bluuebunny/crossref_metadata_2025 huggingface dataset:
Marital Rape: Legal Status and Development
Authors: Abhyankar Kalyani , Datta Anushka
Published: September 2022

Marriage is a pillar of humanity and plays a crucial role in the development of both women and men in society. There are various national and international legislations, which aim at protecting women; however, in a marital relationship, rape is yet not considered as a serious offence. Marital rape is one such concept, which is difficult to understand and comprehend by society in general. However, recent media coverage on few petitions entertained by honourable courts have raised many questions on this subject, which has further led to lengthy and detailed discussion on forms of marital rape, the actions which constitute marital rape, significance of consent in marital rape, whether marital rape needs to be criminalized in modern society and international legislative measures related to marital rape. Victims of marital rape suffer depression, mental distress, gynaecological problems and other severe health issues, which directly impact their lives in a negative manner. This article attempts to uncover the issue of marital rape faced by women in their daily lives by throwing light on women’s rights and find some solutions to the problems, by relying on descriptive and comparative studies.
Multimorbidity of communicable and non-communicable diseases in low- and middle-income countries: A systematic review
Authors: Kaluvu Lucy , Asogwa Ogechukwu Augustina , Marzà-Florensa Anna , Kyobutungi Catherine , Levitt Naomi S , Boateng Daniel , Klipstein-Grobusch Kerstin
Published: September 2022

Objective

The aim of this systematic review is to analyse existing evidence on prevalence, patterns, determinants, and healthcare challenges of communicable and non-communicable disease multimorbidity in low- and middle-income countries (LMICs).

Methods

PubMed, Cochrane, and Embase databases were searched from 1st January 2000 to 31st July 2020. The National Institute of Health (NIH) quality assessment tool was used to critically appraise studies. Findings were summarized in a narrative synthesis. The review was registered with PROSPERO (CRD42019133453).

Results

Of 3718 articles screened, 79 articles underwent a full text review of which 11 were included for narrative synthesis. Studies reported on 4 to 20 chronic communicable and non-communicable diseases; prevalence of multimorbidity ranged from 13% in a study conducted among 242,952 participants from 48 LMICS to 87% in a study conducted among 491 participants in South Africa. Multimorbidity was positively associated with older age, female sex, unemployment, and physical inactivity. Significantly higher odds of multimorbidity were noted among obese participants (OR 2.33; 95% CI: 2.19–2.48) and those who consumed alcohol (OR 1.44; 95% CI: 1.25–1.66). The most frequently occurring dyads and triads were HIV and hypertension (23.3%) and HIV, hypertension, and diabetes (63%), respectively. Women and participants from low wealth quintiles reported higher utilization of public healthcare facilities.

Conclusion

The identification and prevention of risk factors and addressing evidence gaps in multimorbidity clustering is crucial to address the increasing communicable and non-communicable disease multimorbidity in LMICs. To identify communicable and non-communicable diseases trends over time and identify causal relationships, longitudinal studies are warranted.
Physical activity and recurrent fall risk in community-dwelling Japanese people aged 40–74 years: the Murakami cohort study
Authors: Kamimura Shoto , Iida Takashi , Watanabe Yumi , Kitamura Kaori , Kabasawa Keiko , Takahashi Akemi , Saito Toshiko , Kobayashi Ryosaku , Oshiki Rieko , Takachi Ribeka , Tsugane Shoichiro , Iki Masayuki , Sasaki Ayako , Yamazaki Osamu , Watanabe Kei , Nakamura Kazutoshi
Published: September 2022

Background

Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people.

Methods

This cohort study targeted 7,561 community-dwelling individuals aged 40–74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls.

Results

Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33–2.88] and 2.15 [95%CI:1.48–3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49–0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29–0.85]) but not in men.

Conclusions

Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.
Toxic effects on enzymatic activity, gene expression and histopathological biomarkers in organisms exposed to microplastics and nanoplastics: a review
Authors: Patra Indrajit , Huy Dinh Tran Ngoc , Alsaikhan Fahad , Opulencia Maria Jade Catalan , Van Tuan Pham , Nurmatova Kurbanoy Chorievna , Majdi Ali , Shoukat Shehla , Yasin Ghulam , Margiana Ria , Walker Tony R. , Karbalaei Samaneh
Published: September 2022

Microplastics (MPs) and nanoplastics (NPs) have become an important global environmental issue due to their widespread contamination in the environment. This review summarizes existing literature on the effects of MPs/NPs on three important biomarkers including enzymatic activity, gene expression, and histopathology in various organisms from 2016 to 2021 and suggests a path forward for future research. Application of enzymatic activity, gene expression, and histopathology biomarkers are increasingly used in experimental toxicology studies of MPs/NPs because of their early signs of environmental stress to organisms. Between 2016 to 2021, 70% of published studies focused on aquatic organisms, compared to terrestrial organisms. Zebrafish were widely used as a model organism to study adverse impacts of MPs/NPs. Polystyrene (PS) were the most important polymer used in experimental toxicology studies of MPs/NPs. Fewer studies focused on the histopathological alterations compared to studies on enzymatic activity and gene expression of different organisms exposed to MPs/NPs. There is a growing need to better understand toxic effects of environmentally relevant concentrations of MPs/NPs on enzymatic activity, gene expression, and histopathology biomarkers of both aquatic and terrestrial organisms.
Identification of WRKY transcription factor family genes in Pinus massoniana Lamb. and their expression patterns and functions in response to drought stress
Authors: Sun Shuang , Chen Hu , Yang Zhangqi , Lu Jingyu , Wu Dongshan , Luo Qunfeng , Jia Jie , Tan Jianhui
Published: September 2022

Background

Pinus massonianaLamb. is the timber species with the widest distribution and the largest afforestation area in China, providing a large amount of timber, turpentine and ecological products. Seasonal drought caused by climate warming severely constrains the quality and growth ofP. massonianaforests. WRKY transcription factors play an important role in plant responses to abiotic stress. In this study, the molecular mechanisms by whichP. massonianaresponds to drought stress were analysed based on theP. massonianaWRKY (PmWRKY) family of genes.

Results

Forty-three PmWRKYs are divided into three major families, 7 sub-families, and the conserved motifs are essentially the same. Among these 43PmWRKYsexpress under drought stress but with different expression patterns in response to stress.PmWRKYsrespond to drought stress induced by exogenous hormones of SA, ABA, and MeJA. The expression ofPmWRKY6,PmWRKY10, andPmWRKY30up-regulate in different families and tissues under drought stress, whilePmWRKY22down-regulate. Transgenetic tobaccos ofPmWRKY31are with lower malondialdehyde (MDA) content and higher proline (Pro) content than wild type (WT) tobaccos. In transgenic tobaccos ofPmWRKY31, expression levels of related genes significantly improve, and drought tolerance enhance.

Conclusions

This study analysed the molecular biological characteristics of PmWRKYs and investigated the expression patterns and functions ofPmWRKYsin response to drought stress inP. massoniana. The results of this study provide a basis for in-depth research of the molecular functions ofPmWRKYsin response to drought stress.
Cytological, physiological and transcriptomic analysis of variegated Leaves in Primulina pungentisepala offspring
Authors: Chen Jiancun , Li Yueya , He Dong , Bai Meng , Li Bo , Zhang Qixiang , Luo Le
Published: September 2022

Background

Primulina pungentisepala is suitable for use as a potted plant because of its beautiful leaf variegation, which is significantly different in its selfed offspring. However, the mechanism of P. pungentisepala leaf variegation is unclear. In this study, two types of offspring showing the greatest differences were compared in terms of leaf structure, chlorophyll contents, chlorophyll fluorescence parameters and transcriptomes to provide a reference for studying the molecular mechanism of structural leaf variegation.

Results

Air spaces were found between water storage tissue, and the palisade tissue cells were spherical in the white type. The content of chlorophyll a and total chlorophyll (chlorophyll a + b) was significantly lower in the white type, but there were no significant differences in the content of chlorophyll b, chlorophyll a/b or chlorophyll fluorescence parameters between the white and green types. We performed transcriptomic sequencing to identify differentially expressed genes (DEGs) involved in cell division and differentiation, chlorophyll metabolism and photosynthesis. Among these genes, the expression of the cell division- and differentiation-related leucine-rich repeat receptor-like kinases (LRR-RLKs), xyloglucan endotransglycosylase/hydrolase (XET/H), pectinesterase (PE), expansin (EXP), cellulose synthase-like (CSL), VARIEGATED 3 (VAR3), and ZAT10 genes were downregulated in the white type, which might have promoted the development air spaces and variant palisade cells. Chlorophyll biosynthesis-related hydroxymethylbilane synthase (HEMC) and the H subunit of magnesium chelatase (CHLH) were downregulated, while chlorophyll degradation-related chlorophyllase-2 (CHL2) was upregulated in the white type, which might have led to lower chlorophyll accumulation.

Conclusion

Leaf variegation in P. pungentisepala was caused by a combination of mechanisms involving structural variegation and low chlorophyll levels. Our research provides significant insights into the molecular mechanisms of structural leaf variegation.
Pilot study: advanced haemodynamic monitoring after acute spinal cord injury-Keep the pressure up?
Authors: Drotleff Niklas , Jansen Oliver , Weckwerth Christina , Aach Mirko , Schildhauer Thomas Armin , Waydhas Christian , Hamsen Uwe
Published: September 2022

Background

Although the use of vasopressors to maintain haemodynamic goals after acute spinal cord injury (SCI) is still recommended, evidence regarding the target values and possible risks of this practice is limited, and data on haemodynamic parameters unaffected by catecholamines are rare. In this pilot study, we show the haemodynamic profile of patients with acute SCI mainly unaffected by vasopressor use and other factors that influence the cardiovascular system.

Methods

From March 2018 to March 2020, we conducted a prospective, single-centre pilot study of 30 patients with acute SCI. Factors that could affect the cardiocirculatory system other than SCI (sepsis, pre-existing heart disease or multiple trauma) led to exclusion. A total of 417 measurements were performed using the PiCCO™ system.

Results

The mean systemic vascular resistance index (SVRI, 1447.23 ± 324.71 dyn*s*cm−5*m2), mean central venous pressure (CVP, 10.69 ± 3.16) and mean global end-diastolic volume index (GEDVI, 801.79 ± 158.95 ml/m2) deviated from the reference range, while the mean cardiac index (CI), mean stroke volume index (SVI), mean arterial pressure (MAP), and mean heart rate (HR) were within the reference range, as indicated in the literature. A mixed model analysis showed a significant negative relationship between norepinephrine treatment and MAP (83.97 vs. 73.69 mmHg, p < 0.001), SVRI (1463.40 vs. 1332.14 dyn*s*cm−5*m2, p = 0.001) and GEDVI (808.89 vs. 759.39 ml/m2, p = 0.001).

Conclusion

These findings could lead to an adaptation of the target range for SVRI and MAP in patients with acute SCI and therefore reduce the use of vasopressors.
Transitions between degrees of multidimensional frailty among older people admitted to intermediate care: a multicentre prospective study
Authors: Amblàs-Novellas Jordi , Torné Anna , Oller Ramon , Martori Joan Carles , Espaulella Joan , Romero-Ortuno Roman
Published: September 2022

Background

Frailty is a dynamic condition that is clinically expected to change in older individuals during and around admission to an intermediate care (IC) facility. We aimed to characterize transitions between degrees of frailty before, during, and after admission to IC and assess the impact of these transitions on health outcomes.

Methods

Multicentre observational prospective study in IC facilities in Catalonia (North-east Spain). The analysis included all individuals aged ≥ 75 years (or younger with chronic complex or advanced diseases) admitted to an IC facility. The primary outcome was frailty, measured by the Frail-VIG index and categorized into four degrees: no frailty, and mild, moderate, and advanced frailty. The Frail-VIG index was measured at baseline (i.e., 30 days before IC admission) (Frail-VIG0), on IC admission (Frail-VIG1), at discharge (Frail-VIG2), and 30 days post-discharge (Frail-VIG3).

Results

The study included 483 patients with a mean (SD) age of 81.3 (10.2) years. At the time of admission, 27 (5.6%) had no frailty, and 116 (24%), 161 (33.3%), and 179 (37.1%) mild, moderate, and severe frailty, respectively. Most frailty transitions occurred within the 30 days following admission to IC, particularly among patients with moderate frailty on admission. Most patients maintained their frailty status after discharge. Overall, 135 (28%) patients died during IC stay. Frailty, measured either at baseline or admission, was significantly associated with mortality, although it showed a stronger contribution when measured on admission (HR 1.16; 95%CI 1.10–1.22; p < 0.001) compared to baseline (HR 1.10; 1.05–1.15; p < 0.001). When including frailty measurements at the two time points (i.e., baseline and IC admission) in a multivariate model, frailty measured on IC admission but not at baseline significantly contributed to explaining mortality during IC stay.

Conclusions

Frailty status varied before and during admission to IC. Of the serial frailty measures we collected, frailty on IC admission was the strongest predictor of mortality. Results from this observational study suggest that routine frailty measurement on IC admission could aid clinical management decisions.
Effect of β2-microglobulin in evaluating the severity and prognosis of brain injury: a clinical study
Authors: Huo Qiqi , Dong Wenshuo , Gao Yu , Zhang Yi , Liu Xuehua , Yang Lu , Nan Ding , Yang Jing
Published: September 2022

Background

β2-microglobulin has been showing to be vital that associated with brain function and neurological diseases. This study aimed to explore the expressions of β2-microglobulin in blood and urine of the patients with brain injury, and the effect of hyperbaric oxygen therapy on the content of β2-microglobulin.

Methods

This prospective study included 54 patients with brain injury and 11 healthy controls. The patients were further assigned to two groups: the conscious disturbance group (n = 32) and the non-conscious disturbance group (n = 22) depending on the Glasgow Coma Scale (GCS). The patients received routine treatment and two courses of hyperbaric oxygen therapy (2.0ATA, 60 min, once a day, 10 days for a course). In the brain injury group, blood β2-microglobulin (β2MG) and urine β2-microglobulin (β2MU) were detected respectively before and after hyperbaric oxygen therapy (HBOT). Consciousness and cognitive scores were performed, correspondingly.

Results

Compared with those of the control group, levels of β2MG and β2MU in the brain injury group were significantly increased before HBOT (P < 0.05). Whether it was before or after HBOT, β2MG’s content in the conscious disturbance group was higher than that in the non-conscious disturbance group, while β2MU’s content was obviously higher than that of the non-conscious disturbance group only before HBOT (P < 0.05). Besides, the β2MU’s content in the conscious disturbance group was negatively correlated with GCS score (R = -0.351, P < 0.05) and β2MG’s content in the non-conscious disturbance group was positively correlated with the MMSE score grade (R = 0.598, P < 0.05). The ROC curve was used to assess the evaluation of β2MG and β2MU for patients with impaired consciousness with the area under the curve (AUC) of β2MG and β2MU were 0.775 and 0.796, respectively.

Conclusion

The concentrations of blood β2-microglobulin and urinary β2-microglobulin were significantly increased in patients with brain injury. The concentrations of β2-microglobulin were correlated with the degree of consciousness and cognitive function. The changes tendency of β2-microglobulin may be considered as clinical monitoring index to evaluate the patient’s disturbance of consciousness and cognitive degree, and provide a basis for early assessment of prognosis.
Clinical significance of p53 protein expression and TP53 variation status in colorectal cancer
Authors: Kim Kyoung Min , Ahn Ae-Ri , Park Ho Sung , Jang Kyu Yun , Moon Woo Sung , Kang Myoung Jae , Ha Gi Won , Lee Min Ro , Chung Myoung Ja
Published: September 2022

In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.
Can cognition help predict suicide risk in patients with major depressive disorder? A machine learning study
Authors: Zheng Shuqiong , Zeng Weixiong , Xin Qianqian , Ye Youran , Xue Xiang , Li Enze , Liu Ting , Yan Na , Chen Weiguo , Yin Honglei
Published: September 2022

Background

Previous studies suggest that deficits in cognition may increase the risk of suicide. Our study aims to develop a machine learning (ML) algorithm-based suicide risk prediction model using cognition in patients with major depressive disorder (MDD).

Methods

Participants comprised 52 depressed suicide attempters (DSA) and 61 depressed non-suicide attempters (DNS), and 98 healthy controls (HC). All participants were required to complete a series of questionnaires, the Suicide Stroop Task (SST) and the Iowa Gambling Task (IGT). The performance in IGT was analyzed using repeated measures ANOVA. ML with extreme gradient boosting (XGBoost) classification algorithm and locally explanatory techniques assessed performance and relative importance of characteristics for predicting suicide attempts. Prediction performances were compared with the area under the curve (AUC), decision curve analysis (DCA), and net reclassification improvement (NRI).

Results

DSA and DNS preferred to select the card from disadvantageous decks (decks "A" + "B") under risky situation (p = 0.023) and showed a significantly poorer learning effect during the IGT (F = 2.331, p = 0.019) compared with HC. Performance of XGBoost model based on demographic and clinical characteristics was compared with that of the model created after adding cognition data (AUC, 0.779 vs. 0.819, p > 0.05). The net benefit of model was improved and cognition resulted in continuous reclassification improvement with NRI of 5.3%. Several clinical dimensions were significant predictors in the XGBoost classification algorithm.

Limitations

A limited sample size and failure to include sufficient suicide risk factors in the predictive model.

Conclusion

This study demonstrate that cognitive deficits may serve as an important risk factor to predict suicide attempts in patients with MDD. Combined with other demographic characteristics and attributes drawn from clinical questionnaires, cognitive function can improve the predictive effectiveness of the ML model. Additionally, explanatory ML models can help clinicians detect specific risk factors for each suicide attempter within MDD patients. These findings may be helpful for clinicians to detect those at high risk of suicide attempts quickly and accurately, and help them make proactive treatment decisions.
Establishment and validation of nomogram for predicting immuno checkpoint inhibitor related pneumonia
Authors: Li Xiaoqi , Lv Fei , Wang Ying , Du Zhenguang
Published: September 2022

Objective

Cancer is one of the main causes of death worldwide. Although immunotherapy brings hope for cancer treatment, it is also accompanied by immune checkpoint inhibitor-related adverse events (irAEs). Immune checkpoint inhibitor pneumonia (CIP) is a potentially fatal adverse event, but there is still a lack of effective markers and prediction models to identify patients at increased risk of CIP.

Methods

A total of 369 cancer patients treated between 2017 and 2022 with immune checkpoint inhibitors at Shengjing Hospital of China Medical University and Liaoning People's Hospital were recruited for this study. Independent variables were selected by differences and binary logistic regression analysis, and a risk assessment nomogram was constructed for CIP risk. The accuracy and discriminative abilities of the nomogram were evaluated by calibration plots, receiver operating characteristic curves (ROCs) and decision curve analyses (DCAs).

Results

Binary logistic regression analysis showed that smoking history, acute phase proteins [interleukin (IL-6) and C-reactive protein (CRP)], CD8 + T lymphocyte count and serum alveolar protein [surface protein-A (SP-A) and Krebs Von den Lungen-6 (KL-6)] were significantly associated with CIP risk. A nomogram consisting of these variables was established and validated by different analyses.

Conclusions

We developed an effective risk nomogram for CIP prediction in immune-checkpoint inhibitor administrated cancer patients, which will further assist early detection of immunotherapy-related adverse events.
Identification of early biomarkers of transcriptomics in alveolar macrophage for the prognosis of intubated ARDS patients
Authors: Shi Songchang , Wei Shuo , Pan Xiaobin , Zhang Lihui , Zhang Shujuan , Wang Xincai , Shi Songjing , Lin Wei
Published: September 2022

Background

Currently, the rate of morbidity and mortality in acute respiratory distress syndrome (ARDS) remains high. One of the potential reasons for the poor and ineffective therapies is the lack of early and credible indicator of risk prediction that would help specific treatment of severely affected ARDS patients. Nevertheless, assessment of the clinical outcomes with transcriptomics of ARDS by alveolar macrophage has not been performed.

Methods

The expression data GSE116560 was obtained from the Gene Expression Omnibus databases (GEO) in NCBI. This dataset consists of 68 BAL samples from 35 subjects that were collected within 48 h of ARDS. Differentially expressed genes (DEGs) of different outcomes were analyzed using R software. The top 10 DEGs that were up- or down-regulated were analyzed using receiver operating characteristic (ROC) analysis. Kaplan–Meier survival analysis within two categories according to cut-off and the value of prediction of the clinical outcomes via DEGs was verified. GO enrichment, KEGG pathway analysis, and protein–protein interaction were also used for functional annotation of key genes.

Results

24,526 genes were obtained, including 235 up-regulated and 292 down-regulated DEGs. The gene ADORA3 was chosen as the most obvious value to predict the outcome according to the ROC and survival analysis. For functional annotation, ADORA3 was significantly augmented in sphingolipid signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction. Four genes (ADORA3, GNB1, NTS, and RHO), with 4 nodes and 6 edges, had the highest score in these clusters in the protein–protein interaction network.

Conclusions

Our results show that the prognostic prediction of early biomarkers of transcriptomics as identified in alveolar macrophage in ARDS can be extended for mechanically ventilated critically ill patients. In the long term, generalizing the concept of biomarkers of transcriptomics in alveolar macrophage could add to improving precision-based strategies in the ICU patients and may also lead to identifying improved strategy for critically ill patients.
Preoperative inflammatory markers as prognostic predictors after hepatocellular carcinoma resection: data from a western referral center
Authors: Silva João Paulo Maciel , Coelho Fabricio Ferreira , Cassenote Alex Jones Flores , Jeismann Vagner Birk , Fonseca Gilton Marques , Kruger Jaime Arthur Pirola , de Meira Júnior José Donizeti , Nahas Sérgio Carlos , Herman Paulo
Published: September 2022

Background

Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown.

Aim

To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5–10 cm, > 10 cm) in patients undergoing HCC resection with curative intent.

Methods

Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free survival (DFS) curves were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox method was used to identify independent predictors of OS and DFS.

Results

In total, 161 consecutive adult patients were included. A high NLR (> 1.715) was associated with worse OS (P = 0.018). High NLR (> 2.475; P = 0.047) and PLR (> 100.25; P = 0.028) were predictors of short DFS. In HCC < 5 cm, MLR (> 1.715) was associated with worse OS (P = 0.047). In the multivariate analysis, high PLR was an independent predictor of worse DFS [hazard ratio (HR) 3.029; 95%CI 1.499–6.121; P = 0.002].

Conclusion

Inflammatory markers are useful tools to predict long-term outcomes after liver resection in western patients, high NLR was able to stratify subgroups of patients with short OS and DFS, an increased PLR was an independent predictor of short DFS, while high MLR was associated with short OS in patients with early HCC.
Decision-making ethics in regards to life-sustaining interventions: when physicians refer to what other patients decide
Authors: Sterie Anca-Cristina , Jox Ralf J. , Rubli Truchard Eve
Published: September 2022

Background

Health decisions occur in a context with omnipresent social influences. Information concerning what other patients decide may present certain interventions as more desirable than others.

Objectives

To explore how physicians refer to what other people decide in conversations about the relevancy of cardio-pulmonary resuscitation (CPR) or do-not-attempt-resuscitation orders (DNAR).

Methods

We recorded forty-three physician–patient admission interviews taking place in a hospital in French-speaking Switzerland, during which CPR is discussed. Data was analysed with conversation analysis.

Results

Reference to what other people decide in regards to CPR is used five times, through reported speech. The reference is generic, and employed as a resource to deal with trouble encountered with the patient’s preference, either because it is absent or potentially incompatible with the medical recommendation. In our data, it is a way for physicians to present decisional paths and to steer towards the relevancy of DNAR orders (“Patients tell us ‘no futile care’”). By calling out to a sense of membership, it builds towards the patient embracing norms that are associated with a desirable or relevant social group.

Conclusions

Introducing DNAR decisions in terms of what other people opt for is a way for physicians to bring up the eventuality of allowing natural death in a less overt way. Formulating treatment choices in terms of what other people do has implications in terms of supporting autonomous and informed decision making, since it nudges patients towards conformity with what is presented as the most preferable choice on the basis of social norms.
All together now – patient engagement, patient empowerment, and associated terms in personal healthcare
Authors: Hickmann Emily , Richter Peggy , Schlieter Hannes
Published: September 2022

Background

Patients as active partners in their personal healthcare are key drivers to reducing costs, securing an effective usage of resources, and ensuring patient-provider satisfaction. Even though these benefits are acknowledged, a theoretical framework for the plethora of concepts used in this context, such as patient engagement, patient empowerment, or patient involvement is missing. Furthermore, the heterogeneous or synonymous usage of these terms leads to miscommunication, missing standard conceptual measures, and a deficiency in theory building and testing. Our objective is to show what the relationships and distinctions between concepts focussing on patients as active partners in their personal healthcare are.

Methods

A systematic literature review was conducted to consolidate terms related to patients’ having an active role in their healthcare. From 442 articles screened in PubMed, a final set of 17 papers was included. Any articles conceptualising or presenting relationships between the concepts were included. Information was synthesised, and contradictions were unravelled systematically. The concepts and their relationships are structured and represented by employing a concept map.

Results

Patient-centredness is a concept dominantly influenced by health care providers and can enhance patients’ competencies, attitudes, and behaviours towards their personal healthcare. Enabling patients to become more empowered can ultimately lead to their greater involvement and engagement. Fostering an active role of patients can also increase their adherence to the care pathway. In general, patient engagement seems to be the most conclusive and furthest developed concept in terms of turning patients into active partners in their personal healthcare.

Conclusions

We plead for a stricter demarcation and therefore a terminological standardisation of the terms in the future to avoid further ambiguity and miscommunication. The concept map presents a basis for a uniform understanding and application of the concepts. Through a comprehensive understanding of the terms and their dimensions, relationships between the concepts can be utilised, measures can be derived, and theory building and testing can be enhanced, leading to better acceptance and utilisation of concepts in healthcare services. Furthermore, patient engagement is presented to be the most conclusive and furthest developed concept in the subject area.
Regular proton pump inhibitor use and incident dementia: population-based cohort study
Authors: Zhang Peidong , Li Zhihao , Chen Peiliang , Zhang Ao , Zeng Yu , Zhang Xiru , Huang Qingmei , Liu Dan , Qi Songtao , Mao Chen
Published: September 2022

Background

To examine the association between regular use of proton pump inhibitors and the risk of incident dementia, including dementia subtypes, and whether the association differs between APOE genotypes.

Methods

Based on a prospective analysis of data from the UK Biobank, 501,002 individuals (female, 54.4%) aged between 40 and 70 years, who had no prevalent dementia at baseline, were enrolled between 2006 and 2010 and followed up to 2018. We compared all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) incidence rates between proton pump inhibitor users and non-users by the Cox proportional hazard model.

Results

During 4,438,839 person-years of follow-up (median length of follow-up, 9.0 years), there were 2505 incident cases of all-cause dementia, including 932 cases of AD and 524 cases of VaD. The incident rate of all-cause dementia among proton pump inhibitor users was 1.06 events per 1000 person-years, compared with 0.51 events per 1000 person-years among non-users. After adjustment for multiple confounders and indications, the hazard ratios (HRs) of the proton pump inhibitor users were 1.20 (95% CI, 1.07–1.35) for incident all-cause dementia, 1.23 (95% CI, 1.02–1.49) for incident AD, and 1.32 (95% CI, 1.05–1.67) for incident VaD. In addition, the association between proton pump inhibitor use and all-cause dementia differed by APOE genotype (P for interaction = 0.048). Among APOE ε4 heterozygotes, the fully adjusted HR of proton pump inhibitor use was 1.46 (95% CI, 1.22–1.75) and 1.68 (95% CI, 1.36–2.07), especially for individuals aged 65 years and older.

Conclusions

The finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.
The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications
Authors: Hung Chen-Ting , Tsai Yi-Wei , Wu Yu-Shuo , Yeh Chih-Fan , Yang Kai-Chien
Published: September 2022

Fibrosis-related disorders account for an enormous burden of disease-associated morbidity and mortality worldwide. Fibrosis is defined by excessive extracellular matrix deposition at fibrotic foci in the organ tissue following injury, resulting in abnormal architecture, impaired function and ultimately, organ failure. To date, there lacks effective pharmacological therapy to target fibrosis per se, highlighting the urgent need to identify novel drug targets against organ fibrosis. Recently, we have discovered the critical role of a fibroblasts-enriched endoplasmic reticulum protein disulfide isomerase (PDI), thioredoxin domain containing 5 (TXNDC5), in cardiac, pulmonary, renal and liver fibrosis, showing TXNDC5 is required for the activation of fibrogenic transforming growth factor-β signaling cascades depending on its catalytic activity as a PDI. Moreover, deletion of TXNDC5 in fibroblasts ameliorates organ fibrosis and preserves organ function by inhibiting myofibroblasts activation, proliferation and extracellular matrix production. In this review, we detailed the molecular and cellular mechanisms by which TXNDC5 promotes fibrogenesis in various tissue types and summarized potential therapeutic strategies targeting TXNDC5 to treat organ fibrosis.
Digitalized long-lasting insecticidal nets mass distribution campaign in the context of Covid-19 pandemic in Kongo Central, Democratic Republic of Congo: challenges and lessons learned
Authors: Likwela Joris Losimba , Ngwala Phillipe Lukanu , Ntumba Albert Kalonji , Ntale Deogratias Cibinda , Sompwe Eric Mukomena , Mpiana Godé Kanyeba , Tshula Joseph Kalonji , Likwela Tathy Kalonda , Kanku-Ka-Munabe Patrick , Kumbi Adrien N.’siala , Ndahambara Gilbert Kulimushi , Ntale Helen Cibinda , Kiamenga Michele Luntadila , Njila Jules Kabongo , Yav Ghislain Makhan , Baneti Didier Gasigwa , Austin Julian
Published: September 2022

Background

The Democratic Republic of the Congo (DRC) organized a first mass distribution campaign of long-lasting insecticidal nets (LLINs) with digitalized data management with coordinated support from the Ministry of Health (MOH) and Santé Pour Tous En Milieu Rural—an ‘Association sans but lucratif’ (SANRU Asbl), in the context of the Covid-19 pandemic in Kongo Central province. This article describes the planning and implementation process of this campaign as well as the challenges and lessons learned.

Methods

The planning and implementation process was performed in line with the standard guidance issued by the National Malaria Control Programme (NMCP) following the start of Covid-19. The changes and adaptations put in place as well as the challenges encountered are described.

Results

A total of 5,629,211 people were registered (7.7% above projection) in 1,065,537 households (6.2% below projection) giving an average of 5.3 people per household. Of a total of 3,062,850 LLINs ordered, 2,886,096 were distributed to households (94%). Out of 11,070 villages and 3,947 teams planned, 91.7% of villages were reached and 93% of teams were established.

Conclusion

The revision of standards of campaign implementation during Covid-19, as well as effective coordination supported by real-time decision-making through digital data management, have been factors in the success of this campaign. Maintaining this momentum is essential to ensure the continuity of malaria prevention services for the population.
N-3 fatty acid supplementation mediates lipid profile, including small dense LDL, when combined with statins: a randomized double blind placebo controlled trial
Authors: Dogay Us Gediz , Mushtaq Sohail
Published: September 2022

Background

Epidemiological and clinical evidence suggests that high-dose intake of omega 3 fatty acids (n-3 FA) have a favorable role in altering serum triglycerides (TG) and non-high density lipoprotein cholesterol (non-HDL-C) when combined with statins in hyperlipidemic patients. Their efficacy in altering low-density lipoprotein cholesterol (LDL-C) particle size is yet to be established.

Aim

This study evaluated the effects of supplementing 4 g/day Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on serum blood lipids, including small, dense LDL-C particle concentration, in hyperlipidemic patients receiving stable statin therapy.

Methods

In this randomized, placebo-controlled, double-blind parallel group study, 44 patients on statin therapy for > 8 weeks with non-HDL-C concentrations above 130 mg/dL were randomized into two groups. For 8 weeks, together with their prescribed statin, the intervention group received 4 g/day EPA + DHA (3000 mg EPA + 1000 mg DHA in ethyl ester form) and the placebo group received 4 g/day olive oil (OO). Measurements of serum non-HDL-C, TG, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C (including large - LDL I; intermediate - LDL II; and small - LDL III subclasses), very-low-density lipoprotein cholesterol (VLDL-C) concentration, were taken at baseline and post-intervention. Dietary intake was assessed with a weighed intake, 3-day food diary at week 4. Primary outcome measures were percent change in LDL III, non-HDL-C and LDL particle number.

Results

At the end of treatment, the median percent change in serum LDL III concentration was significantly greater in the n-3 FA group plus atorvastatin compared to placebo (− 67.5% vs − 0%, respectively; P < 0.001). Supplementation with n-3 FA plus atorvastatin led to significant reductions in serum non-HDL-C (− 9.5% vs 4.7%, P < 0.01), TG (− 21.5% vs 6.2%, P < 0.001) and VLDL-C (− 36.9% vs 4.0%, P < 0.001) and TC (− 6.6% vs 2.1%, P < 0.001). Between the groups, no significant difference in percent change in the serum concentration of LDL-C, HDL-C, as well as in the LDL I and LDL II subclasses was observed.

Conclusion

In this group of hyperlipidemic patients on a stable statin prescription, OM3 plus atorvastatin improved small dense LDL concentrations, non-HDL-C, VLDL-C and TG to a greater extent than atorvastatin alone. Further studies are warranted in this area.

Trial registration

This trial was retrospectively registered on 23 May 2019 on ClinicalTrials.gov with ID: NCT03961763.
Anthracycline-induced cardiotoxicity: targeting high-density lipoproteins to limit the damage?
Authors: Abrahams Carmelita , Woudberg Nicholas J. , Lecour Sandrine
Published: September 2022

Doxorubicin (DOX) is an anthracycline antibiotic frequently used against a wide range of cancers, including breast cancer. Although the drug is effective as a treatment against cancer, many patients develop heart failure (HF) months to years following their last treatment with DOX. The challenge in preventing DOX-induced cardiotoxicity is that symptoms present after damage has already occurred in the myocardium. Therefore, early biomarkers to assess DOX-induced cardiotoxicity are urgently needed. A better understanding of the mechanisms involved in the toxicity is important as this may facilitate the development of novel early biomarkers or therapeutic approaches. In this review, we discuss the role of high-density lipoprotein (HDL) particles and its components as possible key players in the early development of DOX-induced cardiotoxicity. HDL particles exist in different subclasses which vary in composition and biological functionality. Multiple cardiovascular risk factors are associated with a change in HDL subclasses, resulting in modifications of their composition and physiological functions. There is growing evidence in the literature suggesting that cancer affects HDL subclasses and that healthy HDL particles enriched with sphingosine-1-phosphate (S1P) and apolipoprotein A1 (ApoA1) protect against DOX-induced cardiotoxicity. Here, we therefore discuss associations and relationships between HDL, DOX and cancer and discuss whether assessing HDL subclass/composition/function may be considered as a possible early biomarker to detect DOX-induced cardiotoxicity.
SILAC-based quantitative proteomics to investigate the eicosanoid associated inflammatory response in activated macrophages
Authors: Brace Nicole , Megson Ian L. , Rossi Adriano G. , Doherty Mary K. , Whitfield Phillip D.
Published: September 2022

Background

Macrophages play a central role in inflammation by phagocytosing invading pathogens, apoptotic cells and debris, as well as mediating repair of tissues damaged by trauma. In order to do this, these dynamic cells generate a variety of inflammatory mediators including eicosanoids such as prostaglandins, leukotrienes and hydroxyeicosatraenoic acids (HETEs) that are formed through the cyclooxygenase, lipoxygenase and cytochrome P450 pathways. The ability to examine the effects of eicosanoid production at the protein level is therefore critical to understanding the mechanisms associated with macrophage activation.

Results

This study presents a stable isotope labelling with amino acids in cell culture (SILAC) -based proteomics strategy to quantify the changes in macrophage protein abundance following inflammatory stimulation with Kdo2-lipid A and ATP, with a focus on eicosanoid metabolism and regulation. Detailed gene ontology analysis, at the protein level, revealed several key pathways with a decrease in expression in response to macrophage activation, which included a promotion of macrophage polarisation and dynamic changes to energy requirements, transcription and translation. These findings suggest that, whilst there is evidence for the induction of a pro-inflammatory response in the form of prostaglandin secretion, there is also metabolic reprogramming along with a change in cell polarisation towards a reduced pro-inflammatory phenotype.

Conclusions

Advanced quantitative proteomics in conjunction with functional pathway network analysis is a useful tool to investigate the molecular pathways involved in inflammation.