bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat impacts on school sports club activities in Japan under climate change and the effectiveness of countermeasures
Authors: Oyama Takahiro , Takakura Jun’ya , Hosokawa Yuri , Honda Yasushi , Fujii Minoru , Nakajima Kenichi , Hijioka Yasuaki 
Published: September 2024

Abstract

Millions of students in Japan participate in school sports club activities, where thousands of heat illness cases occur every year. With future climate change, there is concern about the increased health risks posed to students in sports club activities by the worsening heat environment. However, few quantitative evaluations of the impact of heat on sports club activities and countermeasures under climate change have been conducted. Here, we evaluated the impact of heat and effectiveness of countermeasures based on hourly wet-bulb globe temperature (WBGT) projections under multiple climate scenarios. For the 2060s to 2080s, even under the scenario with strict control of greenhouse gas (GHG) emissions (SSP1-1.9), strenuous exercise will be restricted for one to four months in five out of eight WBGT categories defined in this study for Japan and for one to six months in six categories under the scenario with little control of GHG emissions (SSP5-8.5). In three of the four scenarios, unlike in the past, all physical activity should be stopped at least once a week in one or more categories. Countermeasures such as early morning exercise and reducing the frequency of outdoor activities are effective in reducing the risk of heat illness. However, under the most pessimistic scenario, there would be one to four months of restricted periods of strenuous exercise in the warmer regions of Japan, even with such countermeasures. Although heat illness countermeasures are still necessary for sports club activities at present, further countermeasures and behavioral changes are inevitable in the future.
Unraveling Complexity: Mycoplasma Pneumonia Complicated by Hemolytic Anemia, Renal Failure, and Venous Thromboembolism; A Case Report
Authors: Kalwar Asifa , Maqbool Hamza , Kukreja Sandhaya , Zafar Zainab , Ochani Sidhant , Faraz Muhammad 
Published: September 2024

Abstract

Introduction:
Mycoplasma pneumoniae, a common respiratory pathogen, is a leading cause of atypical pneumonia, often presenting with a nonproductive cough, fever, and malaise. While typically causing mild upper respiratory symptoms, M. pneumoniae can lead to severe complications, including hemolytic anemia, acute renal failure, and venous thromboembolism. These complications are relatively uncommon but highlight the pathogen's capacity to affect multiple organ systems. Here, we present a rare and complex case of M. pneumoniae infection complicated by hemolytic anemia, renal failure, and venous thromboembolism in an adult patient.
Case Presentation:
A 58-year-old man with no prior comorbidities presented to the emergency department (ED) with complaints of fever for 12 days, cough, shortness of breath, and generalized fatigue for 10 days. On examination, he was icteric and exhibited coarse breath sounds, and his urine was dark in colour. Despite an initial treatment regimen consisting of ceftriaxone, doxycycline, and methylprednisolone, the patient's condition deteriorated. Investigations revealed pneumonia, hemolytic anemia, and acute renal failure. A respiratory panel identified mycoplasma pneumoniae leading to a diagnosis of complicated mycoplasma pneumonia; his antibiotic regimen was subsequently to azithromycin. The patient was discharged after a week but returned the same day with symptoms indicative of venous thromboembolism. Further evaluation revealed bilateral venous thrombosis and bilateral acute pulmonary embolism, necessitating heparin anticoagulation and a subsequent transition to oral apixaban therapy. The patient was stabilized and discharged, with no complications noted at follow-up.
Discussion
This case underscores the rare but potentially severe extrapulmonary manifestations of M. pneumoniae infection. Hemolytic anemia associated with this pathogen is believed to be due to cold agglutinin antibodies targeting erythrocyte antigens, while renal failure may result from acute tubular injury secondary to hemolysis. Venous thromboembolism, although rare, is increasingly recognized as a complication of M. pneumoniae, particularly in cases where vascular endothelium is directly affected or systemic hypercoagulability is induced.
Conclusion
This case illustrates the complexity of diagnosing and managing severe complications of M. pneumoniae infection, including hemolytic anemia, renal failure, and venous thromboembolism. Early recognition and appropriate management of these complications are crucial to improving patient outcomes and avoiding fatal sequelae.
7aaRGD - a novel SPP1/integrin signaling-blocking peptide reverses immunosuppression and improves anti-PD-1 immunotherapy outcomes in experimental gliomas
Authors: Ellert-Miklaszewska Aleksandra , Pilanc Paulina , Poleszak Katarzyna , Roura Adria-Jaume , Cyranowski Salwador , Ghosh Mitrajit , Baluszek Szymon , Pasierbinska Maria , Gielniewski Bartlomiej , Swatler Julian , Hovorova Yuliana , Wojnicki Kamil , Kaminska Bozena 
Published: September 2024

Abstract

Background
Immune checkpoint inhibitors (ICIs) present clinical benefits in many cancer patients but invariably fail in glioblastoma (GBM), the most common and deadly primary brain tumor. The lack of ICIs efficacy in GBM is attributed to the accumulation of tumor-reprogrammed myeloid cells (GAMs) that create the “cold” immunosuppressive tumor microenvironment (TME), impeding the infiltration and activation of effector T cells. GBM-derived αvβ3/αvβ5-integrin ligands, including SPP1, were shown to mediate the emergence of GAMs. We hypothesized that a combination strategy aiming to block the reprogramming of GAMs using a developed 7aaRGD peptide that targets SPP1/integrin signaling might overcome resistance to ICIs and reinvigorate anti-tumor immunity.
Methods
Matrigel invasion assay was used to test the efficacy of 7aaRGD in glioma-microglia co-cultures. We determined the impact of 7aaRGD, administered as a monotherapy or combined with PD-1 blockade, on tumor growth, GAMs accumulation and phenotypes, arginase-1 levels and neovasculature in experimental gliomas. The effects of treatments on the tumor immune landscape were dissected using multiparameter flow cytometry, immunocytochemistry, cytokine profiling and RNA-seq analysis of sorted GAMs followed by CITE-seq based data deconvolution.
Results
7aaRGD efficiently blocked microglia-dependent invasion of human and mouse glioma cells in vitro. Intratumorally delivered 7aaRGD alone did not reduce tumor growth in orthotopic gliomas but prevented the emergence of immunosuppressive GAMs and led to normalization of peritumoral blood vessels. Combining 7aaRGD with anti-PD-1 antibody resulted in reduced tumor growth, with an increase in the number of proliferating, interferon-ɣ producing CD8+T cells and depletion of regulatory T cells. Transcriptomic profiles of myeloid cells were altered by the combined treatment, reflecting the restored “hot” inflammatory TME and boosted immunotherapy responses. Intratumoral administration of 7aaRGD similarly modified the phenotypes of GAMs in human U87MG gliomas in immunocompromised mice. Exploration of transcriptomic datasets revealed that high expression of integrin receptor coding genes in pre-treatment biopsies was associated with a poorer response to immune check-point blockade in patients with several types of cancers.
Conclusions
We demonstrate that combining the blockade of SPP1/integrin signaling with ICIs modifies innate immunity and reinvigorates adaptive antitumor responses, which paves the way to improve immunotherapy outcomes in GBM.
ICAM-1/CD18-mediated sequestration of parasitized phagocytes in cortical capillaries promotes neuronal colonization by Toxoplasma gondii
Authors: Barragan Antonio , Rodriguez Matias , Hassan Ali , Hoeve Arne ten 
Published: September 2024

Abstract

Microbial translocation across the blood-brain barrier (BBB) is a prerequisite for colonization of the central nervous system. The obligate intracellular parasite Toxoplasma gondii chronically infects the brain parenchyma of humans and animals, in a remarkably stealthy fashion. Here, we addressed the mechanisms of BBB crossing by intracarotid delivery of parasites and parasite-infected leukocytes into the cerebral circulation of mice. Unexpectedly, parasitized dendritic cells (DCs) and other peripheral blood mononuclear cells persistently sequestered in cortical capillaries. Post-replicative egress of T. gondii from sequestered DCs was followed by rapid parasite localization within cortical neurons. Infection-induced microvascular inflammation dramatically elevated the sequestration of parasitized DCs while treatments targeting the ICAM-1/CD18 leukocyte adhesion axis with blocking antibodies strongly reverted sequestration. Secreted parasite effectors TgWIP and GRA15, implicated in leukocyte hypermigration and inflammatory activation, strain genotype-dependently elevated numbers of sequestered parasitized DCs in capillaries and cerebral parasite loads. The data unveil that sequestration of parasitized leukocytes in cortical capillaries, with posterior parasite transmigration across the BBB upon egress, constitutes a mechanism for the rapid reach of T. gondii to cortical neurons during primary infection.
Assessment of microplastic pollution on soil health and crop responses: Insights from dose-dependent pot experiments
Authors: Saha Ankita , Baruah Parishmrita , Handique Sumi 
Published: September 2024

Abstract

Microplastics (MPs) are increasingly recognized as environmental contaminants with complex impacts on soil health and crop productivity. This study investigates the effects of MP contamination in soil through field investigation and pot experiments. Field analysis revealed the presence of polyethylene terephthalate (PET) and high-density polyethylene in soil and plant roots, with visible pollution concentrated in the upper layers. In controlled pot experiments, Brassica juncea (mustard) and Lycopersicum solanaceae (tomato) plants were exposed to PET, polystyrene (PS) and nylon (NL) at different concentrations. The plants exhibited dose-dependent responses, with the treatments of 5% and 10% MPs showing the most detrimental effects (p < 0.05) on soil properties, particularly pH and available nitrogen levels. Both species displayed significantly different responses to treatments (p<0.05). Specifically, PS at a 5% concentration notably suppressed leaf area index while 10% NL resulted in reduced root length and chlorophyll content. PET posed the most significant hindrance to root growth. Interestingly, 10% NL with a high Potential Hazard Index score and a rating of hazard category IV, emerged as the most hazardous polymer at concentrations of 1% and 10%, while at 5%, PS had the most significant impact on plant properties. NL had an overall detrimental effect on mustard plants, whereas PS was more harmful to tomato plants. PET affected both species similarly. The results add to the growing information on the potential risks of MP pollution in the terrestrial environment which supports soil health and dependent organisms.
Stroke Presentations in Emergency Care of Nepal: A Mixed-Methods Study Exploring Epidemiological Characteristics and Delays in Acute Treatment
Authors: Rajbhandari Bibek , Shakya Yogendra Man , Maharjan Ramesh Kumar , Aryal Shiva Sharma , Shah Newton Ashish , Yadav Manish , Bhandari Pratiksha , Regmi Sushant , Bastola Santosh , Luitel Shreekrishna , Shah Sujay , Roy Niraj , Satyal  , Joshi Rupesh , Thapa Paras , Regmi Prakash 
Published: September 2024

Abstract

Introduction: Stroke is a leading cause of morbidity and mortality worldwide, and timely intervention is crucial for improving outcomes. In Nepal, where stroke care is evolving, understanding the epidemiological characteristics and treatment delays is essential for improving emergency care strategies.
Aim: The study aimed to determine the epidemiological profile of stroke cases and explore the reasons for delays in stroke treatment.
Methods: This explanatory sequential mixed-methods study was conducted in the General Practice and Emergency Department (GPED) of Tribhuvan University Teaching Hospital (TUTH) to investigate stroke presentations and treatment delays. Quantitative data collection involved analyzing medical records from August 2022 to September 2023 to establish the epidemiological profile of stroke cases. In addition, 18 in-depth interviews were conducted between February 2024 and March 2024, including 10 stroke patients and 8 family members, to investigate factors contributing to treatment delays. Data analysis included descriptive statistics for quantitative data using STATA version 17 and rapid analysis for qualitative data using MS Excel.
Results: The prevalence of stroke among patients was 2.96% [95% CI: 2.86-3.10], with ischemic stroke being the most common type at 76.34% [95% CI: 73.52-79.06]. The average age of stroke patients was 61.79 years, and 60% of the patients were male. The qualitative findings revealed several important factors that contributed to delays in treatment, such as a lack of awareness of symptoms, limited access to thrombolysis services, delayed diagnosis due to atypical presentation by healthcare professionals, and financial obstacles to accessing treatment.
Conclusions: These findings highlight the importance of enhancing stroke symptom recognition, improving access to thrombolysis services, and addressing financial barriers to treatment. Policy interventions to promote stroke awareness and enhance healthcare infrastructure are warranted to reduce treatment delays and improve patient outcomes.
Subcortical imaging-derived phenotypes are associated with the risk of Parkinson’s disease: A Mendelian Randomization Study
Authors: Chen Zhichun , Liu Jun , You Yong 
Published: September 2024

Abstract

Background
The abnormalities of subcortical structures, such as putamen and caudate, play a key role in the occurrence of Parkinson’s disease (PD); however, whether and how imaging-derived phenotypes (IDPs) in subcortical structures are causally associated with the risk of PD remain poorly understood.
Methods
The causal associations between subcortical IDPs from UK biobank and risk of PD were evaluated with bidirectional two-sample Mendelian randomization (MR) studies.
Results
Totally five subcortical IDPs were found to be causally associated with the risk of PD. Among these IDPs, IDP 168 (Global volume of subcortical gray matter, OR = 1.38 [1.16, 1.63], P = 1.82 x 10− 4), IDP 214 (Right putamen volume, OR = 1.31 [1.15, 1.50], P = 7.71 x 10− 5) and IDP 1441 (T2* signal in right caudate, OR = 1.21 [1.09, 1.35], P = 5.23 x 10− 4) were found to be associated with increased risk of PD. In contrast, IDP 1358 (Mean intensity in right caudate, OR = 0.72 [0.62, 0.85), P = 6.77 x 10− 5) and IDP 1344 (Mean intensity in left caudate, OR = 0.76 [0.65, 0.88], P = 3.23 x 10− 4) were associated with reduced risk of PD.
Conclusions
The specific imaging features of the caudate and putamen are causally associated with altered risk of developing PD, thereby providing new insights into the development of novel predictive imaging biomarkers and therapies for PD patients.
Perceptions of Police among Juvenile Probationers in Sargodha, Pakistan: Influencing Factors and Implications
Authors: Ali Zeeshan 
Published: September 2024

Abstract

The purpose of the study was to investigate the attitudes, beliefs, and feelings that juveniles hold towards law enforcement officers and to identify the factors that shape juveniles' perceptions of the police, including personal experiences, interactions with law enforcement, community environment, and socio-cultural factors in Sargodha city. To achieve the intended objectives of the study, data were collected, analyzed and interpreted. Questionnaire was prepared for respondents. Accordingly, 40 juveniles were approached for the study, which were at probation under probation and parole department of Sargodha. Participants were selected using simple random Convenience sampling technique. The quantitative approach has been used in order to analyze the data using statistical data analysis procedures The findings and results obtained from the questionnaire of this study mostly showed that juvenile probationer perceptions towards law enforcement, reflecting a mixture of trust, skepticism, biasness of police and varying experiences. Understanding these perceptions is crucial for fostering positive police-community relationships and addressing areas of concern to build a safer and more inclusive society. In conclusion, addressing the findings of the survey requires a multifaceted approach that focuses on improving police-community relations, enhancing communication and transparency, strengthening accountability mechanisms, promoting fair and unbiased treatment, investing in infrastructure and resources, promoting positive messaging, and ensuring personal safety and trust. By implementing these recommendations, law enforcement agencies can work towards building stronger, more resilient relationships with the communities they serve.
The effect and mechanism of subsidies on green total factor productivity of enterprises
Authors: Qian Jiali , Zhou Yinxiang 
Published: September 2024

ABSTRACT

Improving green total factor production is crucial to addressing the issue of environmental pollution and global climate change. Government subsidy policy is the key institutional arrangement to improve green total factor productivity. It is of great significance to explore the impact of government subsidy policy on green total factor productivity. Based on A-share listed companies from 2007 to 2022, this study empirically tested the impact of government subsidy policies on enterprises’ improvement of green total factor productivity and its mechanism, as well as conducting an in-depth study on the nature of enterprise property rights, regional, industrial, and firm heterogeneity. The findings are as follows: First, government subsidies have a significant promoting effect on the green total factor productivity of enterprises, and the conclusion is still valid after sensitivity analysis and robustness test. Second, the mechanism test discovered that the resource and signal attributes of government subsidies can boost green total factor productivity by alleviating enterprises financing limitations. Third, further research finds that the promotion effect of government subsidies on green total factor productivity of enterprises is more significant in nonstate-owned enterprises, enterprises in the eastern and western regions, high-tech enterprises and nonhigh-polluting enterprises.
1,2,3-Triazole Linked 7-Chloroquinoline Hybrids: A Promising Pharmacophore for Biological Applications
Authors: Chand Garima , Joshi Penny , Kholia Deepa , Joshi Rini , Kumari Amrita , Upadhyay Santosh K. 
Published: September 2024

Abstract:
Heterocyclic compounds are fundamental in natural products and pharmaceuticals. The
triazole nucleus, in particular, is a versatile structure present in numerous bioactive molecules. 7-
Chloroquinoline is historically significant for its antimalarial properties and exhibits a broad spectrum
of biological activities, including antiviral, anticancer, antibacterial, and anti-inflammatory
effects. This mini-review aimed to compile and discuss 69 biologically active 1,2,3-triazole hybrids
derived from 7-chloroquinoline, highlighting their enhanced bioactivity when combined
with 4,7-dichloroquinoline. A comprehensive review of the literature was conducted to identify
and analyze the synthesis and biological activities of triazole hybrids originating from 4,7-
dichloroquinoline and 7-chloroquinoline. It was found that the 4,7-dichloroquinoline scaffold,
when coupled with triazole derivatives, exhibited enhanced bioactivity, including antimicrobial,
antimalarial, and anticancer effects. This synergy between the two structures underscores their
potential therapeutic applications. The insights provided in this review will serve as a valuable
resource for medicinal chemists exploring triazoles derived from 4,7-dichloroquinoline and 7-
chloroquinoline. The enhanced bioactivity of these hybrids highlights their significance in the
development of new therapeutic agents.
In silico Discovery of Leptukalins, The New Potassium Channel Blockers from the Iranian Scorpion, Hemiscorpius Lepturus
Authors: Khalili-Salmasi Maryam , Nazarian Ahmad , Amirkhani Amir , Mirzahoseini Hasan , Bagheri Kamran Pooshang 
Published: September 2024

Background:
Blocking Kv 1.2 and Kv 1.3 potassium channels using scorpion venom-
derived toxins holds potential therapeutic value. These channels are implicated in autoimmune
diseases such as neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and
type 1 diabetes.

Objective:
The present work aims at the discovery and in silico activity analysis of potassium
channel blockers (KTxs) from the cDNA library derived from the venom gland of Iranian scorpion
Hemiscorpius lepturus (H. lepturus).

Methods:
The sequence regarding potassium channel blockers were extracted based on Gene
Ontology for H. lepturus venom gland. Homology analyses, superfamily, family, and evolutionary
signatures of H. lepturus KTxs (H.L KTxs) were determined by using BLASTP, COBALT,
PROSITE, and InterPro servers. The predicted 3D structures of H.L KTxs were superimposed
against their homologs to predict structure activity relationship. Molecular docking analysis was
also performed to predict the binding affinity of H.L KTxs to Kv 1.2 and Kv 1.3 channels. Finally,
the toxicity was predicted.

Results:
Seven H.L KTxs, designated as Leptukalin, were extracted from the cDNA library of
H. lepturus venom gland. Homology analyses proved that they can act as potassium channel
blockers and they belong to the superfamily and family of Scorpion Toxin-like and Short-chain
scorpion toxins, respectively. Structural alignment results confirmed the activity of H.L KTxs.
Binding affinity of all H.L KTxs to Kv 1.2 and Kv 1.3 channels ranged from -4.4 to -5.5 and -4
to -5.7 Kcal/mol, respectively. In silico toxicity assay showed that Leptukalin 3, Leptukalin 5,
and Leptukalin 7 were non-toxic.

Conclusion:
Three non-toxic KTxs, Leptukalin 3, 5, and 7, were successfully discovered from
the cDNA library of H. lepturus venom gland. Gathering all data together, the discovered peptides
are promising potassium channel blockers. Accordingly, Leptukalin 3, 5, and 7 could be
suggested for complementary in vitro studies and mouse model of autoimmune diseases.