bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bartonella infections are rare in blood-fed Ixodes scapularis and Ixodes pacificus ticks collected from rodents in the United States
Authors: Bai Ying , Osikowicz Lynn M. , Clark Jacoby , Foster Erik , Parise Christina , Maes Sarah , Eisen Rebecca J. 
Published: October 2024

Abstract
Background
Ixodes scapularis and Ixodes pacificus are important vectors of multiple pathogens in the United States. However, their role in transmission of Bartonella spp., which are commonly reported in rodents and fleas, has been debated. Our previous investigation on Bartonella spp. in host-seeking I. scapularis and I. pacificus showed Bartonella spp. were absent in the ticks, suggesting the two species are unlikely to contribute to Bartonella transmission. It is unclear whether the absence of Bartonella spp. in the host-seeking ticks was attributable to ticks not being exposed to Bartonella in nature or being exposed but unable to acquire or transstadially transmit the bacterium. To assess the likelihood of exposure and acquisition, we tested Ixodes spp. ticks collected from rodents for Bartonella infections.

Methods
Blood-fed I. scapularis ticks (n = 792; consisting of 645 larvae and 147 nymphs), I. pacificus ticks (n = 45, all larvae), and Ixodes angustus ticks (n = 16, consisting of 11 larvae and 5 nymphs) collected from rodents from Minnesota and Washington were tested for Bartonella spp. using a quadruplex polymerase chain reaction (PCR) amplicon next-generation sequencing approach that targets Bartonella-specific fragments on gltA, ssrA, rpoB, and groEL. In parallel, rodents and fleas collected from the same field studies were investigated to compare the differences of Bartonella distribution among the ticks, fleas, and rodents.

Results
Bartonella spp. were commonly detected in rodents and fleas, with prevalence of 25.6% in rodents and 36.8% in fleas from Minnesota; 27.9% in rodents and 45.2% in fleas from Washington. Of all tested ticks, Bartonella DNA was detected by gltA in only one larval I. scapularis tick from Minnesota.

Conclusions
The high prevalence of Bartonella spp. in rodents and fleas coupled with extremely low prevalence of Bartonella spp. in blood-fed ticks suggests that although Ixodes ticks commonly encounter Bartonella in rodents, they rarely acquire the infection through blood feeding. Notably, ticks were at various stages of feeding on rodents when they were collected. Laboratory transmission studies are needed to assess acquisition rates in fully blood-fed ticks and to assess transstadial transmission efficiency if ticks acquire Bartonella infections from feeding to repletion.

Graphical Abstract
Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome
Authors: Regmi S. , Ganguly A. , Pathak S. , Primavera R. , Chetty S. , Wang J. , Patel Shaini , Thakor A. S. 
Published: October 2024

Abstract
Background
Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a “head-to-head” comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic “signature”.

Method
This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects.

Results
When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19.

Conclusion
Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.
Advancement in Multi-omics approaches for Uterine Sarcoma
Authors: Wang Wuyang , Hu Yu , Fu Fangfang , Ren Wu , Wang Tian , Wang Shixuan , Li Yan 
Published: October 2024

AbstractUterine sarcoma (US) is a rare malignant tumor that has various pathological types and high heterogeneity in the female reproductive system. Its subtle early symptoms, frequent recurrence, and resistance to radiation and chemotherapy make the prognosis for US patients very poor. Therefore, understanding the molecular mechanisms underlying tumorigenesis and progression is essential for an accurate diagnosis and targeted therapy to improve patient outcomes. Recent advancements in high-throughput molecular sequencing have allowed for a deeper understanding of diseases through multi-omics technologies. In this review, the latest progress and future potential of multi-omics technologies in US research is examined, and their roles in biomarker discovery and their application in the precise diagnosis and treatment of US are highlighted.
Targeting NOX2 and glycolytic metabolism as a therapeutic strategy in acute myeloid leukaemia
Authors: Ijurko Carla , Romo-González Marta , Prieto-Bermejo Rodrigo , Díez-Campelo María , Vidriales María-Belén , Muntión Sandra , Sánchez-Guijo Fermín , Sánchez-Yagüe Jesús , Hernández-Hernández Ángel 
Published: October 2024

AbstractAcute myeloid leukaemia (AML) is a highly heterogeneous malignancy, with a poor 5-year overall survival rate of approximately 30%. Consequently, the search for novel therapeutic strategies is ongoing, and the identification of new vulnerabilities could accelerate progress. Oxidative stress and metabolic rewiring are established hallmarks of cancer, and recent evidence suggests that NADPH oxidases may regulate metabolism, potentially linking these two processes. Increasing research highlights the importance of NOX2 in AML, particularly its role in metabolic regulation. In this study, we investigated the effects of simultaneously inhibiting NOX2 and glycolysis in AML cells. Dual inhibition of NOX2 and glycolysis—by targeting hexokinase or lactate dehydrogenase (LDH)—significantly reduced cell proliferation, markedly impaired clonogenic potential, and induced extensive cell death in a broad panel of AML cell lines. Importantly, these findings were further validated in primary bone marrow samples derived from AML patients, where combined inhibition triggered similar potent anti-leukemic effects. Furthermore, the combined inhibition of NOX2 and LDH enhanced the efficacy of cytarabine (AraC), suggesting this approach could boost the effectiveness of conventional therapies. In an in vivo AML model, targeting NOX2 and LDH in myeloid progenitor cells delayed the onset of leukaemia and extended survival. In conclusion, our findings propose a novel therapeutic strategy for AML through the dual targeting of NOX2 and glycolysis.
The Effects of Aerobic Exercise Training on Testosterone Concentration in Individuals Who are Obese or Have Type 2 Diabetes: A Systematic Review and Meta-Analysis
Authors: Healy Rhiannon , Patten Rhiannon , Bauer Carlie , Woessner Mary N. , Bourke Matthew , Grossmann Mathis , Levinger Itamar 
Published: October 2024

Abstract
Background
Obesity and type 2 diabetes (T2D) are associated with alterations in testosterone concentrations. While evidence indicates that aerobic training can influence testosterone in healthy populations or females with hyperandrogenism, its impact in individuals with obesity or T2D remains unclear. Thus, the aim of this study was to investigate whether aerobic training can influence circulating testosterone concentrations in individuals with obesity or T2D.

Methods
EBSCOhost (CINAHL, MEDLINE, SPORTDiscus), PubMed and Embase were searched for articles published until August 2023. Eligible articles included individuals with obesity or T2D that underwent an aerobic exercise intervention with testosterone concentrations measured at baseline and post intervention. Two reviewers independently screened the seven articles included in this meta-analysis and conducted data extraction and risk of bias assessments.

Results
A total of 103 participants (62 men / 41 women) from three randomised controlled trials and four non-randomised controlled trials were included. Effect sizes were computed with random effects models. Aerobic exercise moderately increased testosterone concentrations in men (g = 0.565, 95% CI = 0.307 to 0.822, p < 0.001), but had no significant effect in women (g = -0.523, 95% CI = -1.541, 0.496, p = 0.314). Aerobic exercise had no significant effect on sex hormone-binding globulin or markers of insulin sensitivity (p > 0.05).

Conclusions
Aerobic training may be used to increase testosterone concentrations in men with obesity or T2D, but potentially has no influence in women. Given the low number of studies, further studies investigating the effect of exercise on circulating sex hormones in men and women with obesity or T2D are needed.
Sudden onset abdominal wall leakages of inguinal hernia in patients undergoing peritoneal dialysis: report of two cases with literature review
Authors: Banshodani Masataka , Kawanishi Hideki , Kajikawa Ryujiro , Shintaku Sadanori , Moriishi Misaki , Nishihara Masahiro , Tsuchiya Shinichiro 
Published: October 2024

Abstract
Background
In this report, we presented two cases of sudden onset abdominal wall leakages of inguinal hernia in patients undergoing peritoneal dialysis (PD).

Case presentation
A total of 519 patients with end-stage kidney disease underwent PD at our hospital between March 2006 and March 2023. Among them, 39 patients [7.5%; 36 men (92%); mean age, 66 years; median PD duration, 1.7 years] developed inguinal hernias, with an incidence rate of 0.85 per 100 dialysis patient-years. Two patients (0.4%; both men; age/PD duration, 65/4.6 years and 74/1.7 years) experienced sudden onset abdominal wall leakages of inguinal hernia, with a rupture rate of 0.04 per 100 dialysis patient-years. In these cases of sudden onset abdominal wall leakages, both patients underwent tension-free hernioplasty; one patient was shifted to hemodialysis due to discomfort experienced from the right groin to the thigh area, while the other patient remained on PD.

Conclusions
Clinicians should consider the possibility of sudden onset abdominal wall leakages of inguinal hernia in PD patients.
Usefulness of hot shot intermittent infusion online hemodiafiltration plus far-infrared therapy for dialysis patients with lower extremity arterial disease: a case report
Authors: Saito Makoto , Jingu Hiroomi , Oyama Yusuke , Tanaka Toshiyuki , Ohama Kazuya 
Published: October 2024

Abstract
Background
Lower extremity arterial disease (LEAD) occurs at a high frequency in dialysis patients and is associated with a poor prognosis. In recent years, intermittent infusion online hemodiafiltration (I-OHDF) combined with far-infrared therapy (FIR) has been reported as being useful in dialysis patients with LEAD. However, there are also reports of worsening of the ulcers and gangrene in some cases. Hot shot I-OHDF (HS I-OHDF), which involves intermittent infusion of heated dialysate, is reported as being more effective than conventional I-OHDF for improving the plasma refilling rate (PRR) and peripheral circulation. We report the case of a patient in whom a lower extremity ulcer healed only after we switched from I-OHDF + FIR to HS I-OHDF + FIR, and the usefulness of this treatment.

Case presentation
The patient was a 41-year-old male dialysis patient with LEAD who showed worsening of the ulcers in the lower extremity before he was switched from I-OHDF plus FIR to HS I-OHDF plus FIR; we compared the changes in the lower extremity blood flow, PRR, degree of wound healing, and subjective symptoms over time after the switch to HS I-OHDF plus FIR as compared with the values prior to the switching. As compared with the values during I-OHDF plus FIR, the lower extremity blood flow and PRR increased markedly during HS I-OHDF plus FIR. The wounds in the lower extremity improved over time during HS I-OHDF plus FIR and showed complete healing after 6 months; evaluation by visual analog scales (VASs) showed improved scores for all of fatigue, pain, coldness, and insomnia, and the patient reported improved subjective symptoms. The mechanism underlying the effectiveness of HS I-OHDF plus FIR in promoting wound healing is unknown, however, we speculated that the temperature change in the intermittent infusion solution resulted in increased blood flow in the true capillaries (resting vessels) and transfer of the nonthermal effects of FIR to more peripheral vessels.

Conclusions
This case demonstrates that combined use of HS I-OHDF with FIR can enhance the efficacy of FIR in dialysis patients with LEAD by increasing the lower extremity blood flow and PRR, which is useful for wound healing.
The potential of fibroblast growth factor-21 and adiponectin as diagnostic biomarkers for type 2 diabetes mellitus: differential levels in response to treatments
Authors: Al-Qusous Madleen Nabeel , Dwairi Rami , Hussein Rasha Mohamed 
Published: October 2024

Abstract
Background
Diabetes mellitus (DM) is a global epidemic disease affecting millions each year. Recent studies have suggested novel biomarkers that are linked to DM. This study aimed to measure the levels of fibroblast growth factor-21 (FGF-21) and adiponectin in the blood of patients with type 2 DM and to assess the variations in their levels in response to the type of treatments. The possible correlations with several biochemical parameters and the diagnostic potential of FGF-21 and adiponectin as biomarkers for DM were also investigated. Eighty subjects were classified into control, Type 2 DM patients who were treated with metformin, Type 2 DM patients who were treated with metformin + oral hypoglycemic agents (OHAs), and Type 2 DM patients who were treated with insulin + metformin + OHAs.

Results
The metformin + OHAs group and the insulin + metformin + OHAs group had higher levels of FGF-21 when compared to the control group. The metformin + OHAs also had significantly higher adiponectin levels when compared to the control or metformin groups. The serum levels of FGF-21 in the diabetic subjects were negatively correlated with LDL, direct bilirubin, albumin, and insulin levels and positively correlated with the duration of DM. However, the serum levels of adiponectin in the diabetic subjects were negatively correlated with weight while positively correlated with potassium levels. Remarkably, FGF-21 and adiponectin were effective biomarkers for diagnosing DM with a specificity of 100% and 90% and sensitivity of 52.3% and 64.5%, respectively.

Conclusion
These findings suggest that FGF-21 and adiponectin play crucial roles in DM diagnosis and prognosis and that their levels change depending on the treatment type.
Prevalence of central nervous system-active polypharmacy in a cohort of older adults in Argentina
Authors: Ferraris Augusto , Angriman Federico , Barrera Tomas , Penizzotto Paula , Faerman Sol , Rivadeneira Washington , Chiessa Alan , Mura Gaspar , Pollán Javier Alberto , Szmulewicz Alejandro G. 
Published: October 2024

Background
Central nervous system (CNS)-active polypharmacy is frequent and potentially harmful in older patients. Data on its burden outside the USA and European countries remain limited.

Aims
To estimate the period prevalence of and factors associated with out-of-hospital CNS-active polypharmacy in older adults.

Method
We used data from a cohort of out-patients aged ≥60 years affiliated to the Hospital Italiano de Buenos Aires’ health maintenance organisation on 1 January 2021. A CNS-active polypharmacy event was defined as the concurrent exposure to ≥3 CNS-active medications (i.e. antidepressants, anti-epileptics, antipsychotics, benzodiazepines, Z-drugs and opioids) through filled out-of-hospital prescriptions. We calculated the period prevalence of CNS-active polypharmacy for 2021. We identified factors associated with CNS-active polypharmacy using a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals (CI).

Results
We included 63 857 patients. Pre-existing mental health diagnoses included anxiety (21%), depressive (14%) and sleep (11%) disorders. CNS-active polypharmacy occurred in 4535 patients, for a period prevalence of 7.1% (95% CI: 6.9–7.3%). The combination of an antidepressant, an antipsychotic and a benzodiazepine accounted for 21% of the CNS-active polypharmacy events. Frontotemporal dementia (odds ratio: 14.67; 95% CI: 4.47–48.20), schizophrenia (odds ratio: 7.93; 95% CI: 4.64–13.56), bipolar disorder (odds ratio: 7.20; 95% CI: 5.45–9.50) and depressive disorder (odds ratio: 3.50; 95% CI: 3.26–3.75) were associated with CNS-active polypharmacy.

Conclusions
One in 14 adults aged 60 years and older presented out-of-hospital CNS-active polypharmacy. Future studies should evaluate measures to reduce CNS-active medication use in this population.
RRx-001 Affects Multiple Toxicities in Patients Receiving Concomitant Chemoradiation for Head and Neck Cancers: Observations of the PREVLAR Phase II Trial
Authors: Bonomi Marcelo , Blakaj D.M. , Sher David , Kabarriti Rafi , Colvett Kyle , Takiar Vinita , Bar-Ad Voichita , Goyal Sharad , Muzyka Brian , Niermann Kenneth , Abrouk Nacer , Oronsky Bryan , Reid Tony , Caroen Scott , Sonis Stephen 
Published: October 2024

PURPOSE
Phase IIa trial results suggested that RRx-001, an nucleotide-binding domain-like receptor protein 3 inhibitor and nuclear factor erythroid 2–related factor 2 activator, attenuated severe oral mucositis (SOM) in patients treated with concomitant chemoradiation (CRT) for oral cancer (OC) and oropharyngeal cancer (OPC). Given the shared pathobiology of CRT injury among other exposed tissues, we initiated a secondary analysis of reported adverse events (AEs) to assess RRx-001's potential benefit on non-SOM regimen-related toxicities.

METHODS
PREVLAR was an open-label randomized trial that has been completed and published. Patients were treated with CRT for locally advanced OC or OPC. Arms 1-3 received doses of RRx-001 twice a week beginning 2 weeks before the start of CRT. Arm 2 (n = 11) received additional RRx-001 once during weeks 2 and 5. Arm 3 (n = 13) received RRx-001 once a week for the first 6 weeks of CRT. Arm 4 (n = 10) received CRT only. Patients received standard intensity modulated radiation therapy (daily fractions of 2-2.2 Gy/minimum cumulative dose of 55 Gy) plus cisplatin. Comprehensive toxicity assessment was based on reported AEs graded using Common Terminology Criteria for Adverse Events v5.0 and categorized with the Medical Dictionary for Regulatory Activities. A two-sided Fisher's exact test was performed to compare AE incidences between RRx-001 arms and standard of care in a secondary analysis of the data. Overall false-positive rate in Fisher's exact test was controlled via Hochberg's adjustment method.

RESULTS
Compared with the control cohort, patients receiving RRx-001 demonstrated fewer AEs attributable to their CRT regimen. Statistically significant differences in AE incidences favoring RRx-001 were dependent on the RRx-001 dosing regimen.

CONCLUSION
This secondary analysis suggests that RRx-001 infusion may reduce multiple, biologically related AEs associated with a standard CRT regimen. More broadly, it suggests that it is possible that agents that effectively target central pathobiology targets may mitigate more than one toxicity.
Somatic DICER1-Mutant Benign Thyroid Nodules in Adults: A Group of Follicular Nodular Disease With Continuous Growth
Authors: Meng Lingyang , Li Haorong , Fu Yi’an , Yu Danyan , Tang Jiamin , Hu Yan , Fei Xiaochun , Yang Kaiyu , Liu Ziyuan , Peng Rongguang , Zhou Yulin , Wang Shu , Yan Jiqi , Shen Liyun , Han Rulai , Ye Lei 
Published: October 2024

Abstract

Context
Germline DICER1 mutations cause familial multinodular goiter (MNG). However, the prevalence of somatic DICER1 mutations in non-MNG benign thyroid nodules and their characteristics remain unknown.

Objective
To determine the prevalence of somatic DICER1-mutant non-MNG benign thyroid nodules and their clinicopathological, molecular, behavioral and transcriptional characteristics.

Methods
Adult-onset thyroid nodules with a pathological diagnosis were genotyped via targeted sequencing. DICER1-mutant nodules were assessed clinically and pathologically. Organoids were established to investigate follicular formation and growth. Transcriptomic analysis was conducted to evaluate transcriptional features, which were validated by immunofluorescence.

Results
Among 931 adult-onset thyroid nodules, we identified 13 benign thyroid nodules with DICER1 hotspot mutations. The majority harbored a somatic DICER1 hotspot mutation with a somatic DICER1 truncating variant. Clinically, 38.5% of the DICER1-mutant nodules exhibited substantial growth. DICER1-mutant nodules with durations longer than 2 years were substantially enlarged (P = .0448). Pathologically, all DICER1-mutant nodules were defined as thyroid follicular nodular disease (TFND). The TFND nodules with DICER1 mutations grew faster than those with wild-type DICER1. Organoid culture of a DICER1-mutant nodule revealed increased active follicular formation. Compared with the normal thyroid tissues, the DICER1-mutant nodules had similar thyroid differentiation scores, significantly higher extracellular signal-related kinase scores (P = .0141) and lower epithelial-mesenchymal transition scores (P = .0001). Moreover, the expression of genes related to follicular polarity, such as CDH16, SLC5A5, TSHR, and TPO, was downregulated in the DICER1-mutant nodules.

Conclusion
Somatic DICER1 2-hit mutations represent a notable percentage in adult patients with TFND, and DICER1-mutant benign thyroid nodules were characterized by continuous growth.