bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of METTL3-METTL14 with an m6A nucleotide reveals insights into m6A conversion and sensing
Authors: Qi Shan , Kumar Abhay , Chen Shuang , Zhou Shuo , Parihar Manish , Villalobos Carmen , Gupta Navom , Chan Siu-Hong , Rao Manjeet K. , McHardy Stanton F. , Haider Shozeb , Gupta Yogesh K.
Published: October 2024

The nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the N6 of adenosine (A) in RNA to m6A and in ssDNA to 6mA. m6A marks are prevalent in eukaryotic mRNAs and lncRNAs and modulate their stability and fate in a context-dependent manner. The cytoplasmic METTL3 can act as a m6A reader. However, the precise mechanism during m6A writing, reading, or sensing is unclear. Here, we present a ~2.5 Å structure of the methyltransferase core of human METTL3-METTL14 in complex with the reaction product mimic, N6-methyladenosine monophosphate (m6A), representing a state post-catalysis but before the release of m6A. m6A occupies an evolutionarily conserved RNA-binding pocket ~16 Å away from the SAM pocket that also frequently mutates in cancer. We propose a two-step model of swiveling of target A upon conversion to m6A and sensing its methylation status by this pocket, enabling it to actuate enzymes’ switch from writer to an m6A-sensor. Cancer-associated mutations show impaired RNA binding dynamics, de-stacking, and defective m6A writing and sensing.
Intricate Interactions between Fine-Scale Genetic Structure, Lifestyle, and Dietary Habits in the Japanese Population
Authors: Seiya Imoto , Chen Yichi , Katayama Kotoe , Ishida Sachiko
Published: October 2024

The fine-scale genetic structure within populations, focusing on demographic histories and migration patterns, has been explored previously. However, limited attention has been paid to understanding how genetic structure influences lifestyle and dietary habits within an epidemiological framework. This study explored the fine-scale genetic structure within a homogeneous Japanese population using advanced unsupervised learning techniques—Principal Component Analysis (PCA), Uniform Manifold Approximation and Projection (UMAP), and Density- Based Spatial Clustering of Applications with Noise (DBSCAN)—coupled with direct-to-consumer genetic testing data. We investigated the associated genetic factors and examined the relationship between the genetic structure and geographic ancestry. Additionally, using cross-sectional data and multinomial logistic regression, we further elucidated the nuanced impacts of lifestyle and dietary factors across genetic clusters, emphasizing the importance of integrating genetic data with epidemiological research. This study introduces a novel framework for genetic epidemiology that considers both genetic and environmental influences.
Unlocking Math Potential in Students from Lower SES Backgrounds – Using Instructional Scaffolds to Improve Performance
Authors: Bach Katharina M. , Reinhold Frank , Hofer Sarah I.
Published: October 2024

Socioeconomic status (SES) influences school success. Students with lower SES may face challenges that this study tries to address by instructional scaffolding. To be effective, such support needs to consider students’ individual strengths and weaknesses. In this study, 321 sixth-grade students used an e-textbook about fractions. They were randomly assigned to receive either adaptive task difficulty, explanatory feedback, or dynamic visualizations as scaffolds or no scaffolding. We assessed their fraction knowledge at pre- and post-test and nine cognitive and motivational-affective variables. Latent profile analyses identified three profiles, with students with lower SES commonly associated with the two profiles with unfavorable learning prerequisites. A linear mixed model revealed that adaptive task difficulty significantly benefited students in the profile with the least favorable prerequisites. Implementing adaptive task difficulty in Math classes might mitigate challenges associated with lower SES, enhancing educational success and equity by addressing individual prerequisites and learning needs.
Breaking the Silence: Confidence and Barriers in Raising Concerns Among Undergraduate Dental Students – “A National Study”
Authors: Hassouneh Layla , Ali Kamran , Glanville Rebecca , Nazzal Hani , Aljamani Sanaa , Quadier Nabilah , Matoug-Elwerfelli Manal
Published: October 2024

Background: Raising concerns in clinical settings, also known as whistleblowing, is vital for safeguarding patient safety and improving the quality of care. Despite research on whistleblowing in medical and nursing fields, there is limited evidence on this topic within dental education. This study aims to assess the self-reported confidence of undergraduate dental students in raising concerns and identify the barriers they encounter.
Methods: This cross-sectional study utilized an online close-ended questionnaire distributed via Google Forms to senior undergraduate dental students from Jordan University of Science and Technology and the University of Jordan. Data collection was voluntary, with subsequent analysis performed using RStudio (version 2023.06.2) incorporating R version 4.0.5. Descriptive statistics including confidence intervals were calculated for each item and for the combined dataset. Analysis of Variance (ANOVA) was used to determine any significant variation between the results by gender and stage of study.
Results: The findings revealed that while students generally felt confident raising concerns related to patient safety, their confidence diminishes when addressing issues related to the conduct of clinical staff or peers. Common barriers reported included fear of causing trouble, lack of support, and fear of being ignored. ANOVA revealed significant variation by gender and year of study, with female students and final-year students reporting greater self-confidence in raising concerns (p < 0.001).
Conclusions: Although dental students show a reasonable level of confidence in raising concerns, the study also identified several barriers. To enhance student confidence and ensure patient safety, it is crucial to improve the supportive environment in dental schools and establish effective reporting mechanisms. Future research should explore the impact of cultural factors on raising concerns in clinical settings and identify additional strategies to support students in raising concerns.
Impact of Drought on Global Food Security by 2050
Authors: Kraklow Vachel , Paff Kirsten , Comeau Darin , Solander Kurt , Pitts Travis , Price Stephen , Xu Chonggang
Published: October 2024

We investigated global food security in response to drought using a process-based crop model within an Earth system model. Globally, future drought losses for annual maize, soybean, rice, and wheat production are projected to be <2%. Despite the small change at the global scale, 62 countries may face drought losses >10% and 24 countries >20%. Vulnerability is highest in countries with lower GDP and higher projected population growth.
A novel Lumbo-Peritoneal Shunt System Including a Gravitational Unit: First Experiences and Clinical Perspectives
Authors: Oros Jan , Kendlbacher Paul , Jussen Daniel , Qasem Lina E. , Finger Tobias , Czabanka Marcus , Prinz Vincent
Published: October 2024

In Europe and North America, hydrocephalus is commonly treated with ventriculo-peritoneal shunts (VPS), while in Japan and other Asian countries, lumboperitoneal shunts (LPS) are preferred. Despite the risk of overdrainage, no adaptable valve with an integrated gravitational unit was available for LPS until recently. We report on a novel modular valve system designed for LPS. We retrospectively analyzed 24 patients who underwent LPS implantation between March 2023 and July 2024. The median age was 64.5 years, with various etiologies including posthemorrhagic hydrocephalus (41.7%), idiopathic normal pressure hydrocephalus (37.5%), and idiopathic intracranial hypertension (8.3%). LPS was also used as salvage therapy in three cases with complex cranial wounds. Relevant complications requiring reoperation occurred in 16.7% of patients, with peritoneal catheter dislocation accounting for 75% of these cases. Overdrainage was observed in 20.8% of patients, but only one serious event necessitated LPS removal. Follow-up showed improvements in gait and vision for iNPH and IIH patients, respectively. This study is the first to use the novel LPS with an integrated gravitational unit, showing promising outcomes across various hydrocephalus etiologies and highlighting its potential as a salvage option for complex cases. Further research with larger cohorts is needed.
HMGB-1 as a predictor of major bleeding requiring activation of a massive transfusion protocol in severe trauma
Authors: Frelich Michal , Bebej Marek , Pavlíček Jan , Burša Filip , Vodička Vojtěch , Švagera Zdeněk , Kondé Adéla , Jor Ondřej , Bílená Markéta , Romanová Tereza , Sklienka Peter
Published: October 2024

Background
Massive bleeding causes approximately 50% of deaths in patients with major trauma. Most patients die within 6 hours of injury, which is preventable in at least 10% of cases. For these patients, early activation of the massive transfusion protocol (MTP) is a critical survival factor. With severe trauma, high-mobility group box 1 (HMGB-1, i.e., amphoterin) is released into the blood, and its levels correlate with the development of a systemic inflammatory response, traumatic coagulopathy, and fibrinolysis. Previous work has shown that higher levels of HMGB-1 are associated with a higher use of red blood cell transfusions. We conducted a retrospective analysis of previous prospective single-center study to assess the value of admission HMGB-1 levels in predicting activation of MTP in the emergency department.
Methods
From July 11, 2019, to April 23, 2022, a total of 104 consecutive adult patients with severe trauma (injury severity score > 16) were enrolled. A blood sample was taken at admission, and HMGB-1 was measured. MTP activation in the emergency department was recorded in the study documentation. The total amount of blood products and fibrinogen administered to patients within 6 hours of admission was monitored.
Results
Among those patients with massive bleeding requiring MTP activation, we found significantly higher levels of HMGB-1 compared to patients without MTP activation (median [interquartile range]: 84.3 µg/L [34.2–145.9] vs. 21.1 µg/L [15.7–30.4]; p < 0.001). HMGB-1 level showed good performance in predicting MTP activation, with an area under the curve of 0.84 (95% CI 0.75–0.93) and a cut-off value of 30.55 µg/L. HMGB-1 levels correlated significantly with the number of red blood cell units (rs [95% CI] 0.46 [0.28–0.61]; p < 0.001), units of fresh frozen plasma (rs 0.46 [0.27–0.61]; p < 0.001), platelets (rs 0.48 [0.30–0.62]; p < 0.001), and fibrinogen (rs 0.48 [0.32–0.62]; p < 0.001) administered in the first 6 hours after hospital admission.
Conclusions
Admission HMGB-1 levels reliably predict severe bleeding requiring MTP activation in the emergency department and correlate with the amount of blood products and fibrinogen administered during the first 6 hours of hemorrhagic shock resuscitation.
Trial registration
NCT03986736 Registration date: June 4, 2019
Azvudine-Centered Comprehensive Therapeutic Strategy for the Treatment of COVID-19 Infection in Kidney Transplant Recipients in the Developing World: An Observational Pilot Study
Authors: Li Xiaoyu , Xu Xin , Leng Wenyuan , Dong Lei , Ji Xing , Zhu Zhenpeng , Xu Chunru , Zhang Meng , Shen Cheng , Xiong Gengyan , Han Wenke , Lin Jian
Published: October 2024

Purpose
Coronavirus disease 2019 (COVID-19) remains a serious challenge for kidney transplant recipients due to their immunocompromised status. Azvudine may be effective in treating COVID-19 in these patients, but its overall efficacy remains unclear.
Methods
Twenty kidney transplant COVID-19 patients at Peking University First Hospital received Azvudine-centered treatment from December 2022 to January 2023. Patients were diagnosed via COVID-19 nucleic acid testing. Demographics and treatment outcomes were collected.
Results
The median duration of Azvudine therapy was 9.6 days (7–14 days), and the median conversion time from positive to negative was 13.22 days (5–33 days). Transplanted renal function improved significantly (estimated glomerular filtration rate increased by 27.29 ml/min/1.73m2, t = 9.755, p < 0.0001; serum creatinine decreased by 57.72 µmol/L, t = 10.45 p < 0.0001). All patients experienced internal environment imbalance during treatment. Half had co-infections, with Mycoplasma pneumonia being the most common (7/20, 35%). The average cost of Azvudine was 220.44 RMB (94.56-342.78 RMB). After a 1-year follow-up, 70% (14/20) of patients maintained normal transplanted kidney function. No Azvudine-related complications were observed, indicating the therapy's initial safety.
Conclusion
This single-center study suggests that Azvudine-centered therapy may be effective and safe for COVID-19 in kidney transplant recipients. Azvudine could be a cost-effective alternative for those with poor access to first-line anti-COVID-19 agents.
Online peer mentoring for youth with learning differences
Authors: Mercier Alecia , Paquette Brianna , Hoeft Fumiko , Richter Caroline G.
Published: October 2024

Youth with learning differences (e.g., specific learning disorder and attention deficit hyperactivity disorder) encounter exacerbated psychological and behavioral challenges compared to typically developing peers. Peer mentoring has proven beneficial in addressing such challenges, yet there is limited research on the efficacy of online peer mentorship programs for this population. This study investigates the effects of an online peer mentoring program on mentees’ mental health, wellbeing, and behavior across 10 outcomes: anxiety, depression, fear, cognitive challenges, behavioral concerns, executive function, sleep difficulties, self-care, interpersonal skills, and self-esteem/self- confidence. Parents retrospectively reported on their child’s mental health, wellbeing, and behavior prior to and since receiving online mentorship. Results indicated significant improvements across all outcomes following online mentorship. These findings highlight the effectiveness of online peer mentorship programs, emphasizing its potential as a valuable tool for supporting youth with learning differences.
The Development and Future of Robotic Distal Pancreatectomy: A Bibliometric Analysis
Authors: Yang Jun , Liu Zixiong , Li Juntao , Luo Quanneng , Ten Xiong , Zhou Minjie , Cheng Wei , Cheng Kang , Zhou Lei
Published: October 2024

Purpose:With the increasing adoption of robot-assisted surgery, particularly in distal pancreatectomy, the field has gained significant traction. This study aims to conduct a comprehensive bibliometric analysis to explore the current landscape, research focuses, and emerging trends in robot-assisted distal pancreatectomy (RDP).
Methods:Utilizing the Web of Science Core Collection (WoSCC), this study identified relevant publications spanning from 2002 to 2024. Analytical tools such as CiteSpace (v6.2.R6) and VOSviewer (v1.6.20) were employed to assess various dimensions including publication quantity, countries, institutions, journals, authors, references, keywords.
Results:A total of 385 journal articles were reviewed, revealing a consistent annual growth in publications over the study period. The United States, England, and Italy emerged as prominent contributors to RDP research, with Amsterdam University and Rotterdam University leading in institutional productivity. "Surgical Endoscopy and Other Interventional Techniques" emerged as the primary journal for RDP publications, featuring high citation rates. Notably, authors Besselink MG and Zureikat AH were identified for their substantial contributions to the field. Research hotspots identified through bibliometric analysis include indications, safety and efficacy, surgical techniques, and the learning curve of RDP. There is a potential emerging interest in Finding higher-level evidence to explore RDP's efficacy for pancreatic cancer treatment as a future research direction.
Conclusion:This study represents the first comprehensive bibliometric analysis of RDP, offering insights into its development, identifying current research hotspots, and predicting future trends. The findings of our study provide practical information for other scholars to grasp research hotspots and research trends.
Increased activation of the WNT pathway in brain tissue from patients with cortical dysplasia type IIb: genetics and functional aspects
Authors: Varella Fabio Jean , Xavier Fernando Antônio Costa , Zanirati Gabriele , Gonçalves João Ismael Budelon , Previato Thales Thor Ramos , Pazzin Douglas Bottega , Pereira-Neto Normando G. , Paglioli Eliseu , Martins William Alves , Palmini Andre , Santos Adriana Souza dos , Abreu José Garcia , Leichtweis Kamila Souto , Machado Denise C. , Costa Jaderson Costa , Marinowic Daniel Rodrigo
Published: October 2024

Focal Cortical Dysplasia (FCD) is a malformation of cortical development characterized by a heterogeneous group of lesions with high epileptogenic activity. The origin of FCD may be related to neuronal proliferation and differentiation, with the Wnt/β-catenin pathway being one of the main factors responsible for mediating these processes. Residual samples were obtained from the neocortex of five patients diagnosed with FCD type IIb who underwent surgery. For the control group, residual samples from patients with hippocampal sclerosis (HS) were used. The samples were used to evaluate relative gene expression levels, immunohistochemical characteristics, and the quantification of proteins related to the WNT pathway by Western blot. Gene expression analysis showed increased fold-changes in the genes LRP5, LRP6, DKK1, and DVL1. Immunohistochemistry analysis revealed that the FCD brain samples exhibited more staining for LRP6 compared to control brain tissue. All patients with FCD showed stronger staining for β-catenin. The increased gene expression of WNT pathway genes, combined with the intensified anti-LRP6 antibody staining and increased β-catenin staining, along with the reduced rate of β-catenin phosphorylation observed in patients with FCD, suggests a more pronounced activation of the WNT pathway.
Exploring the Correlation between Seizure Control and Serum Levels of Antiepileptic Drugs in Pediatric Patients with Epilepsy in Ethiopia: A Retrospective Cross-Sectional Study
Authors: Mante Bamlak Markos , Beyene Ayalew Moges , Lamboro Meskerem Abatkun , Woldu Minyahil Alebachew
Published: October 2024

Introduction: Antiepileptic drugs (AEDs) are frequently used to treat seizures; however, in settings with limited resources, the relationship between seizure control and the plasma levels of these medications in the paediatric population is still not well understood.
Purpose: This study investigated this correlation, aiming to optimize treatment strategies and enhance the well-being of children with epilepsy.
Methods: A retrospective cross-sectional design was employed in three Ethiopian hospitals from September 2021 to February 2022. Data from 81 participants were analysed, with a focus on sociodemographic and clinical characteristics and AED serum levels.
Results: Boys composed 69.1% of the sample, with an average age of 8.56 ± 4.35 years. Generalized seizures were predominant (54.3%). TDM was performed for valproic acid (13.7%), phenytoin (11.7%), phenobarbitone (8.7%), and carbamazepine (1.3%). Post-TDM, 48% of the patients underwent therapeutic interventions. A chi-square test revealed no significant relationship between seizure control and AED concentration (p=0.920). Correlation analysis revealed a fourfold increase in the odds of poor seizure control with antiepileptic polypharmacy (AOR=4.162, p=0.046) and a sevenfold increase with increasing seizure frequency (AOR=6.711, p=0.027). Fisher's exact test indicated a significant correlation between TDM results and AED effectiveness for phenobarbitone, phenytoin, and valproic acid. The lack of a direct correlation between AED concentrations and seizure control emphasizes the multifactorial nature of epilepsy management.
Conclusions: This study emphasizes the need for personalized treatment for pediatric epilepsy, considering factors such as seizure frequency and antiepileptic polypharmacy. This suggests that caution should be taken in antiepileptic polypharmacy and regular seizure frequency assessment. Further research is recommended for improved treatment guidelines.
Family caregivers burden and quality of life among gastric cancer patients: The mediating role of psychological resilience based on Lazarus's transactional model
Authors: Luo Mengjia , Lu Jv , Jing Yifan , Dai Yanran , Ji Gang , Wu Chao , Lang Hongjuan
Published: October 2024

Background
Currently, the incidence of gastric cancer in China is increasing, and with prolonged survival times, the nursing tasks and responsibilities that family caregivers need to undertake are becoming increasingly significant. The level of care provided by this group has a crucial impact on patients’ health-related outcomes. Therefore, decreasing caregivers’ life burden and improving their quality of life is vital for promoting patient recovery.
Purpose
The aim of this study was to investigate the effect of caregiver burden on the quality of life of patients with gastric cancer, and to explore the mediating role of psychological resilience in this relationship.
Methods
Data collection was conducted in the gastrointestinal surgery ward of a Grade III A hospital. 189 family caregivers of gastric cancer patients were surveyed using scales measuring caregiver burden, psychological resilience, and quality of life. Structural equation modeling was employed to validate the research hypotheses proposed, based on Lazarus’s transactional model.
Results
Caregiver burden was negatively correlated with psychological resilience and positively correlated with quality of life (p < .01). Psychological resilience plays a partial mediating role between caregiver burden and quality of life.
Conclusion
Caregiver burden is the key to predicting and reducing the quality of life of caregivers of gastric cancer patients. Psychological resilience is an intervention mechanism that explains how caregiver burden reduces caregiver quality of life in patients with gastric cancer.
Evaluating the Feasibility of Delayed Replantation: Report of 2 Cases
Authors: Nugraha Muhammad Hirzi , Hasan Cahya Yustisia , Haryosuwandito Erdananda
Published: October 2024

Introduction: Losing permanent teeth due to avulsion or extraction can affect patients psychologically and functionally. This condition can be managed through replantation, which involves implanting teeth into the socket. The success of avulsed tooth replantation is highly influenced by the choice of storage media, the duration of the tooth remains outside the socket, and the level of contamination. The key to successful replantation lies in the patient's condition, the donor tooth, and the recipient site.
Objective: To report the management of delayed replantation and its treatment outcomes in several cases.
Cases: The first case is an 11-year-old child who experienced avulsion of the left maxillary central incisor, which was replanted six days later. The second case is a 22-year-old woman who experienced avulsion of tooth 21 and underwent delayed replantation 15 hours later. Both avulsed teeth were treated with root canal treatment, with subsequent successful treatment outcomes afterward.
Conclusion: Delayed replantation treatment provided satisfactory results in all three cases. The replanted teeth showed no complaints, discoloration, or gingival swelling and were completely painless during each case's follow-up period. In Case 1, there was infra-positioning, ankylosis, and external resorption at the mesial alveolar crest of the tooth. Case 2 showed a well-functioning tooth, no periapical lesions, and satisfactory aesthetic results.
Structural and Functional Characteristics of Leptomeningeal Lymphatic Vessels in Leptomeningeal Metastases from Lung Cancer Patients
Authors: Hua Xiaoyu , Ye Minting , Liu Da , Li Hainan , Fan Chongzhu , Mai WenFeng , Jia Wuyi , Yu Xiaojun , Sun Mengnan , Liu Xiangning , Cai Linbo , Shi Changzheng , Lai Mingyao
Published: October 2024

Background: The purpose of this study is to explore whether there are lymphatic vessels in the human leptomeninges, and their potential role in the immune response to central nervous system tumors, in order to determine their significance in the field of tumor biology, especially the role they play in the growth, metastasis, and immune response of tumors.
Methods: We used immunohistochemistry and immunofluorescence techniques to examine the leptomeninges in 46 patients diagnosed with leptomeningeal metastasis in cerebrospinal fluid cytology (29 positive biopsy specimens, 17 negative) as well as 11 epilepsy patients. We visualized lymphatic vessels in the human leptomeninges using LYVE1 and PDPN antibodies, labeled tumor cells with CK, T cells with CD3, and blood vessels with CD31 and α-smooth muscle actin. By comparing the lymphatic vessel density and T cell count in tumor areas versus non-tumor areas, and observing whether there was infiltration of tumor cells into the lymphatic vessels, we analyzed the presence and function of human leptomeningeal lymphatic vessels.
Results: The research results confirmed the existence of lymphatic vessels in the human leptomeninges, with a significant increase in lymphatic vessel density and T cell count around the tumor compared to non-tumor areas (P < 0.05). At the same time, infiltration of tumor cells was observed within the lymphatic vessels.
Conclusions: These findings suggest that the lymphatic vessels in the leptomeninges not only structurally resemble extracranial brain lymphatic vessels, but also function similarly in tumor immune response and metastasis pathways. These findings challenge traditional understanding of immune responses to central nervous system tumors and provide important clues for further research on the role of intracranial lymphatic vessels in tumor biology.
Effect of systemic immunomodulatory therapies on mental health in atopic dermatitis: a systematic review and network meta-analysis
Authors: Liu Ming , Zhang Kaihua , yang Kelu , Gao Ya , Zheng Li , Tian Jinhui , Zhang Yang
Published: October 2024

Background: Atopic dermatitis (AD) is a prevalent chronic skin condition that may cause significant mental health challenges, including anxiety and depression. This study aimed to evaluate the effects of different systemic immunomodulatory therapies on the anxiety and depression in patients with AD.
Methods: We searched the MEDLINE (via Ovid, from 1946), EMBASE (via Ovid, from 1974), the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov from the date of their inception to June 1, 2024. We included randomized controlled trials (RCT) involving both children and adults with moderate-to-severe atopic AD receiving systemic immunomodulatory therapies. Network meta-analysis were performed using mean changes from baseline and their standard deviations (SDs) by Bayesian random effects model. All analyses were conduct using R version 3.6.3.
Results: Eighteen RCTs reported in 15 studies involving 7,784 patients were eligible. The risk of bias of two outcomes reported in each trial were low or probably low. Measured by Hospital Anxiety and Depression Scale, high-certainty evidence demonstrated that “Abrocitinib (200 mg, oral, qd)” (anxiety: MD -1.2, 95%CI: -1.7 to -0.69; depression: MD -1.1, 95%CI: -1.8 to -0.29), “Dupilumab (300 mg, subcutaneously, q1w)” (anxiety: MD -1.9, 95%CI: -2.4 to -1.4, depression: MD -1.8, 95%CI: -2.7 to -0.85), “Dupilumab (300 mg, subcutaneously, q2w)” (anxiety: MD -1.7, 95%CI: -2.2 to -1.2; depression: MD -1.6, 95%CI: -2.3 to -0.76), and “Lebrikizumab (250 mg, subcutaneously, q2w)” (anxiety: MD -1.6, 95%CI: -2.3 to -0.97, depression: MD -1.6, 95%CI: -2.5 to -0.58), were the most effective drugs for both anxiety and depression in both adults and children patients, respectively; “Baricitinib (4 mg, oral, qd)” (MD -1.1, 95%CI: -1.9 to -0.34) was only efficient with depression.
Conclusions: Systemic immunomodulatory therapy could significantly alleviate anxiety and depression in patients with AD, particularly with the subcutaneous administration of Dupilumab at a 300 mg dose.
Outcomes of Popliteal Artery Injuries in a Level 1 Trauma Centre: A 6-year review
Authors: Rensburg Kewen van , Steyn Wilme , Moeng Maeyane Steve , Cassimjee Ismail
Published: October 2024

Purpose To determine modifiable and non-modifiable factors contributing to limb loss in PAI the relevance and accuracy of published scoring systems for PAI within a South African State hospital.Methodology: Retrospective review of patients (> 18 years) with PAI, presenting to CMJAH trauma unit from 1 January 2017 to 31 December 2022.Results Sixty-four patient records were analysed. Thirty (46.9%) had blunt trauma and thirty-four (53.1%) had penetrating trauma. Gunshot wounds (GSW) were the most common mechanism of injury (MOI). Blunt PAI had a 40% amputation rate and penetrating trauma, 33.3%. Forty-seven (73.4%) had a delay to surgery of > 6 hours. The mean time to arrival at our emergency department was 478 min, and the mean time from arrival to surgery was 368 min (total delay of 838 min). The primary amputation rate was 28.6%, and 63.5% had successful limb salvage surgeries. The secondary amputation rate was 7.8%.Conclusion Compared to international literature, our rate of primary amputation is high (10% vs 28.8%) and prolonged ischaemia is the likely cause. Only 17 (26.6%) patients presented before 6 hours. Of the 45 patients that had an attempt at revascularisation, 7.8% had a secondary amputation. Thus, despite prolonged ischaemia, revascularisation should be attempted in patients with at least two viable compartments on fasciotomy. The MESS and POPSAVEIT scoring systems should not be relied on in patients with delayed presentations. Strengthening referral triage for suspected PAI to Level 1 Trauma centres directly will decrease the delays and likely improve the outcomes.
Benefits of Long-Term Combination Therapy with Sildenafil Citrate and Beraprost Sodium in a Dog with Pulmonary Hypertension
Authors: Jang Keunhwan , Han JungWoo , Cho Seung-Bum , Kim SuYeon , Oh Songju , Kim Ha-Jung
Published: October 2024

Background
Pulmonary hypertension, defined as sustained elevated pulmonary artery pressure, can lead to right-sided heart failure if untreated. While sildenafil citrate is a common treatment, recent findings suggest that its combination with beraprost sodium may enhance therapeutic efficacy in human medicine. This case report describes the successful management of canine pulmonary hypertension using combination therapy and suggests potential efficacy in veterinary medicine.
Case presentation
A 12-year-old, spayed female, Pekingese dog was referred to a veterinary medical teaching hospital owing to frequent episodes of syncope and exercise intolerance. On thoracic auscultation, a grade 4 heart murmur was detected on both sides of the chest, along with respiratory sinus arrhythmia. An electrocardiogram showed a right axis deviation, suggesting possible right ventricular hypertrophy. There were no abnormalities in heart size on thoracic radiographs. An increased contact area was observed between the sternum and the right heart in the lateral view owing to the enlarged right-sided heart. No significant pulmonary infiltration, tracheal collapse, or bronchial collapse was observed. Echocardiography revealed moderate tricuspid regurgitation and severe pulmonary hypertension. Based on clinical signs and diagnostic findings, the diagnosis was right-sided heart failure caused by brachycephalic obstructive airway syndrome (BOAS). The initial treatment plan included sildenafil citrate at 2mg/kg PO bid, pimobendan at 0.3mg/kg PO bid, enalapril at 0.5mg/kg PO bid, and furosemide at 1mg/kg PO bid. Despite taking medications for three months, the frequency of syncope episodes remained unchanged, and the pulmonary hypertension failed to improve. Therefore, beraprost sodium, a prostacyclin analog, was added to the treatment regimen. Thereafter, the dog’s clinical signs of syncope significantly improved, although the echocardiographic findings showed no change in tricuspid regurgitation and the severity of pulmonary hypertension (velocity 4.42m/s, pressure gradient 78.2mmHg). The dog maintained these improved clinical signs for 12 months, with a combination of sildenafil citrate at 3 mg/kg PO bid and beraprost sodium at 20 µg/kg PO bid.
Conclusions
This study showed that combining beraprost sodium with sildenafil significantly improved clinical symptoms in cases where sildenafil alone was ineffective, with no adverse effects observed over an extended treatment period.
Patient-Centric Diagnosis of Acute Leukemia: A Machine Learning Approach Utilizing Flow Cytometry Data
Authors: AGRAWAL RIMI , Kapadia Viral
Published: October 2024

As cancer incidence rises due to lifestyle factors, accurate and cost-effective leukemia diagnosis is crucial in medical diagnostics. Early identification of malignant leukocytes remains challenging, prompting this research to employ machine learning (ML) techniques. Using a flow cytometry test of blood cells which including Forward Scatter Signal, Forward Scatter Pulse Width Signal, Side Scatter Signal, and Side Fluorescence Signal, various ML algorithms (SVM, K-Nearest Neighbor, AdaBoost Algorithm, Logistic Regression, Decision Tree, Random Forest) are applied for individual patient diagnosis. This study underscores the significance of ML in processing leukemia flow cytometry test signals, enhancing accuracy, reducing diagnosis time, and offering cost-effective and safer diagnostic services. By utilizing ML-based approaches, clinicians and laboratory experts can potentially enhance the efficiency of Leukemia detection and classification. This article provides an in-depth review of current machine learning models used for detection and classification of Leukemia, highlighting their methodologies for discrete data of flow cytometry test, shedding light on their potential benefits and challenges. Overall, this research contributes to the ongoing efforts to improve Leukemia diagnosis through innovative and advanced computational approaches.
Broad-scale overdose education and naloxone distribution – 5-year follow-up of a regional program in Skåne County, Sweden
Authors: Troberg Katja , Isendahl Pernilla , Dahlman Disa , Håkansson Anders
Published: October 2024

Background
Opioid use disorder is a chronic disorder with a high risk of overdose related morbidity and mortality where a large proportion of these can be averted by timely administration of the antidote naloxone. For naloxone to be present when and where overdoses occur, broad-scale overdose education and naloxone distribution (OEND) must be established. A regional naloxone program was implemented in 2018, in Skåne County, Sweden. This five-year follow-up aims to describe all naloxone-related lay-person events and whether recommendations previously described in the literature were met and to further investigate events conducted by individuals reporting overdose reversals with naloxone on three or more occasions (‘Supersavers’).
Methods
Between June 2018 and June 2023, data was collected in six-month intervals from participating units (n = 52), containing information on trained individuals, gender, year of birth and distributed naloxone kits. Upon naloxone replenishment, patients were asked whether previous naloxone had been used for overdose reversals on someone else, or themselves, had been lost, stolen, or given to someone else.
Results
Training and initial kits had been provided to 2685 individuals at risk of own opioid overdose. Each of the 5900 naloxone kits distributed, contained two naloxone doses. Upon refill (n = 2364), naloxone had been used for overdose reversal in 39% (n = 926) situations. The minimum distribution target of 20 kits per annual opioid overdose death was met annually, while the target of enrolling > 100 individuals at-risk individuals per 100,000 population was first met during the second year. The core group of Supersavers represent 9% (n = 50) of those returning for refill and while reporting 54.5% (n = 292) of all overdose reversals.
Conclusions
Broad-scale naloxone training and distribution reaches a large proportion of individuals at risk of opioid overdose. A continuous focus and priority in supporting units with a high prevalence of individuals witnessing overdose events is of great importance as these individuals report a large proportion of overdose reversals. Likewise, it is of great importance to provide these individuals, i.e. Supersavers, with needed and sufficient support for their continued essential work intervening in overdose situations.
Trial Registration:
Naloxone Treatment in Skåne County – Effect on Drug-related Mortality and Overdose-related Complications, NCT03570099, registered 26 June 2018.
Management of social responsibility strategies of multinational corporations in russia during the war against Ukraine
Authors: Kharchenko Tetyana , Sokhan Inna , Shalimov Volodymyr , Baistriuchenko Nataliia , Klietsova Nataliia
Published: October 2024

This study examined how multinational corporations adapted their corporate social responsibility strategies while operating in russia during the ongoing war against Ukraine. Specifically, the analysis investigated the impact of different corporate social responsibility approaches on financial performance, stakeholder trust, and corporate reputation for multinational corporations operating in russia during the war. A game-theoretic model evaluated three distinct strategies: minimal corporate social responsibility engagement (Strategy 1), increased corporate social responsibility involvement (Strategy 2), and a complete exit from the russian market (Strategy 3). The quantitative analysis showed that companies choosing the exit strategy (Strategy 3) gained the highest payoffs for financial performance, stakeholder trust, and reputation. In contrast, minimal corporate social responsibility engagement (Strategy 1) resulted in negative outcomes, including reputational damage and potential exposure to sanctions. On the other hand, increased corporate social responsibility involvement (Strategy 2) produced neutral outcomes, offering short-term benefits but still leaving companies vulnerable to ongoing risks. The sensitivity analysis confirmed the stability of these outcomes. The study concludes that exiting the russian market not only aligns with ethical standards but also ensures long-term sustainability, offering critical insights for corporations navigating corporate social responsibility challenges in war zones.
AcknowledgmentsWe sincerely express our gratitude to Prof. Dr. Dr. h.c. Marko Sarstedt, the LMU Fellowship Grant (LMU Ukraine support-fund) for the support of Ukrainian scientists.
Inserción profesional docente: desencuentros entre experiencias y políticas de acompañamiento
Authors: Amaro Amaro María Cristina , Ramos Escobar Norma
Published: October 2024

El trabajo presenta una investigación sobre las experiencias del profesorado novel de Educación Básica para analizar el proceso de inserción profesional antes y después de la implementación de las políticas de acompañamiento en México, situación que se concretó en un programa de tutoría puesto en marcha a partir de 2013. Consideramos que el programa intentaba subsanar las dificultades que el profesorado novel experimenta en esta etapa, pero, como se observará desde la perspectiva de la experiencia docente, esto no es así, pues la política tiene serios desencuentros con las realidades que viven los sujetos. La investigación se desarrolló con el método biográfico narrativo a partir de dos tipos de fuentes biográficas. Por un lado, se recuperaron relatos escritos por docentes que se iniciaron en la profesión durante las tres últimas décadas del siglo XX y la primera del siglo XXI, para contrastarlos con relatos orales narrados por docentes que se encontraban en su primer año de inserción profesional entre 2018 y 2022. Los resultados arrojan similitudes significativas en las experiencias de ambos grupos, que son atravesadas por el choque de realidad característico de esa etapa, lo que hace cuestionar la capacidad de las políticas de acompañamiento para lograr cambios estructurales que ayuden a dimensionar la inserción profesional como una parte importante del trayecto de desarrollo profesional docente.
Aurelia aurita jellyfish collagen: Recovery properties
Authors: Barzkar Noora , Sukhikh Stanislav , Zhikhreva Anastasiia , Cheliubeeva Elizaveta , Kapitunova Anastasia , Malkov Danil , Babich Olga , Kulikova Yuliya
Published: October 2024

Wound and burn healing is a complex physiological process that can be facilitated by medications based on marine collagen. In this regard, biomass of the Aurelia aurita jellyfish is a promising alternative source of medical collagen. As the global incidence of burns and wounds continues to grow, new healing methods have become a relevant area of medical science.
This study featured acetic acid as a means of marine collagen extraction from A. aurita biomass. The physical and chemical properties of jellyfish collagen were determined gravimetrically and included such indicators as water solubility and water holding capacity. The molecular weight was defined by gel electrophoresis. The spectral studies relied on the method of UV spectroscopy. The regenerative experiments included such parameters as cytotoxicity, antioxidant properties, adhesion, and wound healing rate, as well as a quantitative PCR analysis.
The optimal conditions for maximal collagen yield were as follows: 0.5 M acetic acid and 48 h extraction time. However, the collagen yield was very low (≤ 0.0185%). The high water holding capacity showed good prospects for A. aurita collagen to be used as hemostatic sponge. The acid-soluble collagen sample had a molecular weight of 100–115 kDa, which made it possible to classify it as type I. A. aurita jellyfish collagen revealed no cytotoxic properties; it had no effect on adhesion, migration, and proliferation of keratinocytes, neither did it affect the expression of cell differentiation markers.
The wound healing model proved that the marine collagen had regenerative properties as it was able to increase the wound healing rate by 24.5%. Therefore, collagen extracted from the biomass of A. aurita jellyfish d emonstrated good p rospects for cosmetology and regenerative medicine.
Risk of Malignancy Index Assessment in Pre and Postmenopausal Women with Adnexal Masses: A Cross-Sectional Study
Authors: Rozina Naurin  , Rubina Naurin  , Tehmina Zafar  , Sobia Zafar  , Rubeena Badar
Published: October 2024

Background: Adnexal mass is a common presentation in gynecological settings. Differentiation between benign and malignant tumors is crucial for deciding the proper place and type of treatment. The RMI is considered a good and reliable tool in pre-operative differentiation of ovarian tumors, but limited work has been done on this tool in low-resource settings.
Objective: To assess the diagnostic accuracy of Risk of malignancy index in differentiating benign from malignant ovarian tumors.
Methods: This cross-sectional study was conducted in Department of Obstetrics & Gynaecology at a Teaching Hospital, Lahore. Eighty females between 30-80 years, admitted with adnexal mass in the Department of Obstetrics & Gynaecology at Central Park Teaching Hospital, Lahore from October 1st to 30th September, 2023 were enrolled. RMI was calculated and findings were compared with histopathology.
Results: Among enrolled 80 females with adnexal mass the mean age of females was 43.70 ± 8.21 years. The mean BMI was 30.60 ± 5.68 kg/m2. The mean duration of post-menopausal bleeding was 14.50 ± 6.22 months. The mean RMI of females was 212.95 ± 159.76. The Sensitivity of RMI was 100%, specificity was 90.6%, PPV was 72.7%, NPV was 100%, and diagnostic accuracy was 92.5% taking histopathological findings as gold standard.
Conclusion: Thus, RMI is found to be a reliable tool for the diagnosis of ovarian malignancy in females with suspicious adnexal mass.
Cyberbullying and Internet Gaming Disorders in Pakistan: Strategies for Mitigation
Authors: Batool Saima
Published: October 2024

Dear Editor,Cyberbullying and internet gaming disorders (IGDs) have emerged as significant concerns in Pakistan, particularly among adolescents. This editorial explores the prevalence, impacts, and potential interventions for these issues, drawing on recentresearch and literature. The need for a multifaceted approach involving parents, educators, communities, and government is emphasized to protect vulnerable populations and promote a healthier digital environment. The advent of widespread internet access in Pakistan has brought numerous benefits, yet it has also introduced challenges such as cyberbullying andinternet gaming disorders (IGDs). These phenomena have serious implications for the mental health and well-being of adolescents. Given the relative novelty of these issues in the local context and the paucity of research, it is crucial to develop a comprehensive understanding and effective strategies for mitigation. According to a met analysis of earlier research, Asianyouth have a high IGD prevalence 1 Defining Cyberbullying and IGDs Cyberbullying lacks a universally accepted definitiondue to its complexity. Alipan and Skues provide a useful framework, describing it as behavior that intentionally harms victims using information and communication technology, perceived as harmful by victims, and witnessed by bystanders as negative2 . IGDs are recognized in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition warranting further study. Vulnerability of Adolescents Adolescents are particularly susceptible to cyberbullying and IGDs due to the developmental changes they experience. The American Academy of Pediatrics recommends against providing personal mobile phones to children under 13 years old, highlighting their vulnerability to risky behaviors3. The prefrontal cortex, responsible for decision making and impulse control, is not fully developed in adolescents, making them prone to impulsive and risky behaviors, including cyberbullying and excessive gaming.
Removal of Cr(VI) in groundwater by controlled release materials based on nano zero-valent iron and activated carbon
Authors: Fu Zhi-hui , Chen Jia-yi , Chen Gang , Hu Cheng , Wang Ting , Qiao Xu-dong , Zhu Hong-na , Chen Hua-li
Published: October 2024

The use of nano zero-valent iron (nZVI) materials for groundwater Cr(VI) removal encountered challenges of agglomeration and low removal efficiency. Controlled release materials (CRMs) gradually release reactive substances or reducing agents, prolonging the release time. Here, we report the development of novel CRMs containing nZVI and activated carbon (AC). During the removal of Cr(VI) in groundwater, the prepared AC/nZVI/CRMs slowly released nZVI, greatly reducing the agglomeration of nZVI. The adsorption capacity of AC-containing CRMs prolonged the residence time of Cr(VI) in water, improving the removal efficiency of the AC/nZVI/CRMs. We found that lower pH enhanced the removal of Cr(VI) by the AC/nZVI/CRMs from simulated groundwater. The removal efficiency of the AC/nZVI/CRMs was also affected by the simulated groundwater environment and decreased with the increasing flow rate of the groundwater. Our results suggested that these novel nZVI-containing CRMs minimized agglomeration during the removal of Cr(VI) by nZVI, exhibited enhanced efficiency under acidic conditions, and facilitated Cr(VI) removal from similar groundwater environments.