements. We hypothesized that training in states with more abortion restrictions and higher maternal mortality would be associated with higher moral distress scores.

Results

Among 245 total responses (61% response rate), 177 complete responses (44% complete response rate) were included for analysis. Most of our respondents identified as female (78.5%), White (71.8%), and training in urban programs (83.1%). 37.9% of respondents reported training in the Northeast, with the remainder of respondents evenly distributed across the United States. The mean score for the validated questions was 85.9 ± 48.8, with female gender identity associated with higher measures of moral distress on the validated portion of the questionnaire as compared to male gender identity (90.1 ± 49.2 vs. 70.4 ± 44.7, p < 0.05), whereas more advanced training was associated with higher measures of moral distress on the supplemental questions as compared to those less advanced in training (20.9 ± 11.8 vs. 28.5 ± 15.9 vs. 25.9 ± 15.6 for PGY-5 vs. PGY-6 vs. PGY-7 and PGY-8 combined, respectively, p < 0.05). After adjustment, higher measure of moral distress on the validated questionnaire was associated with training in states designated “Abortion restrictive” as compared to “Abortion most protective” (beta estimate 27.80 and p < 0.01). Of 34 free responses, 65% referred to limitations on abortion access and reproductive justice as causes of significant moral distress.

Conclusion

MFM fellows who identify as female reported higher measures of moral distress, as well as those training in states with more abortion restrictions. Among free text respondents, abortion restrictions underlie a significant proportion of moral distress.
Short- and long-term comparative effectiveness of nirmatrelvir/ritonavir and molnupiravir in asthma patients: a cohort study
Authors: Lin Guozhang , Wei Yuchen , Guo Zihao , Wang Huwen , Chan Kate Ching Ching , Chan Renee Wan Yi , Hung Chi Tim , Jiang Xiaoting , Li Conglu , Yam Carrie Ho Kwan , Chow Tsz Yu , Wang Yawen , Zhao Shi , Li Kehang , Yang Aimin , Mok Chris Ka Pun , Hui David S. C. , Yeoh Eng Kiong , Chong Ka Chun
Published: February 2025

Background

Few studies evaluated the effectiveness of COVID-19 antivirals specifically in the asthma population This study assessed short- and long-term effects of nirmatrelvir/ritonavir versus molnupiravir in asthma population.

Methods

This is a retrospective cohort study on adult asthma patients infected with COVID-19, using real-world data obtained from the health officials in Hong Kong. Key inclusion criteria were infection with COVID-19 between March 16, 2022, and Oct 30, 2023, age ≥ 18 years, previous asthma diagnosis, and prescription history of an asthma medication. Outcomes included acute and post-acute mortality, post-acute all-cause hospitalization, and cause-specific hospitalization.

Results

1,745 patients were eligible for this study, with a median follow-up time of 365 days (IQR: 335–365). Patients in the nirmatrelvir/ritonavir group had significantly lower risks of acute inpatient death (HR, 0·27 [95% CI, 0·12 to 0·59]; p = 0·0011), post-acute inpatient death (HR, 0·49 [95% CI, 0·28 to 0·85]; p = 0·011), all-cause hospitalization (HR, 0·72 [95% CI, 0·58 to 0·89]; p = 0·0020), and myocardial infarction (HR, 0·10 [95% CI, 0·01 to 0·92]; p = 0·042) than patients in the control group. The risk of all-cause hospitalization was significantly lower in the nirmatrelvir/ritonavir group compared to the molnupiravir group (HR, 0·65 [95% CI, 0·52 to 0·81]; p = 0·00012). Among patients who were prescribed medium-/ high-dose inhaled corticosteroids, the nirmatrelvir/ritonavir group had a lower hazard of asthma exacerbation than the molnupiravir group (HR, 0·58 [95% CI, 0·35 to 0·95]; p = 0.030).

Conclusion

Compared with molnupiravir, nirmatrelvir/ritonavir may offer more benefits in reducing the risk of post-acute sequelae of COVID-19 among asthma patients. In addition, the post-acute benefits of the antivirals were also demonstrated in patients with mild asthma, which have not been generally recommended in existing clinical management guidelines.
Comprehensive evaluation of diabetes subtypes in a European cohort reveals stronger differences of lifestyle, education and psychosocial parameters compared to metabolic or inflammatory factors
Authors: Rohmann Nathalie , Epe Johannes , Geisler Corinna , Schlicht Kristina , Türk Kathrin , Hartmann Katharina , Kruse Lucy , Koppenhagen Julia , Kohestani Ahmad Yusuf , Adam Tanja , Bang Corinna , Franke Andre , Schulte Dominik M. , Hollstein Tim , Laudes Matthias
Published: February 2025

Background

The traditional binary classification of diabetes into Type 1 and Type 2 fails to capture the heterogeneity among diabetes patients. This study aims to identify and characterize diabetes subtypes within the German FoCus cohort, using the ANDIS cohort's classification framework, and to explore subtype-specific variations in metabolic markers, gut microbiota, lifestyle, social factors, and comorbidities.

Methods

We utilized data from 416 participants (208 with diabetes and 208 matched metabolically healthy controls) from the German FoCus cohort. Participants were classified into five subtypes: severe autoimmune diabetes (SAID)-like, severe insulin-deficient diabetes (SIDD)-like, severe insulin-resistant diabetes (SIRD)-like, mild obesity-related diabetes (MOD)-like, and mild age-related diabetes (MARD)-like. Comprehensive characterization included anthropometric measurements, dietary and physical activity questionnaires, blood biomarker analysis, and gut microbiota profiling.

Results

The subtype distribution in the FoCus cohort accounted to SAID-like: 2.84%, SIDD-like: 30.81%, SIRD-like: 32.23%, MOD-like: 17.54%, MARD-like: 16.59%. Of interest, inflammatory markers (C-reactive protein (CRP) and Interleukin-6 (IL-6)) and glucagon-like peptide-1 (GLP-1) levels were similarly elevated across all subtypes compared to controls, indicating common aspects in Type 2 diabetes molecular pathology despite different clinical phenotypes. While the gut microbiota and dietary patterns only showed minor differences, smoking status, sleep duration, physical activity and psychological aspects varied significantly between the subtypes. In addition, we observed a lower educational status especially for SIDD-like and SIRD-like groups, which should be considered in establishing future diabetes-related patient education programs. In respect to the development of cardio-metabolic comorbidities, we observe not only significant differences in the presence of the diseases but also for their age-of onset, highlighting the need for early preventive intervention strategies.

Conclusions

The study validates the ANDIS classification framework's applicability not only at the time point of manifestation but also in cohorts with pre-existing diabetes. While we did not find major differences regarding the classical metabolic, microbial and nutritional parameters, we identified several significant associations with lifestyle factors. Our findings underscore the importance of personalized, subtype-specific therapies not solely focusing on anthropometric and laboratory markers but comprehensively addressing the patient’s own personality and situation of life.
A qualitative study of benzodiazepine/z-drug and opioid co-use patterns and overdose risk
Authors: Family Hannah E. , Vojt Gabriele , Poulter Hannah , Bailey Chris P. , Abdala Sheikh Ana Paula , Cavallo Damiana , Karimi Sara , Booth Nick , Da Silva Peter , Aitken Louise , Stewart Samantha , Hickman Matthew , Henderson Graeme , Scott Jenny , Kesten Joanna M.
Published: February 2025

Background

Co-use of benzodiazepines and/or ‘z-drugs’ along with opioids is linked to the rise in drug related deaths (DRD) in the UK. Understanding patterns of co-use could inform harm reduction strategies for reducing DRDs. This study explored how people co-use, including dosages, timings, methods of administration, use of other substances and desired effects sought.

Methods

Forty-eight semi-structured interviews across Glasgow in Scotland (n = 28), Bristol (n = 10) and Teesside (n = 10) in England with individuals who co-use illicit and/or prescribed opioids and benzodiazepines/z-drugs were conducted. Eighteen interviews were co-facilitated with qualitatively trained local peer researchers. Interviews were analysed using the Framework method.

Results

Six co-use patterns were generated: (1) co-use to aid sleep or come down, (2) curated co-use, opioid agonist therapy (OAT) only (3) morning and evening benzodiazepine doses with opioids throughout the day (4) co-use binges (5) co-use throughout the day, (6) benzodiazepine use throughout the day plus OAT. Patterns one to three reflected more controlled co-use with a focus on self-medicating to give confidence, manage anxiety, promote sleep and come-down from cocaine/ketamine. Patterns four to six involved greater poly-drug use, and less controlled co-use with a focus on seeking euphoria (“warm glow”, “gouching out”) or oblivion (to escape untreated mental health conditions and trauma). Patterns two, three, five and six involved daily co-use. People switched between patterns depending on available resources (e.g. finances) or changes to prescriptions (opioids or benzodiazepines). Near-fatal overdoses were reported by participants across all co-use patterns. Patterns four to six were conceptualised as presenting greater overdose risk due to less controlled co-use and more extensive polydrug use.

Conclusions

The patterns identified provide opportunities for future harm reduction strategies, tailoring advice to patterns of use, updated prescribing guidance and policies, and the need for better access to mental health care, for people who co-use benzodiazepines and opioids to reduce DRDs.
The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κB pathway
Authors: Mukherjee Srimoyee , Barua Atish , Wang Luyang , Tian Bin , Moore Claire L.
Published: February 2025

Background

Macrophages are required for development and tissue repair and protect against microbial attacks. In response to external signals, monocytes differentiate into macrophages, but our knowledge of changes that promote this transition at the level of mRNA processing, in particular mRNA polyadenylation, needs advancement if it is to inform new disease treatments. Here, we identify CFIm25, a well-documented regulator of poly(A) site choice, as a novel mediator of macrophage differentiation.

Methods

CFIm25 expression was analyzed in differentiating primary human monocytes and monocytic cell lines. Overexpression and depletion experiments were performed to assess CFIm25’s role in differentiation, NF-κB signaling, and alternative polyadenylation (APA). mRNA 3’ end-focused sequencing was conducted to identify changes in poly(A) site use of genes involved in macrophage differentiation and function. Cell cycle markers, NF-κB pathway components, and their targets were examined. The role of CFIm25 in NF-κB signaling was further evaluated through chemical inhibition and knockdown of pathway regulators.

Results

CFIm25 showed a striking increase upon macrophage differentiation, suggesting it promotes this process. Indeed, CFIm25 overexpression during differentiation amplified the acquisition of macrophage characteristics and caused an earlier slowing of the cell cycle, a hallmark of this transition, along with APA-mediated downregulation of cyclin D1. The NF-κB signaling pathway plays a major role in maturation of monocytes to macrophages, and the mRNAs of null, TBL1XR1, and NFKB1, all positive regulators of NF-κB signaling, underwent 3’UTR shortening, coupled with an increase in the corresponding proteins. CFIm25 overexpression also elevated phosphorylation of the NF-κB-p65 transcription activator, produced an earlier increase in the NF-κB targets p21, Bcl-XL, ICAM1 and TNF-α, and resulted in greater resistance to NF-κB chemical inhibition. Knockdown of Tables 2 and TBL1XR1 in CFIm25-overexpressing cells attenuated these effects, reinforcing the mechanistic link between CFIm25-regulated APA and NF-κB activation. Conversely, depletion of CFIm25 hindered differentiation and led to lengthening of NFKB1, TAB2, and TBL1XR1 3’ UTRs.

Conclusions

Our study establishes CFIm25 as a key mediator of macrophage differentiation that operates through a coordinated control of cell cycle progression and NF-κB signaling. This linkage of mRNA processing and immune cell function also expands our understanding of the role of alternative polyadenylation in regulating cell signaling.
Salidroside protects against myocardial infarction via activating MIF-mediated mitochondrial quality control
Authors: You Baiyang , Zhang Jie , Yang Chuyan , Dun Yaoshan , Qi Dake , Long Yuqiong , Cheng Jing , Lin Yuan , Zhou Nanjiang , Zeng Tanghao , Dong Jie , Liu Suixin
Published: February 2025

Background

Salidroside is a potential therapeutic agent for myocardial infarction (MI), exerting therapeutic effects on macrophage migration inhibitory factor (MIF)-regulated mitochondrial quality control. Our aim was to explore the mechanism through which the MIF pathway regulates salidroside-mediated resistance to hypoxia-induced cardiomyocyte apoptosis.

Methods

Ligation surgery of the left anterior descending branch of the coronary artery was employed to establish a myocardial infarction mouse model. Salidroside at low and high doses was administered to the mice for 4 weeks after the surgery. Cardiac function was evaluated via echocardiography. Morphological changes, apoptosis, and mitochondrial damage in the myocardium were examined. For the cell experiments, cardiomyocytes were treated with salidroside under oxygen‒glucose deprivation (OGD) conditions and were either treated with recombinant MIF (rMIF) or transfected with Mif-siRNA. Subsequently, mitochondrial quality control and apoptosis were assessed.

Results

Salidroside enhanced mitochondrial quality control in MI model mice, mitigated apoptosis and improved cardiac dysfunction. Transmission electron microscopy indicated that there were fewer damaged mitochondria in the salidroside-treated mice compared with the control mice. MIF and downstream mitochondrial quality control pathways were activated in the mice treated with salidroside. Consistently, the cell experiments demonstrated that salidroside and rMIF alleviated apoptosis, improved impaired mitochondrial quality control in OGD-induced cells and activated MIF signaling in OGD-induced cells. However, these effects of salidroside were partially blocked by Mif-siRNA transfection.

Conclusion

Salidroside alleviated myocardial apoptosis and ameliorated cardiac dysfunction in MI model mice through the MIF pathway and downstream mitochondrial quality control.
Clinical and economic burden of achondroplasia in the United States: results from a retrospective, observational study
Authors: Merchant Nadia , Alvir Jose , Ericksen Paulette Negron , Loftus Jane , Cara Jose Francisco , Slade Alison , Wajnrajch Michael P. , Baker Christine L.
Published: February 2025

Background

Achondroplasia, a disease characterized by disproportionate short stature and increased morbidity, affects daily function and quality of life over the lifetime of the individual. However, data are limited on its economic impact, especially related to healthcare resource utilization (HCRU) and associated costs. This study aimed to characterize the clinical and economic impact of achondroplasia in the US relative to matched non-achondroplasia controls stratified by pediatric and adult populations.

Methods

This retrospective study used data from the IQVIA PharMetrics Plus national claims database from January 2008 to December 2021. Individuals diagnosed with achondroplasia (index event) between July 2008 and December 2020 were matched on age and sex (1:2 ratio) to non-achondroplasia controls. General comorbidities were evaluated in the pediatric and adult populations. All-cause HCRU and direct medical costs were determined for the 12-month post-index period; out-of-pocket (OOP) costs were also determined. Study variables were analyzed using descriptive statistics.

Results

A total of 530 individuals with achondroplasia (47.7% pediatric and 52.3% adults) were matched with 1,060 controls. Individuals in the achondroplasia cohort had higher overall comorbidity burdens than controls. HCRU was higher in the achondroplasia cohort relative to controls, with outpatient visits the most frequently used resource. Inpatient visits were the primary driver of mean (SD) total costs, which were 14-fold higher than controls ($28,386 [$259,858] vs $2,031 [$5,418]) in pediatric individuals, and 4-fold higher in adults $21,579 [$58,817] vs $4,951 [$13,020]); prescriptions accounted for 4.7% and 7.4% of total costs in the pediatric and adult achondroplasia cohorts, respectively. The OOP costs were approximately 3-fold higher in both pediatric and adult individuals with achondroplasia relative to controls.

Conclusions

Individuals with achondroplasia are characterized by a higher comorbidity burden and substantially higher HCRU and related costs relative to matched controls. The results also suggest that despite high HCRU and costs, individuals with achondroplasia likely are not seen by providers early enough nor are they necessarily seen by appropriate specialists, indicating a need for improved care and disease management.
TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients
Authors: Vodnjov Nina , Cerar Andraž , Maver Aleš , Peterlin Borut , Writzl Karin
Published: February 2025

Background

Titin truncating variants (TTNtv-s) are the most common genetic cause of dilated cardiomyopathy (DCM). Only rare TTNtv-s in the constitutively expressed exons of the A-band of the protein titin are associated with DCM according to the guidelines, however, studies in large cohorts of patients with DCM suggest that the region where TTNtv-s are associated with DCM is wider, extending at least into the I-band. The aim of this study was to describe the molecular pathology of TTNtv-s in Slovenian patients with cardiomyopathy and to clinically characterise the most recurrent TTNtv.

Results

We collected all TTNtv-s identified in patients with cardiomyopathy using next-generation sequencing genetic testing between 2010 and July 2024, resulting in 42 unique variants identified in 54 patients. The TTN:c.12478del variant, affecting not the A-band but the proximal I-band, specifically the cardiac-specific N2Bus region, was found to be the most recurrent variant, present in seven (11.6%) probands with DCM. Genetic characterisation revealed a probable founder origin of the variant. Clinical characterisation of these probands revealed a phenotype consistent with DCM and severely reduced left ventricular ejection fraction in all probands. Three (43%) of the probands had atrial fibrillation and/or non-sustained ventricular tachycardia. Based on literature reports and evidence supporting the pathogenicity of the TTN:c.12478del variant affecting the proximal I-band, we classified all rare TTNtv-s in constitutively expressed exons of the I-band as (likely) pathogenic. Therefore, 33 (78.6%) TTNtv-s were classified as (likely) pathogenic (13 in the I-band, affecting 19 probands and 20 in the A-band affecting 25 probands), meaning that TTNtv-s were identified in 44 genotype-positive Slovenian probands with DCM, explaining 73.3% of the molecular pathology of DCM.

Conclusion

We report an almost threefold higher diagnostic yield of TTNtv-s in probands with DCM compared to previously reported findings in cohorts of patients with DCM from other populations. We also highlight the need for screening for rare TTNtv-s in the constitutively expressed exons of the I-band and for TTN:c.12478del in patients with DCM in this geographical region.
Methods for assessing exercise fidelity in unsupervised home-based cardiovascular rehabilitation: a scoping review
Authors: Jarallah Mohammad , Withers Thomas M , Rosewilliam Sheeba , Stathi Afroditi , Greaves Colin J
Published: February 2025

Background

Home-based cardiac rehabilitation is increasingly popular for patients with cardiovascular diseases. However, this mode of rehabilitation involves unsupervised exercise, making it challenging to assess, correct, and monitor exercise fidelity (the extent to which the patient performs the exercise intended by the intervention provider). This review aimed to identify the range, validity, and acceptability of measures for assessing exercise fidelity in unsupervised, home-based cardiovascular rehabilitation.

Methods

We searched PubMed, Embase, CINAHL, Medline, and PsycINFO for studies published between 2000 and 2024 to identify observational studies, trials, and protocols published in English with a home-based cardiovascular rehabilitation intervention and at least one measure of exercise fidelity (e.g., adherence to the intended frequency, intensity, time, type, safety, progression/regression). Two reviewers selected eligible studies and extracted data, including study characteristics, exercise components, adherence definition, adherence measures, and data on measurement validity or acceptability. We conducted a narrative synthesis using a comprehensive definition of exercise fidelity, which evolved as the analysis progressed.

Results

Forty-six articles describing 41 studies were included. Exercise intensity was the most commonly measured fidelity component (38/41 studies), followed by exercise frequency (32/41 studies). Exercise intensity was mostly assessed by wearable devices (28/41 studies). Frequency of exercise was most commonly assessed subjectively using a self-reported exercise log or diary, but also (objectively) using wearable devices. Exercise quantity was most commonly assessed (in terms of time or duration) by self-reported exercise logs, diaries and wearable devices, or (in terms of steps or distance) mostly by wearable devices (pedometers, other step activity monitors). Safety was only assessed in 12/41 studies. No studies assessed progression or regression of exercise, quality of exercise (accuracy of movement) or the appropriateness of progression or regression.

Conclusions

Most studies to date have conceptualised exercise fidelity or adherence narrowly, ignoring important elements of the initial exercise prescription and many have relied on non-validated self-report measures. We present a comprehensive framework for assessing exercise fidelity, which may be useful for designing more robust assessments of exercise fidelity in home-based rehabilitation programmes.
Secure ISAC MIMO systems: exploiting interference with Bayesian Cramér–Rao bound optimization
Authors: Su Nanchi , Liu Fan , Masouros Christos , Alexandropoulos George C. , Xiong Yifeng , Zhang Qinyu
Published: February 2025

In this paper, we present a signaling design for secure integrated sensing and communication (ISAC) systems comprising a dual-functional multi-input multi-output base station that simultaneously communicates with multiple users while detecting targets present in their vicinity, which are regarded as potential eavesdroppers. In particular, assuming that the distribution of each parameter to be estimated is known a priori, we focus on optimizing the targets’ sensing performance. To this end, we derive and minimize the Bayesian Cramér–Rao bound, while ensuring certain communication quality of service by exploiting constructive interference. The latter scheme enforces that the received signals at the eavesdropping targets fall into the destructive region of the signal constellation, to deteriorate their decoding probability, thus enhancing the ISAC’s system physical layer security capability. To tackle the nonconvexity of the formulated problem, a tailored successive convex approximation method is proposed for its efficient solution. Our extensive numerical results verify the effectiveness of the proposed secure ISAC design showing that the proposed algorithm outperforms block-level precoding techniques.
LSM tree read-deletion operations optimization through the implementation of cuckoo filters
Authors: Valverde Humberto Cesar Villalta , Kim KwangSik , Kim Kisu , Kwon Jinman , Lim Jaechoon , Jun Yongjoo
Published: February 2025

This study aims to develop an LSM tree that uses two different kinds of probabilistic data structures (PDS). These two data structures are the Bloom Filters and the state-of-the-art Cuckoo Filter released in 2014 by Fan. Cuckoo filters are a perfect choice for saving space and also for deleting keys that are not needed in the algorithm so the filters are synchronized with the keys of all the SSTables. The implementation in this study of Cuckoo filters showed three main advantages (1) Keys that are deleted in the SSTables are immediately reflected in the Cuckoo Filters (2) When SSTables are merged, Cuckoo Filters are also merged by measuring its load factor for availability (3) The performance of Cuckoo Filters compared to Bloom filters after deleting and query shows better performance despite that cuckoo filters are also being updated. This approach is expected to reduce storage space and the amount of time for queries and deletions on the overall data structure. This new optimized LSM tree is expected to be implemented in HBase as future work to check its performance with a real-world database for more empirical results.
Development of modified multi-parametric CT algorithms for diagnosing clear-cell renal cell carcinoma in small solid renal masses
Authors: Jin Pengfei , Zhang Linghui , Yang Hong , Jiang Tingting , Xu Chenyang , Huang Jiehui , Zhang Zhongyu , Shi Lei , Wang Xu
Published: February 2025

Objective

To refine the existing CT algorithm to enhance inter-reader agreement and improve the diagnostic performance for clear-cell renal cell carcinoma (ccRCC) in solid renal masses less than 4 cm.

Methods

A retrospective collection of 331 patients with pathologically confirmed renal masses were enrolled in this study. Two radiologists independently assessed the CT images: in addition to heterogeneity score (HS) and mass-to-cortex corticomedullary attenuation ratio (MCAR), measured parameters included ratio of major diameter to minor diameter at the maximum axial section (Major axis / Minor axis), tumor-renal interface, standardized heterogeneity ratio (SHR), and standardized nephrographic reduction rate (SNRR). Spearman's correlation analysis was performed to evaluate the relationship between SHR and HS. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors and then CT-score was adjusted by those indicators. The diagnostic efficacy of the modified CT-scores was evaluated using ROC curve analysis.

Results

The SHR and heterogeneity grade (HG) of mass were correlated positively with the HS (R = 0.749, 0.730, all P < 0.001). Logistic regression analysis determined that the Major axis / Minor axis (> 1.16), the tumor-renal interface (> 22.3 mm), and the SNRR (> 0.16) as additional independent risk factors to combine with HS and MCAR. Compared to the original CT-score, the two CT algorithms combined tumor-renal interface and SNRR showed significantly improved diagnostic efficacy for ccRCC (AUC: 0.770 vs. 0.861 and 0.862, all P < 0.001). The inter-observer agreement for HG was higher than that for HS (weighted Kappa coefficient: 0.797 vs. 0.722). The consistency of modified CT-score was also superior to original CT-score (weighted Kappa coefficient: 0.935 vs. 0.878).

Conclusion

The modified CT algorithms not only enhanced inter-reader consistency but also improved the diagnostic capability for ccRCC in small renal masses.
Potential of Garra rufa as a novel high-temperature resistant model fish: a review on current and future approaches
Authors: Shimada Yasuhito , Aydın Baki , Kon-Nanjo Koto , Handayani Kiki Syaputri , Gultom Victor David Nico , Simakov Oleg , Fahrurrozi  , Kon Tetsuo
Published: February 2025

Garra rufa, commonly known as the “doctor fish”, is a freshwater cyprinid native to warm regions of the Middle East. Since the late twentieth century, it has been widely utilized in spas for alternative therapeutics and fish pedicures (or manicures) for dermatological diseases such as psoriasis and eczema. Owing to its unique characteristics, there is growing interest in exploring various applications of G. rufa. This review provides a comprehensive summary of the phylogenetic position, ecology, biological characteristics, and breeding methods of G. rufa, and provides insights into its use as a therapeutic fish. Notably, the ability of G. rufa to thrive in high-temperature environments exceeding 37 °C distinguishes it from other cyprinids and suggests its potential as a model for human diseases, such as human infectious diseases, and in use in cancer xenograft models for high-throughput drug screening. The ongoing genome sequencing project for G. rufa aims to elucidate the mechanisms underlying its high-temperature tolerance and offers valuable genomic resources. These efforts have resulted in significant advances in fish aquaculture, species conservation, and biomedical research.
Cauda equina syndrome: real emergency or a misnomer—prospective observational study in a tertiary care centre
Authors: Fayaz Mohsin , Chibber Sarabjit Singh , Venishetty Nagaraju , Khursheed Aizul , Chaurasia Bipin , Naseer Malik
Published: February 2025

Introduction

Cauda equina syndrome has a devastating effect on quality of life. Early diagnosis and intervention is the current practice, for better outcomes. The purpose of our study is to evaluate the influence of the timing of surgery in cauda equina syndrome outcomes.

Materials and methods

We conducted a prospective study of a cohort of patients presented with cauda equina syndrome. Based on the durations of symptoms, patients were divided into three groups less than 24 h, 24–48 h and more than 48 h. Outcomes in the form of sensations, motor power and bladder control improvements were observed at 6 months postoperatively. Statistical analysis is made in the form of percentage or Fischer’s exact p-value whichever is suitable.

Results

A total of 46 patients were included in the study. All patients have bladder symptoms at presentation. At the end of 6 months, we found that the timing of surgery or duration of symptoms does not have any correlation with outcomes.

Conclusion

Even though early surgical intervention is consensus in cauda equina syndrome, we suggest surgery as soon as pragmatically feasible but not at the expense of patient safety.
Novel synergistic antibacterial activity of meloxicam-curcumin and diclofenac-curcumin combinations against methicillin-sensitive S. aureus and E. faecium
Authors: M. Karajeh Asem , N. Alkaraki Rawan , Gaber Yasser
Published: February 2025

Background

Some nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to have antibacterial activities in different experimental settings. In the current study, the antibacterial activities of meloxicam and diclofenac were evaluated when combined with curcumin, a polyphenolic compound, against clinically relevant bacteria. The aim was to determine whether these combinations could provide a novel, synergistic approach to combat pathogenic bacteria.

Results

The minimum inhibitory concentration (MIC) values of curcumin (CCM), meloxicam (MXM), and diclofenac (DC), alone or in combination, were determined using the microdilution broth method. The CCM/MXM combination exhibited synergistic activity against a methicillin-sensitive Staphylococcus aureus (MSSA) strain which is resistant to chloramphenicol and clindamycin. It reduced MICs up to 32-fold and achieved a fractional inhibitory concentration index (FICI) of 0.28 (FICI < 0.5 indicates synergy). Synergy was also observed against a levofloxacin-resistant Enterococcus faecium (FICI = 0.5). Growth kinetics experiments confirmed these findings, with significant reductions in MSSA and E. faecium growth rates (P < 0.001 and P < 0.01, respectively). Additionally, the biofilm inhibition activity was evaluated.

Conclusion

These findings suggest that curcumin combined with meloxicam could offer a good antibacterial combination specifically for Gram-positive bacteria. This is a promising approach for topical antibacterial preparations, where high local concentrations can be achieved to combat clinical pathogenic bacteria. Further research on these combinations may support their potential as adjunct therapies for managing bacterial infections or cases of topical infection with concurrent inflammatory disorders.
Coblation-assisted endoscopic management of post-radiation choanal stenosis in cases of nasopharyngeal carcinoma
Authors: Agarwal Anushka , Marfatia Hetal , Sahai Anoushka , Choudhary Rekha , Mohapatra Prateek , Jain Anushka
Published: February 2025

Background

This study was undertaken to evaluate the effectiveness of coblation in stenosis release for rehabilitation of patients post-radiotherapy, as literature on the topic is sparse.

Materials and methods

Nine patients who underwent intensity-modulated radiotherapy for stage III–IV nasopharyngeal carcinoma and developed choanal stenosis were included. The stenosis was released using coblation and was combined with posterior septectomy followed by stenting.

Results

The use of coblation resulted in minimal intraoperative bleeding, better visualization, and minimal post-op scarring. Posterior septectomy along with stent placement helped in the maintenance of a patent nasal airway in 88.8% of patients with only one needing revision surgery. Postoperatively, patients were followed up for 1 year, and significant improvement in SNOT 22 scores was seen using the Wilcoxon sign test (p = 0.008).

Conclusion

Coblation-assisted choanal stenosis release with stenting is effective and offers better symptomatic relief, thus improving quality of life and assisting in rehabilitation.
High-dimensional compressive irregular-grid data reconstruction with a fast multidimensional singular spectrum analysis
Authors: Lin Rongzhi , Yu Siwei , Ma Jianwei , Guo Yi , Sacchi Mauricio
Published: February 2025

Spatially irregularly sampled seismic data is unavoidable due to natural obstacles or acquisition designed for compressive sensing. Seismic reconstruction aims to regularize field data and map them from an irregular acquisition grid to regular-grid coordinates. This paper proposes reconstructing high-dimensional arbitrary irregular-grid data with a fast multidimensional singular spectrum analysis (FMSSA) algorithm. The FMSSA filtering algorithm, replacing the traditional MSSA algorithm, acts as a projection operator to avoid explicitly constructing block Hankel matrices, accelerate the rank-reduction procedure, and reduce the memory load. The proposed method, the interpolated-FMSSA (I-FMSSA), can reconstruct data deployed on an irregular grid by introducing an interpolation operator adapted to connect irregular-grid observations and desired regular-grid data without losing accurate spatial coordinates information. Additionally, two commonly used Fourier-based methods for irregular-grid data reconstruction, a modified POCS algorithm and the FISTA algorithm, are used for comparison. Synthetic and real data examples show significant improvement in computational efficiency compared with the traditional I-MSSA method and improvement in reconstruction accuracy compared with the Fourier-based methods for 3D and 5D irregular-grid data reconstruction.