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 How do invasive predators and their native prey respond to prescribed fire?    
Darcy Watchorn
Tim S. Doherty

Darcy Watchorn

and 4 more

June 06, 2024
A document by Darcy Watchorn. Click on the document to view its contents.
Transient cortical blindness after coronary artery bypass surgery
Masood Soltanipur
Hossein Yarmohammadi

Masood Soltanipur

and 4 more

October 17, 2023
IntroductionTransient cortical blindness (TCB) is an infrequent and intriguing postoperative complication following cardiac surgery. It is characterized by the sudden and temporary loss of vision in both eyes, usually resolving within hours (1). By reporting this rare occurrence of TCB after coronary artery bypass grafting (CABG) surgery, we aim to raise awareness among clinicians and researchers about this potential complication.
Rare oto-tricho-tussia/tinnitus: a case report
Habib  Azimi
mohsen Akbaribazm

Habib Azimi

and 3 more

October 17, 2023
A document by Habib Azimi. Click on the document to view its contents.
A 23 years old patient with bilateral hypoplastic thumbs and toes: A case report.
Suaad Hamsho
Mouhammed Sleiay

Suaad Hamsho

and 4 more

October 17, 2023
A 23 years old patient with bilateral hypoplastic thumbs and toes: A case report.Suaad Hamsho, Rheumatology Department, Faculty of medicine, Damascus University, Damascus, Syria.soha.hamsho3@gmail.comMouhammed Sleiay , University of Hama, Faculty of Medicine, Hama, Syriaabdmouh1234mouhmouh@gmail.com (The corresponding author)Mohammed Alaswad , University of Hama, Faculty of Medicine, Hama, Syriadr.aswad97@gmail.comHasan Alsmodi , University of Hama, Faculty of Medicine, Hama, Syriaadda85517@gmail.comKhaled Al-Hakeem , University of Hama, Faculty of Medicine, Hama, Syriakalhkym531@gmail.com
Effects of Establishing Typical Emerging Towns in Arid Oasis on Land Use Change and R...
Qi Zhang
Junling He

Qi Zhang

and 6 more

October 17, 2023
The urbanization process is complex and lengthy, typically bringing dual changes in the socioeconomic structure and ecological environment. However, facing the arid environment and the initial urbanization, emerging towns will undergo an evolutionary process vastly different from traditional cities. This paper takes the example of a typical town, exploring the growth process under the overlapping background of arid conditions and early urbanization. The results show that the initial urbanization of towns in the hinterland of southern Xinjiang has the following characteristics: from refined agricultural planting to shrubs and bare land dominated by natural factors, and then to impervious surfaces. The pattern was complex but the transition direction was clear. Using the town establishment in 2014 as a key node, shrubland emerged as the most sensitive land type of urbanization, with a proportional increase of 142.8% from 2010 to 2015. During this period, 78% of shrubland was transferred from cropland. When analyzing the annual water yield of the town and its surrounding area, it was found that urbanization primarily manifested as increased instability in the water yield of the surrounding region. A detailed study of emerging urbanization in arid areas is crucial to prevent potential urban issues in the future and promote the healthy development of small and medium-sized towns.
Human-Wildlife Conflict in High Altitude: a case from Gaurishankar Conservation Area...
Abhinaya Pathak
Saneer Lamichhane

Abhinaya Pathak

and 18 more

October 17, 2023
The human-wildlife conflict (HWC) is a serious problem that affects both human and wildlife populations worldwide. This study investigates the prevalence and increasing trend of HWC in the Gaurishankar Conservation Area (GCA) of Nepal, with a specific focus on leopard (Panthera pardus) and Himalayan black bear (Ursus thibetanus laniger) as conflict-causing species. The study analyzes a decade of HWC data and identifies goats as the livestock most targeted by leopards. The Dolakha district of GCA experiences the highest number of conflicts, highlighting the need for mitigation measures in the area. In GCA, livestock attacks alone accounted for 85% of compensation, with the remaining 15% for human injuries. Annual attack reports have shown a significant increase, with a 33% rise year-on-year. The rule change in 2076 BS led to 57 more attacks than expected based on the previous year’s growth. While bear attacks showed no significant change post-rule alteration (t = 0.725, p = 0.5105), leopard attack reports surged from 1 to 60 annually, indicating a significant increase in reporting rates (t = 9.77, p = 0.0097). The findings emphasize the economic impact of HWC on local communities and suggest strategies such as increasing prey populations, promoting community education and awareness, enhancing alternative livelihood options such as eco-tourism, and implementing secure enclosures (corrals) to minimize conflicts and foster harmonious coexistence. This research addresses a knowledge gap in HWC in high-altitude conservation areas like the GCA, providing valuable insights for conservation stakeholders and contributing to biodiversity conservation and the well-being of both humans and wildlife. Keywords: Human-wildlife conflict; High altitude, Leopard; Himalayan black bear; Gaurishankar Conservation Area; Conservation intervention; Co-existence
A local inhibitory plasticity rule for control of neuronal firing rate and supralin...
daniel.trpevski
Jeanette Hellgren Kotaleski

Daniel Trpevski

and 2 more

February 13, 2026
Inhibitory synapses can control a neuron's firing rate and also control supralinear dendritic integration. It is not known how inhibitory synapses can learn to perform these functions using only signals available locally at the synaptic site. We study an inhibitory plasticity rule based on the Bienenstock-Cooper-Munro theory in multicompartment models of striatal projection neurons, and show that it can perform these two functions. The rule uses local voltage-gated calcium concentration in the dendrites to regulate inhibitory synaptic strength. We show that, for rate-coded inputs, the rule can achieve precise control of neuronal firing rate after changes in excitatory input rate or excitatory synaptic strength. Additionally, for sparsely-coded inputs that activate localized synaptic clusters in a single dendrite, the rule can either allow or inhibit the evoked evoked supralinear dendritic responses, or equalize their amplitude. Finally, we demonstrate the use of learning to inhibit supralinear dendritic integration for solving the nonlinear feature binding problem (NFBP), in tandem with a simple excitatory plasticity rule. We conclude by discussing why the collateral inhibitory synapses between striatal projection neurons could contribute to solving the NFBP with this plasticity rule.
Increasing periphyton biomass and cyanobacteria in alpine streams with retreating gla...
Georg Niedrist
Maria Chiara Vulcano

Georg Niedrist

and 3 more

October 17, 2023
Deglaciation in mountain catchments changes water source contributions and associated habitat conditions in usually cold and dynamic mountain rivers. Although recent research has listed consequences of glacier retreat for aquatic biodiversity, specific invertebrate and algal groups, quantitative effects on the aquatic food web structure remain poorly understood. In this study we assessed abiotic habitat conditions together with the composition and the biomass of periphyton in 5 catchments in the Central European Alps over the snow-free period and reveal significant links to declining glacier cover. We found that reduced glaciation leads to decreasing sediment concentrations and also to lower runoff, which in combination affects the stability of benthic habitats. The reduced sediment load of the rivers dominates the consequences of glacial retreat in subsequent river habitats more than the decreasing nutrient supply. Periphyton biomass in glacier-fed rivers is expected to increase with ongoing deglaciation and warming, which subsequently favors particularly diatoms and cyanobacteria. This work thus illustrates clear links between decreasing glacier cover and the identity and relevance of aquatic producers in alpine river catchments, and provides evidence for shifting resource base in terms of biomass with potential consequences for its nutritional quality.
Acute kidney injury should not be neglected: optimization of quick Pitt bacteremia sc...
Jiaqi Cai
GUANHAO ZHENG

Jiaqi Cai

and 4 more

October 17, 2023
Background: Taking the therapeutic difficulties and mortality of bloodstream infection (BSI) into consideration, it is essential to investigate other potential affecting factors on mortality in BSI patients and examine the utility of current quick Pitt bacteremia (qPitt) score for improving survival rate. Methods: Medical information from MIMIC-IV database was utilized to perform a retrospective cohort investigation. Rist factors associated with mortality were examined by multivariate logistic regression modelling. The area under the receiver operating characteristic curve (AUC) was used for assessing the discriminatory capability of prediction models. Results: In total, 1,240 eligible BSI patients were included. After adjustment of age, community-onset BSI, indwelling invasive lines and Glasgow Coma Scale (GCS) ≤ 8, acute kidney injury (AKI) was identified as a notable risk factor on 14-day mortality. Except for altered mental status, four other main components of the original qPitt were significantly associated with 14-day mortality. Hence, we established a modified qPitt (m-qPitt) by adding AKI and replacing altered mental status with GCS ≤ 8. AUC for m-qPitt and qPitt were 0.723 (95% confidence interval [CI] 0.683-0.759) and 0.708 (95% CI 0.669-0.745) in predicting 14-day mortality, respectively. Moreover, the m-qPitt also had an acceptable performance and discrimination power [0.700 (95% CI 0.666-0.732)] in predicting 28-day mortality. Conclusions: AKI was a significant influence factor on BSI patients’ survival. Compared with original qPitt, our new m-qPitt was proved to have a better predictive performance for predicting mortality in BSI patients. More studies should be carried out to validate the practicability of m-qPitt further.
Molecular comparison of Staphylococcus aureus strains based on the Tn916 transposon a...
Cesar Augusto Roque-Borda
 Hengameh Feyzbakhsh  Markhali

Cesar Augusto Roque-Borda

and 4 more

October 17, 2023
Staphylococcus aureus is a major agent of hospital-acquired infections. It has become one of the most important health problems in the world due to its potential pathogenicity and growing resistance to antimicrobial medications. The present research confirmed the presence of the tet(M) gene and the Tn916 transposon after the detection of tetracycline-resistant strains of S. aureus. The genetic polymorphism of S. aureus strains was investigated by comparing the positions of Tn916 and Shine-Dalgarno sequence. A total of 30 pathogenic strains of S. aureus were used. The strain resistance was measured against five antibiotics, including tetracycline, by using antibiotic discs. The presence of the tet(M) gene and Tn916 transposon was studied in all strains by the PCR technique. Sequence sizes between these genetic elements were also tested with specific primers of the Tn916 transposon and Shine-Dalgarno sequences. The size of the produced bands was determined. Then, the presence and absence of the bands were converted to a 0-1 binary matrix, and the phylogenic tree of these strains was drawn and clustered in the Past3 software package. All studied strains of S. aureus were resistant to tetracycline and had the tet(M) gene and the Tn916 transposon. The investigation of the distances between Tn916 and Shine-Dalgarno sequences revealed different band patterns among these strains. The phylogenetic clustering based on the PCR band pattern classified the strains that were entirely similar in terms of all antibiogram tests, tet(M), and Tn916 transposon presence into seven separate clusters, reflecting the genetic diversity and polymorphism of these strains. Our findings can be useful in the search for effective treatments against S. aureus.
The role of adenoid immune phenotype in polysensitized children with allergic rhiniti...
YOUJIN LI
Lanye Hu

YOUJIN LI

and 5 more

October 17, 2023
Background: There has been increasing interest in elucidating the relationship between adenoid hypertrophy (AH) and allergic rhinitis (AR). However, the impact of aeroallergen sensitization patterns on children concurrently experiencing AH and AR remains unclear. Methods: Patients aged 2-8 years (January 2019 to December 2022) with nasal symptoms were assessed for allergies, adenoid size and respiratory viral infection history. The levels of serum total immunoglobulin E (IgE) and specific IgE and flexible nasal endoscopy were performed. We analyzed the relationship between AH and sensitization patterns and lymphocyte subpopulations in adenoid samples using flow cytometry. Results: 5281 children were enrolled in our cohort. 56.5% of children was diagnosed with AR and 48.6% with AH. AR was more prevalent in AH children compared to nAR. Compared to non-sensitized, those with AR polysensitized to molds had a higher prevalence of AH (adjusted OR 1.61, 95%CI 1.32-1.96) and a greater occurrence of two or more respiratory viral infections, particularly in cases with adenoidectomy. In AH-AR children, adenoid tissues showed reduced frequencies and corrected absolute counts of regulatory T cells (Tregs), activated Tregs, class-switched memory B cells (CSMB), natural killer (NK) T cells and NK subpopulations compared to AH-nAR children. Polysensitization in AH-AR children correlated with lower CSMB frequencies. Conclusion: Polysensitivity to molds significantly increased the risk of AH in children with AR. Adenoids of AR children demonstrated less number of B cells, NK cells and Treg cells with an effector/memory phenotype, which was closely linked to sensitization models and respiratory viral infection, particularly concerning CSMB.
Anesthetic management of acute right heart failure in patients with pulmonary embolis...
shasha zhang
Fangeng Meng

shasha zhang

and 5 more

October 17, 2023
A document by shasha zhang. Click on the document to view its contents.
Next-Generation Cranial Nerve Stimulation and Neuromodulation Techniques: Potential a...
Kaan Ozdemir

Kaan Ozdemir

October 17, 2023
Background: Parkinson’s disease (PD) is a pervasive neurodegenerative disorder that significantly impacts the quality of life of affected individuals. Current treatment options such as pharmacological interventions and deep brain stimulation have notable limitations in their efficacy and are linked with various side effects. This review aims to examine the potential of innovative cranial nerve stimulation and neuromodulation techniques for treating PD. Methods: A comprehensive literature search was conducted using relevant keywords across major databases to identify recent advancements in cranial nerve stimulation devices, stimulation protocols, and their clinical applications for PD. The process aimed to collate information on emerging technologies, including non-invasive and minimally invasive devices, offering more targeted and personalized treatment approaches. Results: The review highlights innovative devices and stimulation protocols showing potential in PD treatment. The safety and efficacy of these techniques were compared with conventional treatments based on results from clinical trials. We analyzed the advantages and limitations of these next-generation cranial nerve stimulation and neuromodulation techniques, with a special focus on their potential to improve patient outcomes and enhance quality of life. Conclusion: Next-generation cranial nerve stimulation and neuromodulation techniques hold substantial promise for more effective and better-tolerated PD treatments. These innovative strategies potentially pave the way for novel clinical applications and improved patient care. The review also discusses translational challenges and suggests future research directions to maximize the therapeutic potential of these promising techniques in PD treatment.
Characterization of phage vB_EcoP_HC25 and its therapeutic effect on chicken colibaci...
Yueying Wang
Heping Li

Yueying Wang

and 10 more

October 17, 2023
APEC (avian pathogenic Escherichia coli) infections result in huge economic losses, the emergence of antibiotic resistance bacteria has brought enormous pressure to public health. Bacteriophage therapy has proved to be an attractive candidate for decreasing drug-resistant bacteria. In this paper, a novel Escherichia coli phage vB_EcoP_HC25 was isolated from sewage. Phage vB_EcoP_HC25 had an elongated head, and a short tail, exhibiting the typical features of the rare C3 morphotype phages. The optimal MOI of vB_EcoP_HC25 phage was 0.01, the latency of vB_EcoP_HC25 was 30 min, and approximately 60 min for the lytic phase. The lysis amount was approximately 105 PFU/cell. Phage vB_EcoP_HC25 exhibited wide pH stability (pH 5~11) and good temperature tolerance (< 60℃). In addition, the genomic analysis revealed that phage vB_EcoP_HC25 did not carry any virulence factor genes or antibiotic resistance genes. Moreover, it was found that vB_EcoP_HC25 is a promising candidate phage for biocontrol against antibiotic-resistant Escherichia coli in milk and chicken meat. In addition, the results of the mental state, behavior, serum inflammatory factors, and intestinal morphological analysis indicated that phage vB_EcoP_HC25 was effective to control colibacillosis in chicks infected with E. coli.
Comparison of dopamine release and uptake parameters across sex, species and striatal...
Lindsey Kuiper
Alyssa West

Lindsey Kuiper

and 6 more

October 17, 2023
For over three decades, fast scan cyclic voltammetry (FSCV) has been used to selectively measure neurotransmitters such as dopamine (DA) with high spatial and temporal resolution, providing detailed information about regulation of DA in the extracellular space. FSCV is an optimal method for determining concentrations of stimulus-evoked DA in brain tissue. When modeling diseases involving disturbances in DA transmission, preclinical rodent models are especially useful because of the availability of specialized tools and techniques that serve as a foundation for translational research. There is known heterogeneity in DA dynamics between and within DA-innervated brain structures and between males and females. However, systematic evaluations of sex- and species-differences across multiple areas are lacking. Therefore, using FSCV, we captured a broad range of DA dynamics across five sub-regions of the dorsal and ventral striatum of males and females of both rats and mice that reflect the functional heterogeneity of DA kinetics and dynamics within these structures. While numerous differences were found, in particular we documented a strong, consistent pattern of increased DA transporter activity in females in all of the regions surveyed. The data herein are intended to be used as a resource for further investigation of DA terminal function.
Immunometabolic stress and herbal medicines in atherosclerosis
Tianzhen Liang
Xiaofeng Xia

Tianzhen Liang

and 2 more

October 17, 2023
Atherosclerosis is a widespread illness that gravely endangers human health and is the fundamental pathological foundation of many cardiovascular and cerebrovascular diseases. The absorption and storage of oxidatively modified LDL by certain specofoc cells in immune cells, such as macrophages, causes varieties of immunooxidative processes. These processes of stress lead to plaque rupture through inflammatory processes, and then drives the development of atherosclerotic lesions. Now, the medications for the treatment of atherosclerosis are mostly lipid-lowering, anticoagulant, and thrombolytic agents, but the therapeutic outcomes are insufficient. It is determined that traditional Chinese medicine has achieved good clinical efficacy in treating atherosclerotic illnesses. However, the mechanism of TCM therapy for atherosclerosis needs to be elucidated. This paper highlights the target mechanism and structural features of traditional Chinese medicine components and compounds in controlling the connections mentioned above and then regulating atherosclerosis, hoping to propose novel techniques for treating and preventing the disease.
Deciphering the Significance of Metal Ions in the Pathogenesis of Alzheimer's Disease...
Liang JunYi
Yueyang Wang

Liang JunYi

and 6 more

October 17, 2023
Alzheimer’s disease (AD), a neurodegenerative condition, is characterized by its progressive cognitive decline, which includes memory impairment, language alterations, visuospatial challenges, and compromised executive functions. The primary pathological features of AD involve the formation of extracellular senile plaques primarily composed of β-amyloid (Aβ) and the accumulation of hyperphosphorylated tau proteins, leading to the creation of neurofibrillary tangles. With an aging global population and a lack of effective AD treatments, there is an urgent need for comprehensive AD research. Metallic elements like iron, zinc, copper, and manganese play essential roles in human development, metabolic pathways, and brain maturation. Accumulating evidence suggests that these metal ions significantly influence the development of AD, contributing to processes such as Aβ deposition, oxidative stress, neuroinflammatory responses, and disruptions in autophagy and apoptosis, among other cascading effects. Therefore, a thorough investigation into the relationship between metals and AD is crucial, not only to identify new pre-pathogenic interventions targeting metal ions but also to support the development of tailored AD treatments. This manuscript extensively explores the connection between metallic elements, specifically copper, iron, zinc, and manganese, in physiological processes and their intricate relationship with AD. It emphasizes the importance of understanding the regulation of the metal ion signaling network throughout the AD continuum to offer new perspectives and potential approaches for developing innovative metal ion modulators to combat AD. This research holds promise for addressing the global challenge of AD.
The new nomenclature by the EAACI – was drug hypersensitivity (p-i) forgotten?
Werner Pichler

Werner Pichler

October 17, 2023
The new nomenclature by the EAACI – was drug hypersensitivity (p-i) forgotten?The EAACI position paper on nomenclature by M Julel(1) is coauthored by 40 (!) scientists and addresses many old and new concepts in connection with allergic and hypersensitivity diseases with the aim to better define and categorize them. Such an undertaking must rest on solid facts and should not omit crucial findings.Immune stimulation by antigen or not? The authors are focusing on classical, antigen (protein) driven reactions, which are developing based on an interplay of dendritic cells, lymphocytes and other cells to handle an antigen and to react to it (1). Although the authors claim to include drug hypersensitivity (DH), they completely omit the fact that drugs can stimulate the immune system in an alternative, unorthodox way (“p harmacological interaction with i mmune receptors”, p-i concept)(2-4). Thereby an initial off target activity of a drug with certain structures of TCR or HLA is followed by complex immune activations, which can result in inflammatory reactions manifested as exanthems, DRESS, SJS/TEN, AGEP (2-4). Various types of p-i can occur together (3, 5).Problem of cytotoxicity : the cytotoxic functions of T cells as an own category (formerly G&C Type IVc) is omitted and handled as part of a type IVa/T1 reaction: This is problematic:Cytotoxicity plays a role in all T cell mediated DH (exanthema, DRESS, AGEP, SJS/TEN) (2, 3) and is often associated with massive eosinophilia (e.g. DRESS). Why is this so? The reason is that both, cytotoxicity and eosinophilia, do NOT arise from a classical antigen driven mechanism (3, 5). E.g., the eosinophilia in DH is not due to the development of a classical Th2/IVb reaction, but is due to a certain type of p-i, which results in massive IL-5 production (5).The unusual induction of cytotoxicity in DH includes also CD4 cells, which are the predominant cytotoxic cells in drug induced exanthema (2). Thus, cytotoxicity in DH is not restricted to CD8 and NK cells, as stated (1).Analysis of drug specific T cell clones has revealed that many are cytotoxic, but do not secrete IFNg, or vice versa, many IFNg producing T cells are not cytotoxic.New classification: The 1967 nomenclature by G&C promoted an unknown area (immunology) into the clinic; the revised version (G&C I-IV a, b, c, d; (2)) connected T cell reactions with activation of inflammatory cells and different clinical pictures and thus helped to better understand different forms of DH. The proposed new nomenclature (1) tries to combine quite different topics like immune reactivity (I-IV), disposition (V, VI) and pharmacological/toxic actions (VII). Actually, types I-IVabcd(2) were only slightly changed (→ I-IVa,b,c) in(1). Thereby the use of the same label (e.g. IVc) for different manifestations (IVc for cytotoxic reactions in(2), but neutrophilic in (1)) programs for misunderstandings.The main problem of (1) is that unorthodox immunity (p-i) was omitted, and thus DH cannot be explained or classified. As discussed (6), DH like ACD can rely on classical immunity like formation of drug/hapten protein complexes (= a new antigen) and such reactions follow G&C I-IV; But the majority of DH are due to unorthodox immune reactions (different forms of p-i(3-5)), which do NOT follow G&C! They are labelled separately (4-6), and these unorthodox immune reactions are actually the main reason why G&C needs to be revised(5, 6).In summary, although DH may not be the main interest of many allergologists, the omittance of unorthodox immune stimulations (p-i) in an official EAACI nomenclature paper, claiming to cover allergy and hypersensitivity, is not understandable. It should be clearly stated that this position paper (1) addresses only antigen reactions but not unorthodox ways of immune stimulations (DH). Surely, unorthodox immune stimulations by drugs, known since > 20 years (2), are still a difficult topic and needs education – but just ignoring these findings is no solution.Hoping that this critic is considered helpful;Best regardsWerner J PichlerADR-AC; Holligenstr 91, CH 3008 Bern, SwitzerlandP.S:The references (e.g. nr 74) do not correspond to the text; this needs to be corrected;Legend fig 5/line7: ….in a process called \southarmonization haptenation
TREATMENT OF RECURRENT PEDIATRIC MYELODYSPLASTIC SYNDROME POST HEMATOPOIETIC STEM CEL...
Franziska Wachter
Yana Pikman

Franziska Wachter

and 12 more

October 17, 2023
Introduction Survival is dismal for the 40-60% of children with MDS who relapse post allogeneic HCT1,2,3. Strategies to decrease relapse risk include use of cytoreduction prior to HCT or maintenance treatment after HCT, data on the utility of these approaches remains limited4-12. Rapid withdrawal of immune suppression or use of donor lymphocyte infusion (DLI) can enhance the graft versus leukemia effect and achieve disease control in some cases13,14. Addition of hypomethylating agents to DLI may provide additional benefit15 and second HCT should be considered16-21. While several novel therapies may alter the future landscape of MDS therapy22-28 (Table 1), the optimal approach to relapsed pediatric MDS remains unclear. We report the management of a child who relapsed less than 70 days after initial HCT. Our approach demonstrates that multimodal therapy may permit prolonged survival with excellent quality of life (QOL) despite lack of long-term cure.
Rituximab-induced psoriasis in a patient with pemphigus vulgaris: A case report and l...
Leila Ghadirzade
Shima Moslemi Haghighi

Leila Ghadirzade

and 3 more

October 17, 2023
IntroductionPsoriasis and pemphigus are two chronic inflammatory immune mediated cutaneous disorders. Rituximab (MabThera, Rituxan) is a chimeric murine/human anti-CD20 monoclonal antibody known as a potential drug for treatment of pemphigus vulgaris. It is administrated via intravenous infusion (1). Here we present a case of a 48-years-old patient affected with pemphigus vulgaris and developed psoriatic plaques on her scalp, trunk and arms four months after the second course of rituximab.
The Prevalence of Polypharmacy In Older Europeans: A Multi-country Database Study of...
Marion Bennie
Yared Santa-Ana-Tellez

Marion Bennie

and 12 more

October 17, 2023
Aim: To measure the prevalence of polypharmacy and describe the prescribing of potentially inappropriate medication (PIM) in older people with polypharmacy in primary care. Methods: A multi-country retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain, UK. We used anonymized longitudinal patient level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9, and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. PIM defined: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the health care context to interpret findings. Results: Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The health care context information explained possible underreporting for PIM. Conclusion: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worrying high usage of PIM (PPIs and benzodiazepines) supports current efforts to improve polypharmacy management across Europe.
A reconfigurable DNA framework nanotube-assisted antiangiogenic therapy for effective...
Wei Li
Zhongliang Wang

Wei Li

and 11 more

October 17, 2023
With the burgeoning development of antiangiogenic therapy, various of antiangiogenic drugs have been developed and applied to cancer treatment. Nonetheless, for antiangiogenic drugs, the confined tumor targeting ability as well as the nonspecific bio-distribution often compromises the therapeutic outcome and causes serious multi-organ injury. In this study, we programme a reconfigurable DNA framework nanotube (rDFN) for manageable delivery of antiangiogenic drugs to minimize their damage to normal tissues. The fastened tubular structure of rDFN circumvented the direct expose of cargo endostar (Endo), a China Food and Drug Administration-approved antiangiogenic drug, to normal tissues. Meanwhile, the outside bedeck of rDFN with AS1411, a specific DNA aptamer for tumor-overexpressed nucleolin, conferred the encased Endo with greater tumor-targeting ability. Upon entry into tumor sites, nucleolin-responsive fasteners would be opened, allowing the controlled release of Endo. Based on the protective loading and activable unloading of Endo, an amplified anti-tumor effect and a reduced multi-organ injury were concurrently achieved. Conclusively, our work opens a new avenue for reducing antiangiogenic therapy-induced multi-organ injury.
Dynamic Restoration Electricity Price Optimization Method to Enhance the Resilience o...
Hongkun Wang
yu jie Gao

Hongkun Wang

and 4 more

October 17, 2023
Resilience is one of the main features of smart distribution network, and a microgrid access to the distribution network provides an effective way to improve resilience. Microgrid and distribution network belong to different interests, so it is necessary to use price leverage to actively guide microgrids and flexible resources within microgrid to participate in post-disaster restoration of distribution network and enhance the resilience. Firstly, this paper proposes a dynamic restoration electricity price response mechanism for distribution network after extreme disasters and constructs a power response model for loads and electric vehicles within the microgrid. Secondly, the optimal scheduling model of distribution network with multiple-microgrid is proposed to improve the restoration rate of critical loads(RRCL) in the distribution network. Single microgrid achieves the largest microgrid revenue and restoration contribution, and multi-microgrid uses the power headroom index to optimize the dynamic restoration electricity price to achieve the smallest power purchase cost of distribution network. Finally, the optimal scheduling method for resilience enhancement of distribution networks with MMG considering dynamic restoration electricity price response mechanism is validated by dual microgrid access to IEEE 33-node distribution system. The simulation results show that the proposed optimization method effectively improves the RRCL of distribution network.
High-throughput quantitative analysis of mitotic defects in fission yeast using Imagi...
Martin Prevorovsky
Viacheslav Zemlianski

Martin Prevorovsky

and 3 more

October 16, 2023
In this study, we introduce a novel approach for the high-throughput quantitative analysis of mitotic defects in the fission yeast Schizosaccharomyces pombe using Imaging Flow Cytometry (IFC). Fission yeast is a valuable model organism for cell cycle research, and the ‘cut’ phenotype, indicative of mitotic catastrophe, has been instrumental in discovering cell cycle regulators. Traditional fluorescence microscopy methods for quantifying ‘cut’ events suffer from subjectivity and limited throughput. Our IFC pipeline overcomes these limitations by automating the detection of ‘cut’ cells based on the unique characteristic of daughter cell nuclei becoming trapped in the cell wall during aberrant mitosis. We demonstrate the pipeline’s effectiveness using wild-type and mutant strains, with results validated against manual scoring. Our study establishes IFC as a powerful tool for investigating mitotic fidelity in fission yeast, with implications for advancing cell biology research.
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