bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRF2 loss is associated with reduced MHC I pathway transcripts in subsets of most human cancers and causes resistance to checkpoint immunotherapy in human and mouse melanomas
Authors: Sari Gulce , Dhatchinamoorthy Karthik , Orellano-Ariza Laura , Ferreira Lindsay M , Brehm Michael A. , Rock Kenneth 
Published: September 2024

Abstract

Background
In order for cancers to progress, they must evade elimination by CD8 T cells or other immune mechanisms. CD8 T cells recognize and kill tumor cells that display immunogenic tumor peptides bound to MHC I molecules. One of the ways that cancers can escape such killing is by reducing expression of MHC I molecules, and loss of MHC I is frequently observed in tumors. There are multiple different mechanisms that can underly the loss of MHC I complexes on tumor and it is currently unclear whether there are particular mechanisms that occur frequently and, if so, in what types of cancers. Also of importance to know is whether the loss of MHC I is reversible and how such loss and/or its restoration would impact responses to immunotherapy. Here, we investigate these issues for loss of IRF1 and IRF2, which are transcription factors that drive expression of MHC I pathway genes and some killing mechanisms.
Methods
Bioinformatics analyses of IRF2 and IRF2-dependent gene transcripts were performed for all human cancers in the TCGA RNAseq database. IRF2 protein-DNA-binding was analyzed in ChIPseq databases. CRISRPcas9 was used to knock out IRF1 and IRF2 genes in human and mouse melanoma cells and the resulting phenotypes were analyzed in vitro and in vivo.
Results
Transcriptomic analysis revealed that IRF2 expression was reduced in a substantial subset of cases in almost all types of human cancers. When this occurred there was a corresponding reduction in the expression of IRF2-regulated genes that were needed for CD8 T cell recognition. To test cause and effect for these IRF2 correlations and the consequences of IRF2 loss, we gene-edited IRF2 in a patient-derived melanoma and a mouse melanoma. The IRF2 gene-edited melanomas had reduced expression of transcripts for genes in the MHC I pathway and decreased levels of MHC I complexes on the cell surface. Levels of Caspase 7, an IRF2 target gene involved in CD8 T cell killing of tumors, were also reduced. This loss of IRF2 caused both human and mouse melanomas to become resistant to immunotherapy with a checkpoint inhibitor. Importantly, these effects were reversible. Stimulation of the IRF2-deficient melanomas with interferon induced the expression of a functionally homologous transcription factor, IRF1, which then restored the MHC I pathway and responsiveness to CPI.
Conclusions
Our study shows that a subset of cases within most types of cancers downregulates IRF2 and that this can allow cancers to escape immune control. This can cause resistance to checkpoint blockade immunotherapy and is reversible with currently available biologics.
The effects of chrononutrition, chronotype and sleep behavior variabilities on adiposity traits and appetite sensations among a sample of urban Malaysian adults: a cross-sectional study
Authors: Say Yee-How , Nordin Mimi Shamirah , Ng Alvin Lai Oon 
Published: September 2024

Abstract

Background
We investigated the association of chrononutrition (circadian timing of food intake) and sleep behavior (sleep time, wake up time, sleep duration) variabilities, and chronotype with adiposity traits and appetite sensations among a sample of urban Malaysian adults at Sunway City.
Methods
A total of 220 participants (M/F = 57/163; aged 22.02 ± 5.19), recorded their meal times, dietary intake, and appetite sensations (via Visual Analogue Scale) before and after meals, for two weekdays and one weekend. Sleep behavior was tracked objectively using an activity wristband, while chronotype was assessed by the Morningness-Eveningness Questionnaire. Anthropometrics and body compositions like waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), total body fat (TBF), visceral fat level (VFL), skeletal muscle percentage (SM) and resting metabolism (RM) were measured.
Results
Chrononutrition and sleep behaviors did not differ significantly between genders, but overall participants had significantly later breakfast, lunch, eating midpoint, wake up time, sleep duration, lunch and afternoon latencies during weekend, compared to weekdays. Those who belonged to the delay eating jetlag group had significantly higher weekday, but lower weekend eating windows. Larger caloric intake later in the day was significantly associated with lower BMI, TBF and VFL, but higher SM. Interestingly, higher days of skipping breakfast were significantly associated with lower WC, WHR, and RM. Delay lunch and eating jetlag classes were significantly associated with higher WHR and SM, respectively. Delayed morning and afternoon chrononutrition behaviors were associated with higher hunger and eating thoughts, and lower fullness sensations pre- and post-meals. The morning chronotype was associated with lower satisfaction and fullness sensations post-breakfast, but higher same sensations pre-dinner.
Conclusions
In conclusion, our study found that larger caloric intake later in the day and advanced lunch jetlag led to lower adiposity, which could be due to lower pre- and post-meal hunger sensations associated with healthier chrononutrition behaviors and morning chronotype. However, the notion of breakfast-skipping leading to obesity was not supported. Here, we offered new insights into modern eating and sleeping habits influencing adiposity and appetite sensations.
Knowledge, attitude and practice about effects of oil pulling and its health benefits among Undergraduate Dental students in Bareilly city:A cross sectional study
Authors: De Sriparna , Sharma Shivangi , N Sathyajith , Vashisth Pallavi , Dua Rasleen , Maheshwari Priya 
Published: September 2024

BACKGROUND-Despite the growing and advancing technological methods of treating various diseases, the most straightforward and less complicated method of treating diseases without any side effects dates back to ancient ayurvedic herbs and practices.
AIM-This survey was conducted to evaluate and compare the knowledge,attitude and practice of the dental students towards oil pulling and its role in maintaining oral hygiene.
METHODOLOGY-This survey was conducted using a pre-validated questionnaire consisting of 16 questions about the knowledge,attitude and practice regarding oil pulling and its effects on oral health that was circulated among the dental students.Descriptive statistics was used in terms of the frequency and percentage and the independent t-test were employed to check the association between the survey questions.
RESULTS-Out of 120 dental students, 61.7% knew what oil pulling is. Although 49.2% think that dentist should prescribe oil pulling for maintenance of oral hygiene,40.8% are not sure whether it can be used for daily use.
CONCLUSION-This study highlights need for educational interventions on the importance of oil pulling.More awareness needs to be created among the dental students regarding how oil pulling positively influences oral health and serves to be an affordable and less harmful alternative to chemical medication.
Dynamics of postural control indicators during postneonatal medical habilitation in infants with impaired motor development, born at different gestational ages
Authors: Samsonova T. V. , Krivonogov V. A. , Nazarov S. B. 
Published: September 2024

Abstract. Diseases of the nervous system, among which perinatal lesions of the central nervous system and their consequences, occupy a leading place in the structure of morbidity and disability in infants of the first year of life. An urgent clinical task is to search for new objective criteria for the effectiveness of ongoing treatment and rehabilitation measures in patients who suffered perinatal lesions of the nervous system. Purpose. To assess the dynamics of postural control indicators during the postneonatal medical habilitation in infants with impaired motor development, born at different gestational ages. Material and methods. We examined 64 infants of the first year of life with impaired motor development, born at different stages of gestation (main group) and 16 healthy full-term infants (control group). Patients of the main group were divided into 4 subgroups: 1st (n = 16) were extremely premature, 2nd (n = 16) — moderately premature, 3rd (n = 16) — late preterm and 4th (n = 16) — full-term infants. The examination was conducted at 3–4 months of calendar (for full-term) and corrected (for premature babies) age and included a clinical assessment of postural control and computer stabilography, which were conducted before and after completion of the course of medical habilitation. Results. The severity of the dynamics of postural control indicators in infants of different gestational ages with impaired motor development was different and was maximum in very premature patients. Conclusion. The identified features of the dynamics of clinical and functional indicators in infants of the studied subgroups indicate the prospect of further development of objective criteria for assessing the effectiveness of treatment and habilitation measures. Their use will help ensure a personalized approach to the management of patients with motor development disorders and increase the effectiveness of medical habilitation.
Associations of polymorphisms of glutathione-S-transferase and N-acetyltransferase 2 genes in children with acute lymphoblastic leukemia
Authors: Sjemschikova Yu. P. , Stepanenko L. A. , Peretolchina N. P. , Bokova T. A. , Barzunova T. V. , Kozlov Yu. A. , Malov S. I. , Tolmacheva O. P. , Malov I. V. 
Published: September 2024

The development of personalized medicine is inextricably linked with the study of the patient’s genetic profile, which determines not only the features of the course of the disease, but also the risks of its occurrence. Purpose. The aim of the work was to study possible associations between the genetic polymorphisms GSTT1, GSTM1, NAT2 and predisposition to the development of acute lymphoblastic leukemia in children of the East Siberian region. Material and methods. A total of 82 children with acute lymphoblastic leukemia and 227 healthy volunteers with no history of hematological pathology were examined. Deletion polymorphisms in the glutathione S-transferase GSTT1 and GSTM1 genes were detected by polymerase chain reaction (PCR) with electrophoretic detection of amplification products in agarose gel; the type of acetylation was determined by genotyping SNP rs1495741 of the NAT2 gene by conducting a polymerase chain reaction in real time. The material for the study was DNA samples isolated from buccal epithelium samples. Results. Statistical processing allowed us to draw the following conclusions: the rate of acetylation of xenobiotics does not affect the risk of acute lymphoblastic leukemia in children of the Caucasian ethnic group of the East Siberian region. Conclusion. There is no associative relationship between deletions in the GSTM1 and GSTT1 genes and the risk of developing acute lymphoblastic leukemia in children of the Caucasian ethnic group of the East Siberian region. It was found that the risk of developing acute lymphoblastic leukemia in children was significantly higher with the variant of combinations of alleles of the rapid type of NAT2 acetylation and normal activity of GSST1 and GSTM1 (G/G, active, active).
The importance of determining the concentration of myco- phenolic acid in children with steroid-dependent nephrotic syndrome
Authors: Morozov S. L. , Dlin V. V. , Obukhova V. A. , Petrosyan E. K. , Zolkina I. V. , Pakhomova V. P. , Voinova V. Yu. 
Published: September 2024

Despite the significant effectiveness of steroid therapy, specialists face serious difficulties in managing patients with steroid-dependent nephrotic syndrome, which requires the prescription of immunosuppressive therapy. Among the available adjuvant drugs, mycophenolate mofetil stands out as a preferred option due to its safety profile, good tolerability, and high efficacy. Currently, only a few studies are presented in the literature on the effectiveness of the use of mycophenolic acid in children with nephrotic syndrome, which is explained by the complexity of the pharmacokinetics of the drug. The article presents the results of a study whose purpose was to evaluate the value of determining mycophenolic acid in patients with steroid-dependent nephrotic syndrome to maintain stable clinical and laboratory remission of the disease. The study examined 78 patients aged 1 to 18 years with steroid-dependent nephrotic syndrome. The results demonstrated that determination of mycophenolic acid concentrations in children with steroid-dependent nephrotic syndrome is an effective method for monitoring therapy for nephrotic syndrome in aunts. Determining the concentration of mycophenolic acid at the C0 point is a highly specific and sensitive method for predicting the development of relapses of the disease, while a mycophenolic acid concentration level of more than 3.2 μg/ml can serve as a minimum guideline for monitoring the use of mycophenolic acid in children with steroid-dependent nephrotic syndrome.
Change and coincidence risk analysis of floods in the Mahanadi River Basin, India
Authors: Ravichandran Shalini , Reddy Venuthurla Manohar , Ray Litan Kumar 
Published: September 2024

ABSTRACT

Coincidence flood risk due to the simultaneous flood occurrences on both mainstream and its tributary results in downstream inundation of a confluence. Therefore, this study was taken up for coincidence flood risk analysis of Mahanadi River basin considering the annual maximum (AM) and the peak over threshold (POT) series. In this study, the Mann–Kendall trend test was performed to analyze the trend in flood magnitudes, while circular statistics was used to analyze the persistence in flood timing. The joint distributions between the streams were established using bivariate copula functions considering flood magnitudes and occurrence dates as variables. The results of MK test revealed a mixture of significant and insignificant trends for AM series for the selected stations, while the trends were insignificant for POT series. Additionally, the flood occurrence dates showed a high level of persistence. It is evident from the results that the coincidence risk is high for Seorinarayan–Bamnidhi confluence point with a risk value of 7.63 × 10−3. The coincidence risk increases mostly from late July to mid-September, and the coincidence risk is high for more frequently occurring flood events. The obtained results will help in prioritizing flood hazard zones for effective flood mitigation strategies in Mahanadi River basin.
Serum Biochemical Factors as Indicators of Osteoporosis: A Cross-Sectional Study
Authors: Yaribeygi Habib , Bayat Nooshin , Alishiri Gholamhosein , Maleki Mina , Jamialahmadi Tannaz , Sahebkar Amirhossein 
Published: September 2024

Introduction:
Osteoporosis is a bone condition that disrupts bone structure, reduces its strength, and increases the risk of fractures. While osteoporosis is
commonly recognized as a disorder affecting the elderly, it can also develop in younger adults and be accompanied by other disorders. Screening
individuals and diagnosing those at higher risk of osteoporosis early may significantly reduce the likelihood of complications and associated costs.

Objective:
Serum biochemical factors are rather easily measured and accessible, making them valuable as predictive indicators for the prognosis and early
diagnosis of osteoporosis. However, there is not enough evidence about possible relationships between these factors and osteoporosis in different
bones.

Methods:
In this descriptive cross-sectional study, we analyzed osteoporotic indices, including bone marrow density (BMD), T-score, Z-score, and
standardized BMD, in a large population of individuals at risk of osteoporosis. We then investigated potential relationships between biochemical
values and osteoporosis indices in the evaluated subjects. The collected data were analyzed using the Kruskal-Wallis test and Spearman correlation
coefficient methods.

Results:
A total of 1104 patients were enrolled, with 87.7% being female and 12.3% male. The mean age of the patients was 56.48 ± 11.62 ( ± SE) years.
Among them, 251 patients had normal bone density, while 556 patients had osteopenia, and 270 patients had osteoporosis. The Kruskal-Wallis
analysis demonstrated that serum levels of Calcium (p=0.014), Phosphorus (p =0.002), and Vitamin D3 (p =0.045) were positively associated with
the risk of osteoporosis, whereas serum albumin (p =0.005) and Alkaline phosphatase (p =0.002) levels were negatively associated. Additionally,
the Spearman correlation coefficient showed a negative association between hemoglobin levels and BMD in both the spine (p =0.046) and femur (p
=0.049).

Conclusion:
Serum levels of biochemical factors may serve as primary predictive markers for the early diagnosis of individuals at higher risk of osteoporosis
and bone fractures. In addition to factors involved in calcium homeostasis, serum levels of albumin and hemoglobin are also associated with BMD
scores and the development of osteoporosis.
Insights into the Evolutionary Dynamics: Characterization of Disintegrin and Metalloproteinase Proteins in the Venom Gland Transcriptome of the Hemiscorpius lepturus Scorpion
Authors: Rami Abbas , Damizadeh Benjamin , Behdani Mahdi , Kazemi-Lomedasht Fatemeh 
Published: September 2024

Background:
The Disintegrin and Metalloproteinase (ADAM) family, also known as
the metalloproteinase/disintegrin/cysteine-rich (MDC) proteins, includes both secreted and transmembrane
molecules involved in critical biological processes, such as cell migration, adhesion,
and signaling. This study aimed to investigate the evolutionary relationships and structural characteristics
of disintegrin and metalloproteinase proteins identified in the venom gland transcriptome
of the scorpion Hemiscorpius lepturus.

Methods:
Using bioinformatics tools, we analyzed the open reading frame, conserved motifs, and
primary, secondary, and tertiary structures of these proteins. Five proteins, named HLDisMet1,
HLDisMet2, HLDisMet3, HLDisMet4, and HLDisMet5, were identified. Their predicted 3-D
structures were within normal ranges (Z-score between -4 to -9).

Results:
Phylogenetic analysis revealed that HLDisMet1 shares similarities with proteins from
various spider species (Nephila pilipes, Argiope bruennichi, Araneus ventricosus, and Trichonephila
inaurata madagascariensis), HLDisMet2 with the scorpion Centruroides sculpturatus, HLDis-
Met4 with the scorpion Tityus serrulatus, and HLDisMet5 with several snake species (Python
bivittatus, Vipera anatolica senliki, Protobothrops mucrosquamatus, and Naja naja).

Conclusion:
These findings highlight the significant similarities between HLDisMet proteins and
those found in other venomous species, suggesting a complex and diverse evolutionary pathway
for venom components. The cross-species conservation observed may indicate a convergent evolutionary
strategy, where different species independently develop similar venom components to
adapt to similar ecological niches or prey types. This study highlights the evolutionary significance
of venom diversification and its potential applications in understanding venom biology
across different species.
Iron Dysregulation: Unveiling Predictive Biomarkers for Severity in COVID-19 Patients
Authors: Shaghaghi Zahra , Hashemi Seyyed Hamid , Alvandi Maryam , Marzhoseyni Zeynab , Ghasemi Basir Hamidreza , Mohamadi Tayeb , Farzipour Soghra 
Published: September 2024

Objective:
This study aimed to elucidate the association between iron dysregulation
and the severity of COVID-19, examining serum levels of iron-related biomarkers in hospitalized
patients. The primary objective was to identify reliable predictors for disease severity, specifically
focusing on the role of ferritin, Hemoglobin (Hb), Total Iron-binding Capacity (TIBC), and iron.

Materials and Methods:
The study enrolled 117 consecutive COVID-19 patients, classified into
mild, severe, and critical groups. Serum levels of Hb, TIBC, iron, and ferritin were measured using
standardized methods. Data were analyzed using ROC analysis, logistic regression models,
and correlation assessments. The study adhered to ethical guidelines, obtaining informed consent
from all participants.

Results:
Results revealed a consistent elevation in iron and ferritin levels as disease severity increased,
accompanied by a reciprocal decline in Hb and TIBC. Ferritin emerged as a robust predictor
for disease prognosis, with an AUC of 0.808, providing a sensitivity of 62.50% and a specificity
of 91.74%. Age and education were identified as exacerbating factors influencing patient outcomes.
The findings have been found to align with previous studies linking higher ferritin levels
to adverse outcomes, supporting ferritin’s utility as a prognostic marker.

Conclusion:
The intricate relationship between iron metabolism and COVID-19 severity has been
highlighted in this study, emphasizing elevated ferritin levels as potential predictors for severe outcomes
and indicators of inflammation-induced cellular damage. These findings may contribute
valuable insights into personalized patient management strategies and the potential for targeted interventions
in severe COVID-19 cases. Further research involving larger populations is essential
to validate these observations and enhance our understanding of the complex host response to
SARS-CoV-2.
Evaluation of Novel Diaza Cage Compounds as MRP Modulators in Cancer Cells
Authors: Döring Henry , Kreutzer David , von Veh Jannis , Ritter Christoph A. , Hilgeroth Andreas 
Published: September 2024

Aim:
Novel MRP modulators are needed to combat MRP-mediated multidrug resistance (MDR) in
cancer cells. Background: Anticancer drug resistance is the main problem in cancer therapy. Causative multidrug
efflux pumps are attractive target structures for the development of inhibitors of their activity.

Objective:
We synthesized novel cage dimeric 1,4-dihydropyridines to evaluate them as MRP modulators in
cancer cells targeting MRP1, MRP2, and MRP4.

Methods:
Cage compounds were synthesized by solution dimerization of monomeric 1,4-dihydropyridines and a
final functionalization reaction. The MRP modulation was determined in cellular efflux assays by the use of the
flow cytometry technique as well as cellular fluorescent measurements with each fluorescent substrate of the
efflux pumps.

Results:
Difluoro phenyl and methoxy or dimethoxy benzyl substitutions were most favourable for the MRP1 and
MRP2 inhibition, whereas monofluor phenyl and dimethoxy benzyl substitutions were most favourable for the
MRP4 inhibition.

Conclusion:
Effective inhibitors were identified that were demonstrated to restore the respective cancer cell line
sensitivity for the anticancer drug as a proof-of-concept that encourages further preclinical studies.