bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific dementia risk in known or suspected obstructive sleep apnea: a 10-year longitudinal population-based study
Authors: Braley Tiffany J , Lyu Xiru , Dunietz Galit Levi , Schulz Paul C , Bove Riley , Chervin Ronald D , Paulson Henry L , Shedden Kerby 
Published: October 2024

Abstract

Study Objectives
To evaluate sex-specific associations between known or suspected obstructive sleep apnea (OSA) and dementia risk over 10 years among older women and men.

Methods
This study included 18 815 women and men age 50+ years (dementia-free at baseline) who participated in the Health and Retirement Study (HRS), a nationally representative cohort of US adults. Presence of OSA was defined by self-reported diagnosis or key HRS items that correspond to elements of a validated OSA screening tool (STOP-Bang). Incident dementia cases were identified using a validated, HRS-based algorithm derived from objective cognitive assessments. Survey-weighted regression models based on pseudo-values were utilized to estimate sex- and age-specific differences in cumulative incidence of dementia by OSA status.

Results
Data from 18 815 adults were analyzed, of which 9% of women and 8% of men (weighted proportions) met criteria for incident dementia. Known/suspected OSA was more prevalent in men than in women (weighted proportions 68% vs. 31%). Unadjusted sex-stratified analyses showed that known/suspected OSA was associated with higher cumulative incidence of dementia across ages 60–84 years for women and men. By age 80, relative to adults without known/suspected OSA, the cumulative incidence of dementia was 4.7% higher (CI 2.8%, 6.7%) for women with known/suspected OSA, and 2.5% (CI 0.5%, 4.5%) for men with known/suspected OSA, respectively. Adjusted associations between age-specific OSA and cumulative incidence of dementia attenuated for both women and men but remained statistically significant.

Conclusions
OSA contributes to dementia risk in older adults, particularly women. This study illuminates the impact of a potentially modifiable yet frequently overlooked risk factor for dementia onset.
The effects of deep brain stimulation on sleep: a systematic review and meta-analysis
Authors: Wadhwa Aryan , Pacheco-Barrios Niels , Tripathy Shreya , Jha Rohan , Wadhwa Millen , Warren Aaron E L , Luo Lan , Rolston John D 
Published: October 2024

Abstract

Background
Deep brain stimulation (DBS) is a standard treatment for movement disorders, epilepsy, and others, yet its influence on postprocedural sleep quality remains an under-researched topic.

Study Objectives
We performed a systematic review and meta-analysis of all DBS effects on sleep.

Methods
The use of preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) was utilized. We extracted demographic data, disease type/duration, DBS target, stimulation laterality (unilateral vs bilateral), follow-up lengths, and sleep pre/post-op measurements with polysomnography or across four standard sleep scales. The Cochrane methodology for evaluating RCTs was employed using the risk of bias assessments, data synthesis, and statistical methods, including forest plots (risk ratio; M-H random effects; 95% CI).

Results
Sixty-three studies were included in the overall analysis, representing 3022 patients. In a subgroup meta-analysis of subthalamic nucleus (STN) DBS for Parkinson’s disease (PD), patients showed significant sleep improvement at three but not 12 months postoperatively with PDSS, at 12 but not 3 months with Epworth sleep scale, and at 6 months with nonmotor symptom scale. Pittsburgh sleep quality index (PSQI) showed no significant improvement in sleep at any time. Bilateral DBS showed significantly more improvement than unilateral DBS in the PSQI at 6 but not 3 months. Polysomnography showed significant sleep improvement at 1 week but not at 3 or 6 months. Most studies showed no significant sleep improvement for globus pallidus internus, centromedian thalamus, and ventral intermediate nucleus DBS.

Conclusions
STN-DBS for PD likely improves sleep; however, significant standardization in sleep scale outcome reporting and follow-up time is needed to effectively determine the target-dependent effects of DBS surgery on sleep.
Breast Milk Application as a Natural Method for Umbilical Cord Care: A Community-Label 3-Arm Pilot Clinical Trial
Authors: Alemu Bekalu Kassie , Wondimagegn Leltework Yismaw , Bazezew Yibelu , Liyeh Tewachew Muche , Muluneh Abebaw Abeje , Mihretie Gedefaye Nibret , Sema Alekaw , Endalifer Melese Linger , Azeze Getnet Gedefaw , Woldeamanuel Gashaw Garedew , Tlaye Kenean Getaneh , Lee Wing Fong , Wang Yao , Wang Chi Chiu 
Published: October 2024

Abstract

Objective
To compare the effects of human breast milk with those of chlorhexidine and the dry method on umbilical cord separation in Ethiopia.

Methods
This open-label 3-arm nonrandomized pilot clinical trial was conducted among 45 neonates (15 in each arm) with more than 630 home visits. After a standard cord cut, human breast milk, chlorhexidine, or nothing was applied once per day for 7 days. The primary outcome was the duration of cord separation, while the secondary outcomes were umbilical cord infection, neonatal fever, jaundice, feeding and breathing difficulty, and persistent crying.

Results
There were statistically significant differences in the time-to-cord separation between the human breast milk group and the chlorhexidine (P < 0.001) and dry alone (P = 0.038) groups. Compared to those of chlorhexidine, the rates of cord separation among human breast milk and the dry-alone group were 16.02, with 95% confidence intervals (3.81, 37.43; P < 0.001) and 3.15 (0.99, 10.00; P = 0.052), respectively. One (6.7%) cord site infection was observed in the dry-alone groups only.

Conclusion
This community-label study indicated that human breast milk application significantly shortened the length of umbilical cord separation time compared to chlorhexidine and dry methods. A large-scale randomized controlled trial is needed to confirm these results.

Registration
PACTR202310902873290; https://pactr.samrc.ac.za
Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Voriconazole for Predicting the Clinical Outcomes of Adult Patients with Invasive Aspergillosis
Authors: Duangpraphat Monchai , Wilson Richard C. , Rawson Timothy M. , Santimaleeworagun Wichai , Nasomsong Worapong , Holmes Alison H. , Vasikasin Vasin 
Published: October 2024

Background:
Voriconazole is the first-line therapy for invasive aspergillosis (IA). To determine the minimum inhibitory concentration of Aspergillus, a voriconazole pharmacokinetic–pharmacodynamic (PK–PD) model linked to galactomannan response was developed and evaluated, and its clinical correlation for IA treatment was elucidated.

Methods:
Adult patients with probable or definite IA and at least one serum voriconazole measurement were included. A two-compartment voriconazole PK model was linked to a previously described PD model of galactomannan response. PK and PD parameters were estimated using a nonparametric adaptive grid technique. The relationship between the ratio of voriconazole exposure that induced half-maximum galactomannan response (EC50) and the observed terminal galactomannan concentration was evaluated. The factors associated with the PK–PD parameters and mortality were also determined.

Results:
Between January 2013 and December 2022, 41 patients were prescribed voriconazole for IA. The 30-day mortality rate was 17%. A high correlation was found for the observed–predicted Bayesian posterior estimates of voriconazole and galactomannan levels. Moreover, a nonlinear relationship was identified between AUC:EC50 and terminal galactomannan. The factors associated with higher AUC:EC50 were intravenous administration and intubation. In the survival analysis, higher EC50 tended to be associated with mortality, higher AUC was significantly associated with increased mortality, and higher AUC:EC50 tended to be associated with higher mortality. After adjusting for the intravenous route, higher AUC and AUC:EC50 were not associated with mortality.

Conclusions:
Individual EC50 estimation can provide insights into in vivo host and organism responses. Elevated EC50 showed comparable and unfavorable trends to higher minimum inhibitory concentration. Thus, determining EC50 might help guide individualized target serum voriconazole levels.
Never Assume Successful Treatment of Septic Arthritis: Bacteria Isolated at Revision ACL Reconstruction 3 Years After Primary ACL Reconstruction “Successfully” Treated for Infection
Authors: Nicholas Patrick Richard Michael , Jones Mary , Williams Andy 
Published: October 2024

Abstract:
Infection after anterior cruciate ligament (ACL) reconstruction is uncommon with an incidence of between 0.1% and 2.25%. Delayed or ineffective treatment may lead to destruction of articular cartilage. Furthermore, joint stiffness may complicate recovery. As in all cases of septic arthritis, antibiotic therapy alone is inadequate, and surgical lavage and debridement of abnormal tissue are required. In approximately 85% of cases, retention of the ACL graft is possible. It is known that bacteria can lie “dormant” without causing clinically noticeable infection, especially when adhering to orthopedic implants only to reactivate later and cause clinically obvious infection. There are no reports in the literature relating to bacteria causing septic arthritis of a primary ACL reconstruction that was apparently successfully treated being isolated in subsequent revision ACL reconstruction after a new injury. Such a case is presented.

Level of Evidence:
Level IV.
The accuracy of fine-needle aspiration cytology and ultrasonography in assessing thyroid nodules in correlation with histopathology: a retrospective study
Authors: Alhajlan Mana , Al-Masabi Mohammed , Al Mansour Mohammed , Saihb Abdullah , AlAyed Salem , Alwadai Rakan , Alhamami Abdullah , Alzarra Abdullah , Almarzooq Mohammed , Ahmed Faisal 
Published: October 2024

Background:
Accurately diagnosing thyroid nodules is vital for preventing unnecessary surgeries and providing prompt therapy. Although fine-needle aspiration cytology (FNAC) and ultrasonography (US) are widely used diagnostic methods, their reliability is questioned. This study investigates the effectiveness of US and FNAC in thyroid nodule diagnosis and differentiates benign from malignant nodules in relation to final histopathological diagnosis.

Method:
A retrospective study including 307 adult patients with thyroid diseases who underwent neck US and FNAC before surgery was conducted between April 2019 and May 2023. The diagnostic efficacy of US, FNAC, and their combination usage was compared to histopathological results.

Result:
Histopathological findings revealed that 187 (61%) cases were benign, while 120 (39%) were malignant. The US features of ‘taller-than-wider’ forms and hypoechoic appearance had the highest diagnostic accuracy in characterizing malignant thyroid nodules, with 83 and 73% accuracy, respectively. The combination of US parameters demonstrated high sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 88.33, 63.10, 60.6, and 89.4%, with a statistically significant area under the ROC curve (AUC: 0.828, P<0.001) than individual parameters. FNAC’s sensitivity, specificity, PPV NPV, and accuracy in detecting malignant lesions were 50, 95, 86, 75, and 77%, respectively, with acceptable discrimination and statistical significance (AUC: 0.723, P<0.0001). The combination of US parameters and FNAC significantly improved the AUC value (AUC: 0.878, P<0.0001), sensitivity (83.33%), and specificity (79.14%). Univariate analysis showed that hypoechoic appearance, heterogenicity, large mass size (>4 cm), ‘taller-than-wider’, infiltrative margins, and microcalcifications were risk factors for malignancy in thyroid nodules and were statistically significant (all P-values <0.05).

Conclusion:
Combining US characteristics with FNAC results can afford the maximum analytical accuracy in distinguishing benign from malignant thyroid nodules. This strategy is practical due to its simplicity, minimal invasiveness, and cost-effectiveness, enabling robust management regimens and avoiding additional surgical procedures.
Misuse of External Urine Management Devices in Hospitalized Patients
Authors: Crosby Lauren , Booher Lydia 
Published: October 2024

Abstract
External urine management devices were introduced into healthcare as a novel solution to avoid indwelling urinary catheter placement and the associated urinary tract infection risk for adult patients. These devices are favored among healthcare workers and patients. However, the downstream impacts of this device can be detrimental to patient outcomes when immobility is promoted through their use. Clinical nurse specialists are the ideal team member to evaluate the introduction of new technology to promote patient-focused care over task-focused care.
A Quantitative Comparison Between Human and Artificial Intelligence in the Detection of Focal Cortical Dysplasia
Authors: Walger Lennart , Bauer Tobias , Kügler David , Schmitz Matthias H. , Schuch Fabiane , Arendt Christophe , Baumgartner Tobias , Birkenheier Johannes , Borger Valeri , Endler Christoph , Grau Franziska , Immanuel Christian , Kölle Markus , Kupczyk Patrick , Lakghomi Asadeh , Mackert Sarah , Neuhaus Elisabeth , Nordsiek Julia , Odenthal Anna-Maria , Dague Karmele Olaciregui , Ostermann Laura , Pukropski Jan , Racz Attila , von der Ropp Klaus , Schmeel Frederic Carsten , Schrader Felix , Sitter Aileen , Unruh-Pinheiro Alexander , Voigt Marilia , Vychopen Martin , von Wedel Philip , von Wrede Randi , Attenberger Ulrike , Vatter Hartmut , Philipsen Alexandra , Becker Albert , Reuter Martin , Hattingen Elke , Sander Josemir W. , Radbruch Alexander , Surges Rainer , Rüber Theodor 
Published: October 2024

Objectives
Artificial intelligence (AI) is thought to improve lesion detection. However, a lack of knowledge about human performance prevents a comparative evaluation of AI and an accurate assessment of its impact on clinical decision-making. The objective of this work is to quantitatively evaluate the ability of humans to detect focal cortical dysplasia (FCD), compare it to state-of-the-art AI, and determine how it may aid diagnostics.

Materials and Methods
We prospectively recorded the performance of readers in detecting FCDs using single points and 3-dimensional bounding boxes. We acquired predictions of 3 AI models for the same dataset and compared these to readers. Finally, we analyzed pairwise combinations of readers and models.

Results
Twenty-eight readers, including 20 nonexpert and 5 expert physicians, reviewed 180 cases: 146 subjects with FCD (median age: 25, interquartile range: 18) and 34 healthy control subjects (median age: 43, interquartile range: 19). Nonexpert readers detected 47% (95% confidence interval [CI]: 46, 49) of FCDs, whereas experts detected 68% (95% CI: 65, 71). The 3 AI models detected 32%, 51%, and 72% of FCDs, respectively. The latter, however, also predicted more than 13 false-positive clusters per subject on average. Human performance was improved in the presence of a transmantle sign (P < 0.001) and cortical thickening (P < 0.001). In contrast, AI models were sensitive to abnormal gyration (P < 0.01) or gray-white matter blurring (P < 0.01). Compared with single experts, expert-expert pairs detected 13% (95% CI: 9, 18) more FCDs (P < 0.001). All AI models increased expert detection rates by up to 19% (95% CI: 15, 24) (P < 0.001). Nonexpert+AI pairs could still outperform single experts by up to 13% (95% CI: 10, 17).

Conclusions
This study pioneers the comparative evaluation of humans and AI for FCD lesion detection. It shows that AI and human predictions differ, especially for certain MRI features of FCD, and, thus, how AI may complement the diagnostic workup.
Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function
Authors: Reddy Deepa , Lin Zhucheng , Ramanathan Sujay , Luo Xuan , Pande Richa , Tian Yuzhen , Side Christine , Barker Jacqueline M. , Sacan Ahmet , Blendy Julie A. , Ajit Seena K. 
Published: October 2024

ABSTRACTMorphine and other synthetic opioids are widely prescribed to treat pain. Prolonged morphine exposure can paradoxically enhance pain sensitivity in humans and nociceptive behavior in rodents. To better understand the molecular mechanisms underlying opioid-induced hyperalgesia, we investigated changes in miRNA composition of small extracellular vesicles (sEVs) from the serum of mice after a morphine treatment paradigm that induces hyperalgesia. We observed significant differential expression of 18 miRNAs in sEVs from morphine-treated mice of both sexes compared to controls. Several of these miRNAs were bioinformatically predicted to regulate cyclic AMP response element binding protein (CREB), a well-characterized transcription factor implicated in pain and drug addiction. We confirmed the binding and repression ofCrebmRNA by miR-155 and miR-10a. We tested if serum-derived sEVs from morphine-treated mice could elicit nociceptive behavior in naïve recipient mice. Intrathecal injection of 1 μg sEVs did not significantly impact basal mechanical and thermal threshold in naïve recipient mice. However, prophylactic 1 μg sEV administration in recipient mice resulted in faster resolution of complete Freund’s adjuvant-induced mechanical and thermal inflammatory hypersensitivity. Other behaviors assayed following administration of these sEVs were not impacted including sEV conditioned place preference and locomotor sensitization. These results indicate that morphine regulation of serum sEV composition can contribute to analgesia and suggest a potential for sEVs to be a non-opioid therapeutic intervention strategy to treat pain.
Expression-Driven Genetic Dependency Reveals Targets for Precision Medicine
Authors: Elmas Abdulkadir , Layden Hillary M. , Ellis Jacob D. , Bartlett Luke N. , Zhao Xian , Kawabata-Iwakawa Reika , Obinata Hideru , Hiebert Scott W. , Huang Kuan-lin 
Published: October 2024

AbstractCancer cells are heterogeneous, each harboring distinct molecular aberrations and are dependent on different genes for their survival and proliferation. While successful targeted therapies have been developed based on driver DNA mutations, many patient tumors lack druggable mutations and have limited treatment options. Here, we hypothesize that new precision oncology targets may be identified through “expression-driven dependency”, whereby cancer cells with high expression of a targeted gene are more vulnerable to the knockout of that gene. We introduce a Bayesian approach, BEACON, to identify such targets by jointly analyzing global transcriptomic and proteomic profiles with genetic dependency data of cancer cell lines across 17 tissue lineages. BEACON identifies known druggable genes, e.g.,BCL2, ERBB2, EGFR, ESR1, MYC, while revealing new targets confirmed by both mRNA- and protein-expression driven dependency. Notably, the identified genes show an overall 3.8-fold enrichment for approved drug targets and enrich for druggable oncology targets by 7 to 10-fold. We experimentally validate that the depletion ofGRHL2,TP63, andPAX5effectively reduce tumor cell growth and survival in their dependent cells. Overall, we present the catalog of express-driven dependency targets as a resource for identifying novel therapeutic targets in precision oncology.
Investigating the role of CpG island DNA methylation at 3’UTRs in cancer
Authors: Wilson Claire , Kanhere Aditi 
Published: October 2024

AbstractDNA methylation is one of the most important epigenetic processes that regulates gene expression. While the human genome is predominately methylated, CpG-rich regions known as CpG islands (CGIs) are unmethylated and are sites of transcriptional control. While the importance of CGI and DNA methylation at gene promoters is well understood, the significance of CGIs at 3’ untranslated regions (3’UTRs) remains largely unexplored. In this study, we characterised CGIs located within 3’UTRs and investigated their role in gene regulation. Here, we show that around 3% of CGIs (909 CGIs) are exclusively located at 3’UTR and are not associated with any nearby promoters. Importantly, 3’UTR CGIs are highly conserved, with a conservation score even higher than promoter CGI implying their importance. In contrast to promoter CGIs which are predominantly unmethylated, 3’UTR CGIs are often methylated. Genes with 3’UTR CGIs are associated with several different cancers and cancer-related signalling pathways. Moreover, 3’UTR CGIs are differentially methylated in cancers, with changes in methylation associated with changes in gene expression. Together this data suggests the importance of 3’UTR CGIs and their methylation in gene expression regulation in cancer.
Prioritization of Lung Cancer Candidate Genes using Moment of Inertia Tensor Analysis
Authors: Dwivedi Ayushi , Thippana Mallikarjuna , Manimaran P. , Vindal Vaibhav 
Published: October 2024

AbstractA variety of factors contribute to the complexity of lung cancer progression. To comprehend the disease, candidate genes must be investigated. Present study aimed to employ an alignment-free method to prioritize candidate genes based on the physicochemical properties of the amino acids. It uses the moment of inertia tensor that measures the mass distribution around an axis of rotation, to compute the rotational energy and angular momentum of amino acids in protein sequences. The computed features were compared to those of established lung cancer genes, leading to the identification of 26 candidate genes with a high degree of similarity. These genes participate in critical biological processes that regulate the mitotic cell cycle and cell development. The prognostic significance of these genes was also assessed and four genes (IL1A, CDC25C, IL4R, and TGFBR1) were found to be associated with poor survival. Additionally, the role of prioritized genes and potential drugs that target these genes in other cancer types was also examined. Our method will help to discover new biomarkers and intervention strategies for lung cancer.