bluuebunny/crossref_metadata_2025 huggingface dataset:
Pan-cancer analysis identifies SPEN mutation as a predictive biomarker with the efficacy of immunotherapy
Authors: Li Ya-Dong , Huang Hao , Ren Zheng-Ju , Yuan Ye , Wu Hao , Liu Chuan
Published: August 2023

The association between specific genetic mutations and immunotherapy benefits has been widely known, while such studies in pan-cancer are still limited. SPEN, mainly involved in X chromosome inactivation (XCI), plays an essential in tumorigenesis and sex differences in cancer. Thus, we firstly analyzed the potential role of SPEN in the TCGA pan-cancer cohort and clinical samples. Bioinformatics analysis and immunohistochemistry (IHC) staining confirm that the expression of SPEN is significantly different in various cancers and may involve RNA splicing and processing via enrichment analysis. Then, our data further revealed that those patients with SPEN mutation could predict a better prognosis in pan-cancer and had distinct immune signatures, higher tumor mutation burden (TMB), and microsatellite instability (MSI) in common cancer types. Finally, the cancer patients from 9 studies treated with immune checkpoint inhibitors were included to investigate the efficacy of immunotherapy. The results further showed that SPEN mutation was associated with better clinical outcomes (HR, 0.74; 95%CI, 0.59–0.93, P = 0.01), and this association remained existed in female patients (HR, 0.60; 95%CI, 0.38–0.94 P = 0.024), but not in male patients (HR, 0.82; 95%CI, 0.62–1.08 P = 0.150). Our findings demonstrated that SPEN mutation might strongly predict immunotherapy efficacy in pan-cancer.
Propensity score-matched analysis comparing hippocampus-avoidance whole-brain radiotherapy plus simultaneous integrated boost with hippocampus‑avoidance whole-brain radiotherapy alone for multiple brain metastases-a retrospective study in multiple institutions
Authors: Wang Xiaoliang , Chen Jinping , Lei Zhanquan , Chen Haihong , Zhang Yufang , Liu Gang , Li Shaomin , Zheng Zhenhua , Wang Hui
Published: August 2023

Background

The optimal treatment for multiple brain metastases has been recently controversially discussed.This study was aimed to explore the feasibility of Hippocampus-Avoidance Whole-Brain Radiotherapy plus a simultaneous integrated boost (HA-WBRT + SIB) in patients with multiple brain metastases and assess tumor control in comparison with Hippocampus-Avoidance Whole-Brain Radiotherapy (HA-WBRT) alone for brain metastases.

Methods

In this study, 63 patients with multiple brain metastases (≥ 4 metastases) had undergone HA-WBRT + SIB between January 2016 and December 2020 in the observation group:HA-WBRT (30 Gy in 12 fractions, the maximum dose of the hippocampus ≤ 14 Gy) plus a simultaneous integrated boost (48 Gy in 12 fractions) for brain metastases.Overall Survival (OS), Median survival,intracranial control (IC = control within the entire brain), intracranial progression-free survival (iPFS) and adverse events were compared with the control group (a HA-WBRT retrospective cohort) by propensity score matching analysis.

Results

After 1:1 propensity score matching,there were 56 patients in each group (the observation group, the control group). OS, median survival and iPFS were significantly longer in the observation group (18.4 vs. 10.9 months, P<0.001), (13.0 vs. 8.0 months, P<0.001), (13.9 vs.7.8 months, P<0.001). In comparison of 1-year-IC rates, the observation group also demonstrated higher than the control group (51.8% vs. 21.4%, P = 0.002), respectively. Seven hippocampal metastases were found in the control group (4/56,7.1%) and the observation group (3/56,5.4%) after HA-WBRT. The death rate of intracranial progression were 23.2% in the observation group and 37.5% in the control group.All adverse events were not significant difference between the two groups (P>0.05).

Conclusions

HA-WBRT + SIB resulted in better OS,median survival, IC, iPFS, an acceptable risk of radiation response, and a potential way of declining neurocognitive adverse events, which may be a better treatment for patients with multiple brain metastases.
Ten-year retrospect of the investigation of proximal limbs metastasis in cancer: a multi-center study on survival outcome, limb function status and surgical procedures analysis
Authors: Zhang Chao , Wang Jun , Wu Haixiao , Lin Yile , Chekhonin Vladimir P. , Peltzer Karl , Bukharov Artem V. , Kaprin Andrey D. , Guo Xu , Liu Zheng
Published: August 2023

Background

The aim of study was to evaluate survival outcome and limb function in cancer patients with proximal limbs metastasis. Associated factors on survival outcome and limb function were identified. The comparative analysis between intramedullary nailing and prosthesis surgery in cancer patients with proximal limb metastasis was performed.

Methods

In this five-center retrospective study, patients diagnosed with limbs metastasis were collected. Descriptive statistics was used and log-rank test was performed to analyze the survival in subgroups. The Cox proportional hazards regression analysis was performed to identify the independent prognostic factors. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate limb function after surgery, and t test or analysis of variance (ANOVA) was utilized in subgroup analysis.

Results

A total of 316 patients with limb metastasis were included with mean age at 61.0 years. The most common primary tumor was breast, followed by renal cancer and lung cancer. The median overall survival was 24.0 months and the 1-, 3- and 5-year survival rates were 86.9%, 34.7% and 6.8%, respectively. Primary tumor type, visceral metastasis and chemotherapy were proved to be the independent prognostic factors. The mean Musculoskeletal Tumor Society (MSTS) score was 20.5, significant difference was observed in subgroup of solitary/multiple bone metastasis, with/without pathological fracture, and type of surgery.

Conclusion

The present study concluded that primary tumor type, visceral metastasis and chemotherapy were three factors affecting the survival of patients. Compared with intramedullary nailing, the patients underwent prosthesis surgery showed better limb function, this procedure should be encouraged in patients with indication.
The benefits of nurturing care interventions on early child development and care: findings from a quasi-experimental study in a humanitarian setting
Authors: Sargsyan Viktoria , Tenorio Ana , Uwera Mediatrice , Gasirikare Andre , Habyarimana Jean Aime , Salcido Jennifer S , Felner Christy , Rasheed Muneera A.
Published: August 2023

Background

The study objective was to determine if a nurturing care parenting intervention delivered in a humanitarian setting in Rwanda would benefit early development, learning, and care outcomes for young children under five years and their caregivers compared to standard care.

Methodology

Rwanda’s Mugombwa, Kansi, and Kigeme refugee camps and host communities implemented the parenting program. Via a quasi-experimental research design, the study assessed the effects of intervention delivered as a high dose (HD: 12 group sessions and four home visits) or low dose (LD: 6 group sessions and two home visits) on child and caregiver outcomes compared to the control group from similar settings receiving standard care. The Ages and Stages Questionnaires-3 (ASQ-3) assessed child development outcomes. The Multiple Indicator Cluster Survey questionnaire assessed parenting practices concerning early learning and stimulation.

Findings

The assessment included 733 children and families in total: HD = 314, LD = 240, control = 179. The researchers found no significant difference in child development scores between the intervention and control groups. Significantly higher proportion of caregivers exposed to HD and LD packages had engaged in early learning and stimulation practices compared to the control group, respectively, with 211(67.2%), 148 (61.7%) vs. 66 (36.9%), p < 0.001 caregivers engaged in 4 or more activities in the past three days. Similarly, on responsive feeding items, a higher percentage of HD and LD group caregivers were engaged in positive behaviours compared to the control group: 164 (52.2%), 108 (45%) vs. 62 (34.6%), p = 0.001. The study found no difference between the study arms regarding caregiver mental health.

Conclusion

Parenting programmes in humanitarian settings can improve nurturing care practices, even with a low dose, which is essential to strengthening children’s resilience in at-risk conditions. Further studies in humanitarian contexts are crucial to understand the implementation needs in sensitive contexts.
Pulmonary tuberculosis case notification and burden of drug resistance among children under 15 years of age in Ethiopia: sub-analysis from third-round drug resistance tuberculosis survey
Authors: Abebaw Yeshiwork , Abebe Markos , Tola Habteyes Hailu , Mehammed Zemedu , Getahun Muluwork , Gamtesa Dinka Fikadu , Diriba Getu , Hailu Michael , Yirgu Hailegiorgis , Sheth Anandi Nayan , Argaw Rahel , Abegaz Woldaregay Erku
Published: August 2023

Introduction

Data on the burden of bacteriologically confirmed childhood Tuberculosis (PTB) and drug-resistant TB in Ethiopia is limited due to difficulties related to its diagnosis in this population. Therefore, this study aimed to assess bacteriologically confirmed childhood PTB Case Notification Rates (CNRs) and the burden of Drug Resistant-Tuberculosis among children in Ethiopia.

Method

Retrospective secondary clinical and laboratory data were obtained from 3rd round national DR-TB survey which was conducted between August 2017 and January 2019. We used IBM SPSS 24 for sub-analysis of 3rd round Drug Resistant-Tuberculosis data. Descriptive statistics were used in computing the association between the sociodemographic characteristics and PTB CNRs, and the strength of the associations was determined using binary logistic regression with Odds ratios (OR) with a 95% confidence interval (CI).

Result

Overall, 102 bacteriologically confirmed childhood PTB cases were identified with a median age of 12 (range 1–14) years. Of these, 54 (52.9%) were females and 81 (79.4%) lived in rural areas. HIV-TB co-infection cases were 5/102 (4.3%) and the majority (98%) of cases were newly diagnosed children. Nationally, the incidence of bacteriologically confirmed childhood PTB was calculated to be 5.1 per 100,000 children. The burden of Drug Resistant-Tuberculosis to at least one of the five first-line anti-TB drugs tested was five (6.5%) cases and one (1.3%) was found to be a Multi-drug resistant tuberculosis case. Drug-resistant tuberculosis was significantly associated with the age group 10–14 years (P = 0.002; [AOR] 29.76; [95% CI, 3.51-252.64]) and children living in urban areas (P = 0.027; [AOR] 5.76; 95% CI, 1.22–27.09).

Conclusion

Bacteriologically confirmed childhood PTB cases increased as the age of the children increased. Most of the bacteriologically confirmed childhood PTB and the identified drug Resistant-Tuberculosis cases were new cases. Also, rural children were more affected by TB than their urban, counterparts Drug Resistant-Tuberculosis was higher in urban resident children.
Spatial spillover impact of determinants on child mortality in Pakistan: evidence from Spatial Durbin Model
Authors: Sheikh Muhammad Ramzan , Khan Sami Ullah , Ahmed Munir , Ahmad Rashid , Abbas Asad , Ullah Irfan
Published: August 2023

Background

Child mortality is a major challenge to public health in Pakistan and other developing countries. Reduction of the child mortality rate would improve public health and enhance human well-being and prosperity. This study recognizes the spatial clusters of child mortality across districts of Pakistan and identifies the direct and spatial spillover effects of determinants on the Child Mortality Rate (CMR).

Method

Data of the multiple indicators cluster survey (MICS) conducted by the United Nations International Children’s Emergency Fund (UNICEF) was used to study the CMR. We used spatial univariate autocorrelation to test the spatial dependence between contiguous districts concerning CMR. We also applied the Spatial Durbin Model (SDM) to measure the spatial spillover effects of factors on CMR.

Results

The study results showed 31% significant spatial association across the districts and identified a cluster of hot spots characterized by the high-high CMR in the districts of Punjab province. The empirical analysis of the SDM confirmed that the direct and spatial spillover effect of the poorest wealth quintile and MPI vulnerability on CMR is positive whereas access to postnatal care to the newly born child and improved drinking water has negatively (directly and indirectly) determined the CMR in Pakistan.

Conclusion

The instant results concluded that spatial dependence and significant spatial spillover effects concerning CMR exist across districts. Prioritization of the hot spot districts characterized by higher CMR can significantly reduce the CMR with improvement in financial statuses of households from the poorest quintile and MPI vulnerability as well as improvement in accessibility to postnatal care services and safe drinking water.
Adverse childhood experiences and living in the socially deprived areas in adulthood: a cross-sectional study of the nationwide data in Japan
Authors: Sasaki Natsu , Tabuchi Takahiro , Fujiwara Takeo , Nishi Daisuke
Published: August 2023

Objectives

This study aimed to examine whether having adverse childhood experiences (ACEs) was associated with living in a deprived area in adulthood.

Methods

The cross-sectional study was conducted by using nation-wide data in 2022 of the Japan COVID-19 and Society Internet Survey (JACSIS). Participants were community dwelling people 18 years or older. ACEs were assessed by Japanese version of 15-items ACE measurement tool (ACE-J). Living condition was measured by Area Deprived Index (ADI) and Densely Inhabited District (DID) based on zip code. Multivariable logistic regression to analyze the associations between ADI and ACE 4 + was conducted, controlling for individual-level factors, such as age, sex, marital status, and education, as an additional analysis.

Results

The total of 27,916 participants were included in the analysis. The prevalence of emotional neglect, childhood poverty, and school bullying were 38.2%, 26.5%, 20.8%, respectively. 75% of the population had one or more ACE(s). The number of ACEs was associated with significantly higher risk of living in deprived area in the adulthood (p = 0.001). ACEs were not associated with living in density area. The association between ADI and ACEs 4 + was non-significant after controlling the individual-level factors.

Conclusion

People with higher number of ACEs tend to live in deprived areas in adulthood. Policy makers in highly deprived areas can apply the trauma-informed approach for the community care and support, which is critical to mitigating deficit perspectives and facilitating comprehensive support for those with ACEs.
The role of 99mTc-DPD bone SPECT/CT in the management of growth disturbance of the long bones in pediatric patients: a retrospective observational study
Authors: Shin Chang Ho , Whi Wonseok , Cho Yoon Joo , Yoo Won Joon , Choi In Ho , Cheon Gi Jeong , Cho Tae-Joon
Published: August 2023

Backgrounds

Determining the precise localization of diseased physes is crucial for guiding the treatment of growth disturbances. Conventional radiography, computed tomography (CT), and magnetic resonance imaging only provide information on physeal anatomy. Planar bone scintigraphy and bone single-photon emission computed tomography (SPECT) resolutions are suboptimal for clinically managing growth disturbances. Bone SPECT/CT, which provides high-resolution functional information, can be a useful tool for evaluating growth disturbances. The purposes of this study were to identify the conditions in which bone SPECT/CT outperforms planar scintigraphy or SPECT for evaluating the location and activity of diseased physes and to assess surgical outcomes using bone SPECT/CT findings in pediatric patients experiencing long bone growth disturbances.

Methods

Fifty-nine patients who underwent bone SPECT/CT between January 2018 and January 2021 to evaluate physeal activity using technetium-99 m-labeled 2,3-dicarboxypropane-1,1-diphosphonate (99mTc-DPD) were included. The proportions of patients for whom certain modalities provided sufficient data for selecting treatment plans for growth disturbances were compared based on the site of the diseased physis, growth disturbance cause, and shape of deformity (i.e., SPECT/CT vs. planar scintigraphy and SPECT/CT vs. SPECT). For assessing surgical outcomes, progression of post-surgical deformity was investigated by measuring the angles reflecting the degree of deformity, iliac crest height difference, or ulnar variance on radiographs.

Results

Bone SPECT/CT was sufficient for selecting a treatment plan, but planar scintigraphy or SPECT alone was insufficient in every 10 patients with diseased physes inside the femoral head (p = 0.002) and in every six with physes that were severely deformed or whose locations were unclear on conventional radiography (p = 0.03). In the proximal or distal tibia, where the tibial and fibular physes often overlapped on planar scintigraphy due to leg rotation, bone SPECT/CT was sufficient in 33/34 patients (97%), but planar scintigraphy and SPECT were sufficient in 10/34 (29%) (p < 0.001) and 24/34 (71%) patients, respectively (p = 0.004). No progression or deformity recurrence occurred.

Conclusions

Bone SPECT/CT may be indicated in proximal femoral growth disturbance, when the physis is unclear on conventional radiography or severely deformed, the leg exhibits rotational deformity, or the patient is noncompliant.
Prevalence and influencing factors of malocclusion in adolescents in Shanghai, China
Authors: Yin Jiaming , Zhang Hao , Zeng Xiaoli , Yu Jin , Wang Huning , Jiang Yiwei , Da Dongxin , Li Qiang , Zhang Ying
Published: August 2023

Background

The main purpose of the study was to investigate the prevalence and related risk factors of malocclusion in permanent dentition among adolescents in Shanghai, and provide basic data for government’s preventive strategies and intervention plans.

Methods

1799 adolescents aged 11–15 years old from 18 middle schools in 6 districts of Shanghai were recruited to investigate oral health status and related risk factors using cluster random sampling method in 2021. Malocclusion and caries were examined by on-site inspection. The investigation criteria referred to Bjoerk and the recommendation of the WHO. The malocclusion inspection items included molars relationship, canine relationship, overbite, overjet, midline displacement, anterior crossbite, posterior crossbite, scissors bite, crowding and spacing. The subjects were asked to fill in a questionnaire including parents’ education level, oral health behaviors and dietary habits. The chi-square test and logistic regression analysis were used to analyze the relationship between malocclusion and risk factors.

Results

1799 adolescents were included in the study and the prevalence of malocclusion in adolescents in Shanghai was 83.5%, and the proportion of molar relationship class I, class II, and class III was 48.9%, 14.7%, and 19.0%, respectively. The most common occlusal characteristic of malocclusion was anterior crowding, followed by midline irregularities and deep overbite, with prevalence rates of 44.8%, 39.0% and 38.6%, respectively. The prevalence rate of adolescents with caries was 34.3%. Those who had dental caries and preferred soft food were more likely to have abnormal occlusal characteristics (p < 0.05).

Conclusion

The prevalence of malocclusion in adolescents in Shanghai is high, so it is of great significance to strengthen oral health education, allocate proper preventive strategies and carry out the early correction if necessary.
Association between oral hypofunction and general health: a systematic review
Authors: Limpuangthip Nareudee , Komin Orapin
Published: August 2023

Background

Oral hypofunction comprises 7 oral function conditions, including mastication, swallowing, pronouncing, oral hygiene, and oral dryness. However, it remains unresolved whether having oral hypofunction and each individual condition adversely affect general health. This study aimed to investigate the association between oral hypofunction and general health, encompassing physical, psychological, and social dimensions.

Methods

Oral hypofunction was diagnosed following the criteria proposed by the 2016 Japan Society of Gerodontology, comprising 7 oral function conditions. Oral hypofunction was diagnosed when at least 3 conditions presented. The selected studies eligible for reviewing were based on the PI(E)CO criteria: P (population), adult and older adults; I/E (intervention/exposure), having oral hypofunction by considering overall and individual 7 oral function conditions; C (comparator), not having oral hypofunction; O (outcome), the general health status, encompassing physical, psychological, and social dimensions. Electronic search limited to English articles was performed through PubMed, Scopus, and Cochrane Database of Systematic Reviews databases from January 2016 to June 2023. The included studies were assessed for quaility and risk of bias using the modified Newcastle-Ottawa scale. Qualitative analyses were performed on the general outcome, and having oral hypofunction considering overall and individual oral function conditions.

Results

Ten studies were included in the final syntheses. One was a prospective cohort, one was a case-control, and the others were cross-sectional studies. All included studies were high quality. General health outcomes were mostly frailty, sarcopenia, and malnutrition, whereas mild cognitive impairment,social withdrawal, and gastric cancer prognosis were identified in one of the included studies. The association between general health and having oral hypofunction was stronger than when considering an individual condition. The health outcomes were predominantly associated with mastication and swallowing, whereas their relationships with oral hygiene and dryness were less likely to be reported.

Conclusions

The present review found an association between the presence of oral hypofunction and impaired general health. However, the specific impact on individual physical, psychological, and social dimensions cannot be distinctly delineated. Further prospective studies are required to clarify the causal-effect relationship between oral and general health.
Emotional intelligence among medical students in Sweden – a questionnaire study
Authors: Bitar Aziz , Amnelius Lava , Kristoffersson Emelie , Boman Jens
Published: August 2023

Background

Emotional intelligence (EI), the ability to understand and regulate one’s and other’s emotions, has been linked to academic and clinical performance and stress management, making it an essential skill to develop during medical school. Nevertheless, uncertainty remains about the impact of medical education on EI, its association with sociodemographic factors, and the potential moderating role of gender. Therefore, this study aimed to explore levels of global EI among Swedish medical students based on their completed semesters while analyzing the potential moderator role of gender and identifying potential EI differences associated with age, gender, prior education, work experience, and previous experience working in a leadership position.

Methods

The participants were medical students in semesters 1, 3, 5, 7, 9, and 11 at a Swedish University. Participants answered the self-report Trait Emotional Intelligence Questionnaire - Short Form (TEIQue-SF) and demographic questions. For each participant, the mean global trait EI was calculated (range 1–7), and differences were compared based on semesters and sociodemographic factors. In addition, we investigated the relationship between semester and EI scores with gender as a moderator.

Results

Of the 663 invited medical students, 429 (65%) responded, including 269 women (62.7%), 157 men (36.6%), and 3 identifying as others (0.7%). The participants had a mean global trait EI score of 5.33. Final-year students demonstrated significantly higher global trait EI scores than first-year students, and gender did not have a moderating effect across semesters. Furthermore, students in the age group 25–29 years showed higher EI scores compared to those in the age group 21–24 years, while there were no significant differences in EI scores for older students (≥ 30 years) compared to other age groups. Higher EI scores were also positively associated with previous work-and leadership experiences. Gender and previous education did not significantly impact EI scores.

Conclusions

Our findings suggest that higher EI scores are associated with semesters of medical education, age, and previous work and leadership experience. Future longitudinal studies are needed to identify factors that could improve EI among medical students to design curricular activities aimed at supporting the EI of the next generation of physicians.
Effects of rational emotive behavior therapy on alexithymia, anxiety, depression and sleep quality of older people in nursing homes: a quasi-experimental study
Authors: Qin Ning , Li Jie , Wu Xiaoqi , Zhang Chun , Luo Yating , Dong Xiaoqian , Cao Huan , Wang Sha , Liu Min , Xie Jianfei , Cheng Andy SK
Published: August 2023

Background

Alexithymia, a subclinical cognitive-affective impairment, is prevalent in older people and increases the risk of mental disorders. There is a vast alexithymia treatment gap, with majority of older people in nursing homes lacking access to adequate mental health care. The study aimed to evaluate the effects of rational emotive behavior therapy (REBT) on alexithymia, anxiety, depression and sleep quality of older people in nursing homes.

Methods

This quasi-experimental study was conducted with two groups (the control group and intervention) from March to November 2021. This study enrolled 86 participants, two of whom were lost to follow-up; 42 received usual care (control group) and 42 received REBT based on usual care (intervention group) in nursing homes. The older people in both groups were evaluated at baseline (T0), within one-week post-intervention (T1), and at 3-month follow-up (T3). Generalized estimating equations were used by SPSS version 26 to assess the differential change in the outcomes between the two groups.

Results

The intervention group shows significantly greater improvement in alexithymia than the control group at both T1 (β = -8.167, 95%CI= -10.965, -5.368, P < 0.001) and T2 (β=-4.119, 95%CI= -7.171, -1.067, P = 0.008). The two groups showed significant differences at both T1 and T2 in both difficulty identifying feelings and difficulty describing feelings. Compared to the control group, the intervention group shows a significant improvement in sleep quality at T2 (β = -2.048, 95%CI=-4.004, -0.091, P = 0.040). The two groups showed significant differences at both T1 and T2 in both sleep disturbance and daytime dysfunction. For depression and anxiety, no significant differences were found between the intervention and control groups.

Conclusions

REBT showed to be an effective method for improving alexithymia and sleep quality of older people in nursing homes. However, it failed to significantly alleviate anxiety and depression at least in a short-term trial. Refining this intervention may have a broader, more substantial impact on future research.
Prognostic value of high-sensitivity C-reactive protein in patients undergoing percutaneous coronary intervention with different glycemic metabolism status
Authors: Li Le , Liu Shangyu , Zhang Zhuxin , Zhou Likun , Zhang Zhenhao , Xiong Yulong , Hu Zhao , Yao Yan
Published: August 2023

Background

High-sensitivity C-reaction protein (hsCRP), a biomarker of residual inflammatory risk, has been demonstrated with poor cardiovascular outcomes. We aimed to investigate the prognostic value of hsCRP in patients undergoing percutaneous coronary intervention (PCI) with or without diabetes mellitus (DM).

Methods

In this large-scale, prospective cohort study, we enrolled 8050 consecutive patients who underwent PCI for coronary artery stenosis. All subjects were stratified as high hsCRP (> 3 mg/L) and low hsCRP (≤ 3 mg/L) and were divided into four groups (hsCRP-L/non-DM, hsCRP-H/non-DM, hsCRP-L/DM, hsCRP-H/DM). The primary endpoint of the study was major adverse cardiovascular events (MACEs), including all-cause mortality, myocardial infarction, stroke, and unplanned vessel revascularization, evaluated at a 3 year follow-up.

Results

After 35.7 months (interquartile range: 33.2 to 36.0 months) of median follow-up time, 674 patients suffered from MACEs. We found elevated hsCRP was highly associated with an increased risk of MACEs in both diabetic (hazard ratio [HR] = 1.68, 95% confidence interval CI 1.29–2.19, P < 0.001) and non-diabetic patients (HR = 1.31, 95% CI: 1.05–1.62, P = 0.007) after adjustment for other confounding factors. Kaplan-Meier survival analysis showed the highest incidence of MACEs in hsCRP-H/DM (P < 0.001). In addition, the results of the restricted cubic spline analysis suggested a positive linear relationship between hsCRP and MACEs.

Conclusion

Elevated hsCRP is an independent risk factors of MACEs in patients undergoing PCI irrespective of glycemic metabolism status.
Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40–65: a prospective cross-sectional study
Authors: Zhang Chong-Yu , Xu Ru-Qin , Wang Xiao-Qiao , Sun Lin-Feng , Mo Pei , Cai Ren-Jie , Lin Xiao-Zhen , Luo Cheng-Feng , Ou Wen-Chao , Lu Lie-Jing , Zhong Yun , Chen Jia-Yuan
Published: August 2023

Background

Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD.

Methods

Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model.

Results

We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2–2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables.

Conclusion

This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.
Circulating PCSK9 as a prognostic biomarker of cardiovascular events in individuals with type 2 diabetes: evidence from a 16.8-year follow-up study
Authors: Ruscica Massimiliano , Macchi Chiara , Giuliani Angelica , Rizzuto Alessandra Stefania , Ramini Deborah , Sbriscia Matilde , Carugo Stefano , Bonfigli Anna Rita , Corsini Alberto , Olivieri Fabiola , Sabbatinelli Jacopo
Published: August 2023

Background

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality, being twofold to fourfold more common in patients with type 2 diabetes mellitus (T2DM) than in individuals without diabetes. However, despite this decade-old knowledge, the identification of a specific prognostic risk biomarker remains particularly challenging.

Methods

Taking advantage of a large sample of Caucasian patients (n = 529) with a diagnosis of T2DM followed for a median of 16.8 years, the present study was aimed at testing the hypothesis that fasting serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could be prognostic for major adverse cardiovascular events (MACE) and all-cause mortality.

Results

Median levels of PCSK9 were 259.8 ng/mL, being higher in women compared to men and increasing even more in the presence of a complication (e.g., diabetic kidney disease). PCSK9 positively correlated with markers of blood glucose homeostasis (e.g., HbA1c, fasting insulin and HOMA-IR) and the atherogenic lipid profile (e.g., non-HDL-C, apoB and remnant cholesterol). Serum PCSK9 predicted new-onset of MACE, either fatal or non-fatal, only in women (Odds Ratio: 2.26, 95% CI 1.12–4.58) and all-cause mortality only in men (Hazard Ratio: 1.79, 95% CI 1.13–2.82).

Conclusions

Considering that up to two-thirds of individuals with T2DM develop ASCVD in their lifetime, the assessment of circulating PCSK9 levels can be envisioned within the context of a biomarker-based strategy of risk stratification. However, the sex difference found highlights an urgent need to develop sex-specific risk assessment strategies.

Trial registration: It is a retrospective study.
A malaria death due to an imported Plasmodium falciparum infection in Sri Lanka during the prevention of re-establishment phase of malaria
Authors: Seneviratne Shilanthi , Fernando Deepika , Chulasiri Pubudu , Gunasekera Kumudu , Thenuwara Nethmini , Aluthweera Champa , Wijesundara Anula , Fernandopulle Rohini , Mendis Kamini , Wickremasinghe Rajitha
Published: August 2023

Background

Sri Lanka has maintained a rigorous programme to prevent the re-establishment of malaria ever since the disease was eliminated in October 2012. It includes efforts to sustain case surveillance to ensure early diagnosis and management of malaria. Yet, in April of 2023 the death occurred of an individual with imported malaria.

Case presentation

The deceased was a 37-year-old Sri Lankan male who returned to Sri Lanka on the 10th of April after a business trip to several countries including Tanzania. He was febrile on arrival and consulted three Allopathic Medical Practitioners in succession in his home town in the Western Province of Sri Lanka, over a period of 5 days starting from the very day that he arrived in the country. Malaria was not tested for at any of these consultations and his clinical condition deteriorated. On the evening of 14th of April he was admitted to the medical intensive care unit of a major private hospital in the capital city of Colombo with multiple organ failure. There, on a request by the treating physician blood was tested for malaria and reported early the next morning as Plasmodium falciparum malaria with a high parasitaemia (> 10%). The patient died shortly after on the 15th of April before any anti-malarial medication was administered. The deceased had been a frequent business traveller to Africa, but with no past history of malaria. He had not taken chemoprophylaxis for malaria on this or previous travels to Africa.

Discussion

The patient’s P. falciparum infection progressed rapidly over 5 days of arriving in Sri Lanka leading to severe malaria without being diagnosed, despite him seeking healthcare from three different Medical Practitioners. Finally, a diagnosis of malaria was made on admission to an intensive care unit; the patient died before anti-malarial medicines were administered.

Conclusions

This first death due to severe P. falciparum malaria reported in Sri Lanka after elimination of the disease was due to the delay in diagnosing malaria.
Voices of those living with type 2 diabetes in Belize: barriers to care before and during the COVID-19 pandemic
Authors: Allen Lindsay P. , Ellis Lucia , Engleton Christophe , Valerio Valerie Lynette , Hatala Andrew R.
Published: August 2023

Belize has the highest national prevalence of type 2 diabetes (T2D) of Central and South America, and fifth direst in the world. T2D is the leading cause of death in Belize, a country facing burdens of increasing prevalence with few resources. Since March of 2020, the COVID-19 pandemic has exacerbated the difficulties of those living with T2D in Belize. To address T2D issues in Belize, our interdisciplinary research team explored the barriers to care and self-management for adult patients with T2D in Belize prior to and during the COVID-19 pandemic.

Research relationships between Canadian (ARH) and Belizean (LE) authors have been ongoing since 2016. Together we used a qualitative Constructivist Grounded Theory design generating knowledge through 35 semi-structured patient interviews, 25 key informant discussions, and participant observation with field notes between February 2020 to September 2021. We used Dedoose analysis software for a systematized thematic coding process, as well as iterative verification activities. Findings revealed several barriers to care and self-management, including: 1) the tiered health and social care system with major gaps in coverage; 2) the unfulfilled demand for accurate health information and innovative dissemination methods; and 3) the compounding of loss of community supports, physical exercise, and health services due to COVID-19 restrictions. In the post-pandemic period, it is necessary to invest in physical, nutritional, economic, and psychosocial health through organized activities adaptable to changeable public health restrictions. Recommendations for activities include sending patients informational and motivational text messages, providing recipes with accessibly sourced T2D foods, televising educational workshops, making online tools more accessible, and mobilising community and peer support networks.
Spatial and temporal trends of overweight/obesity and tobacco use in East Africa: subnational insights into cardiovascular disease risk factors
Authors: Keino Barbara Chebet , Carrel Margaret
Published: August 2023

Background

Cardiovascular disease (CVD) is increasing in Sub-Saharan Africa (SSA). Overweight/obesity and tobacco use are modifiable CVD risk factors, however literature about the spatiotemporal dynamics of these risk factors in the region at subnational or local scales is lacking. We describe the spatiotemporal trends of overweight/obesity and tobacco use at subnational levels over a 13-year period (2003 to 2016) in five East African nations.

Methods

Cross-sectional, nationally representative Demographic and Health Surveys (DHS) were used to explore the subnational spatiotemporal patterns of overweight/obesity and tobacco use in Burundi, Kenya, Rwanda, Tanzania, and Uganda, five East African Community (EAC) nations with unique cultural landscapes influencing CVD risk factors. Adaptive kernel density estimation and logistic regression were used to determine the spatial distribution and change over time of CVD risk factors on a subnational and subpopulation (rural/urban) scale.

Results

Subnational analysis shows that regional and national level analysis masks important trends in CVD risk factor prevalence. Overweight/obesity and tobacco use trends were not similar: overweight/obesity prevalence increased across most nations included in the study and the inverse was true for tobacco use prevalence. Urban populations in each nation were more likely to be overweight/obese than rural populations, but the magnitude of difference varied widely between nations. Spatial analysis revealed that although the prevalence of overweight/obesity increased over time in both urban and rural populations, the rate of change differed between urban and rural areas. Rural populations were more likely to use tobacco than urban populations, though the likelihood of use varied substantially between nations. Additionally, spatial analysis showed that tobacco use was not evenly distributed across the landscape: tobacco use increased in and around major cities and urban centers but declined in rural areas.

Conclusions

We highlight the importance of de-homogenizing CVD risk factor research in SSA. Studies of national or regional prevalence trends mask important information about subpopulation and place-specific behavior and drivers of risk factor prevalence. Spatially explicit studies should be considered as a vital tool to understand local drivers of health, disease, and associated risk factor trends, especially in highly diverse yet low-resourced, marginalized, and often homogenized regions.
Development and validation of a nomogram prediction model for hypertension-diabetes comorbidity based on chronic disease management in the community
Authors: Wu Yan , Tan Wei , Liu Yifeng , Li Yongli , Zou Jiali , Zhang Jinsong , Huang Wenjuan
Published: August 2023

Purpose

​Develop and validate a nomogram prediction model for hypertension-diabetes comorbidities based on chronic disease management in the community.

Patients and methods

The nomogram prediction model was developed in a cohort of 7200 hypertensive patients at a community health service center in Hongshan District, Wuhan City. The data were collected from January 2022 to December 2022 and randomly divided into modeling and validation groups at a 7:3 ratio. The Lasso regression model was used for data dimensionality reduction, feature selection, and clinical test feature construction. Multivariate logistic regression analysis was used to build the prediction model.

Results

The application of the nomogram in the verification group showed good discrimination, with an AUC of 0.9205 (95% CI: 0.8471–0.9527) and a good calibration effect. Decision curve analysis demonstrated that the predictive model was clinically useful.

Conclusion

This study presents a nomogram prediction model that incorporates age, waist-height ratio and elevated density lipoprotein cholesterol (HDL-CHOLESTEROL), which can be used to predict the risk of codeveloping diabetes in hypertensive patients.
KRT18 regulates trophoblast cell migration and invasion which are essential for embryo implantation
Authors: Liang Xiaoling , Qiu Xiaoxiao , Ma Yana , Xu Wenzhi , Chen Sijia , Zhang Peipei , Liu Mengying , Lin Xiaona
Published: August 2023

Female infertility is a worldwide concern that impacts the quality of life and well-being of affected couples. Failure of embryo implantation is a major cause of early pregnancy loss and is precisely regulated by a programmed molecular mechanism. Recent studies have shown that proper trophoblast adhesion and invasion are essential for embryo implantation. However, the potential regulatory mechanism involved in trophoblast adhesion and invasion has yet to be fully elucidated. KRT18 has been reported to play a critical role in early embryonic development, but its physiological function in embryo implantation remains unclear. In the present study, we revealed that KRT18 was highly expressed in trophoblast cells and that knockdown of KRT18 in mouse embryos inhibited embryo adhesion and implantation. In vitro experiments further showed that silencing KRT18 disturbed trophoblast migration and invasion. More importantly, we provide evidence that KRT18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells through microscale thermophoresis (MST) analysis and molecular biology experiments. In brief, our data reveal that KRT18, which is highly expressed in trophoblast cells, plays an important role in the regulation of trophoblast invasion and adhesion during embryo implantation by directly binding to E-cadherin.
Resident physician duty hours, resting times and European Working Time Directive compliance in Spain: a cross-sectional study
Authors: Sanchez Martinez D. A. , Carrasco Picazo J. P. , Estrella Porter P. D. , Ruiz-Montero R. , Aginagalde Llorente A. H. , García-Camacho E. , Navarro J. , Cerame del Campo A.
Published: August 2023

Background

There is a growing interest in understanding the impact of duty hours and resting times on training outcomes and the well-being of resident physicians. However, to this date no state-wide analysis exists in any European country.

Objectives

Our aim is to describe the shift work scheduling and to detail the degree of compliance with the Spanish legislation and the European Working Time Directive (EWTD) of Spanish resident physicians, focusing on territorial and specialty distribution.

Material and methods

A descriptive cross-sectional analytical study was designed through an online survey adapted from the existing literature.

Results

Out of the 2035 surveyed resident physicians undergoing PGT in Spain, 80.49% exceeded the 48 h per week limit set by the EWTD and 13% of them did not rest after a 24-h on-call shift. The mean number of on-call shifts in the last 3 months was 15.03, with the highest mean reported in Asturias, La Rioja, and Extremadura. 51.6% of respondents had a day-off after a Saturday on-call shift. Significant differences are observed by region and type of specialty.

Conclusion

Resident physicians in Spain greatly exceed the established 48 h/week EWTD limit. Likewise, non-compliance with labor regulations regarding mandatory rest after on-call duty and minimum weekly rest periods are observed.
ACLY as a modulator of liver cell functions and its role in Metabolic Dysfunction-Associated Steatohepatitis
Authors: Convertini Paolo , Santarsiero Anna , Todisco Simona , Gilio Michele , Palazzo Donatella , Pappalardo Ilaria , Iacobazzi Dominga , Frontuto Maria , Infantino Vittoria
Published: August 2023

Background

Non-alcoholic Fatty Liver Disease (NAFLD), now better known as Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD) and its progression to Nonalcoholic Steatohepatitis (NASH), more recently referred to as Metabolic (Dysfunction)-Associated Steatohepatitis (MASH) are the most common causes of liver failure and chronic liver damage. The new names emphasize the metabolic involvement both in relation to liver function and pathological features with extrahepatic manifestations. This study aims to explore the role of the immunometabolic enzyme ATP citrate lyase (ACLY), with a critical function in lipogenesis, carbohydrate metabolism, gene expression and inflammation.

Methods

ACLY function was investigated in TNFα-triggered human hepatocytes and in PBMC-derived macrophages from MASH patients. Evaluation of expression levels was carried out by western blotting and/or RT-qPCR. In the presence or absence of ACLY inhibitors, ROS, lipid peroxidation and GSSG oxidative stress biomarkers were quantified. Chromatin immunoprecipitation (ChIP), transient transfections, immunocytochemistry, histone acetylation quantitation were used to investigate ACLY function in gene expression reprogramming. IL-6 and IL-1β were quantified by Lumit immunoassays.

Results

Mechanistically, ACLY inhibition reverted lipid accumulation and oxidative damage while reduced secretion of inflammatory cytokines in TNFα-triggered human hepatocytes. These effects impacted not only on lipid metabolism but also on other crucial features of liver function such as redox status and production of inflammatory mediators. Moreover, ACLY mRNA levels together with those of malic enzyme 1 (ME1) increased in human PBMC-derived macrophages from MASH patients when compared to age-matched healthy controls. Remarkably, a combination of hydroxycitrate (HCA), the natural ACLY inhibitor, with red wine powder (RWP) significantly lowered ACLY and ME1 mRNA amount as well as IL-6 and IL-1β production in macrophages from subjects with MASH.

Conclusion

Collectively, our findings for the first time highlight a broad spectrum of ACLY functions in liver as well as in the pathogenesis of MASH and its diagnostic and therapeutic potential value.

Graphical Abstract