bluuebunny/crossref_metadata_2025 huggingface dataset:
A sub-super solution method to continuous weak solutions for a semilinear elliptic boundary value problems on bounded and unbounded domains
Authors: Ghanmi Abdeljabbar , Alzumi Hadeel Z. , Zeddini Noureddine
Published: June 2024

In this paper, we prove the existence of solutions for an elliptic system. More precisely, we combine the potential theory with the sub-super solution method and use the properties of the well-known Kato class to justify our existence results. The novelty of our study is that we consider either the bounded or the exterior domain; Also, the nonlinearities may be singular near the boundary. Some examples are presented to validate our main results.
Dynamics and numerical simulations of a generalized mosquito-borne epidemic model using the Ornstein-Uhlenbeck process: Stability, stationary distribution, and probability density function
Authors: Niu Wenhui , Zhang Xinhong , Jiang Daqing
Published: June 2024

In this paper, we proposed a generalized mosquito-borne epidemic model with a general nonlinear incidence rate, which was studied from both deterministic and stochastic insights. In the deterministic model, we proved that the endemic equilibrium was globally asymptotically stable when the basic reproduction number $ R_0 $ was greater than unity and the disease free equilibrium was globally asymptotically stable when $ R_0 $ was lower than unity. In addition, considering the effect of environmental noise on the spread of infectious diseases, we developed a stochastic model in which the infection rates were assumed to satisfy the mean-reverting log-normal Ornstein-Uhlenbeck process. For this stochastic model, two critical values, known as $ R_0^s $ and $ R_0^E $, were introduced to determine whether the disease will persist or die out. Additionally, the exact probability density function of the stationary distribution near the quasi-equilibrium point was obtained. Numerical simulations were conducted to validate the results obtained and to examine the impact of stochastic perturbations on the model.
A robust regional eigenvalue assignment problem using rank-one control for undamped gyroscopic systems
Authors: He Binxin , Liu Hao
Published: June 2024

Considering the advantages of economic benefit and cost reduction by using rank-one control, we investigated the problem of robust regional eigenvalue assignment using rank-one control for undamped gyroscopic systems. Based on the orthogonality relation, we presented a method for solving partial eigenvalue assignment problems to reassign partial undesired eigenvalues accurately. Since it is difficult to achieve robust control by assigning desired eigenvalues to precise positions with rank-one control, we assigned eigenvalues within specified regions to provide the necessary freedom. According to the sensitivity analysis theories, we derived the sensitivity of closed-loop eigenvalues to parameter perturbations to measure robustness and proposed a numerical algorithm for solving robust regional eigenvalue assignment problems so that the closed-loop eigenvalues were insensitive to parameter perturbations. Numerical experiments demonstrated the effectiveness of our method.
Convergence of distributed approximate subgradient method for minimizing convex function with convex functional constraints
Authors: Pioon Jedsadapong , Petrot Narin , Nimana Nimit
Published: June 2024

In this paper, we investigate the distributed approximate subgradient-type method for minimizing a sum of differentiable and non-differentiable convex functions subject to nondifferentiable convex functional constraints in a Euclidean space. We establish the convergence of the sequence generated by our method to an optimal solution of the problem under consideration. Moreover, we derive a convergence rate of order $ \mathcal{O}(N^{1-a}) $ for the objective function values, where $ a\in (0.5, 1) $. Finally, we provide a numerical example illustrating the effectiveness of the proposed method.
Le foyer obscur de l’évidence
Authors: Mehl Édouard
Published: June 2024

L’œuvre de Jean-Luc Nancy se tisse autour du concept d’existence, modifié ou plutôt explicité comme co-existence. Nancy effectue sur l’existence l’opération que Heidegger menait à propos de l’être-au-monde ; en effet, comme Heidegger pouvait dire qu’il n’y a pas d’abord un sujet, puis un monde, puis la question de savoir comment le premier accède au second, Nancy affirme, à propos du Mitsein, de l’être-avec, de la socialité au sens le plus pur et le plus éminent, qu’il n’y a pas d’abord un sujet, un moi, puis un autre moi, puis la question de savoir comment l’un accède à l’autre, et comment ils peuvent communiquer ensemble. Il faut partir de « nous », et du sens que « nous » sommes, donc d’une « analytique coexistentiale ».
Poétique du désir selon Thérèse d’Avila et Jean de la Croix
Authors: Sesé Bernard
Published: June 2024

Dans cet article, initialement publié en 2007 dans l’ouvrage collectif Figures du désir dans la littérature de langue espagnole, Bernard Sesé analyse le désir comme moteur fondamental de l’expérience mystique dans les œuvres de Thérèse d’Avila et de Jean de la Croix.
Exploring human appreciation and perception of spontaneous urban fauna in Paris, France
Authors: Duffaut Chloé , Brondeau Florence , Gasparini Julien
Published: June 2024

City-dwellers are often confronted with the presence of many spontaneous animal species which they either like or dislike. Using a questionnaire, we assessed the appreciation and perception of the pigeon (Columba livia), the rat (Rattus norvegicus), and the hedgehog (Erinaceus europaeus) by people in parks, train stations, tourist sites, community gardens, and cemeteries in Paris, France. Two hundred individuals were interviewed between May 2017 and March 2018. While factors such as age, gender, level of education or place or location of the survey did not appear to be decisive in analyzing the differential appreciation of these species by individuals, there was a clear difference in appreciation based on the species and the perceived usefulness of the animal, which is often poorly understood. The rat was disliked (with an average appreciation score of 2.2/10), and the hedgehog was liked (with an average appreciation score of 7.7/10). The case of the pigeon is more complex, with some people loving or hating it, and many others being indifferent (with an average appreciation score of 4.7/10). The most common descriptor associated with pigeons and rats is the word "dirty", while for for hedgehogs it is "cute". Like Driscoll (1995) who found a positive correlation between perceived usefulness an appreciation given to the species, we assume that providing information to the citizens about the ecosystem services provided by unappreciated urban species could improve their perception of these animals, thus enabling better coexistence.
Nudging Data Privacy of Mobile Health Applications in Saudi Arabia
Authors: Sabur Abdulhakim , Showail Ahmad J.
Published: June 2024

Mobile health apps are a digital era revolution, facilitating direct patient-physician communication, lab and test orders, and medication refills. Despite these benefits, security and privacy issues arise due to handling sensitive data. This paper assesses the security and privacy of Saudi Arabian mobile healthcare apps, gauging compliance with the Personal Data Protection Law (PDPL). Results highlight varied PDPL compliance, underscoring the imperative for enhanced security measures in the digital healthcare landscape.
Algorithm for Automatic Layout of Graphic Language and Its Application in Graphic Design
Authors: Tao Zongxiao
Published: June 2024

When using traditional algorithms to describe graphic languages, the results obtained are not accurate due to the lack of strict standards. In this case, the size and position of the graphic display cannot be accurately determined. Aiming at these problems, we propose a new automatic typesetting algorithm for graphic languages. Use the constant method to calculate the display size of buffered images in graphic design. The ant colony algorithm is used to solve the optimal solution, so that the optimal display position of the graphics in the graphic design can be obtained. Graphics are powerful. For example, excellent graphics such as the presentation of forms, the expression and transmission of information, often make people feel relaxed and empathetic, shorten the distance between each other, and make communication smoother. As a result, graphic languages have become an important part of modern graphic design and are used more and more frequently. This paper attempts to analyze the representation of graphic language, aiming to demonstrate its important role in graphic design.
CONVERSIONE E IMPEGNO CULTURALE DI AGOSTINO GEMELLI IN DUE RECENTI STUDI
Authors: Tira Alessandro
Published: June 2024

The essay takes into account a couple of recent studies about the personal path of Edoardo Gemelli, later known in religion as father Agostino. As a medical student at the University of Pavia and Ghislieri College, Edoardo used to profess socialist ideas, but during his years there, he experienced a spiritual emergency, which urged him to the conversion to the Catholic faith. Figures, friends and the cultural milieu of that time are the matter of the study by Luciano Pazzaglia, who carried out a research about Gemelli’s early life. Also the study by Michele Madonna is closely related to those years and to the same perspective of Gemelli’s social and religious engagement. Here, the author explores the main issues about the relations between Church and State, which were debated during the first thirty years of the Catholic journal “Vita & Pensiero”.
Dynamics of Community Resilience in Flood-prone Areas of Southeast Asia: A Key Component of the Public Health Agenda
Authors: Lugova Halyna , Haque Mainul
Published: June 2024

Communities across Southeast Asia face challenges posed by natural disasters, including floods, which disproportionately impact vulnerable populations. In light of the growing frequency and severity of extreme weather events attributed to climate change, there is a pressing need to explore and strengthen community flood resilience. Community resilience is pivotal in mitigating flood-related damages and fostering successful recovery efforts. This paper examines the socio-economic and environmental factors shaping community resilience in flood-prone areas of Southeast Asia. Socio-demographic determinants, exposure to floods, social cohesion, communication networks, socio-economic status, and cultural diversity significantly influence resilience capabilities, with disparities exacerbating socio-economic inequality. The interplay of these factors underscores the complexity of community disaster resilience, with some factors acting as moderators, mediators, or confounders in shaping outcomes. The paper highlights that understanding the dynamics of community resilience formation is imperative for informed policy interventions to enhance disaster preparedness and response in flood-prone areas of Southeast Asia. The contributors to flood resilience are interrelated with social determinants of health, underscoring the vital role of broader socio-economic and environmental factors in shaping community well-being. Future research should explore the relationships within these complex dynamics to guide effective resilience-building strategies tailored to local contexts.
Assessment of thyroid function in children and adolescents with chronic liver diseases
Authors: Mahfouz Aml A. , Hassan Azza , Raafat Shaymaa
Published: June 2024

Introduction

The majority of hepatic patients are clinically euthyroid. However, liver disorders may alter thyroid hormone metabolism, including substantial abnormalities of either euthyroid sick syndrome (ESS), autoimmune thyroid disorders, or subclinical hypothyroidism (SH). But there are few studies conducted on children with chronic liver diseases (CLD) to assess thyroid functions.

Aim

The study aimed to evaluate thyroid profiles in patients with CLD.

Patients and methods

An observational, cross-sectional study including patients with CLD attending Hepatology Clinic at Alexandria University Children’s Hospital from June 2021 to June 2022. One hundred and two children were included and a history taking and clinical examination were performed. Assessment of severity using a modified Child–Pugh score was done. Laboratory investigations in the form of liver, lipid, and thyroid profiles were done.

Results

One hundred and two children with CLD were included in this study, 50 (49.0%) females and 52 (51.0%) males. The most common diagnosis in the studied cases was autoimmune hepatitis (24.5%), followed by glycogen storage disease. Out of 14 (13.7%) aberrant outcomes of thyroid function, seven (6.9%) patients had ESS, and seven (6.9%) individuals had SH. By univariate analysis, alkaline phosphatase and serum albumin level were significant risk factors for SH. Furthermore, melena and hepatic encephalopathy were significant risk factors for ESS.

Conclusion

Thyroid dysfunction might occur in CLDs either in the form of SH or ESS. The prevalence of thyroid disease in children with CLD exceeded 10%, which signifies the importance of screening for thyroid dysfunctions in this cohort.
Risk factors, antimicrobial susceptibility, and outcome of methicillin-resistant Staphylococcus aureus bacteremia in critically ill children with sepsis in a tertiary hospital in Egypt
Authors: El-Halaby Hanan , Elbayoumi Mohamed A. , Elhusseiny Ahmed , El-Shahawy Heba A. , Noaman Ahmed
Published: June 2024

Background

Staphylococcus aureus bacteremia (SAB) and methicillin-resistant Staphylococcus aureus (MRSA) infection are associated with unfavorable outcomes.

Aim

To reveal the risk factors, sensitivity to antibiotics, and outcome of MRSA bacteremia in infants and children with sepsis.

Settings and design

A prospective observational cross-sectional study was performed in Mansoura University Children’s Hospital from March 2023 to January 2024.

Patients and methods

The study involved infants and children diagnosed with sepsis and confirmed SAB on blood culture. Demographic data and blood culture with antibiotics sensitivity were recorded. Risk factors for MRSA bacteremia, antibiotic susceptibility, and mortality are the study outcomes.

Statistical analysis used

Multivariate analysis was done to assess the predictors of MRSA infection.

Results

A total of 319 patients were admitted with sepsis. SAB was isolated from 133 patients, 99 (74.4%) with methicillin-sensitive Staphylococcus aureus and 34 (25.6%) with MRSA. Risk factors for the development of MRSA infection are the presence of hospital-acquired infection (adjusted odds ratio=6.95), prolonged mechanical ventilation, presence of shock, and decreased body weight. Mortality was higher in the MRSA group (20.6 vs. 6.1%, P=0.014) with prolonged median duration of pediatric intensive care unit admission (19.5 vs. 14 days; P=0.040). Linezolid and teicoplanin were the most efficient antibiotics used in MRSA with 100% sensitivity in-vitro cultures, whereas resistance to erythromycin (90.9%) was documented.

Conclusion

MRSA poses a significant threat in pediatric sepsis. The presence of hospital-acquired infection and prolonged mechanical ventilation are the chief predictors of MRSA infection. Linezolid and teicoplanin are the most sensitive antibiotics used in MRSA management.
Evaluation of Serum Vitamin D Level in Full-Term Neonates with Hypoxic–Ischemic Encephalopathy
Authors: Elgayar Ahmed A. , El-Sharkawy Hamed M. , El-Bindary Amal S. , Nassar Mohamed A. , Hamza Mohamed B.
Published: June 2024

Background

Vitamin D has a role in minimizing the extent of neuronal cell injury and death in neonatal hypoxic–ischemic encephalopathy (HIE).

Aim

To assess the serum level of vitamin D in full-term babies with HIE.

Patients and methods

This case–control study was conducted on 40 full-term neonates. Cases were grouped into two groups: group A: 30 full-term neonates diagnosed as HIE; clinical diagnosis was based on Sarnat staging. Group B: 10 healthy full-term neonates. Patients in group A were further subdivided into three equal groups: group A1: grade I HIE, group A2: grade II HIE, and group A3: grade III HIE.

Results

The following investigations were done for groups A and B: Apgar score after 1 and 5 min, convulsions, metabolic acidosis need for respiratory support, blood urea, serum creatinine, C-reactive protein level, serum calcium levels, and 25(OH) vitamin D measurements at 12 and 72 h postnatal. Apgar score, pH, total and ionized calcium, and 25(OH)-D were significantly reduced in HIE (specially grade III), while blood urea, serum creatinine, and C-reactive protein were significantly higher in HIE neonates (grade III).

Conclusion

We could assume that the more severe the grade of HIE, the worse are the laboratory findings.
Transferrin receptor 1 rs3817672 variant genotyping in Egyptian children diagnosed with iron-deficiency anemia: a case–control study
Authors: El-Gendy Wessam , Hassab Hoda , Ismail Hamis , Tahoun Mona
Published: June 2024

Background

Cell surface transferrin receptor 1 (TFR1) is a gatekeeper controling cellular iron uptake. The association of iron-deficiency anemia (IDA) in humans with TFR1 variants was not extensively studied. Among these variants is TFR1 rs3817672, an exonic missense variation that may affect the TFR1 protein structure. This is the first study in Egypt and the second worldwide that genotype TFR1 rs3817672 variant in IDA pediatric patients.

Aim

The aim of the current study was to investigate the association between TFR1 rs3817672 variant with susceptibility risk for IDA.

Patients and methods

The study was conducted on 50 IDA Egyptian pediatric patients and 50 healthy controls. Complete blood count, iron profile, and TFR1 rs3817672 variant genotyping were performed for all participants.

Results

TT genotype was associated with a high risk of IDA among cases compared to controls in the recessive model (odds ratio 24, 95% confidence interval 5.253–109.650, P≤0.001) with the predominance of T allele (odds ratio 7.3187, 95% confidence interval 3.919–13.669, P≤0.001). TT genotype was associated with a significant decrease in serum iron (P=0.001 and 0.003) and transferrin saturation (P=0.003 and 0.005) compared to CT genotype and CC+CT genotypes in the recessive model, respectively. In IDA patients, serum iron had a significant positive correlation with transferrin saturation (r=0.984, P≤0.001) and a significant negative correlation with total iron-binding capacity (r=−0.555, P≤0.001).

Conclusion

TT genotype was the predominant genotype among Egyptian pediatric IDA patients. TFR1 rs3817672 genotyping might be used as a potential screening test for IDA risk susceptibility in pediatrics.
Prevalence and outcome of inborn errors of metabolism among high-risk neonates: an Egyptian single-center study
Authors: Mokhtar Wesam A. , Hesham Mervat A. , Abdo Shams S.
Published: June 2024

Background

Inborn errors of metabolism (IEM) are genetic disorders caused by incompetence in enzymatic reactions of intermediary metabolism due to an insufficient amount or unstable form of the involved enzyme.

Aim

To assess the prevalence and outcome of IEM among high-risk neonates for early diagnosis and detection of treatable causes to minimize morbidity and mortality rate in neonates.

Methods

This cross-sectional study was carried out on 684 neonates at the Neonatal Intensive Care Unit in the Pediatrics Department at Zagazig University Children’s Hospital from February 2020 to February 2023. Extended metabolic screen (EMS) was done for full-term neonates and preterm of more than 32 weeks of gestation. Further investigations such as plasma ammonia, plasma lactate, urine organic acid analysis, blood gas, serum anion gap, and the blood glucose level were also measured.

Results

The prevalence of IEM was 4.4%. The most common presentations among the cases of IEM were not doing well, respiratory distress, encephalopathy, and convulsion. As regards provisional diagnosis, 11 cases were diagnosed as maple syrup urine disease, 5 cases with glycine encephalopathy, 5 cases with medium-chain acyl CoA dehydrogenase deficiency,4 cases with methylmalonic acidemia, 2 cases with isovaleric acidemia, 2 cases with citrullinemia type 1, and one case with propionic academia; 12 (40%) of IEM cases died.

Conclusion

IEM disorders are not rare diseases in high-risk neonates with attention to consanguinity, which is a common tradition in our country. The delay in diagnosis of IEM leads to high morbidity and mortality.
Prevalence and impact of interleukin-6 and interleukin-10 polymorphisms in Egyptian children with immune thrombocytopenic purpura
Authors: Ramadan Hala , Mahmoud Mona M. , Elhawary Eslam E. , Hablas Nahed M.
Published: June 2024

Background

Recent findings demonstrate that complex immune system dysregulation plays a role in the etiology of immune thrombocytopenic purpura (ITP) Aim

Aim

The current study aimed to assess the prevalence and impact of interleukin-6 (IL-6) and IL-10 polymorphisms and levels in Egyptian children with ITP.

Patients and methods

In this case–control study, 25 Egyptian children with newly diagnosed ITP took apart. Their mean age was 9±2.56. They were treated at Tanta University Hospital’s Hematology Unit, Pediatric Department. Furthermore, 25 healthy age-matched and sex-matched children were included as controls. Both groups were subjected to complete blood count, PCR for IL-6 572G>c=rs1800796 and IL-10 627A>C=rs1800872, and enzyme-linked immunosorbent assay measurement of serum levels of IL-6 and IL-10.

Results

Eight percent of our patients tested positive for IL-6 (572) polymorphism (G/C), 4% tested positive in controls. Meanwhile 4% of cases tested positive for IL-10 (627) polymorphism (A/C), indicating that there was no statistically significant difference between groups. Patients’ levels of IL-6 and IL-10 were considerably higher (P<0.0001). Moreover, there was a statistically significant difference between the acute and chronic cases, with the former having a higher level. The levels of IL-6 and IL-10 and the platelet count showed a statistically significant strong negative correlation.

Conclusion

IL-10 polymorphisms are thought to play a part in the pathogenesis of childhood ITP. Moreover, IL-6, seems to predict susceptibility to primary ITP in Egyptian children making both promising biomarkers of clinical progression. However, a sizable prospective study is required to find out how cytokine gene polymorphisms affect childhood ITP.
Diagnostic and Prognostic Value of DNA Repair Gene XRCC1 ARG399GLN Polymorphism in Childhood Acute Lymphoblastic Leukemia: A Single-Center Egyptian Study
Authors: Hablas Nahed M. , Mahmoud Mona M. , Qassem Shaima S. , Morad Lamia M.
Published: June 2024

Background

Repair pathways for DNA damage are essential for repairing various forms of DNA damage. Leukemia risk may be increased by poor DNA repair. This study was conducted to better understand the significance of XRCC1Arg399 Gln polymorphisms in acute lymphoblastic leukemia (ALL) susceptibility and prognosis.

Patients and methods

Twenty children with ALL participated in the pediatric trial at Tanta University. Thirty healthy controls were of the same age and sex. Complete blood counts, bone marrow aspirates, immunophenotyping, flow cytometry, and XRCC1 genotyping by PCR were performed.

Results

The allele Gln/Gln was found in one (3.3%) of the controls and two (10%) cases had an odds ratio of 0.13 (0.27–38.1), P=0.34. Eight (40%) patients and six controls [odds ratio of 2.66 (0.75–9.4), P=0.11], had the Arg/Gln allele. Finally, 23 (76.7%) members of the control group and 10 (50%) patients carried this allele (Arg/Arg). The genotype’s prognostic value for alleles: two (20%) of patients with the allele (Arg/Arg) were refractory. Two (25%) patients died during the induction for the allele (Arg/Gln), while four (50%) patients were refractory. Last but not least, no one experienced total remission under the allele (Gln/Gln).

Conclusion

The XRCC1 polymorphism is not linked to the development of ALL; nevertheless, having mutant alleles was linked to a poorer prognosis.
Body composition analysis in children with chronic kidney disease on regular hemodialysis
Authors: Elbarky Amany , El-Kaffas Asmaa , Gamal Rasha M. , Abdelnabi Hend H. , Elrifaey Shymaa
Published: June 2024

Background

Children with chronic kidney disease (CKD), particularly those on hemodialysis, are at high risk for protein-energy malnutrition.

Aim

In this study, we aimed to analyzed the nutritional parameters of children with CKD undergoing hemodialysis (HD) by performing a body composition analysis.

Patients and methods

This cross-sectional study included 40 children undergoing HD and 50 matched controls. All participants underwent a 3-day dietary recall, anthropometric measurements, nutritional and laboratory assessments, and finally a bioelectrical impedance analysis was conducted using the TANITA Body Composition Analyzer.

Results

Anthropometric measures, caloric and protein intake were significantly reduced in cases compared with controls. The children undergoing HD had lower body composition (fat mass, fat mass index, fat-free mass index, skeletal muscle mass, total body water%, basal metabolic rate, and phase angle) when compared with controls.

Conclusions

Children with CKD, especially those on HD, have poor nutritional status and need regular comprehensive assessment using bioelectrical impedance analysis to improve growth outcomes.
High prevalence of cagA positive Vac A s1m1 Helicobacter pylori strains isolated from patients suffering from various gastroduodenal diseases in Guwahati, Assam, India
Authors: Mahant Shweta , Singh Sarika , Dutta Sangitanjan , Sharma Nisha , Das Prasenjit , Mukhopadhyay Asish Kumar , Das Kunal , Das Rajashree
Published: June 2024

Aim and Background:

Genotyping of H. pylori strains was identified on formalin-fixed paraffin wax-embedded tissue (FFPE) sections and correlated with severity grades of gastric mucosal pathologies in biopsies from upper gastrointestinal (UGI) tract from Guwahati, Assam.

Materials and Methods:

In total, 168 gastric biopsies collected from patients with UGI symptoms underwent histological evaluation as per the updated Sydney system.

Result:

H. pylori-like organisms were identified with Warthin and Starry stain, and virulent genes were amplified using polymerase chain reaction (PCR) from genomic DNA extracted from FFPE sections by using QIAamp® DNA FFPE Tissue Kit. Histological examination identified H. pylori-like organisms in 100 biopsies, of which 96 were urease + ve. The prevalence of H. pylori infection was high in age groups 71–80 (88.8%) as compared to other age groups, and it was higher in females (78.9%) when compared to males. The prevalence of virulent genes in biopsies was 88.5% cagA and vacA s1m1, 31.2% iceA1, 32.2% iceA2, and 85.2% babA2. The histological parameters mononuclear cell infiltrate (P = 0.04) and atrophy (P = 0.03), showed statistically significant association with iceA2 and intestinal metaplasia with cagA (P = 0.01) vacAs1m1 (P = 0.01) and babA (P = 0.02) genotypes. Gastric erosion due to H. pylori infection and atrophy showed a significant association. A high bacterial density score was seen with the virulent genotypes.

Conclusion:

Our work reports for the first time a high prevalence (88.5%) of H. pylori cagA vacA s1m1 genotype in Guwahati, Assam. Association of gastric atrophy and intestinal metaplasia was seen with virulent genotypes. Results show the effectiveness of the FFPE kit for DNA extraction in remote areas where transportation and storage of biopsies are otherwise difficult.
Higher expression of BRCA1, and CHUK and lower expression of NFKBIA, ESR1, PIK3R1, and PPARG in HAM/TSP compared to ATLL, a diverse pathological consequence
Authors: Yaslianifard Sahar , Movahedi Monireh , Yaslianifard Somayeh , Mozhgani Sayed-Hamidreza
Published: June 2024

Background:

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL) are both severe diseases caused by Human T-lymphotropic virus type 1 (HTLV-1) infection, while about 95% of infected cases remain asymptomatic. Genes that play a role in ATLL development are assumed to be dissimilar from the ones that are crucial factors for HAM/TSP occurrence.

Objective:

The expression of six genes including BRCA1, CHUCK, ESR1, NFKBIA, PIK3R1, and PPARG were assessed in two groups of HAM/TSP and ATLL patients. Materials and Methods: cDNA was synthesized from purified RNA, and RT-qPCR was conducted to assess the expression of the genes in two groups. Any possible correlation among the genes’ expression was also calculated. Results: BRCA1 and CHUCK expressions were higher in HAM/TSP patients in comparison with ATLL patients. However, ESR1, NFKBIA, PIK3R1, and PPARG are more expressed in ATLL cases than HAM/TSP. A significant positive correlation was observed between BRCA1 and NFKBIA in HAM/TSP group. In addition, a significant negative correlation between PIK3R1 and PPARG in HAM/TSP and between ESR1 and NFKBIA in the ATLL group was obtained.

Conclusion:

HAM/TSP or ATLL stem from a disturbance in the expression of diverse genes and these dissimilarities should be discovered to reach a better understanding of disease treatment as well as screening and assessing the asymptomatic carriers’ condition for developing severe disease.
Variations in platelet indices in patients with diabetes mellitus and hypertension: A case-control study from a tertiary hospital in North Bengal
Authors: Roy Poulami , Deb Novonil , Lahiri Pratibha Rao , Goswami Bidyut Krishna
Published: June 2024

Background:

Platelet indices (PI) have emerged as a useful tool for identifying platelet dysfunction and cardiovascular risk in various diseases, including diabetes mellitus (DM) and hypertension. This study aimed to investigate the variation of PI in patients with DM and hypertension in the northern part of West Bengal.

Materials and Methods:

A case-control study was conducted, which included 1096 participants, comprising 264 healthy controls, 472 individuals with DM, 220 individuals with hypertension, and 140 individuals with both hypertension and DM. PI were measured using automated hematology analyzers, and statistical analysis was performed to determine the differences in PI among the different groups.

Result:

The study results revealed that PI were significantly higher in individuals with DM and hypertension compared to healthy controls. The mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR) were significantly higher in patients suffering from DM, hypertension and both when compared to healthy controls.

Conclusion:

The findings of this study suggest that PI can be used as a reliable and cost-effective tool for identifying platelet dysfunction and cardiovascular risk in individuals with DM and hypertension. PI can serve as a useful collaborative tool for identifying individuals at high risk of cardiovascular events in these conditions.
Assessment of cyclin D1 activity in tumors and tumor budding and its prognostic significance in tumor budding in colorectal carcinomas
Authors: Coban Ganime , Arici Dilek S. , Tekden Busra C. , Yildiz Pelin , Kiran Tugce , Toluk Özlem , Turk Haci M. , Şahin Nurhan
Published: June 2024

Background:

The most important prognostic parameter is staging in colorectal cancers, and tumor budding (TB) is among the independent prognostic parameters that are increasing in significance. Cyclin D1 expression has been associated with poor prognosis as a marker of various tumors.

Aims and Objectives:

In this study, the aim was to determine the activity of cyclin D1 in colon adenocarcinomas, tumors, and tumor buds and to compare the results with prognostic parameters.

Materials and Methods:

This study included 167 patients who were operated on for colorectal tumors. In subjects, tumor budding was evaluated on hematoxylin and eosin-stained slides, and cyclin D1 was applied immunohistochemically. The cyclin D1 intensity of staining was studied in both tumors and TB and its correlation with prognostic parameters in TB was examined.

Results:

Lymph node (LN) metastasis was present in 93 (55.7%) of the cases, and distant metastasis in 35 (21%) cases. Tumor budding was present in 152 (91%) of the cases, and high-grade TB was detected in 55 (36.2%). The incidence of TB was higher in patients with LN metastasis (P = 0.02) and in patients with Stages 3 and 4 (P = 0.07). The intensity of cyclin D1 in intermediate and high-grade TB staining was higher. Cyclin D1 staining was more intense in patients with LN metastases and distant metastases as we determined, but it was not statistically significant.

Conclusion:

Thus, based on our study findings, the increased expression of cyclin D1, which is more concentrated in TB than tumors, may indicate a poor prognosis. In contrast, we found no statistically significant correlation between cyclin D activity and prognostic parameters in TB.
The immunohistochemical expression of c-MET and RON in lung adenocarcinoma with clinicopathologic correlation
Authors: Kim Young-Ah , Sung Woo Jung
Published: June 2024

Background:

Mesenchymal epidermal transition (MET) and receptor originating from nantes (RON) are transmembrane tyrosine kinase receptors. Both are members of a proto-oncogene family and thus play a role in the pathogenesis of various cancers and acquired resistance to kinase inhibitors in lung cancer.

Aims:

The aim of this study was to investigate the immunohistochemical expression of c-MET and RON in lung adenocarcinoma and its clinicopathologic correlation.

Settings and Design:

Retrospective study.

Materials and Methods:

The immunohistochemical c-MET and RON expression in specimens obtained from lung adenocarcinoma (n = 175) and associated clinicopathologic parameters were evaluated.

Statistical Analysis Used:

The correlation between c-MET and RON expression was analyzed by Chi-square test. A Cox proportional hazards model and Kaplan-Meier curve analysis were used to evaluate the risk factors and prognosis.

Results:

High expression of the c-MET protein showed a strong correlation with that of RON (P = 0.013, kappa = 0.183). Five-year survival and recurrence-free 5-year survival were not associated with high expression of c-MET or RON. High c-MET expression was significantly associated with age older than 60 years (P = 0.000), tumor differentiation (P = 0.009), lymphovascular invasion (P = 0.016), and pleural invasion (P = 0.005). High RON expression was associated with a solid growth pattern (P = 0.001) and pleural invasion (P = 0.002).

Conclusions:

The results point to the potential of immunohistochemical expression of c-MET and RON as useful prognostic markers of unfavorable histopathologic features in lung adenocarcinoma.
Renal allograft failure resulting from diffuse cortical necrosis
Authors: Fernandes Gwendolyn , Patil Manali , Harinkhede Nupur , Khumanthem Gloria , Rojekar Amey
Published: June 2024

Cortical necrosis of the renal allograft is an extremely rare but serious complication of renal transplantation and can lead to graft failure. Few cases have been reported in the literature to date. We present a rare case of a 28-year-old woman with chronic kidney disease for the past four years who was on biweekly hemodialysis and referred to our tertiary care center for a living-related renal transplant. The patient developed tacrolimus toxicity on the second day post-transplant. The renal biopsy performed on third day after transplant showed ischemic acute tubular injury. C4d and donor-specific antibodies were negative. On day 12 post-transplant, USG Doppler of the renal allograft showed thrombosis of the renal vein, and an open wedge biopsy was performed that showed extensive renal cortical necrosis. A month and half later, the patient developed pus collection anterior to the transplanted kidney and a fistula from the perinephric space up to the skin with persistent pus discharge. Two months later, a graft nephrectomy was performed, and diffuse cortical necrosis of renal allograft with a thick band of exudate on the capsule was diagnosed on histopathology. Ureteral necrosis and thrombosis of both renal artery and renal vein were also seen. In this case, the etiology of graft cortical necrosis is multifactorial and includes acute ischemia, urologic complications, and sepsis. To prevent graft failures, it is critical to differentiate thrombosis caused by surgical complications from hyperacute or acute humoral rejection.
An unusual case of scalp ulceration
Authors: Gupta Sonali , Singh Poonam , Asati Dinesh P. , Gowda Shreya K.
Published: June 2024

Granulomatosis with polyangiitis, a form of necrotizing vasculitis can present as a limited variant with the involvement of a single organ system. The superficial protracted form can present as face and scalp ulceration for chronic periods of time. Diagnosis can be established histopathologically by examining the involvement of blood vessels. Here, we present a case of scalp ulceration that was diagnosed as a limited variant and started on steroids and immunosuppressants with excellent response.
Karyomegalic interstitial nephritis, a fascinating histopathologic entity for pathologists: Be watchful of the FAN1 gene mutations
Authors: Walia Gurpreet K. , Vankalakunti Mahesha , Akal Ramanjit S. , Jha Vijoy K.
Published: June 2024

Karyomegalic interstitial nephritis (KIN) is an uncommon autosomal recessive disease, which is characterized by enlarged and hyperchromatic nuclei of the renal tubular epithelial cells. It is associated with mutations in Fanconi anemia-associated nuclease 1 gene, which is responsible for DNA repair, and these pathogenic mutations are responsible for progressive renal failure in young adults. We present a case of a 29-year-old female with end-stage renal disease who had a family history of early-onset renal failure in two of the siblings. Her elder sister with chronic kidney disease stage III was advised to be biopsied to look for any familial causes. Stained sections of renal biopsy revealed normal glomeruli. Tubular epithelial cells showed nuclear changes focally like hyperchromasia, karyomegaly, and anisonucleosis. On direct immunofluorescence, all glomeruli were negative for deposits with all antisera. Based on these findings, a final opinion of KIN was given.
Bing–Neel syndrome: A rare complication of waldenstrom macroglobulinemia
Authors: Kudva Ranjini , Monappa Vidya , Menon Girish
Published: June 2024

Central nervous system involvement is a rare complication of Waldenstrom macroglobulinemia (WM) accounting for 1–2% cases. This syndrome is called Bing–Neel syndrome (BNS) after the people who first described it in 1936. Although WM has a good prognosis, with the onset of this syndrome, most patients fare poorly with a high mortality rate. A 77/male, a known case of WM, presented with left upper limb weakness of 2 weeks duration. Magnetic resonance imaging brain showed diffuse pachymeningeal thickening along bilateral frontoparietal convexity. Biopsy showed lymphoplasmacytic lymphoma favoring a diagnosis of BNS. The patient was started on chemotherapy (rituximab + ibrutinib). At 3 months following diagnosis, the patient was admitted with Gram-negative septicemic shock and failed to recover from it. BNS is a rare complication of WM, associated with poor prognosis and an aggressive clinical course. It can occur during the course of treatment of WM, as was seen in this case. Accurate diagnosis with appropriate treatment plays a crucial role in patient management.
Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions
Authors: Pérez-Núñez Ramón , González María Fernanda , Avalos Ana María , Leyton Lisette
Published: June 2024

Astrocytes are the most abundant type of glial cell in the central nervous system. Upon injury and inflammation, astrocytes become reactive and undergo morphological and functional changes. Depending on their phenotypic classification as A1 or A2, reactive astrocytes contribute to both neurotoxic and neuroprotective responses, respectively. However, this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries. Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles, which emphasizes the heterogeneous nature of their reactivity. Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types, releasing cytokines, and influencing the immune response. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior, as evidenced by in silico, in vitro, and in vivo results. In astrocytes, inflammatory cues trigger a cascade of molecular events, where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses. Here, we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation. We highlight the involvement of various signaling pathways that regulate astrocyte reactivity, including the PI3K/AKT/mammalian target of rapamycin (mTOR), αvβ3 integrin/PI3K/AKT/connexin 43, and Notch/PI3K/AKT pathways. While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage, evidence suggests that activating this pathway could also yield beneficial outcomes. This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation. The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior. The findings should then be validated using in vivo models to ensure real-life relevance. The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage, although further studies are required to fully comprehend its role due to varying factors such as different cell types, astrocyte responses to inflammation, and disease contexts. Specific strategies are clearly necessary to address these variables effectively.
Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds
Authors: Masone Antonio , Zucchelli Chiara , Caruso Enrico , Musco Giovanna , Chiesa Roberto
Published: June 2024

PrPSc, a misfolded, aggregation-prone isoform of the cellular prion protein (PrPC), is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, posing challenges for the development of effective therapies. Since PrPC is the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity, it represents an attractive therapeutic target for prion diseases. In this minireview, we briefly outline the approaches to target PrPC and discuss our recent identification of Zn(II)-BnPyP, a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action. We argue that in-depth understanding of the molecular mechanism by which Zn(II)-BnPyP targets PrPC may lead toward the development of a new class of dual mechanism anti-prion compounds.
Association between vedolizumab and risk of clostridium difficile infection in patients with ulcerative colitis: A systematic review and meta-analysis
Authors: Alghamdi Maha , Alyousfi Dareen , Mukhtar Mariam S. , Mosli Mahmoud
Published: June 2024

Background:

The medical treatment of ulcerative colitis (UC) includes the use of biological agents such as vedolizumab, a gut-selective alpha4beta7 (ɑ4β7) antagonist. The mechanism of action of vedolizumab involves interfering with leukocyte trafficking into the gut vasculature, which halts inflammation. Due to this mechanism of action, concerns have arisen regarding an increased risk of gut infections, specifically, clostridium difficile infection (CDI). The aim is to provide clarity regarding the association between the use of vedolizumab as a therapy for ulcerative colitis and the risk of developing CDI.

Methods:

A systematic literature review was conducted, starting with the scoping search, followed by backward snowballing parallel with keyword-based search to identify related articles. A quality assessment was conducted on the initially selected articles and excluded low-quality papers.

Results:

Pooled analyses indicated that there was no significant association between the use of vedolizumab and the risk of developing CDI (effect size = 0.03 [-0.02, 0.07]).

Conclusions:

Vedolizumab does not increase the risk of CDI in patients with UC. Further studies are needed to confirm these findings.
A benign masquerade of eyelid malignancy: Discoid lupus erythematosus
Authors: Durairaj Arjun , Arora Rohan , Menon Vikas , Subramanian Krishnakumar
Published: June 2024

A 50-year-old female presented with redness and itching over her right lower eyelid for 6 months. She had a diffusely hyperpigmented lesion with a purplish hue over her right lower eyelid. There was diffuse loss of eyelashes and obliteration of meibomian gland openings along the lesion. The ocular examination was otherwise unremarkable. In view of the clinical features, the possibility of squamous cell carcinoma was considered, and an incisional biopsy was performed. Histopathology was suggestive of discoid lupus erythematosus. The patient was treated with oral hydroxychloroquine sulfate for 6 months. The lesion regressed, and no new lesions developed over a 2-year follow-up. This report showcases how a benign lesion can rarely present with clinical features classically associated with a malignant pathology and highlights the importance of histopathological evaluation for proper diagnosis.
Safe Utilization and Sharing of Genomic Data: Amendment to the Health and Medical Data Utilization Guidelines of South Korea
Authors: Park Hyojeong , Park Jongkeun , Woo Hyun Goo , Yun Hongseok , Lee Minho , Hong Dongwan
Published: June 2024

Purpose In 2024, medical researchers in the Republic of Korea were invited to amend the health and medical data utilization guidelines (Government Publications Registration Number: 11-1352000-0052828-14). This study aimed to show the overall impact of the guideline revision, with a focus on clinical genomic data.Materials and Methods This study amended the pseudonymization of genomic data defined in the previous version through a joint study led by the Ministry of Health and Welfare, the Korea Health Information Service, and the Korea Genome Organization. To develop the previous version, we held three conferences with four main medical research institutes and seven academic societies. We conducted two surveys targeting special genome experts in academia, industry, and institutes.Results We found that cases of pseudonymization in the application of genome data were rare and that there was ambiguity in the terminology used in the previous version of the guidelines. Most experts (>~90%) agreed that the ‘reserved’ condition should be eliminated to make genomic data available after pseudonymization. In this study, the scope of genomic data was defined as clinical next-generation sequencing data, including FASTQ, BAM/SAM, VCF, and medical records. Pseudonymization targets genomic sequences and metadata, embedding specific elements, such as germline mutations, short tandem repeats, single-nucleotide polymorphisms, and identifiable data (for example, ID or environmental values). Expression data generated from multi-omics can be used without pseudonymization.Conclusion This amendment will not only enhance the safe use of healthcare data but also promote advancements in disease prevention, diagnosis, and treatment.