High Death Rate Research Articles

Comparative Characteristics of Mortality of Children Due to Road Traffic Injuries in the Kyrgyz Republic

High death rates due to road accidents are characteristic of most countries of the world and the problem is global. The United Nations General Assembly has adopted an ambitious goal to halve the number of road traffic fatalities and injuries worldwide by 2030. In the Kyrgyz Republic, the number of traffic accidents increased from 5868 in 2016 to 7041 cases in 2022. In the dynamics of road accidents in the regions of the republic, an increase trend in 2019-2020 was revealed, which was replaced by a decrease in 2022, with the exception of the city of Bishkek with a sharp increase of +70.2%. Regions with a high frequency of road accidents were Chui, Issyk-Kul regions and the cities of Bishkek and Osh. Starting from 2018, 2019 and 2021, with road accidents due to the fault of the driver, injuries to children increased, especially in 2021 in all regions of the republic. In 2022, injuries decreased, only in the Batken, Naryn and Chui regions there was an increase. By region, Batken, Talas, Jalal-Abad and Issyk-Kul regions prevail. The highest rates of increase in mortality of children in road accidents due to the fault of the driver were observed in 2019-2022. Regions with a high mortality rate of children in traffic accidents due to the fault of the driver include the Chui, Talas, Naryn and Issyk-Kul regions. It is necessary in road safety policy to ensure a holistic (systemic) approach to solving the problem of reducing road traffic injuries and mortality.

A STUDY ON REPRODUCTIVE LIFE OF THE BENGALEE HINDU FEMALES: A COMPARATIVE ANALYSIS

Reproduction is the process by which new individuals of a species are produced and the genetic materials are passed through generation after generation (Tortora, 2003). The existence of a species is maintained through the urge for the reproduction. Pearl (1939) accounted the urge for reproduction as basic attribute of all living organisms. The expressive form of this urge for the reproduction could be accounted as reproductivity or fertility. The urge for the reproduction in human could not be expressed in its full strength due to several restrictive factors work on it. Demographically observed fertility or infertility is the result of a well-defined number of both biological and behavioural factors, which serve to mediate the influence of culture, society, economic conditions, living standards, and other similar background determinants on individual reproductive behavior (Frank et al., 1994). The hedonistic attitude of human for the reduction of fertility would be described through the "Demographic Transition Model" (DTM) which defines the transition from high birth rates and high death rates to low birth rates and low death rates as part of the economic development of a country from a pre-industrial to an industrialized economy (Thompson, 1929). In the present study an attempt has been made to understand the current status of the reproductive life of the contemporary Bengalee females and the effect of demographic transition as well as fertility transition on the same. Materials of the present cross sectional study comprises with 200 adult married Bengalee females belonging to different caste group lived in a semi urban region of west Bengal. Mean age of the population was 32.63 ± 10.64. The result shows a remarkable decadal change in the reproductive life of the population. Age at menarche seems to follow the secular trend to being decreasing when comparing with a data (mean age 12.79 ± 41.37 and 13.41 ± 1.48 respectively). Comparison with a previous work revealed that the rate of literate women, employed women, the family income etc have been increased noticeable. The number of contraceptive used or adopt family planning families has also been increased remarkably in comparison with the earlier data (64.5 % and 56% respectively). Accordingly the rate of live birth has been decreased. The present study also differs from the age at marriage and marriage conception interval (MCI). Thus the present work revealed that the females (mothers) as well as the couples are more conscious about their reproductive life and adopt different family planning methods. Sharp decadal changes on their reproductive life could also be noticed which may be the ultimate result of the demographic transition.

Neonatal mortality during the war in Tigray: a cross-sectional community-based study

Neonatal mortality is among the key national and international indicators of health services. The global Sustainable Development Goal target for neonatal mortality is fewer than 12 deaths per 1000 livebirths, by 2030. Neonatal mortality estimates in the 2019 Ethiopian Demographic Health Survey found 25·7 deaths per 1000 livebirths. Subnational surveys specific to Tigray, Ethiopia, reported a neonatal mortality lifetime prevalence of 7·13 deaths. Another government report from the Tigray region estimated a neonatal mortality rate of ten deaths per 1000 livebirths in 2020. Despite the numerous interventions in Ethiopia's Tigray region to achieve the Sustainable Development Goals, the war has disrupted most health services, but the effect on neonatal mortality is unknown. Thus, this study aimed to investigate the magnitude and causes of neonatal mortality during the war in Tigray. A cross-sectional community-based study was conducted in Tigray to evaluate neonatal mortality that occurred from Nov 4, 2020, to May 30, 2022. Among the 31 districts, 121 tabias were selected using computer-generated random sampling, and 189 087 households were visited. We adopted a validated WHO 2022 verbal autopsy tool, and data were collected using an interviewer-administrated Open Data Kit. In the absence of the mother, other respondents to the verbal autopsy interview were household members aged 18 years and older who provided care during the final illness that led to death. 29 761 livebirths were recorded during the screening of 189 087 households. Verbal autopsy was administered for 1158 households with neonatal deaths. 317 neonates were stillborn, and 841 neonatal deaths were recorded with the WHO 2022 verbal autopsy tool from Nov 4, 2020, to May 30, 2022, in 31 districts. The neonatal mortality rate was 28·2 deaths per 1000 livebirths. 476 (57%) of the 841 neonatal deaths occurred at home and 296 (35%) in health facilities. A high rate of neonatal deaths was reported in rural districts (80% [673 of 841]) compared with urban districts (20% [168 of 841]), and 663 (79%) deaths occurred during the early neonatal period, in the first week of life (0-6 days). The leading causes of neonatal death were asphyxia (35% [291 of 834]), prematurity (30% [247 of 834]), and infection (12% [104 of 834]). Asphyxia (37% [246 of 663]) and infection (28% [50 of 178]) were the leading causes of death for early and late neonatal period deaths, respectively. Neonatal mortality in Tigray is high due to preventable causes. An urgent response is needed to prevent the high number of neonatal deaths associated with the depleted health resources and services resulting from the war, and to achieve the Sustainable Development Goal on neonatal mortality. UNICEF and United Nations Fund for Population Activities. For the Tigrigna translation of the abstract see Supplementary Materials section.

A promising perspective through potential antimicrobial, anti‐cancer, and antiviral activity against SARS‐CoV‐2 of silver(I) complexes: Synthesis, characterization, density functional theory calculations, and in‐silico molecular docking studies

This study tends to accomplish the sustainable development goal, which calls for all healthy lives. Antibiotic resistance, cancer, and severe acute respiratory syndrome coronavirus all showed high death rates in recent years. Our approach is to make better medications available to fight these feared health issues. In this context, three silver(I) complexes (1–3) based on the antibiotic gemifloxacin (HGMF) were synthesized and thoroughly examined using analytical, spectral, and thermal methods. The density functional theory suggested that complex 1 has a bent coordination environment while 2 and 3 have a distorted trigonal planar geometry. The optimal donor and acceptor centers were determined by the natural‐bond orbital analysis. Interaction of complexes with calf‐thymus DNA has been investigated and their binding constants were ordered as 3 > 2 > 1. The antimicrobial activity against 10 pathogenic microorganisms demonstrated that complex 3 exhibited superior activity compared with standard antibiotics. Testing against mammalian cell lines, liver carcinoma, breast carcinoma, and colon carcinoma revealed that complex 3 showed remarkable cell growth inhibition activity with IC50 values ranging from 3.0 to 9.3 μg/mL. Studies of Molecular docking against SARS‐CoV‐2 main protease Mpro (ID: 6 WTT) proved a powerful type of interaction at the active site. Complex 3 exhibits a potent inhibition effect with a total binding energy of −12.58 kcal/mol compared with the reference ligand inhibitor K36 suggesting its ability to block viral protease. This study presents promising bioactive candidates that have a practical impact on various medicinal fields.

Roaming Dogs, Intense Brown Dog Tick Infestation, and Emerging Rocky Mountain Spotted Fever in Tijuana, México.

A two decades-long epidemic of Rocky Mountain spotted fever in northern México reached the U.S. border city of Tijuana in 2021. Cases were near the city periphery in marginalized areas, some lacking infrastructure such as streets or utilities. We worked in the three census areas where human cases were reported and in 12 additional control Áreas Geoestadisticas Básicas. There were dogs, the primary tick host and Rickettsia rickettsii reservoir, in 76% of homes, with 2.2 owned dogs per home on average, approximately equal numbers of roaming dogs were seen, and 46.2% of owned dogs were allowed to roam in the street. Sixty-eight percent of people had heard of Rocky Mountain spotted fever (RMSF), and 35% self-reported tick infestation, including 19% of homes without dogs. Ticks appeared to move among houses of adjacent neighbors. Of 191 examined dogs, 61.8% were tick-infested, with 6-fold increased odds if they were allowed to roam. Although no dogs were Rickettsia polymerase chain reaction-positive, we found one R. rickettsii- and 11 Rickettsia massiliae-infected ticks. The rickettsial IgG seroprevalence by immunofluorescence antibody assay was 76.4%, associated with unhealthy body condition, adults, dogs with >10 ticks, more dogs being seen in the area, and dogs being permitted in the street. Insufficient medical and canine management resources have contributed to a case fatality rate of RMSF that has exceeded 50% in areas. High canine seroprevalence suggests risks to people and dogs; unfortunately, herd immunity is impeded by high turnover in the canine population owing to the birth of puppies and high death rates. Binational One Health workers should monitor disease spread, enact canine population management and tick eradication, and provide prevention, diagnostic, and treatment support.

Cyclovirobuxine D inhibits hepatocellular carcinoma growth by inducing ferroptosis of hepatocellular carcinoma cells

ObjectiveHepatocellular carcinoma (HCC) is one cancer with high death rates. Nowadays, there are no effective drugs to treat it. Cyclovirobuxine D (CVB-D) is the primary ingredient of the traditional Chinese medicine (TCM) Buxus microphylla. Here, we try to explore the impacts of CVB-D on human HCC cells and explain the potential mechanisms.MethodsHepG2 and Huh-7 cells were used for our experiments. The cell viability and half inhibitory concentration (IC50) were detected by MTT assays. The apoptosis ratio was examined by Annexin V-FITC/7AAD staining and flow cytometry (FCM). The Fe2+ content was examined by ferrous ion content assays. The malondialdehyde (MDA) content was evaluated by lipid peroxidation MDA assays. The reactive oxygen species (ROS) level was examined by the DCFH-DA probe. The expression of apoptotic markers (Bax and Bcl-2) and ferroptosis-related proteins (GPX4 and FSP1) was detected by western blotting. The in vivo curative effect of CVB was explored using xenograft models established in C-NKG mice.ResultsThe cell viability could be inhibited by CVB-D in HepG2 and Huh-7 cells. The IC50 value of CVB-D on HepG2 and Huh-7 cells are 91.19 and 96.29 µM at 48 h, and 65.60 and 72.80 µM at 72 h. FCM showed that the apoptosis rate was increased by CVB-D in HepG2 and Huh-7 cells. Next, ferrous ion content assays showed that the level of Fe2+ was increased by CVB-D in HepG2 and Huh-7 cells. Then, we found the level of MDA and ROS was increased by CVB-D. And the Fe2+ promotion by CVB-D could be reversed by Fer-1. Additionally, western blotting assays showed that the expression of GPX4 and FSP1 was inhibited by CVB-D in HepG2 and Huh-7 cells. Moreover, in vivo, CVB-D displayed excellent anticancer effects in HCC tumor-bearing C-NKG mice.ConclusionCVB-D suppresses the growth in HCC cells through ferroptosis.

Investigation of Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, and Polyoma viruses (JC virus, BK virus) among Gastric cancer patients: A cross sectional study.

Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV. Evaluation of EBV, CMV, HHV-6,and JCV, BKV frequency among gastric cancer patients. In this cross-sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin-fixed paraffin-embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV-6, JCV, and BKV frequency. The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV-6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected.

Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry

BackgroundIn recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings.MethodsWe conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use.ResultsWe interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment.ConclusionIn a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

COVID-19 Case Growth Prediction Using a Hybrid Fuzzy Time Series Forecasting Model and a Machine Learning Approach

The COVID-19 pandemic has evolved into a global health crisis, with Indonesia particularly affected due to its high death rates compared to the rest of Asia. A significant number of unacknowledged, undocumented, or unaddressed cases further exacerbate the situation in Indonesia. Challenges arise from the growing patient population and a scarcity of resources, medical experts, and facilities. This study analyzes the daily development of COVID-19 cases in Indonesia, aiming to estimate the number of confirmed cases, recoveries, and fatalities. Introducing a novel hybrid forecasting model, we utilize the Holt-Winter triple exponential smoothing statistical method and the fuzzy time series rate of change algorithm. We apply the Triple Exponential Smoothing Holt Winter statistical model to predict future periods to the fuzzy time series. Based on the testing results, our proposed hybrid forecasting model demonstrates a very high level of predictive capacity. The acquired data are highly accurate, with a 0.15 percent confirmation rate, 0.15 percent recovery rate, and a 0.20 percent mortality rate, along with an average absolute error of less than 10% for each COVID-19 case. The findings indicate that early awareness by the COVID-19 Task Force of the status of cases is highly advantageous. This awareness can aid in formulating appropriate policies for future planning, organization, and accelerated treatment of COVID-19 in Indonesia. Consequently, successful efforts can be made to slow the emergence and spread of COVID-19 in the country.

Determinant and Impact of Left Ventricular Hypertrophy (LVH) in Chronic Renal Failure (CRF) Patients

Left ventricular hypertrophy is the most common cardiovascular complication in chronic renal failure. It appears to be associated with excess mortality. Objective: To determine the factors associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD), and to describe their influence on renal function. Patients and methods: This was a descriptive and analytical study conducted over 6 years (January 1, 2012 to December 31, 2017) on CKD patients who had an electrocardiogram or cardiac ultrasound. Results: A total of 329 patients were included. LVH was found in 223 patients, a prevalence of 68%. The sex ratio M/F was 2.1. Mean age was 51.05±14.17 years (range 11-95 years). Arterial hypertension predominated (97% of cases), followed by diabetes (26%).Univariate and multivariate analysis showed that LVH was associated with: age ≤51 years (p=0.0037) and with arterial hypertension (p=0.0018) and anemia (p=0.0018). Over a 5-year period, CKD patients with LVH experienced a more rapid decline in renal function than those without LVH (p<0.0001). There was also a higher rate of death in patients with LVH (83%) than in those without (46%) during a 5-year follow-up. Conclusion: LVH is an important factor in the poor prognosis of CKD. This calls for systematic screening and early management by a multidisciplinary team.

Cancer Detection Using Deep Learning

Abstract: One of the most prevalent diseases is cancer. Cancer is a dangerous condition with a high death rate if it is not found and treated at an early stage. This study aims to build a precise and impartial model for detecting two types of cancers (Skin Cancer, and Oral Cancer) using Deep-Learning techniques. Machine learning and computer vision techniques, particularly Convolutional Neural Networks (CNNs), help to develop this system. Deep learning techniques can help us to detect and classify skin cancer from dermoscopy images, and oral cancer from histopathological images. Cancer will be more correctly identified with Convolutional Neural Network (CNN) technology. It increases the likelihood of curing cancer before it spreads. The advantage of using CNN architectures for cancer detection is that they can learn complex features from the images and classify them. This paper proposes a deep-learning-based approach for the diagnosis of skin cancer, and oral cancer based on predefined CNN architecture DenseNet. This model intends to improve detection and clinical decision-making. It helps healthcare to fight against cancer.

Application of Deep Learning with ResNet50 for Early Detection of Melanoma Skin Cancer

Cancer is a type of disease that can be fatal. Some of the cancers with the highest death rates in Indonesia include uterine cancer, breast cancer and skin cancer. The most malignant types of skin cancer are melanoma, which has a high mortality rate, especially if not detected in the early stages, and non-melanoma skin cancer (NMS Cs). Management of this disease depends on whether the type of skin cancer is malignant (malignant) or non-malignant (benign). Therefore, we need a system that can classify types of skin cancer with high accuracy. In this research, the author will use deep learning with the InceptionV3 and ResNet50 algorithms to carry out classification. The aim of this research is to classify types of skin cancer using the InceptionV3 and ResNet50 architecture. The skin cancer dataset used consists of two classes, namely Benign and Malignant, with a total of 3297 data, consisting of 660 data for testing and 2637 data for training. Research stages include data acquisition, preprocessing, classification, and analysis of results. Experimental results show that ResNet-50 produces the best performance with an accuracy level of 0.87. Innovations from this research include using a larger dataset, testing two deep learning architectures, modifying hyperparameters, and using a different layer architecture, which produces better accuracy than previous research. It is hoped that the results of this research can be applied to classify skin cancer more accurately.

Research progress on the relationship between traumatic brain injury and brain‐gut‐microbial axis

AbstractTraumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain‐gut‐microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.

استكشاف عوامل الخطر والنتائج للأطفال الذين يولدون بوزن منخفض في وحدة العناية المركزة للأطفال الرضع في مستشفى مصراتة - تحليل استرجاعي (2022)

Objective: To examine the characteristics and outcomes of low-birth-weight (LBW) newborns admitted to the NICU at Misurata Teaching Hospital in 2022, and to identify key factors influencing their survival. Patient’s and methods: a retrospective descriptive study included 199 LBW newborns (<2.5kg) admitted to the NICU during the study period. Data were collected from medical records and analyzed using descriptive statistics. Results: Maternal factors: Mothers aged 30-35 years had the highest mortality burden. Clear amniotic fluid was associated with the highest death rate, despite being the most common finding. Gestational age showed a clear inverse relationship with survival, with mortality reaching 100% for infants born before 28 weeks. Low APGAR scores were a significant predictor of mortality. RDS and sepsis were the most common diagnoses, with RDS having the highest mortality rate. Elective caesarean section had the lowest mortality rate, while normal vaginal delivery and urgent C-section had higher rates. Cephalic presentation, though most common, had a higher mortality rate than breech presentation. Conclusion: LBW newborns in Misurata Teaching Hospital faced a complex interplay of maternal, neonatal, and delivery-related factors influencing their survival. Further investigation into maternal factors and individualized delivery management is warranted to improve the prognosis of LBW newborns in this population.

Abstract 7664: Early detection of racial disparity and treatment resistance in triple negative breast cancer

Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young Black/African American (AA) women. Black/AA patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. With the approval of pembrolizumab, the addition of immune checkpoint blockade (ICB) to neoadjuvant chemotherapy (NACT) has become the standard of care (SOC) for high-risk early-stage TNBC. The pathologic complete response (pCR) is a reliable prognostic marker that correlates with tumor remission and good outcome, whereas pathologic incomplete response (pIR) with high residual cancer burden (RCB) is often associated with early relapse, treatment resistance, and poor survival. Many similarly-treated patients with identical TNM and RCB classifications still experience racial disparity, different relapse rates, and disparate survival. Current methods fall short in predicting tumor recurrence/chemo-resistance/patient survival with high accuracy in the clinic. Methods: We detected a major racial disparity in our large regional cohorts of TNBC patients (> 1,000 patients), of which 48% patients are Black/AA and 48% patients are white patients, at the Sentara Cancer Network and VCU Massey Comprehensive Cancer Center, that have historically provided excellent healthcare and quality cancer care to the social-economically-disadvantaged, medically underserved, and underinsured racial/ethnic minorities in low income communities in Virginia. Despite Sentara/VCU’s best efforts, Black/AA breast cancer patients still suffer 70-100% higher MBC mortality, and the worst survival compared to their white counterparts, based on our clinical studies and the SEER/CDC databases. Result: We showed that persistent EGFR/RAS/SIAH pathway activation is a major driving force of TNBC malignancy. The most downstream and evolutionarily conserved signaling gatekeeper, SIAH, is an RING domain E3 ligase that is a high-resolution prognostic biomarker for patient risk stratification and racial disparity prediction in TNBC. High SIAH expression in residual tumors reflects ineffective NACT/IO therapy and persistent EGFR/K-RAS/SIAH pathway activation (ON) that drives tumor relapse, resistance, and reduced survival. Low SIAH expression in residual tumors reflects effective NACT/IO therapy and EGFR/K-RAS/SIAH pathway inactivation (OFF) that predicts tumor remission, good outcome, and prolonged survival. We found that SIAH expression is 2.0-fold higher in Black/AA patients’ residual tumors than in the white patients’ residual tumors, mirroring a 1.8-2.0-fold higher death rates in the Black/AA patients than the white patients. Conclusion: In this study, we demonstrate the prognostic power of SIAH for patient risk stratification, therapy quantification, and relationship to cancer racial disparity in TNBC. Citation Format: Amy H. Tang, Richard A. Hoefer, Mary L. Guye, Billur Samli, Janet S. Winston, Jennifer Koblinski, Valentina Robila, Michael O. Idowu, Rick J. Jansen, Harry D. Bear. Early detection of racial disparity and treatment resistance in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7664.

Abstract 4826: Cancer mortality attributable to area-level socioeconomic inequalities in Japan from 2015 to 2020

Abstract Background: In the 3rd Healthy Japan 21 and the 4th National Cancer Plan, the government focused on reducing health inequalities. However, current monitoring of socioeconomic inequalities in cancer is still insufficient to set the targets for the plan. To prioritize strategy aimed at reducing socioeconomic inequalities in cancer mortality, we estimated the population attributable risk fraction (PAF) and excess death due to socioeconomic inequalities, by sex, age group and cancer site. Method: We used the areal deprivation index (ADI) to establish area-based socioeconomic status. We categorized municipalities to ADI quintile weighted by the size of population, Q1 is the least deprived and Q5 the most deprived group. Excess death due to socioeconomic inequalities was calculated by the difference between observed number of deaths and expected death of Q2 to Q5 group with Q1 as standard population. We used cancer mortality data obtained from vital statistics in 2015-2020. Results: In total, about 12000 male and 2800 female excess deaths per year due to socioeconomic inequalities were estimated; that is 5.5% and 1.8% as PAF. PAF due to socioeconomic inequalities limited to premature death, less than 75 years old, was estimated as 7.6% in men and 3.3% in women. By age group, the 0-39 years group showed the largest PAF at 15.7% in men and 16.6% in women. In men of all age groups, except 0-39 years, lung cancer was the highest excess death due to socioeconomic inequalities. For women, some cancer sites (breast, ovary, esophagus) showed an opposite association, Q1 was the highest mortality group. Therefore, total excess death was lower than in men. In women of all ages, the highest rate of excess death due to socioeconomic inequalities was gallbladder cancer. For the 0-39 years group, a high rate of excess death in stomach, leukemia, and cervical cancer was observed. Discussion: Excess death and PAF due to socioeconomic inequalities differed by sex and age group. A greater impact of socioeconomic inequality on cancer mortality was observed in men than in women. Among women, further attention should be paid to areal variation of cancer death related to socioeconomic inequalities, based on the different area-based indices. Citation Format: Yuri Ito, Tomoki Nakaya, Manami Inoue, Tomotaka Sobue, Hitoshi Nakagama. Cancer mortality attributable to area-level socioeconomic inequalities in Japan from 2015 to 2020 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4826.

A systematic review and meta-analysis of serum cystatin C levels and acute ischemic stroke outcomes.

Acute ischemic stroke (AIS) has a high rate of death and causes long-term disability, leading to a global economic burden annually. Therefore, discovering biomarkers to improve AIS patient prognosis is critical. Previous studies reported an association between serum cystatin C (CysC) levels and outcomes in AIS patients, but the results remain controversial. This systematic review and meta-analysis aimed to explore the relationship between serum CysC and AIS patient outcomes using currently available studies. The literature search included PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wan Fang databases. Outcomes included poor functional recovery, cognitive dysfunction and death. Weighted mean difference (WMD) with 95% confidence interval (95% CI) was used as an effect index for measurement data. Results demonstrated that serum CysC was significantly higher in AIS patients with poor functional recovery (WMD = 0.18, 95% CI: 0.08-0.28), cognitive dysfunction (WMD = 0.16, 95% CI: 0.09-0.23) and death (WMD = 0.32, 95% CI: 0.02-0.62) than in the control groups when follow-up time was <1 month. These findings show that high serum CysC levels were associated with poor AIS patient outcomes. Further studies are needed to examine whether reducing serum CysC can prevent poor outcomes in AIS patients.

The COVID-19 disaster in Mexico City: Exploring risk drivers at the local scale

The COVID-19 pandemic had a significant impact on the inhabitants of Mexico City. With over 9 million people living in 16 districts, infections and mortality rates varied greatly. In this article, demographic and socio-economic factors were analyzed to determine vulnerability and exposure to COVID-19 during the crisis from 27 February 2020 to 10 May 2021. The study revealed that mortality and infections were distributed differently across the districts of Mexico City. The districts with the most confirmed cases did not necessarily have the highest death rates. Many deaths were linked to age and comorbidities, such as hypertension, diabetes, and obesity. Poverty, overcrowding, the lack of space, and basic services contributed to vulnerability and exposure to the disease. Inequalities in the city’s development over time resulted in varying degrees of vulnerability and exposure to COVID-19, leading to different patterns of infections and deaths across the districts. The prevalence of infections in the city´s southwestern districts can be attributed to the combination of marginalization, poverty, and inadequate services. Conversely, the northwest areas of the city, with a higher concentration of elderly residents, experienced a greater number of fatalities.

Unveiling the Molecular Mechanism of Trastuzumab Resistance in SKBR3 and BT474 Cell Lines for HER2 Positive Breast Cancer.

HER2-positive breast cancer is one of the most prevalent forms of cancer among women worldwide. Generally, the molecular characteristics of this breast cancer include activation of human epidermal growth factor receptor-2 (HER2) and hormone receptor activation. HER2-positive is associated with a higher death rate, which led to the development of a monoclonal antibody called trastuzumab, specifically targeting HER2. The success rate of HER2-positive breast cancer treatment has been increased; however, drug resistance remains a challenge. This fact motivated us to explore the underlying molecular mechanisms of trastuzumab resistance. For this purpose, a two-fold approach was taken by considering well-known breast cancer cell lines SKBR3 and BT474. In the first fold, trastuzumab treatment doses were optimized separately for both cell lines. This was done based on the proliferation rate of cells in response to a wide variety of medication dosages. Thereafter, each cell line was cultivated with a steady dosage of herceptin for several months. During this period, six time points were selected for further in vitro analysis, ranging from the untreated cell line at the beginning to a fully resistant cell line at the end of the experiment. In the second fold, nucleic acids were extracted for further high throughput-based microarray experiments of gene and microRNA expression. Such expression data were further analyzed in order to infer the molecular mechanisms involved in the underlying development of trastuzumab resistance. In the list of differentially expressed genes and miRNAs, multiple genes (e.g., BIRC5, E2F1, TFRC, and USP1) and miRNAs (e.g., hsa miR 574 3p, hsa miR 4530, and hsa miR 197 3p) responsible for trastuzumab resistance were found. Downstream analysis showed that TFRC, E2F1, and USP1 were also targeted by hsa-miR-8485. Moreover, it indicated that miR-4701-5p was highly expressed as compared to TFRC in the SKBR3 cell line. These results unveil key genes and miRNAs as molecular regulators for trastuzumab resistance.

Cardiogenic shock and chronic kidney disease: Dangerous liaisons

BackgroundChronic kidney disease (CKD) is one of the leading causes of death worldwide, closely interrelated with cardiovascular diseases, ultimately leading to the failure of both organs – the so-called “cardiorenal syndrome”. Despite this burden, data related to cardiogenic shock outcomes in CKD patients are scarce. MethodsFRENSHOCK (NCT02703038) was a prospective registry involving 772 patients with cardiogenic shock from 49 centres. One-year outcomes (rehospitalization, death, heart transplantation, ventricular assist device) were analysed according to history of CKD at admission and were adjusted on independent predictive factors. ResultsCKD was present in 164 of 771 patients (21.3%) with cardiogenic shock; these patients were older (72.7 vs. 63.9years) and had more comorbidities than those without CKD. CKD was associated with a higher rate of all-cause mortality at 1month (36.6% vs. 23.2%; hazard ratio 1.39, 95% confidence interval 1.01–1.9; P=0.04) and 1year (62.8% vs. 40.5%, hazard ratio 1.39, 95% confidence interval 1.09–1.77; P<0.01). Patients with CKD were less likely to be treated with norepinephrine/epinephrine or undergo invasive ventilation or receive mechanical circulatory support, but were more likely to receive renal replacement therapy (RRT). RRT was associated with a higher risk of all-cause death at 1month and 1year regardless of baseline CKD status. ConclusionsCardiogenic shock and CKD are frequent “cross-talking” conditions with limited therapeutic options, resulting in higher rates of death at 1month and 1year. RRT is a strong predictor of death, regardless of preexisting CKD. Multidisciplinary teams involving cardiac and kidney physicians are required to provide integrated care for patients with failure of both organs.