bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced pharmacological and pharmacokinetic evaluation of 1,3 dimethylpurine-2,6-dione derivative (GR-14) with prominent mood modulating activity in rats
Authors: Cios Agnieszka , Chłoń-Rzepa Grażyna , Jastrzębska-Więsek Magdalena , Pociecha Krzysztof , Wójcik-Pszczoła Katarzyna , Pękala Elżbieta , Wesołowska Anna
Published: November 2024

Background Research on new candidates for antidepressant/anxiolytic drugs from the group of long-chain arylpiperazines (LCAPs) containing a 1,3-dimethylpurine-2,6-dione as a terminal amide fragment fits into modern exploration trend. This study aimed to examine, for the first time in rats, pharmacodynamic (antidepressant- and anxiolytic-like) and pharmacokinetic properties of 7-(5-(4-(3-chlorophenyl)piperazin-1-yl)pentyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione hydrochloride (GR-14).
Methods Antidepressant- and anxiolytic-like activities have been conducted in the forced swim (FST) and Vogel conflict drinking tests, respectively. Pharmacokinetic characteristic of GR-14, distribution into rat tissues as well as several in vitro ADME-Tox parameters (hepatocytotoxic, neurocytotoxic, metabolic stability) have been defined.
Results GR-14 produces strong and dose-dependent antidepressant- and anxiolytic-like effects in both tests used. Pharmacokinetic findings demonstrate that GR-14 reveals linear pharmacokinetics tested after intravenous (iv) and was rapidly absorbed after oral (po) administration. It rapidly crosses the blood-brain barrier (BBB) which is vital for therapeutic effects in vivo in psychiatric diseases, depression and anxiety. Moreover, it is slowly eliminated from the brain, maintaining concentrations higher than those in plasma at the last time point measured. Further studies have also shown that GR-14 is characterized as average high clearance drug in rat liver microsomes ​​and exerts neither hepatocytotoxic or neurocytotoxic effects in vitro.
Conclusion The tested derivative GR-14 presents prominent mood modulating activity in rats, has promising pharmacokinetic parameters and a good safety profile. The beneficial pharmacology and pharmacokinetics of GR-14 in vivo are in a high concordance with its profile in vitro, thus underlining very hopeful properties to support the early development process.
Multimodal tumor suppression by METTL3 gene knockdown in melanoma and colon cancer cells
Authors: Bazargani Arezoo , Taha Masoumeh Fakhr , Soltani Bahram Mohammad , Javeri Arash
Published: November 2024

The m6A methyltransferase METTL3 is involved in regulating mRNA biogenesis, degradation and translation via N6-methyladenosine (m6A) modification. Altered m6A homeostasis is linked to development, progression, invasion and metastasis of some cancers. In the current study, we aimed to investigate the impact of METTL3 knockdown by shRNA on proliferation and invasiveness of human colorectal and melanoma cancer cell lines. A specific shRNA against METTL3 mRNA was designed and inserted into an expression vector. Highly invasive colorectal cancer cell line SW480 and melanoma cell line A375 were cultured and transfected by METTL3-shRNA and scramble-control vectors and kept under culture condition for two weeks. The cells were harvested for analysis of gene expression by qPCR, invasion assay using 3D spheroid assay and cell cycle and apoptosis analyses. In the METTL3-shRNA transfected cells, the expression of METTL3, VIM, SNAI1, SNAI2, ZEB1, CDH1 and TGFB1 genes were downregulated significantly compared to the scramble-control transfected cells. Expression of b-catenin, N-cadherin, vimentin, ZEB1, pro- and active MMP2, OCT4A, SOX2 and MYC proteins were also downregulated following METTL3 knockdown. Transfection by METTL3-shRNA reduced proliferation rate of the cells and increased the apoptotic rate significantly. Both migration and invasion rate of the cancer cells transfected with METTL3-shRNA were significantly decreased. These results have shown a pro-oncogenic role for METTL3 in colorectal and melanoma cancer cells and provided evidence that METTL3 inhibition may serve as a common approach for tumor suppression among different types of cancer although this requires further investigation.
Traumatic Pediatric Cervical Spine Injury – A Proposed Clearance Algorithm Incorporating A Novel Time Delay
Authors: Fischer Victoria E. , Mahadev Vaidehi M. , Bethel Jacob A. , Quirarte Jaime A. , Hammack Robert J. , Gragnaniello Cristian , Tarasiewicz Izabela
Published: November 2024

Purpose Pediatric cervical spine injury (pCSI) is rare. Physiological differences necessitate alternate management from adults. Yet, no standardized pediatric protocols exist. Previous investigations applying adult-validated clinical decision rules (CDRs) – Nexus Criteria (NX) and Canadian C-spine Rules (CCR) – to children are mixed. We hypothesized a combined NX+CCR approach applied at a novel 24 h timepoint would enhance screening efficacy in select patients.
Methods We conducted a retrospective review of a prospectively-collected database over 15 months at a pediatric-capable Level-1 trauma center. Age and mechanism determined initial inclusion. NX and CCR criteria were collected and retroactively applied on arrival (T0) and 24 h later (T1). Statistical analyses were performed in SPSS.
Results 306 patients met inclusion. Current practices compel computed tomography (CT) overuse for craniocervical evaluations: 298 (97.4%) underwent >1 CT. Of cervical spines imaged (n=175), 161 (92.0%) underwent CT while 74 (42.3%) underwent magnetic resonance imaging with 14 (18.9%) completed after 72 h. Of collars placed on arrival (n=181), 136 (75.1%) were cleared before discharge with 86 (63.2%) CTs denoting preferred clearance modality; CT utilization was unchanged when stratified by age < 5 years (p=0.819). Notably, we found more patients met NX+CCR criteria at T1 versus T0 (p=0.008) without missed pCSI.
Conclusion We showed incorporating a novel time delay before a second CDR reapplication may enhance screening efficacy in pCSI. Our new algorithm combines these study findings with other literature-based recommendations and thus, may represent a standardizable option for evaluating pCSI in acute trauma setting.
Free fat flap transfer in recurrent neurogenic thoracic outlet syndrome pain treatment: FIRST study
Authors: Thuau François , Gadbled Guillaume , Goronflot Thomas , Perrot Pierre , Poinas Alexandra , Lancien Ugo
Published: November 2024

Background: Neurogenic thoracic outlet syndrome (NTOS), characterized by brachial plexus compression, causes chronic pain and numbness in the upper extremities. Recurrences are common after surgical treatment, which typically includes an anterior scalenectomy and rib resection. Brachial plexus neurolysis and flap coverage can reduce scar fibrosis and prevent further recurrence. The latissimus dorsi flap is a common choice for this purpose. However, perforator fat flaps minimize donor site complications by avoiding muscle harvesting. Furthermore, a free flap transfer prevents new scars from developing in an already painful anatomical region. Given the lack of literature on this subject, we plan to use validated and recommended questionnaires to investigate the impact on pain and quality of life of brachial plexus wrapping with a free fat flap following neurolysis in cases of recurrent NTOS (R-NOS).
Methods: FIRST is a single-center, prospective observational study recruiting participants over 24 months. Eligible patients over the age of 18 are treated with brachial plexus neurolysis and a free perforator fat flap for R-NTOS. The study aims to enroll 20 patients and involves preoperative and postoperative assessments at a six-month follow-up. The primary outcome, measured using numerical scales, is pain reduction. Secondary outcomes include decreased painful body surface area, maximum and average pain levels, changes in quality of life (QoL), upper limb function, and anxiety-depressive symptoms, which are measured using various validated scales and questionnaires.
Discussion: The novelty of this study lies in its ability to provide information on the impact of free perforator fat flaps in R-NTOS treatment using validated, standardized and recommended methods of assessment for neuropathic pain, particularly considering the psychosocial impact.
Active adhesion improves adaptive flight for feathered wings
Authors: Haughn Kevin , Auletta Jeffrey , Hrynuk John , Henry Todd
Published: November 2024

Birds change the shape of their wings to adapt to dynamic environments, such as dense cities and forests. Engineers have explored using avian-informed designs with feather-based wing morphing to achieve similar capabilities with small aircraft. Unlike engineered systems, natural feathers prevent separation during morphing with microscopic features. Without a fastening mechanism, gaps can form throughout the wing, reducing the transverse force generation necessary for rapid change in flight path, thus impairing maneuverability. Here we show how active feather fastening adapts wing force and moment generation to improve maneuverability, efficiency, and stability over inactive feathers. Further, the active feathers offer a desirable relationship between velocity and these metrics, improving on, or maintaining comparable performance to, baseline rigid wings. As small aircraft are expected to fly faster, further, and with advanced aerobatic capability, feathered morphing wings incorporating electrostatic adhesion will advance aircraft adaptability for successful operation in complex environments.
Curing kinetics and thermal stability enhancement of epoxy system via co-curing with octapolyether (amine)- terminated POSS
Authors: Farhadinejad Zeinab , Karimi Majid , Ehsani Morteza
Published: November 2024

Polyhedral oligomeric silsesquioxanes (POSS) are considered as effective materials to improved mechanical and thermal properties of epoxy resins for high performance applications, but can suffer from phase separation. Herein, POSS structure was synthesized in a way which contained eight long polyether chains with amino-functional groups which was named OPEA-POSS and utilized as co-curing agent for epoxy resin. OPEA-POSS structure was characterized by Fourier Transform Infrared Spectra (FT-IR), Nuclear Magnetic Resonance spectra (1H-NMR and 13C-NMR) and Gel Permeation Chromatography (GPC). The curing kinetics was studied by Differential Scanning Calorimetry (DSC) which revealed that the curing reaction order n is 1.66 and the activation energy Ea is 58.1kJ/mol based on Kissinger-Akahira-Sunose (KAS) approach which was in reliable agreement with Kissinger method. Also DSC analysis indicated that the sample co-cured by 5wt% of OPEA-POSS was the optimal hybrid with higher cuing enthalpy than the other hybrids, and although it had lower crosslinking density, it had higher glass transition temperature (Tg) than the neat epoxy. Thermogravimetric analysis (TGA) revealed that thermal stability of OPEA-POSS/epoxy hybrid was higher than the neat epoxy, and OPEA-POSS increased the char yield from 3.5–11.55% which improved the thermal stability. Energy Dispersive X-ray analysis (EDX) along with other analysis results showed that no phase separation was occurred and the system was completely homogeneous.
Application and evaluation of carbonate apatite granules for mandibular bone defect reconstruction after jawbone cyst enucleation–A retrospective case series
Authors: Fukuda Naoyuki , Takamaru Natsumi , Akita Kazuya , Kudoh Keiko , Ishikawa Kunio , Miyamoto Youji
Published: November 2024

Purpose
To evaluate the effectiveness of CO3Ap granules in the mandibular bone defects by using computed tomography (CT) images.
Methods
This study was retrospective case series of mandibular bone defect reconstruction using CO3Ap granules. Six patients with jawbone cysts treated by simultaneous grafting CO3Ap granules after cyst enucleation were enrolled. Patients without grafting CO3Ap granules were excluded. Mandibular bone height including buccolingual bone height, the change of perpendicular distance between the buccolingual line to the alveolar ridge, and the three-dimensional volume of remaining CO3Ap granules were analyzed using CT images obtained at 3, 6, 12, 18, and 24 months postoperatively.
Results
Postoperative CT images showed that cortical and cancellous bone-like structures were formed on the grafting area periphery and inside the defect, respectively, with gradual resorption of the CO3Ap granules. Furthermore, there was no evidence of leaving bone defect even at the center of the lesion when the defect was successfully reconstructed by filling it with CO3Ap granules. The percentage volume of remaining CO3Ap granules to the volume at 3 months postoperatively were 76.1 ± 13.1%, 35.8 ± 22.5%, 25.0 ± 13.0%, and 9.9 ± 6.4% at 6, 12, 18, and 24 months postoperatively, and the volume reduction rate increased significantly within 12 months postoperatively.
Conclusion
Grafting CO3Ap granules after the enucleation of a jawbone cyst is a good reconstructive treatment option for postoperative prosthetic treatment because CO3Ap granules are gradually replaced by new bone while preserving the contour of the mandibular bone.
Impact of Air Pollutants and Meteorological Parameters on Severe Pneumonia in Older Adults
Authors: Safçi Sinem Berik , Aybal Esra , Gungor Omur
Published: November 2024

Background
This study aimed to investigate the relationship between air pollutants, weather parameters, and the characteristics and mortality of pneumonia in the older adult population.
Methods
This retrospective, observational, cross-sectional study included a total of 388 patients. Air pollutants and meteorological parameters were retrieved from official databases. Statistical tests were conducted using correlation and binary logistic regression analyses.
Results
The mean age of the 388 patients aged was 77.63 years. PSI (pneumonia severity index) was inversely correlated with nitric oxide (NO) exposure and positively correlated with ozone (O3) exposure (r = -0.199 and r = 0.313, respectively). An increase in humidity and wind speed over three days was positively correlated with PSI (r = 0.319 and r = 0.144, respectively). Increased O3 exposure during the three- and seven-day periods preceding the patient visit increased the risk of death at a similar rate (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03). Increased humidity exposure was also associated with higher mortality (OR: 1.06, 95% CI: 1.01–1.11).
Conclusion
Meteorological changes and air pollution are factors that can increase the severity and mortality risk of pneumonia in the older adult population. Increased wind speed can elevate pneumonia severity, while high O3 and humidity exposure can heighten both the severity and mortality associated with the disease.
Ethical Approval Number and Date:
This study received approval from the Ethics Committee of Adana City Research and Education Hospital with protocol number 3263 (date: March 28, 2024).
Detecting and Controlling DNA Translocation through a Nanopore using a van der Waals Heterojunction Diode
Authors: Chen Sihan , Huang Siyuan , Son Jangyup , Han Edmund , Watanabe Kenji , Taniguchi Takashi , Huang Pinshane , King William , Zande Arend van der , Bashir Rashid
Published: November 2024

A long-unrealized goal in solid-state nanopore sensing is to achieve out-of-plane electrical sensing and control of DNA during translocation, which is a prerequisite for base-by-base ratcheting that enables DNA sequencing in biological nanopores. Two-dimensional (2D) heterostructures, with their capability to construct out-of-plane electronics with atomic layer precision, are ideal yet unexplored candidates for use as electrical sensing membranes. Here we demonstrate a nanopore architecture using a vertical 2D heterojunction diode consisting of p-type WSe2 on n-type MoS2. This diode exhibits rectified interlayer tunneling currents modulated by ionic potential, while the heterojunction potential reciprocally rectifies ionic transport through the nanopore. We achieve concurrent detection of DNA translocation using both ionic and diode currents and demonstrate a 2.3-fold electrostatic slowing of translocation speed. Encapsulation layers enable robust operation while preserving the spatial resolution of atomically sharp 2D heterointerface for sensing. These results establish a paradigm for out-of-plane electrical sensing and control of single biomolecules.
Patients’ and nurses’ perceptions and experiences of a digitally enabled cardiac telerehabilitation program - a qualitative study
Authors: Braver Justin , Tsindos Tess , Carrington Melinda J , Keating Catherine , Ayton Darshini
Published: November 2024

Background. Secondary prevention cardiac rehabilitation programs are paramount to prevent cardiovascular disease morbidity and mortality. However, they remain underutilized. Digital health programs provide an opportunity for healthcare delivery by breaking down access barriers. However, evidence for their implementation is lacking. Further evidence to ascertain the drivers for uptake and acceptance of digitally enabled cardiac telerehabilitation programs is required.
Aims. To explore the perceptions and experiences of patients and their nurses enrolled in a digitally enabled cardiac telerehabilitation program, aiming to ascertain the drivers for program acceptance.
Methods. A qualitative study utilizing semi-structured telephone interviews was conducted. Researchers independently analyzed data deductively to categorise participant perceptions about the program into positive, neutral or negative. The transcripts were then reviewed inductively to code for program benefits, challenges, and recommendations for improvement.
Results. 12 out of 52 participants and 2 cardiac nurses, from across Australia, who had completed the intervention, participated in the semi-structured telephone interviews. Key benefits were the personalised nurse telehealth consultations (12/12), education aimed at maintaining learned healthy behaviours (10/12) and remote patient monitoring (5/12). However, digital connectivity was a challenge for patients. Nurses found that trust building was a challenge given there was no face-to-face care.
Conclusion. Digitally enabled cardiac telerehabilitation is well accepted by patients and their nurses. Remote monitoring in combination with personalised telehealth nurse consultations enhance patient-clinician communication and were key success factors in this model of care. Challenges with digital connectivity should be considered and addressed in future interventions. Further quantitative research is necessary to validate these findings.
Nano-Zero-Valent Iron Incorporated Acidified Activated Carbon Coupled with Persulfate Catalyst for High-Efficient Degradation of Phenol from Water
Authors: Jia Zhongqi , Hao Linlin , Liu Xianbin
Published: November 2024

Phenol is a widely utilized raw material in industrial processes, posing a significant threat to human health and aquatic ecosystems. A highly efficient persulfate (PS) catalyst was prepared for the removal of bio-refractory phenol from water. Nano-zero-valent iron (nZVI) has a high reduction potential and can effectively activate PS, but its susceptibility to agglomeration, oxidation and low electron transfer efficiency limit its application. In this study, nZVI was incorporated into activated carbon acidified with hydrochloric acid (HAC-nZVI) to improve its usability. The optimal conditions were determined as follows: the C/Fe ratio was 2:1, the dosage of HAC-nZVI was 0.5 g L− 1, the PS concentration was 5.5 mM, and the optimal initial pH was 7.0. The maximum phenol removal efficiency of over 90% was achieved within 30 min by using HAC-nZVI. The contribution of different oxidatively active species was quantified, with SO4·− and ·OH contributing 50.5% and 37.0% respectively, playing a major role in phenol removal, while O2− and 1O2 contributing 12.5%, playing a secondary role. The mechanism based on the phase transformation of Fe(0/II/III) was elucidated by using XPS and free radical analysis. The intermediate products of the phenol degradation were identified and two possible removal pathways were inferred. The toxicity prediction software indicated that the toxicity and environmental risk of the phenol intermediates in the reaction system were generally reduced.
Three-dimensional numerical simulation of the geyser phenomenon caused by entrapped air release in a baffle-drop shaft
Authors: Yang Qian , Yang Qinghua
Published: November 2024

To mitigate the structural and ground safety risks caused by the high-speed air-water mixture during the geyser process in a baffle-drop shaft, a three-dimensional (3-D) numerical model test was conducted. This study systematically examined the effects of void fraction and inlet pipe diameter on pressure and geyser intensity. It also analyzed the variation law of impact load on the baffles at the shaft bottom, and suggested the installation of a throttling orifice plate in the mid-shaft to regulate the geyser intensity. The findings indicate that the inlet pipe pressure initially decreases and then increases with rising void fraction, reaching a minimum pressure between 0.2 and 0.4. The geyser intensity reaches its maximum when the diameter ratio of the inlet pipe to the drop shaft is1:2. Additionally, the impact load on the baffle decreases continuously from the bottom to the top, with the impact load near the dividing wall and shaft wall being greater than that at the baffle edge for the same baffle. Installing an orifice plate in the mid-shaft can effectively control the geyser intensity, with the impact load on the orifice plate being ten times greater than that on the baffle load at the shaft’s bottom. These results can serve as a valuable reference for the safe design of the baffle-drop shafts.
Unbiased picture of the ligand docking process for the hevein protein–oligosaccharide complex
Authors: Yui Toshifumi , Uto Takuya
Published: November 2024

The ligand-docking behavior of hevein, the major latex protein from the rubber tree Hevea brasiliensis (Euphorbiaceae), has been investigated by the unguided molecular dynamics (MD) simulation method. An oligosaccharide molecule, initially placed in an arbitrary position, was allowed to move around hevein for a prolonged simulation time, on the order of microseconds, with the expectation of spontaneous ligand docking of the oligosaccharide molecule to the binding site of hevein. In the binary solution system consisting of a hevein molecule and a chito-trisaccharide (GlcNAc3) molecule, three out of the six separate simulation runs successfully reproduced the complex structure of the observed binding from. It appeared that the surface topology formed by two aromatic side chains of the hevein molecule played a role in orienting the GlcNAc3 molecule in the correct direction. We also performed MD simulations of the ternary solution system containing a cello-hexasaccharide (Glc6) molecule in addition to hevein and a chito-hexasaccharide (GlcNAc6) molecule. Formation of hevein–GlcNAc6 complex structures was exclusively observed, while the Glc6 molecule remained in the solvent phase throughout the simulations. Obviously, the acetamide groups of GlcNAc play a role in detecting the binding site and its vicinity on the protein surface.
Green synthesis of silver sulfide quantum dots using Artemisia dracunculus alcoholic extract and evaluation of its cytotoxic effect on HFF2 cells
Authors: Mohammadi Ali , Belbasi Mohadese , Safari Hajar , Sharafi Ali , Yazdinezhad Alireza , Danafar Hossein , mahammadiamfazli mehran
Published: November 2024

Due to their special features, quantum dots have recently attracted the attention of researchers in the fields of imaging, drug delivery, and cancer treatment. In this study, we prepared Ag2S quantum dots (QDs) intending to control the nucleus growth and reduce toxicity in Artemisia dracunculus (tarragon) extract substrate using the green synthesis method. Synthesized nanoparticles were analyzed using different characterization techniques. The DLS data analysis showed that Ag2S QDs prepared by the green synthesis method have a mean size of 56 nm, which is smaller compared to chemical synthesis. Additionally, the synthesis of Ag2S QDs with tarragon extract decreased the zeta potential from − 13 eV to -21 eV, which can be effective in enhancing colloidal stability and increasing their presence in the bloodstream. Examining the hemolysis data showed that the synthesis of Ag2S QDs with tarragon extract significantly reduces the lysis of red blood cells by modifying the surface chemistry. The cell culture data also confirmed the results of hemolysis, indicating increased cell viability with Ag2S QDs tarragon.
Dual Functionality of Schiff Base: Sensing of metal ions and Broad-Spectrum Antibacterial Effects
Authors: Alnajeebi Afnan M. , Shafie Alaa , Al-Saidi Hamed M. , Ashour Amal Adnan , Felemban Mohammed Fareed , Tayeb Faris J.
Published: November 2024

In this study, a novel Schiff base sensor (SBS) was synthesized and characterized for its dual functionality as a sensor for Ag+ and Fe3+ ions and its broad-spectrum antibacterial activity. The structural properties of the Schiff base were confirmed using fluorescence and 1H NMR spectroscopy. The sensing ability of the Schiff base was evaluated toward Hg2+, Fe3+, K+, Mg2+, Ni2+, Li+, Ca2+, Cu2+, Cr3+, Cd2+, Co2+, Na+, Ag+, and Zn2+ through fluorescence studies. Among the tested metal ions, SBS demonstrating high selectivity and sensitivity toward Ag+ and Fe3+ ions, with notable changes in fluorescence spectra upon binding. These changes were due to formation of complexes SBS-Ag+ and SBS-Fe3+. The limit of detection (LOD) was calculated to be 0.0028 ppm (0.026 µM), for Ag+ and 0.0014 ppm (0.024 µM) for Fe3+. Furthermore, the Schiff base and its metal complexes SBS-Ag+ and SBS-Fe3+ were tested for antibacterial activity against various bacterial strains. The results revealed significant enhancement in antibacterial efficacy upon coordination with Ag+ and Fe3+, indicating that the Schiff base-metal complexes exhibit superior activity compared to the free ligand. The improved biological activity is attributed to the metal coordination, which increases the lipophilicity of the complexes, facilitating their penetration into bacterial cell membranes.
Sleep medication and risk of cognitive decline in community-dwelling older adults: The YAHABA study
Authors: Sato Yuriko , Akasaka Hiroshi , Hosokawa Kazuki , Yamaguchi Takashi , Nozaki Ryota , Terauchi Takahiro , Hirai Eisuke , Sato Mitsunobu , Ishizuka Naoki , Maeda Tetsuya
Published: November 2024

The prevalence of dementia has increased in recent years, and sleep disorders are common among older adults. The purpose of this study was to clarify the association between sleep medication and cognitive function in older adults. Community-dwelling older adults were evaluated face-to-face for cognitive function and classified into normal, mild cognitive impairment, and dementia groups. Their history of sleep medication, including benzodiazepines (BZDs), Z-drugs (ZDs), and other medications, was also collected through personal interviews. Statistical analyses using trend analysis and binomial logistic regression analysis with two covariate models were performed to investigate the association between sleep medication and cognitive decline. A total of 869 participants were enrolled, and 12.5% of them were taking sleep medication. Trend analysis showed a significant association between BZD and/or ZD use and cognitive impairment (p = 0.003). Binary logistic regression analysis with multivariate adjustment showed that BZD and/or ZD users had 1.66 times higher odds ratio of cognitive decline compared with non-users (95% confidence interval: 1.07–2.56, p = 0.023). This study demonstrated that sleep medication is associated with a higher risk of cognitive decline in community-dwelling older adults. The findings are important to advance cognitive healthcare management for older adults.
Efficacy of high sensitivity c- reactive protein, Lipoprotein A and Troponin I levels in Predicting Cardiovascular Disease Severity on Coronary Angiogram- A Prospective Study
Authors: Khobragade Abhishek , Porwal Sanjay , Patted Suresh , Ambar Sameer , Prasad  , Metgudmath Vijayanand , Hesarur Vishwanath
Published: November 2024

Background:
Cardiovascular diseases (CVDs) continue to be the primary cause of death globally, significantly contributing to health deterioration and increased healthcare expenses. Annually, CVDs are responsible for more deaths than any other disease, causing approximately 17.9 million deaths, which equates to around 31% of global mortality. This study investigated the efficacy of high sensitivity c- reactive protein (hs-CRP), Lipoprotein A levels (Lipo A), and Troponin I (Trop I) levels in predicting CVD severity on coronary angiogram
Materials and Methods:
This prospective observational study included 211 patients aged 18 years and above, with a diagnosis of acute coronary syndrome (ACS), visiting the Department of Cardiology. Detailed history was recorded, and laboratory investigations included hs-CRP, Lipo A, Trop I, and Lipid Profile, and all the patients were subjected to coronary angiography. Coronary angiogram was studied and severity of CVD was noted, based on SYNTAX I and II.
Results:
The mean age of study patients was 62.82±10.17 years, with age ranging from 34 to 89 years, and majority being male (70.1%). 78.7% of patients were hypertensive and 71.6% were diabetic. Most common signs and symptom were chest pain (96.2%) and dyspnoea (87.2%). The higher levels of mean hs-CRP, Lipo A, Trop I, and LDL were significantly associated with severity of CVD on coronary angiogram (p<0.001).
Conclusion:
Higher levels of hs- CRP, Lipo A and Trop I can be a reliable predictor of severity of CVD on coronary angiograma.
An Outbreak Of Ralstonia Insidiosa In Hospitalized Children
Authors: Copana-Olmos Raul , Calderon-Lopez Maria , Ramos-Cardenas Roxana , Ledezma-Hurtado Wara , Calle-Cruz Hirma , Cano-Guzman Fatima
Published: November 2024

Introduction: Healthcare-associated infections are a public health problem, resulting in increased morbidity, mortality and costs to patients. The present study aims to analyze an in-hospital outbreak of Ralstonia insidiosa in children admitted to a pediatric referral hospital, with a focus on the control and prevention measures implemented. Methodology: An observational prospective study was conducted from the beginning of an outbreak of Ralstonia insidiosa to its end, with emphasis on the control measures implemented by a pediatric referral hospital. Results: We found 19 cases in 19 epidemiological weeks, with an attack rate of 1.76%, mainly affecting children hospitalized for more than 14 days, with invasive devices, admitted to pediatric intensive care (PICU) and with underlying disease. The clinical presentation was characterized by vomiting, fever and cough. The control of the outbreak was archived based on the installation of epidemiological and antimicrobial surveillance approach. Conclusions: We conclude that Ralstonia insidiosa is an emerging nosocomial, opportunistic and antibiotic-resistant pathogen affecting children with risk factors (invasive devices, immunocompromised and admitted to PICU), in whom it causes morbidity and mortality; furthermore, decision making based on a combined approach of epidemiological and antimicrobial surveillance with available resources can serve to control the outbreak.
The Effect of Using Topical Insulin on the Healing of Pressure Ulcers among Intensive Care Unit Patients
Authors: Qaysi Wafaa , Ghoul Ibrahim , Alshawish Eman
Published: November 2024

Background
Pressure ulcers pose significant challenges to healthcare systems, imposing a substantial burden on both patients and providers. Treatment strategies are diverse, but this study aimed to evaluate the effectiveness of topical insulin therapy in enhancing pressure ulcer healing among intensive care unit patients in Northern West Bank, Palestine.
Methods
An observational study in a Palestinian intensive care unit involved 68 patients split into two groups: one received topical insulin dressing, the other standard care. Patients were aged 18–70 with stage 2 or 3 pressure ulcers smaller than 10 cm². Exclusions included grade 1, 4, un-stage-able ulcers, insulin allergy, certain vascular diseases, pregnancy, immunodeficiency, and other conditions. The Braden Scale assessed ulcer risk on days 1, 3, 5, and 7, and the PUSH tool measured healing before and after treatment.
Results
The Insulin group had significantly better pressure ulcer healing than the Non-insulin group (p < 0.05). No significant differences were found in PUSH scores between diabetic and non-diabetic patients, gender, or blood sugar levels. Photographs confirmed these results.
Conclusion
Topical insulin is a safe, effective treatment for stage 2 and 3 pressure ulcers. Early skin assessment is recommended upon hospital admission, and further research is needed in larger populations.
Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia
Authors: Wangondu Ruth , Ashcraft Emily , Chang Ti-Cheng , Roberts Kathryn , Brady Samuel , Fan Yiping , Evans William , Relling Mary , Crews Kristine , Yang Jun , Yang Wenjian , Pounds Stanley , Wu Gang , Devidas Meenakshi , Maloney Kelly , Mattano Leonard , Schore Reuven , Angiolillo Anne , Larsen Eric , Salzer Wanda , Burke Michael , Loh Mignon , Jeha Sima , Pui Ching-Hon , Inaba Hiroto , Cheng Cheng , Mullighan Charles
Published: November 2024

Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-ALL. The relationship between the type of IKZF1 alteration, disease subtype and outcome are incompletely understood. Leukemia subtype and genomic alterations were determined using transcriptome and genomic sequencing and SNP microarray in 688 pediatric patients with B-ALL in St. Jude Total Therapy 15 and 16 studies. IKZF1 alterations were identified in 115 (16.7%) patients, most commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%). These alterations were associated with 5-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). IKZF1 deletions of exon 4-7 (P = 0.0002), genomic IKZF1plus with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adversely prognostic factors. Associations of genomic IKZF1plus and exon 4-7 deletions with adverse outcomes were confirmed in an independent cohort. Genomic IKZF1plus with any IKZF1 deletion, IKZF1 deletion of exon 4-7, and unfavorable subtype confer increased risk of relapse. The type of IKZF1 alteration, together with the subtype, are informative for risk stratification and predict response in patients with B-ALL.
Association between Echocardiographic Parameters of Cardiac Structure and Function and Mild Cognitive Impairment
Authors: Zhang Kai , Liu Xiaoxia , Huang Siyu , Liu Xinrui , Zhao Meiqi , Xue Chao , Xia Shijun , Dong Jianzeng , Kong Yu , Ma Changsheng
Published: November 2024

Background: Cardiovascular diseases (CVDs) marked with cardiac morphological or hemodynamical abnormalities are associated with mild cognitive impairment (MCI). The links between cardiac structure and function and MCI are not well understood. We aimed to explore the association between echocardiographic parameters of cardiac structure and function and MCI in CVD patients.
Methods: We conducted an age-, gender-, and education level-matched case-control study in general CVD participants with a 1:3 ratio of MCI (Montreal Cognitive Assessment [MoCA] score <26 and Mini-Mental State Examination [MMSE] score ≥24) and cognitively normal participants at a tertiary hospital in Beijing, China. The echocardiographic cardiac parameters and cognitive status were retrieved through the clinical electronic database from May 2021 to August 2023. Principal component analysis (PCA), negative binomial, and conditional multivariate regression were performed.
Results: A total of 1136 CVD participants (mean age, 61.1 ± 8.3 years) were included in the study, comprising 289 (25.3%) MCI and 847 cognitively normal participants. Compared to cognitively normal participants, MCI participants had a higher prevalence of left ventricular (LV) diastolic dysfunction (54.0% vs. 40.3%; P<0.001) and greater interventricular septal thickness (IVST) (1.04 ± 0.17 cm vs. 1.00 ± 0.20 cm; P=0.002). LV diastolic dysfunction (Beta [SE], 0.234 [0.045]; P<0.001) and IVST (Beta [SE], 0.034 [0.016]; P=0.036) were negatively correlated with the MoCA score of global cognitive function. LV diastolic dysfunction (OR, 2.03; 95% CI, 1.48-2.79; P<0.001) and IVST (OR, 1.14; 95% CI, 1.03-1.27; P=0.014) were positively associated with MCI, independent of diagnosed CVDs and the conventional MCI risk factors.
Conclusions: General CVD patients with abnormal echocardiographic LV diastolic dysfunction and IVST were associated with cognitive decline, suggesting further cognitive assessment for MCI.
Trial registration: Retrospectively registered.
A Tale of Two Mice: genetics of model mouse strains suggest a transcriptional basis for risk and resistance in idiopathic pulmonary fibrosis
Authors: Fennell Thea , Beržanskytė Ieva , Gam Rihab , Zhu Wencan , Sung Minkyung , Tandon Himani , Murray Lynne A. , Gough Julian
Published: November 2024

Background
Idiopathic pulmonary fibrosis (IPF) is a terminal inflammatory lung disease that causes permanent scarring (fibrogenesis). Bleomycin (BLM) is a drug used to induce fibrosis in mouse models, typically C57BL/6. However, meta-analyses show inter-strain heterogeneity in response, e.g. resistance in BALB/c. This study extends transcriptomic analysis of IPF to a resistant strain, qualifying inferences from the standard model and suggesting genetic risk factors to inform clinical research.
Methods
Transcriptomic datasets were generated from C57BL/6 and BALB/c mice. Test mice were administered BLM – with tissue samples sequenced from control, test, and contralateral lungs at the fibrogenesis stage of the BLM model (7–14 days after injection). Differentially expressed genes (DEGs) were calculated between treatments and strains, followed by gene network and transcription factor (TF) target enrichment analysis of DEGs. Additionally, strain-specific genetic variants were identified in fibrosis-related genes, complemented by analysing human genome-wide association (GWAS) datasets. An in vitro model of TGF𝛽-stimulated stress fibre deposition was used in parallel to confirm transcriptomic findings.
Results
DEGs calculated between treatment groups were enriched for general fibrosis-related processes across strains. Some fibrogenic processes and functional modules, however, were specifically enriched in C57BL/6, which was orthogonally validated by in vitro TGFβ assays. Conversely, the anti-fibrotic DEG Ctsk was upregulated under fibrosis in BALB/c specifically. TF target enrichment analysis of cross-strain and cross-treatment DEGs, using perturbation data, further identified them as significantly overrepresentative of FOSL1-sensitive genes. Subsequent genetic analysis revealed a non-conservative variant (P170L) located in BALB/c FOSL1. Furthermore, analysis of data from the 100,000 Genomes Project associated human FOSL1 variants with IPF.
Conclusions
Transcriptional differences in IPF have been characterised for C57BL/6 and BALB/c strains, supporting the consensus on IPF resistance in BALB/c. Analysis of gene set expression within and between strains principally implicates genes sensitive to the TF FOSL1. The significance of this novel finding is amplified by the discovery of a highly non-conservative P170L mutation in the bZIP domain of BALB/c FOSL1. Mechanistic investigation of FOSL1 activity – and potentially other regulators, e.g. Nos2, Il6 – is thus recommended as preclinical IPF research.
Characteristics, outcomes, and prognostic factors in patients with penetrating and blunt traumatic diaphragmatic injury: a nationwide retrospective cohort study in Japan
Authors: Shinjo Takafumi , Izawa Yoshimitsu , Yonekawa Chikara , Matsumura Tomohiro , Mato Takashi
Published: November 2024

Background
Traumatic diaphragmatic injury (TDI) is well-known worldwide as rare and life-threatening. However, because no nationwide cohort study of penetrating and blunt TDI has been conducted in Japan and other countries where penetrating trauma is relatively uncommon, the clinical characteristics of all TDI are unknown. Our purposes were to describe the characteristics of TDI patients, to compare penetrating TDI with blunt TDI, and to identify risk factors for mortality in Japan.
Methods
We retrospectively identified TDI patients between 2004 and 2019 using data from the Japan Trauma Data Bank. We extracted data on patient demographics, type of trauma, cause of trauma, physiological parameters, region of concomitant injury, associated injury, and management. We compared penetrating TDI and blunt TDI for each variable. The primary outcome was mortality. Multivariable logistic regression analysis was performed to identify risk factors for mortality.
Results
A total of 1147 patients (0.3%) had TDI, of which 771 were eligible for analysis (excluding 308 in cardiac arrest on arrival). Blunt TDI represented 70% and penetrating TDI 30%. In penetrating TDI, the most common cause was self-inflicted (49%), and compared to blunt TDI, males were 69% of patients (vs. 66%; P = 0.50) and the mortality rate was 8.3% (vs. 26%; P < 0.001). Multivariable analysis found that age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01–1.04), Injury Severity Score (OR 1.03, 95%CI 1.006–1.06), Revised Trauma Score (OR 0.55, 95%CI 0.45–0.67), severe concomitant abdominal injury (OR 2.45, 95%CI 1.32–4.56), severe concomitant upper extremity injury (OR 3.38, 95%CI 1.24–9.17), computed tomography (CT) (OR 0.32, 95%CI 0.15–0.69), and diaphragm repair (OR 0.44, 95%CI 0.25–0.78) were independent predictors of mortality.
Conclusions
In Japan, we found that penetrating TDI was mainly caused by self-injury and the male-female ratio was the same as for blunt TDI, although blunt TDI was much more frequent. TDI was considered highly lethal, with over 25% of patients in cardiac arrest on arrival. Our unique independent predictors were CT, severe concomitant abdominal injury, and severe concomitant upper extremity injury. These findings may help in the management of TDI in countries with less common penetrating trauma.
Efficacy and Prognostic Factors of Surgical Resection for Pulmonary Metastases from Ovarian Cancer
Authors: Tsukamoto Yo , Ohtsuka Takashi , Yamauchi Yoshikane , Mun Mingyon , Matsuguma Haruhisa , Hashimoto Hiroshi , Fukuda Hiroki , Yosihno Ichiro , Shintani Yasushi , Kawamura Masafumi
Published: November 2024

Objective:
Pulmonary metastases from ovarian cancer are rare, and the efficacy of surgical intervention is unclear. This study aimed to validate the efficacy of surgical intervention for pulmonary metastases from ovarian cancer.
Methods:
Cases were taken from the database of the Metastatic Lung Tumor Study Group of Japan from 1996 to 2021, which prospectively registers surgical cases of pulmonary metastases at participating centers. Only patients who underwent radical surgery for pulmonary metastases from ovarian cancer were included. Factors associated with overall survival (OS) were analyzed.
Results:
The analysis included 48 patients with a mean age of 53.2 years old. The 5-year overall survival rate was 69.9% (95% confidence interval [CI] 51.9–82.2%), with a median survival period of 121 months (95% CI 64–134 months). Predictors of poorer OS included preoperative extrapulmonary metastasis (Hazard ratio [HR] 5.354, 95% CI 1.248–22.97; p = 0.024), elevated preoperative tumor marker levels (HR 2.999, 95% CI 1.028–8.705; p = 0.044), and a disease-free interval of less than 24 months (HR 4.355, 95% CI 1.004–18.89; p = 0.049). On multivariable analysis, preoperative extrapulmonary metastasis remained an independent prognostic factor (HR 6.229, 95% CI 1.216–31.92; p = 0.028).
Conclusions:
This study represents the largest number of patients for assessing the resection of pulmonary metastases from ovarian cancer. Preoperative extrapulmonary metastasis serves as an adverse prognostic factor, emphasizing the need for careful consideration of surgical indications.
The impact of a low-calorie, reduced-fat diet on liver attenuation imaging: A randomized clinical trial
Authors: Li Renjie , Li Jie , He Danni , Sui Yajuan , Liu Wenfen , Li Wentao , Meng Wenyi , Peng Jiahui , Xu Zuofeng
Published: November 2024

Purpose: To investigate whether a low-calorie, reduced-fat diet affects liver Attenuation Imaging (ATI) measurements.
Methods: A total of 320 patients were enrolled in this prospective study. They were randomly assigned to four groups: a fasting group; a postprandial 0.5-hour examination group; a postprandial 2-hour examination group; and a postprandial 4-hour examination group. All participants first underwent liver ATI examination in a fasting state. Those in the postprandial groups then consumed a low-calorie, reduced-fat diet before undergoing a second ATI examination at 0.5h, 2h, or 4h after the meal, respectively. The ATI values were compared among the groups. The differences between postprandial and fasting ATI values were also analyzed for the postprandial groups. Additionally, the consistency of the grading diagnosis of hepatic steatosis between the postprandial and fasting states was evaluated in the postprandial groups.
Results: The ATI values for the postprandial 0.5h group, postprandial 2h group, and postprandial 4h group were not significantly different from the fasting group's ATI value (P = 0.576, 0.471, and 0.992, respectively). No significant differences were noted in the ATI values that were recorded during the postprandial and fasting states within each of the postprandial groups (P= 0.573, 0.076, and 0.805, respectively). The consistency of the grading diagnosis of hepatic steatosis between the postprandial and fasting states across the three postprandial groups was high according to three different diagnostic criteria.
Conclusion: Consuming a low-calorie, reduced-fat diet has no significant effects on liver ATI measurements and the grading diagnosis of hepatic steatosis.
Clinical Trial Number: (ChiCTR2200062314,August 2022)
A methodology for building a medical ontology a with a limited domain experts’ involvement
Authors: Azzi Sabrina
Published: November 2024

Ontology development is a multidisciplinary work involving domain experts and knowledge engineers. Bringing together such a team to develop an ontology of quality is not easy. Therefore, ontologies are often created with limited expertise either in the medical domain or in ontology engineering. Unfortunately, the existing methodologies do not provide much guidance on how the different steps of ontology development should be performed, particularly in the case of reduced involvement of domain experts. This challenge is getting more difficult when there is a multitude of medical knowledge sources and ontologies covering parts of the domain, and often each having a different representation of the same concept. This research presents a methodology for creating a medical ontology of quality with limited involvement of the domain experts. The latter are only consulted in the domain definition and evaluation phases. We combine building an ontology from codified knowledge and ontology reuse to enhance reusability and interoperability. The methodology is inspired by METHONTOLOGY for which we make several improvements, especially in the ontology reuse phase. We provide a proof of concept of the proposed methodology with a case study involving the development of the pneumonia diagnosis ontology (PNADO).