bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between BMI trajectories in late-middle age and subsequent dementia risk in older age: a 26-year population-based cohort study
Authors: Qin Zijian , Liu Zheran , Li Ruidan , Luo Yaxin , Wei Zhigong , He Ling , Pei Yiyan , Su Yonglin , Hu Xiaolin , Peng Xingchen
Published: November 2023

Background

The association between body mass index (BMI) and dementia risk differs depending on follow-up time and age at BMI measurement. The relationship between BMI trajectories in late-middle age (50–65 years old) and the risk of dementia in older age (> 65 years old) has not been revealed.

Methods

In the present study, participants from the Health and Retirement Study were included. BMI trajectories were constructed by combining BMI trend and variation information. The association between BMI trajectories at the age of 50–65 years and dementia risk after the age of 65 years was investigated. Participants with European ancestry and information on polygenic scores for cognitive performance were pooled to examine whether genetic predisposition could modify the association.

Results

A total of 10,847 participants were included in the main analyses. A declining BMI trend and high variation in late-middle age were associated with the highest subsequent dementia risk in older age compared with an ascending BMI trend and low variation (RR = 1.76, 95% CI = 1.45–2.13). Specifically, in stratified analyses on BMI trajectories and dementia risk based on each individual's mean BMI, the strongest association between a declining BMI trend with high variation and elevated dementia risk was observed in normal BMI group (RR = 2.66, 95% CI = 1.72–4.1). Similar associations were found when participants were stratified by their genetic performance for cognition function without interaction.

Conclusions

A declining BMI trend and high variation in late-middle age were associated with a higher risk of dementia. Early monitoring of these individuals is needed to prevent dementia in older individuals.
Visceral fat area measured by electrical bioimpedance as an aggravating factor of COVID-19: a study on body composition
Authors: Carvalho Juliana Bonfleur , de Andrade Grasiela Konkolisc Pina , do Nascimento Ludiane Alves , Golin Natalia , Rodrigues Ana Lucia Chalhoub Chediac , Suiter Erika , Soprani Maryana Virginia Orellana , Nadolskis Ariane Severine
Published: November 2023

Introduction

Severe forms of COVID-19 are more common in patients with abnormal fat distribution, particularly high visceral adiposity. The patient’s muscle strength may be reduced during the acute phase of the infection. Electrical bioimpedance (BIA) is a non-invasive method for measuring body compartments and estimating visceral fat area (VFA) that can be used at the bedside.

Objective

To assess the association between several body composition parameters, primarily high adipose tissue and high VFA, in patients with and without a diagnosis of COVID-19 infection, and whether it worsened the severity parameters.

Methods

This retrospective cohort study was conducted in a private hospital in the city of São Paulo from March 2020 to August 2021. The demographic and clinical data was collected from medical reports. Body composition is assessed using the InBODY® model S10 bioelectrical impedance device and a Jamar® digital hydraulic manual dynamometer with a scale from 0 to 90 kg is used to measure handgrip strength (HGS).

Results

A total of 96 patients with a mean age of 69.1 years (SD 15) were divided into two groups of 48 individuals, with and without COVID-19 infection. Body mass index (odds ratio [OR]: 4.47, 95% confidence interval [CI]: 1.69, 11.83), fat mass (OR: 2.03, 95% CI: 0.48, 8.55), and VFA (OR: 1.08, 95% CI: 0.33, 3.53) were all higher in the infection group. When COVID-19 patients were evaluated, those with higher VFA had longer hospital stays (OR: 0.99, 95% CI: 0.97, 1.01) and used more vasoactive drugs (p = 0.043). Patients with COVID-19 with poor handgrip strength were 3.29 times more likely to require a prolonged intensive care unit (ICU) stay.

Conclusion

The study concluded that excess weight and body fat are significantly associated with COVID-19 involvement, but the severity is primarily related to a greater area of visceral fat. The use of bioimpedance for visceral fat measurement was effective, as it is a simple method performed in the hospital setting that does not require the use of radiation.
Epidemiology of neonatal sepsis in two neonatal intensive care units in Krakow, Poland in 2016–2017 years
Authors: Golińska Edyta , Kozień Ł , Tomusiak-Plebanek A , Kędzierska J , Dorycka M , Lauterbach R , Pawlik D , Rzepecka-Węglarz B , Janiszewska M , Heczko PB , Wojkowska-Mach J , Strus M
Published: November 2023

Background

Sepsis in low-birth-weight neonates remains one of the most significant causes of neonatal morbidity and mortality. Approximately 3 million newborns suffer from sepsis globally every year. The aim of this study was to compare demographic and clinical features, as well as etiology and antibiotic susceptibility, of the main pathogens related to neonatal sepsis in two neonatal intensive units during a two-year period.

Methods

We observed early-onset (EO-BSI) and late-onset bloodstream infections (LO-BSI) cases in two high-reference neonatal intensive care units (NICU) over a 24-month period (2016–2017). Samples of patients’ blood were tested for the presence of the microorganisms. All bacterial isolates were tested for susceptibility to antibiotics.

Results

The majority of sepsis cases weighed above 1000 g and were born by cesarean section. About 10% of the EO-BSI group died. There were differences in the EO-BSI /LO-BSI ratio in the compared wards due to differences among the admitted children. The most common pathogens isolated from blood were coagulase-negative staphylococci (CoNS) were represented by two dominating species: S. epidermidis and S. haemolyticus, followed by Klebsiella spp. strains and E.coli, which were mostly found in EO-BSI cases. No single S. agalactiae (GBS) strain was isolated. The majority of CoNS strains were resistant to methicillin, half were resistant to aminoglycosides, and one-third were resistant to macrolides and lincosamides. Half of the Gram-negative rods were resistant to beta-lactams.

Conclusions

The epidemiology of sepsis in two observed NICUs is comparable to data obtained from other studies with a predominance of methicillin-resistant CoNS in LO-BSI and beta-lactam resistant E. coli in EO-BSI. It is of importance that the campaign for controlling GBS carriage in pregnant women in Poland resulted in the disappearance of GBS as a cause of sepsis. Unfortunately, there are no such measures to control E.coli related sepsis.
RTEL1 gene polymorphisms and neuroblastoma risk in Chinese children
Authors: Zhang Ting , Zhou Chunlei , Guo Jiejie , Chang Jiamin , Wu Haiyan , He Jing
Published: November 2023

Background

Neuroblastoma, a neuroendocrine tumor originating from the sympathetic ganglia, is one of the most common malignancies in childhood. RTEL1 is critical in many fundamental cellular processes, such as DNA replication, DNA damage repair, genomic integrity, and telomere stability. Single nucleotide polymorphisms (SNPs) in the RTEL1 gene have been reported to confer susceptibility to multiple cancers, but their contributing roles in neuroblastoma remain unclear.

Methods

We conducted a study on 402 neuroblastoma cases and 473 controls to assess the association between four RTEL1 SNPs (rs3761124 T>C, rs3848672 T>C, rs3208008 A>C and rs2297441 G>A) and neuroblastoma susceptibility.

Results

Our results show that rs3848672 T>C is significantly associated with an increased risk of neuroblastoma [CC vs. TT/TC: adjusted odds ratio (OR)=1.39, 95% confidence interval (CI)=1.02-1.90, P=0.038]. The stratified analysis further indicated that boy carriers of the rs3848672 CC genotype had a higher risk of neuroblastoma, and all carriers had an increased risk of developing neuroblastoma of mediastinum origin. Moreover, the rs2297441 AA genotype increased neuroblastoma risk in girls and predisposed children to neuroblastoma arising from retroperitoneal.

Conclusion

Our study indicated that the rs3848672 CC and rs2297441 AA genotypes of the RTEL1 gene are significantly associated with an increased risk of neuroblastoma in Chinese children in a gender- and site-specific manner.
Prevalence and risk factors of emergence agitation among pediatric patients undergo ophthalmic and ENT Surgery: a cross-sectional study
Authors: Yu Hong , Sun Xiaohui , Li Ping , Deng Xiaoqian
Published: November 2023

Background

Some studies reported that pediatric patients undergoing otorhinolaryngology (ENT) and ophthalmic surgeries have higher incidences of emergence agitation (EA). Children with EA tend to carry the risk of self-harm, have longer periods of recovery and delayed hospital discharge. Consequently, EA needs to be monitored and risk factors ought to be emphasized to implement preventative measures. The objective of this study was to describe EA and to identify risk factors after pediatric ophthalmic or ENT surgery.

Methods

Between September 2021 and December 2021, a cross-sectional study was conducted in 100 children aged of 0–12 years who underwent ophthalmic or ENT surgery. The Watcha scale was used to observe and record EA, which was defined at levels of 3 or 4 at any time in the post-anesthesia care unit (PACU). The pain intensity was graded with the Face, Legs, Activity, Cry, Consolability (FLACC) Scale after surgery. Patient and surgery-related characteristics, the behavioral criteria of EA, the pharmacologic and non-pharmacologic interventions and recovery outcomes were objectively recorded. A binary logistic regression model was constructed to identify the associated factors of EA.

Results

From the 100 analyzed children, 58 were males and 42 were females, and 44 patients received ophthalmic surgery and 56 ENT surgery. The median age was 6 (IQR 4–7) years. The overall incidence of EA among pediatrics was 30% (34.5% for ENT and 24.4% for ophthalmic surgery). High preoperative modified Yale Preoperative Anxiety scale (m-YPAS) grade (OR = 1.19, 95%CI 1.06–1.33, P = 0.003) and high postoperative FLACC score (OR = 3.36, 95%CI 1.88–6.02, P < 0.001) were risk factors for EA.

Conclusions

This study identified that preoperative anxiety and postoperative pain are associated with EA in children after ophthalmic or ENT surgery. Preoperative anxiety assessment and management, and administration of adjunct analgesic treatments should be considered in the routine care.
Social media use and everyday cognitive failure: investigating the fear of missing out and social networks use disorder relationship
Authors: Montag Christian , Markett Sebastian
Published: November 2023

Background

Nearly five billion individuals worldwide are using social media platforms. While the benefits of using social media, such as fostering social connections, are clear, ongoing discussions are focused on whether excessive use of these platforms might have adverse effects on cognitive functioning. Excessive social media use shares similarities with addictive behaviors and is believed to result from a complex interplay of individual characteristics, emotions, thoughts, and actions. Among these contributing factors, one of particular interest is the Fear of Missing Out (FoMO), a state where an individual apprehends that others are experiencing rewarding moments in their absence (but see more information on the FoMO trait/state debate in this article).

Methods

In this study, we aimed to explore the intricate relationships between FoMO, tendencies towards Social Networks Use Disorder (SNUD), and everyday cognitive failures. To achieve this, we gathered a large sample of N = 5314 participants and administered a comprehensive set of questionnaires. These included a Fear of Missing Out (FoMO) scale, which assessed both trait and state aspects of FoMO, the Social Networking Sites-Addiction Test (SNS-AT), designed to gauge tendencies towards SNUD, and the Cognitive Failure Questionnaire (CFQ), which measured everyday cognitive lapses.

Results

Our findings revealed that among non-users of social media, both FoMO and everyday cognitive failures were at their lowest levels. Further, in the group of social media users, we observed a significant relationship between FoMO and cognitive failures, which was mediated by SNUD tendencies. This mediation was particularly pronounced for the state component of FoMO, which encompasses maladaptive thoughts related to online behavior.

Conclusions

While our study is cross-sectional and thus cannot establish causality, one plausible interpretation of our findings is that higher FoMO tendencies may trigger excessive social media use, which in turn could lead to cognitive failures, possibly due to distraction and reduced attention to everyday tasks.
Escitalopram versus other antidepressive agents for major depressive disorder: a systematic review and meta-analysis
Authors: Yin Juntao , Song Xiaoyong , Wang Chaoyang , Lin Xuhong , Miao Mingsan
Published: November 2023

Background

Escitalopram is selective serotonin reuptake inhibitors (SSRIs) and one of the most commonly prescribed newer antidepressants (ADs) worldwide. We aimed to explore the efficacy, acceptability and tolerability of escitalopram in comparison with other ADs in the acute-phase treatment of major depressive disorder (MDD).

Methods

Medline/PubMed, EMBASE, the Cochrane Library, CINAHL, and Clinical Trials.gov were searched from inception to July 10, 2023. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. All randomized controlled trials comparing escitalopram against any other antidepressant for patients with MDD. Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, risk ratios (RRs) were calculated with 95% confidence intervals (CI). Continuous data were analyzed using standardized mean differences (with 95% CI) using the random effects model.

Results

A total of 30 studies were included in this meta‑analysis, among which sixteen trials compared escitalopram with another SSRI and 14 compared escitalopram with a newer AD. Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (RR 0.67, 95% CI 0.50—0.87). Escitalopram was also more effective than citalopram in terms of remission (RR 0.53, 95% CI 0.30—0.93).

Conclusions

Escitalopram was superior to other ADs for the acute phase treatment of MDD in terms of efficacy, acceptability and tolerability. However, no significant difference was found between escitalopram and other ADs in early response or follow-up response to treatment of MDD.
Perceived health inequalities: are the UK and US public aware of occupation-related health inequality, and do they wish to see it reduced?
Authors: Bridger Emma K. , Tufte-Hewett Angela , Comerford David A.
Published: November 2023

Background

One underexamined factor in the study of lay views of socioeconomic health inequalities is occupation-related health. Examining health by occupational social class has a long history in the UK but has been comparatively overlooked in US public health literatures, where the relationship between health and work has attended more to hazard exposure.

Methods

Representative samples of the UK and US indicated the perceived and ideal lifespan of people working in “higher managerial/professional” and “routine” occupations. We examine perceptions of inequality and desires for equality across occupation groups as a function of country and key socio-demographic variables.

Results

67.8% of UK and 53.7% of US participants identified that professionals live longer than routine workers. Multivariate models indicated that US participants were markedly less likely to be aware of occupation-related inequalities after controlling for age, gender, and education. Awareness was negatively related to age (in the US) and recent voting behaviours (both samples). Desiring equal life expectancy was less likely in the US sample, and less likely across both samples among older participants and those with lower levels of education.

Conclusion

Employing a novel approach to measuring perceived and ideal life expectancy inequality, this is the first study to examine perceptions of lifespan inequality by occupational groups. It reports widespread understanding of the occupation-related gradient in lifespan and a desire that these inequalities be eliminated in the UK, but considerably less awareness and desire for equality in the US. Greater tolerance for social status inequalities in the US than other similar countries appear to also extend to differences in life expectancy.
Ukrainian migrants’ and war refugees’ admissions to hospital: evidence from the Polish Nationwide General Hospital Morbidity Study, 2014–2022
Authors: Lewtak Katarzyna , Poznańska Anna , Kanecki Krzysztof , Tyszko Piotr , Goryński Paweł , Jankowski Krzysztof , Nitsch-Osuch Aneta
Published: November 2023

Background

Considering the rapid influx of Ukrainian migrants and war refugees into Poland, the knowledge of their health condition is becoming increasingly important for health system policy and planning.

The aim of the study was to assess war-related changes in the frequency and structure of hospitalizations among Ukrainian migrants and refugees in Poland.

Methods

The study is based on the analysis of hospital admission records of Ukrainian patients, which were collected in the Nationwide General Hospital Morbidity Study from 01.01.2014 to 31.12.2022.

Results

In the study period, 13,024 Ukrainians were hospitalized in Poland, 51.7% of whom had been admitted to hospital after February 24, 2022. After the war broke out, the average daily hospital admissions augmented from 2.1 to 21.6 person/day. A noticeable increase in the share of women (from 50% to 62%) and children (from 14% to 51%) was also observed. The average age of patients fell from 33.6 ± 0.2 years to 24.6 ± 0.3 years. The most frequently reported hospital events among the migrants until 23.02.2022 were injuries (S00-T98) – 26.1%, pregnancy, childbirth and the puerperium (O00-O99) – 18.4%, and factors influencing health status and contact with health services (Z00-Z99) – 8.4%. After the war started, the incidence of health problems among migrants and war refugees changed, with pregnancy, childbirth and the puerperium (O00-O99) being the most common – 14.9%, followed by abnormal clinical and lab findings (R00-R99) – 11.9%, and infectious and parasitic diseases (A00-B99) – 11.0%.

Conclusions

Our findings may support health policy planning and delivering adequate healthcare in refugee-hosting countries.
Effects of virtual interventions based on the theory of planned behavior to improve obesity-preventive lifestyle among girls, during COVID-19 pandemic
Authors: Moghimi Rafat , Nasirzadeh Mostafa , Ahmadinia Hassan , Pourmahmoudi Azizollah , Karimi Mahdi Abdol
Published: November 2023

Background

Adolescence is a critical period for the spread of obesity and overweight. This research was conducted with the aim of determining the effect of an educational intervention based on the theory of planned behavior on promoting obesity-related behaviors in overweight female students in Gachsaran.

Methods

this quasi-experimental study was conducted on 90 female students of the first secondary school in the form of two intervention and control groups. Information related to nutritional status and the structures of the theory of planned behavior were collected using a researcher-made questionnaire whose validity and reliability have been confirmed. The educational intervention was carried out during five virtual training sessions. The data obtained three months after the intervention were analyzed using SPSS statistical software, version 20, using independent t-tests, paired t-tests, and equivalent non-parametric tests.

Results

The present study showed that the scores of the constructs of awareness, perceived behavior control, subjective norms, intention, and nutritional behaviors were significantly improved after the intervention (p < 0.001). The results of the Mann-Whitney test showed that the two intervention and control groups did not have a significant difference in terms of the average overall physical activity score after the intervention (p = 0.078).

Conclusion

The results of the present study showed that training based on the theory of planned behavior in the conditions of COVID-19 disease and in a virtual form had an effect on nutritional behavior but could not increase physical activity behavior in adolescents with weight loss.
A resilience view on health system resilience: a scoping review of empirical studies and reviews
Authors: Copeland Samantha , Hinrichs-Krapels Saba , Fecondo Federica , Santizo Esteban Ralon , Bal Roland , Comes Tina
Published: November 2023

Background

Prompted by recent shocks and stresses to health systems globally, various studies have emerged on health system resilience. Our aim is to describe how health system resilience is operationalised within empirical studies and previous reviews. We compare these to the core conceptualisations and characteristics of resilience in a broader set of domains (specifically, engineering, socio-ecological, organisational and community resilience concepts), and trace the different schools, concepts and applications of resilience across the health literature.

Methods

We searched the Pubmed database for concepts related to ‘resilience’ and ‘health systems’. Two separate analyses were conducted for included studies: a total ofn = 87 empirical studies on health system resilience were characterised according to part of health systems covered, type of threat, resilience phase, resilience paradigm, and approaches to building resilience; and a total ofn = 30 reviews received full-text review and characterised according to type of review, resilience concepts identified in the review, and theoretical framework or underlying resilience conceptualisation.

Results

The intersection of health and resilience clearly has gained importance in the academic discourse with most papers published since 2018 in a variety of journals and in response to external threats, or in reference to more frequent hospital crisis management. Most studies focus on either resilience of health systems generally (and thereby responding to an external shock or stress), or on resilience within hospitals (and thereby to regular shocks and operations). Less attention has been given to community-based and primary care, whether formal or informal. While most publications do not make the research paradigm explicit, ‘resilience engineering’ is the most prominent one, followed by ‘community resilience’ and ‘organisational resilience’. The social-ecological systems roots of resilience find the least application, confirming our findings of the limited application of the concept of transformation in the health resilience literature.

Conclusions

Our review shows that the field is fragmented, especially in the use of resilience paradigms and approaches from non-health resilience domains, and the health system settings in which these are used. This fragmentation and siloed approach can be problematic given the connections within and between the complex and adaptive health systems, ranging from community actors to local, regional, or national public health organisations to secondary care. Without a comprehensive definition and framework that captures these interdependencies, operationalising, measuring and improving resilience remains challenging.
Are breast cancer patients with suboptimal adherence to cardiovascular treatment more likely to discontinue adjuvant endocrine therapy? Competing risk survival analysis in a nationwide cohort of postmenopausal women
Authors: Artignan Juliette , Capmas Perrine , Panjo Henri , Constantinou Panayotis , Pelletier-Fleury Nathalie
Published: November 2023

Background

High rates of discontinuation undermine the effectiveness of adjuvant endocrine therapy (AET) among hormone-receptive breast cancer patients. Patient prognosis also relies on the successful management of cardiovascular risk, which affects a high proportion of postmenopausal women. As with AET, adherence with cardiovascular drugs is suboptimal. We examined whether patient adherence with cardiovascular drugs was associated with the rate of AET discontinuation in a French nationwide claims database linked with hospitalisation data.

Methods

We identified postmenopausal women starting AET between 01/01/2016 and 31/12/2020 and taking at least two drugs for the primary prevention of cardiovascular disease (antihypertensive drugs, lipid-lowering drugs and platelet aggregation inhibitors) before AET initiation. Adherence was assessed for each drug class by computing the proportion of days covered. Women were categorised as fully adherent, partially adherent or fully non-adherent with their cardiovascular drug regimen based on whether they adhered with all, part or none of their drugs. AET discontinuation was defined as a 90-day gap in AET availability. Time to AET discontinuation according to levels of cardiovascular drug adherence was estimated using cumulative incidence curves, accounting for the competing risks of death and cancer recurrence. Multivariate cause-specific Cox regressions and Fine-and-Gray regressions were used to assess the relative hazards of AET discontinuation.

Results

In total, 32,075 women fit the inclusion criteria. Women who were fully adherent with their cardiovascular drugs had the lowest cumulative incidence of AET discontinuation at any point over the 5-year follow-up period. At 5 years, 40.2% of fully non-adherent women had discontinued AET compared with 33.5% of partially adherent women and 28.8% of fully adherent women. Both partial adherence and full non-adherence with cardiovascular drugs were predictors of AET discontinuation in the two models (cause-specific hazard ratios 1.16 [95% CI 1.10–1.22] and 1.49 [95% CI 1.39–1.58]; subdistribution hazard ratios 1.15 [95% CI 1.10–1.21] and 1.47 [95% CI 1.38–1.57]).

Conclusion

Clinicians should be aware that patients who do not adhere with their entire cardiovascular drug regimen are also more likely to discontinue AET. This stresses the importance of integrated care, as suboptimal adherence with both treatment components poses a threat to achieving ideal patient outcomes.
Modulation of SLFN11 induces changes in DNA Damage response in breast cancer
Authors: Raynaud Christophe Michel , Ahmed Eiman I. , Jabeen Ayesha , Sanchez Apryl , Sherif Shimaa , Carneiro-Lobo Tatiana C. , Awad Amany , Awartani Dina , Naik Adviti , Thomas Remy , Decock Julie , Zoppoli Gabriele , Bedongnetti Davide , Hendrickx Wouter R. L.
Published: November 2023

Background

Lack of Schlafen family member 11 (SLFN11) expression has been recently identified as a dominant genomic determinant of response to DNA damaging agents in numerous cancer types. Thus, several strategies aimed at increasing SLFN11 are explored to restore chemosensitivity of refractory cancers. In this study, we examined various approaches to elevate SLFN11 expression in breast cancer cellular models and confirmed a corresponding increase in chemosensitivity with using the most successful efficient one. As oncogenic transcriptomic downregulation is often driven by methylation of the promotor region, we explore the demethylation effect of 5-aza-2′-deoxycytidine (decitabine), on the SLFN11 gene. Since SLFN11 has been reported as an interferon inducible gene, and interferon is secreted during an active anti-tumor immune response, we investigated the in vitro effect of IFN-γ on SLFN11 expression in breast cancer cell lines. As a secondary approach to pick up cross talk between immune cells and SLFN11 expression we used indirect co-culture of breast cancer cells with activated PBMCs and evaluated if this can drive SLFN11 upregulation. Finally, as a definitive and specific way to modulate SLFN11 expression we implemented SLFN11 dCas9 (dead CRISPR associated protein 9) systems to specifically increase or decrease SLFN11 expression.

Results

After confirming the previously reported correlation between methylation of SLFN11 promoter and its expression across multiple cell lines, we showed in-vitro that decitabine and IFN-γ could increase moderately the expression of SLFN11 in both BT-549 and T47D cell lines. The use of a CRISPR-dCas9 UNISAM and KRAB system could increase or decrease SLFN11 expression significantly (up to fivefold), stably and specifically in BT-549 and T47D cancer cell lines. We then used the modified cell lines to quantify the alteration in chemo sensitivity of those cells to treatment with DNA Damaging Agents (DDAs) such as Cisplatin and Epirubicin or DNA Damage Response (DDRs) drugs like Olaparib. RNAseq was used to elucidate the mechanisms of action affected by the alteration in SLFN11 expression. In cell lines with robust SLFN11 promoter methylation such as MDA-MB-231, no SLFN11 expression could be induced by any approach.

Conclusion

To our knowledge this is the first report of the stable non-lethal increase of SLFN11 expression in a cancer cell line. Our results show that induction of SLFN11 expression can enhance DDA and DDR sensitivity in breast cancer cells and dCas9 systems may represent a novel approach to increase SLFN11 and achieve higher sensitivity to chemotherapeutic agents, improving outcome or decreasing required drug concentrations. SLFN11-targeting therapies might be explored pre-clinically to develop personalized approaches.
Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation
Authors: Yang Mengmeng , Xia Longqing , Song Jia , Hu Huiqing , Zang Nan , Yang Jingwen , Zou Ying , Wang Liming , Zheng Xiaoyue , He Qin , Liu Jidong , Liu Fuqiang , Liang Kai , Sun Lei , Chen Li
Published: November 2023

Metabolic dysfunction-associated fatty liver disease (MAFLD) is frequently linked to type 2 diabetes mellitus (T2DM), and both conditions exacerbate the progression of the other. However, there is currently no standardized treatment or drug for MAFLD. In this study, A MAFLD animal model through a high-fat diet (HFD) along with administration of streptozotocin (STZ), and palmitic acid (PA)-induced AML12 cells were treated by puerarin. The objective of this study was to assess the therapeutic effect of puerarin, a flavonoid substance that possesses various pharmacological properties, on MAFLD. The results showed that puerarin administration enhanced glucose tolerance and insulin sensitivity, while also mitigating liver dysfunction and hyperlipidemia in MAFLD mice. Moreover, puerarin attenuated oxidative stress levels and inflammation in the liver. Transmission electron microscopy and Western blot analysis indicated that puerarin inhibited ferroptosis in vivo. Further mechanistic investigations revealed that puerarin upregulated SIRT1 expression, increased nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, and facilitated translocation into the nucleus. The protective effect of puerarin on PA-induced AML12 cells was diminished by the utilization of EX-527 (a SIRT1 inhibitor) and Nrf2 siRNA. Overall, the results demonstrate that puerarin ameliorates MAFLD by suppressing ferroptosis and inflammation via the SIRT1/Nrf2 signaling pathway. The results emphasize the possible medicinal application of puerarin for managing MAFLD.
Plasma exosomes improve peripheral neuropathy via miR-20b-3p/Stat3 in type I diabetic rats
Authors: Li Jiayang , Wu Guangzhi , Li Weiye , Zhou Xiongyao , Li Weizhen , Xu Xiong , Xu Ke , Cao Rangjuan , Cui Shusen
Published: November 2023

Background

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and the main cause of non-traumatic amputation, with no ideal treatment. Multiple cell-derived exosomes have been reported to improve the progression of DPN. Blood therapy is thought to have a powerful repairing effect. However, whether it could also improve DPN remains unclear.

Results

In this study, we found that microRNA (miRNA) expression in plasma-derived exosomes of healthy rats (hplasma-exos) was significantly different from that of age-matched DPN rats. By injection of hplasma-exos into DPN rats, the mechanical sensitivity of DPN rats was decreased, the thermal sensitivity and motor ability were increased, and the nerve conduction speed was accelerated. Histological analysis showed myelin regeneration of the sciatic nerve, increased intraepidermal nerve fibers, distal local blood perfusion, and enhanced neuromuscular junction and muscle spindle innervation after hplasma-exos administration. Compared with plasma exosomes in DPN, miR-20b-3p was specifically enriched in exosomes of healthy plasma and was found to be re-upregulated in the sciatic nerve of DPN rats after hplasma-exos treatment. Moreover, miR-20b-3p agomir improved DPN symptoms to a level similar to hplasma-exos, both of which also alleviated autophagy impairment induced by high glucose in Schwann cells. Mechanistic studies found that miR-20b-3p targeted Stat3 and consequently reduced the amount of p-Stat3, which then negatively regulated autophagy processes and contributed to DPN improvement.

Conclusions

This study demonstrated that miRNA of plasma exosomes was different between DPN and age-matched healthy rats. MiR-20b-3p was enriched in hplasma-exos, and both of them could alleviated DPN symptoms. MiR-20b-3p regulated autophagy of Schwann cells in pathological states by targeting Stat3 and thereby inhibited the progression of DPN.

Graphical Abstract
Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy
Authors: Zhao Yuge , He Ruiqing , Zang Jie , Yin Weimin , Su Runping , Xiong Wei , Xu Weihua , Zhang Jiaxin , Liu Yiqiong , Ren Tianbin , Huang Yongzhuo , Li Yongyong
Published: November 2023

Intestinal epithelia impairment of inflammatory bowel disease (IBD) leads to the leakage of bacteria and antigens and the consequent persistent immune imbalance. Restoring the epithelial barrier is a promising therapeutic target but lacks effective and safe clinical interventions. By identifying the catalase (CAT) presence in the IBD pathological environment, we herein develop a CAT-catalyzed pathologically coating on the damaged epithelial barrier to inhibit intestinal leakage for IBD therapy. With the codelivery of CaO2 (a CAT substrate) and dopamine, the nanosystem can enable CAT-catalyzed oxygen (O2) production and in-situ polymerization of dopamine and then yield a thin and integrative polydopamine (PDA) coating on the intestinal barrier due to the highly adhesive property of PDA. In vivo study demonstrates that PDA coating provides not only a protective barrier by restricting intestinal leakage but also a favorable anti-inflammation effect. Beyond drug management, this work provides a physical repair strategy via catalyzed coating for IBD therapy.
Perioperative predictive factors of failure to rescue following highly advanced hepatobiliary-pancreatic surgery: a single-institution retrospective study
Authors: Fukada Masahiro , Murase Katsutoshi , Higashi Toshiya , Yasufuku Itaru , Sato Yuta , Tajima Jesse Yu , Kiyama Shigeru , Tanaka Yoshihiro , Okumura Naoki , Matsuhashi Nobuhisa
Published: November 2023

Background

Failure to rescue (FTR), defined as a postoperative complication leading to death, is a recently described outcome metric used to evaluate treatment quality. However, the predictive factors for FTR, particularly following highly advanced hepatobiliary-pancreatic surgery (HBPS), have not been adequately investigated. This study aimed to identify perioperative predictive factors for FTR following highly advanced HBPS.

Methods

This single-institution retrospective study involved 177 patients at Gifu University Hospital, Japan, who developed severe postoperative complications (Clavien–Dindo classification grades ≥ III) between 2010 and 2022 following highly advanced HBPS. Univariate analysis was used to identify pre-, intra-, and postoperative risks of FTR.

Results

Nine postoperative mortalities occurred during the study period (overall mortality rate, 1.3% [9/686]; FTR rate, 5.1% [9/177]). Univariate analysis indicated that comorbid liver disease, intraoperative blood loss, intraoperative blood transfusion, postoperative liver failure, postoperative respiratory failure, and postoperative bleeding significantly correlated with FTR.

Conclusions

FTR was found to be associated with perioperative factors. Well-coordinated surgical procedures to avoid intra- and postoperative bleeding and unnecessary blood transfusions, as well as postoperative team management with attention to the occurrence of organ failure, may decrease FTR rates.
Clinicopathological characteristics and prognosis of metaplastic breast cancer versus triple-negative invasive ductal carcinoma: a retrospective analysis
Authors: Yang Xiaolu , Tang Tiantian , Zhou Tao
Published: November 2023

Background

Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC).

Methods

We retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups’ disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS.

Results

A total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90–3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03–3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05–15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03–13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05–11.75, P = 0.04).

Conclusions

The clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.
Pregnancy prediction via ultrasound-detected endometrial blood for hormone replacement therapy-frozen embryo transfer: a prospective observational study
Authors: Ke Xue , Liang Xue-fei , Lin Yong-hong , Wang Fang
Published: November 2023

Background

This study aimed to assess the predictive value of endometrial blood flow branches on pregnancy outcomes after hormone replacement therapy-frozen embryo transfer (HRT-FET).

Methods

This prospective observational study involved 292 reproductive-aged women who underwent endometrial receptivity assessment in a tertiary care academic medical center in southwest China using power Doppler ultrasonography during HRT-FET. Three-dimensional power Doppler ultrasound was performed on the day of endometrial transformation and the day before embryo transfer. The endometrial blood flow branches of the endometrial and subendometrial regions were compared in the non-pregnant and pregnant groups at the two time points mentioned above.

Results

The endometrial blood flow branches were higher in pregnant patients than in non-pregnant patients on the day of endometrial transformation (P = 0.009) and the day before embryo transfer (P = 0.001). Changes in endometrial blood flow pattern and endometrial blood flow branches at the two time points did not differ among the pregnancy outcome samples. After adjusting for age, antral follicles, and embryos transferred, the endometrial blood flow branches on the day before embryo transfer was the independent factor influencing the chance of clinical pregnancy, with an odds ratio of 3.001 (95% confidence interval: 1.448 − 6.219, P = 0.003).

Conclusions

Endometrial blood flow perfusion during the peri-transplantation period of the HRT-FET cycle is a good indicator of pregnancy outcomes, suggesting that valuation of endometrial branches via power Doppler ultrasound is a simple and effective approach for achieving indicator measurements.
14-3-3 $$\upzeta /\updelta$$-reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
Authors: Woo Marcel S. , Nilsson Johanna , Therriault Joseph , Rahmouni Nesrine , Brinkmalm Ann , Benedet Andrea L. , Ashton Nicholas J. , Macedo Arthur C. , Servaes Stijn , Wang Yi-Ting , Tissot Cécile , Arias Jaime Fernandez , Hosseini Seyyed Ali , Chamoun Mira , Lussier Firoza Z. , Karikari Thomas K. , Stevenson Jenna , Mayer Christina , Ferrari-Souza João Pedro , Kobayashi Eliane , Massarweh Gassan , Friese Manuel A. , Pascoal Tharick A. , Gauthier Serge , Zetterberg Henrik , Blennow Kaj , Rosa-Neto Pedro
Published: November 2023

Introduction

Synaptic loss is closely associated with tau aggregation and microglia activation in later stages of Alzheimer’s disease (AD). However, synaptic damage happens early in AD at the very early stages of tau accumulation. It remains unclear whether microglia activation independently causes synaptic cleavage before tau aggregation appears.

Methods

We investigated 104 participants across the AD continuum by measuring 14-3-3 zeta/delta ($$\upzeta /\updelta$$

ζ
/
δ

) as a cerebrospinal fluid biomarker for synaptic degradation, and fluid and imaging biomarkers of tau, amyloidosis, astrogliosis, neurodegeneration, and inflammation. We performed correlation analyses in cognitively unimpaired and impaired participants and used structural equation models to estimate the impact of microglia activation on synaptic injury in different disease stages.

Results

14-3-3 $$\upzeta /\updelta$$

ζ
/
δ

was increased in participants with amyloid pathology at the early stages of tau aggregation before hippocampal volume loss was detectable. 14-3-3 $$\upzeta /\updelta$$

ζ
/
δ

correlated with amyloidosis and tau load in all participants but only with biomarkers of neurodegeneration and memory deficits in cognitively unimpaired participants. This early synaptic damage was independently mediated by sTREM2. At later disease stages, tau and astrogliosis additionally mediated synaptic loss.

Conclusions

Our results advertise that sTREM2 is mediating synaptic injury at the early stages of tau accumulation, underlining the importance of microglia activation for AD disease propagation.
Discontinuation of antidepressant treatment: a retrospective cohort study on more than 20,000 participants
Authors: Garcia-Marin Luis M. , Mulcahy Aoibhe , Byrne Enda M. , Medland Sarah E. , Wray Naomi R. , Chafota Freddy , Lind Penelope A. , Martin Nicholas G. , Hickie Ian B. , Rentería Miguel E. , Campos Adrian I.
Published: November 2023

Background

Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation.

Methods

We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent.

Results

Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications.

Conclusions

Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.
Admitting the heterogeneity of social inequalities: intersectionality as a (self-)critical framework and tool within mental health care
Authors: Funer Florian
Published: November 2023

Inequities shape the everyday experiences and life chances of individuals at the margins of societies and are often associated with lower health and particular challenges in accessing quality treatment and support. This fact is even more dramatic for those individuals who live at the nexus of different marginalized groups and thus may face multiple discrimination, stigma, and oppression. To address these multiple social and structural disadvantages, intersectional approaches have recently gained a foothold, especially in the public health field. This study makes an empirically informed argument for the merits of increasing the use of intersectional frameworks in the mental health field. In the mental health field, the potential for greater attention to multiple unjustified disadvantages appears to be of particular importance, as many mental health service users already face stigma and discrimination because of their mental health issues and thus may benefit particularly frequently and far-reachingly from effective problem awareness about multiple disadvantages. Intersectional approaches may help address the complexity, interdependence, and mutual constitution of social inequalities better than previous approaches that examined only one category of sociostructural stratification. By helping to identify the needs of those at the greatest risk of poor health, intersectional frameworks and tools can contribute not only to better address the needs of multiple disadvantaged individuals with mental health issues but also to the promotion of equity in the field of mental health, contributing to the reduction of health disparities.