bluuebunny/crossref_metadata_2025 huggingface dataset:
An empirical ethics study of the coherence of NICE technology appraisal policy and its implications for moral justification
Authors: Charlton Victoria , DiStefano Michael
Published: March 2024

Background

As the UK’s main healthcare priority-setter, the National Institute for Health and Care Excellence (NICE) has good reason to want to demonstrate that its decisions are morally justified. In doing so, it has tended to rely on the moral plausibility of its principle of cost-effectiveness and the assertion that it has adopted a fair procedure. But neither approach provides wholly satisfactory grounds for morally defending NICE’s decisions. In this study we adopt a complementary approach, based on the proposition that a priority-setter's claim to moral justification can be assessed, in part, based on the coherence of its approach and that the reliability of any such claim is undermined by the presence of dissonance within its moral system. This study is the first to empirically assess the coherence of NICE’s formal approach and in doing so to generate evidence-based conclusions about the extent to which this approach is morally justified.

Methods

The study is grounded in the theory, methods and standards of empirical bioethics. Twenty NICE policy documents were coded to identify and classify the normative commitments contained within NICE technology appraisal policy as of 31 December 2021. Coherence was systematically assessed by attempting to bring these commitments into narrow reflective equilibrium (NRE) and by identifying sources of dissonance.

Findings

Much of NICE policy rests on coherent values that provide a strong foundation for morally justified decision-making. However, NICE’s formal approach also contains several instances of dissonance which undermine coherence and prevent NRE from being fully established. Dissonance arises primarily from four sources: i) NICE’s specification of the principle of cost-effectiveness; ii) its approach to prioritising the needs of particular groups; iii) its conception of reasonableness in the context of uncertainty, and iv) its concern for innovation as an independent value.

Conclusion

At the time of analysis, the level of coherence across NICE policy provides reason to question the extent to which its formal approach to technology appraisal is morally justified. Some thoughts are offered on why, given these findings, NICE has been able to maintain its legitimacy as a healthcare priority-setter and on what could be done to enhance coherence.
Culture of patient care among international nursing students: a focused ethnographic study
Authors: Shali Mahboube , Bakhshi Fatemeh , Hasanpour Marzieh
Published: March 2024

Background

This study was conducted to describe and explain the culture of patient care in international nursing students.

Methods

This qualitative study was conducted using focused ethnography. Participants (n = 21) were purposefully selected from non-Iranian international students and their nursing instructors. Data collection included semi-structured interviews, and field-note taking. Data were analyzed with the Roper and Shapira inductive approach of ethnographic content analysis.

Results

The cultural model of the study included the acquisition of cultural competence through acceptance of differences and finding commonalities. Subcategories were: “avoiding cultural bias”, “trying to be on the path of adaptation”, “appealing to the support and companionship of colleagues”, “coping with culture shock”, “acculturation”, “getting help from cultural intelligence”, “cultural empathy”, and “language and communication enhancement”.

Conclusion

Cultural competence is teachable. The pattern of formation is through accepting differences and searching for commonalities. Suggestions for promoting the culture of care among international students include effective use of peer groups and teaching different national ethnicities and cultures.
Developing a capacity-building intervention for healthcare workers to improve communication skills and awareness of hard of hearing and D/deaf patients: results from a participatory action research study
Authors: Grazioli Véronique S. , Graells Madison , Schmutz Elodie , Cantero Odile , Sebaï Tanya , Favre Vanessa , Richème-Roos Jessica , Morisod Kevin , Jeanneret Michel , Singy Pascal , Bodenmann Patrick
Published: March 2024

Background

Healthcare workers (HCWs) are commonly not prepared to properly communicate with D/deaf and hard of hearing (HoH) patients. The resulting communication challenges reinforce the existing barriers to accessing and benefiting from quality of care in these populations. In response, this study aimed to develop and evaluate a capacity-building intervention for HCWs to raise their awareness of D/deaf and HoH individuals’ experiences in healthcare and improve their capacity to communicate with these populations.

Methods

This study featured a participatory action research design using qualitative and quantitative methods. The intervention was developed and tested through 4 iterative phases. Reactions (i.e., satisfaction and perception of the intervention content, quality, appropriateness and usefulness) were assessed quantitatively and qualitatively after the intervention, whereas perceived knowledge and self-efficacy in communicating with D/deaf and HoH patients and organizational payoffs (use frequency of basic rules and tools improving communication) were quantitatively assessed before, after and 6-month post-intervention.

Results

Main qualitative and quantitative findings showed that the final version of the intervention reached high levels of satisfaction among participants. Next, perceived knowledge and self-efficacy scores obtained after receiving the intervention and 6 months later were significantly higher than those yielded in the initial assessment, although both scores significantly decreased at 6 months (compared to the scores obtained just after the intervention). Finally, findings showed no significant changes in organizational payoffs after receiving the intervention. Echoing these results, main qualitative findings documented that after receiving the intervention, participants felt more confident yet not more equipped to communicate with D/deaf and HoH patients.

Conclusions

Findings suggest that the capacity-building intervention is a promising means to sustainably increase HCWs’ perceived knowledge and self-efficacy on how communicating with D/deaf and HoH patients, although complementary approaches and follow-up intervention reminders may be necessary to enable practice changes in the working environment.
Implementation of large, multi-site hospital interventions: a realist evaluation of strategies for developing capability
Authors: Long Janet C , Roberts Natalie , Francis-Auton Emilie , Sarkies Mitchell N , Nguyen Hoa Mi , Westbrook Johanna I , Levesque Jean-Frederic , Watson Diane E , Hardwick Rebecca , Churruca Kate , Hibbert Peter , Braithwaite Jeffrey
Published: March 2024

Background

This study presents guidelines for implementation distilled from the findings of a realist evaluation. The setting was local health districts in New South Wales, Australia that implemented three clinical improvement initiatives as part of a state-wide program. We focussed on implementation strategies designed to develop health professionals’ capability to deliver value-based care initiatives for multisite programs. Capability, which increases implementers’ ability to cope with unexpected scenarios is key to managing change.

Methods

We used a mixed methods realist evaluation which tested and refined program theories elucidating the complex dynamic between context (C), mechanism (M) and outcome (O) to determine what works, for whom, under what circumstances. Data was drawn from program documents, a realist synthesis, informal discussions with implementation designers, and interviews with 10 key informants (out of 37 identified) from seven sites. Data analysis employed a retroductive approach to interrogate the causal factors identified as contributors to outcomes.

Results

CMO statements were refined for four initial program theories: Making it Relevant– where participation in activities was increased when targeted to the needs of the staff; Investment in Quality Improvement– where engagement in capability development was enhanced when it was valued by all levels of the organisation; Turnover and Capability Loss– where the effects of staff turnover were mitigated; and Community-Wide Priority– where there was a strategy of spanning sites. From these data five guiding principles for implementers were distilled: (1) Involve all levels of the health system to effectively implement large-scale capability development, (2) Design capability development activities in a way that supports a learning culture, (3) Plan capability development activities with staff turnover in mind, (4) Increased capability should be distributed across teams to avoid bottlenecks in workflows and the risk of losing key staff, (5) Foster cross-site collaboration to focus effort, reduce variation in practice and promote greater cohesion in patient care.

Conclusions

A key implementation strategy for interventions to standardise high quality practice is development of clinical capability. We illustrate how leadership support, attention to staff turnover patterns, and making activities relevant to current issues, can lead to an emergent learning culture.
Sex differences in cardiologic medication provision for adults with coronary heart disease: an analysis of health claims data from 2018 to 2020 in Saxony-Anhalt, Germany
Authors: Fleischer Steffen , Heinrich Stephanie , Meyer Gabriele , Mikolajczyk Rafael , Lückmann Sara Lena
Published: March 2024

Background

Coronary heart diseases (CHDs) have experienced the largest increase worldwide as a cause of death, accounting for 16% of all deaths. In Saxony-Anhalt, a federal state in Germany, both CHD morbidity and acute myocardial infarction mortality rates are particularly high. Several risk factors associated with CHDs have been studied in Saxony-Anhalt, but sex differences in service use and medication have not been investigated. This study therefore aimed to investigate sex differences in the quality and quantity of cardiological care provided to adults with CHD.

Methods

This study used health claims data from 2018 to 2020 to analyse the utilisation of healthcare services and adherence to medication-related guideline recommendations in primary and specialist care. The sample included 133,661 individuals with CHD from a major statutory health insurance company (Germany).

Results

Almost all CHD patients (> 99%) received continuous primary care. Continuous cardiologist utilisation was lower for females than for males, with 15.0% and 22.2%, respectively, and sporadic utilisation showed greater differences, with 33.5% of females and 43.4% of males seeking sporadic cardiologist consultations. Additionally, 43.1% of the identified CHD patients participated in disease management programmes (DMPs). The study also examined the impact of DMP participation and cardiologist care on medication uptake and revealed that sex differences in medication uptake, except for statin use, were mitigated by these factors. Statins were prescribed to 42.9% of the CHD patients eligible for statin prescription in accordance with the QiSA indicator for statin prescription eligibility. However, there were significant sex differences in statin utilisation. Female CHD patients were less likely to use statins (35.2%) than male CHD patients were (50.1%). The difference in statin utilisation persisted after adjustment for DMP participation and cardiologist consultation.

Conclusions

This study highlights sex differences in the utilisation of cardiological healthcare services for patients with CHD in the Saxony-Anhalt cohort. These findings underscore the continuing need for interventions to reduce sex inequalities in accessing healthcare and providing health care for patients with CHD. Factors at the health care system, patient, and physician levels should be further investigated to eventually improve statin prescription in people with CHD, especially women.
A CTL − Lys immune function maintains insect metamorphosis by preventing gut bacterial dysbiosis and limiting opportunistic infections
Authors: Xiong Pei , Wang Wen-Wen , Liu Xu-Sheng , Wang Yu-Feng , Wang Jia-Lin
Published: March 2024

Background

Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive.

Results

We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster.

Conclusions

A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL − Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.
Use of the energy waveform electrocardiogram to detect subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus
Authors: Soh Cheng Hwee , de Sá Alex G. C. , Potter Elizabeth , Halabi Amera , Ascher David B. , Marwick Thomas H.
Published: March 2024

Background

Recent guidelines propose N-terminal pro-B-type natriuretic peptide (NT-proBNP) for recognition of asymptomatic left ventricular (LV) dysfunction (Stage B Heart Failure, SBHF) in type 2 diabetes mellitus (T2DM). Wavelet Transform based signal-processing transforms electrocardiogram (ECG) waveforms into an energy distribution waveform (ew)ECG, providing frequency and energy features that machine learning can use as additional inputs to improve the identification of SBHF. Accordingly, we sought whether machine learning model based on ewECG features was superior to NT-proBNP, as well as a conventional screening tool—the Atherosclerosis Risk in Communities (ARIC) HF risk score, in SBHF screening among patients with T2DM.

Methods

Participants in two clinical trials of SBHF (defined as diastolic dysfunction [DD], reduced global longitudinal strain [GLS ≤ 18%] or LV hypertrophy [LVH]) in T2DM underwent 12-lead ECG with additional ewECG feature and echocardiography. Supervised machine learning was adopted to identify the optimal combination of ewECG extracted features for SBHF screening in 178 participants in one trial and tested in 97 participants in the other trial. The accuracy of the ewECG model in SBHF screening was compared with NT-proBNP and ARIC HF.

Results

SBHF was identified in 128 (72%) participants in the training dataset (median 72 years, 41% female) and 64 (66%) in the validation dataset (median 70 years, 43% female). Fifteen ewECG features showed an area under the curve (AUC) of 0.81 (95% CI 0.787–0.794) in identifying SBHF, significantly better than both NT-proBNP (AUC 0.56, 95% CI 0.44–0.68, p < 0.001) and ARIC HF (AUC 0.67, 95%CI 0.56–0.79, p = 0.002). ewECG features were also led to robust models screening for DD (AUC 0.74, 95% CI 0.73–0.74), reduced GLS (AUC 0.76, 95% CI 0.73–0.74) and LVH (AUC 0.90, 95% CI 0.88–0.89).

Conclusions

Machine learning based modelling using additional ewECG extracted features are superior to NT-proBNP and ARIC HF in SBHF screening among patients with T2DM, providing an alternative HF screening strategy for asymptomatic patients and potentially act as a guidance tool to determine those who required echocardiogram to confirm diagnosis.

Trial registration LEAVE-DM, ACTRN 12619001393145 and Vic-ELF, ACTRN 12617000116325
The worsening effect of paroxysmal atrial fibrillation on left ventricular function and deformation in type 2 diabetes mellitus patients: a 3.0 T cardiovascular magnetic resonance feature tracking study
Authors: Li Xue-Ming , Yan Wei-Feng , Shi Ke , Shi Rui , Jiang Li , Gao Yue , Min Chen-Yan , Liu Xiao-Jing , Guo Ying-Kun , Yang Zhi-Gang
Published: March 2024

Background

Atrial fibrillation (AF) has been linked to an increased risk of cardiovascular death, overall mortality and heart failure in patients with type 2 diabetes mellitus (T2DM). The present study investigated the additive effects of paroxysmal AF on left ventricular (LV) function and deformation in T2DM patients with or without AF using the cardiovascular magnetic resonance feature tracking (CMR-FT) technique.

Methods

The present study encompassed 225 T2DM patients differentiated by the presence or absence of paroxysmal AF [T2DM(AF+) and T2DM(AF−), respectively], along with 75 age and sex matched controls, all of whom underwent CMR examination. LV function and global strains, including radial, circumferential and longitudinal peak strain (PS), as well as peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were measured and compared among the groups. Multivariable linear regression analysis was used to examine the factors associated with LV global strains in patients with T2DM.

Results

The T2DM(AF+) group was the oldest, had the highest LV end‑systolic volume index, lowest LV ejection fraction and estimated glomerular filtration rate compared to the control and T2DM(AF−) groups, and presented a shorter diabetes duration and lower HbA1c than the T2DM(AF−) group. LV PS-radial, PS-longitudinal and PDSR-radial declined successively from controls through the T2DM(AF−) group to the T2DM(AF+) group (all p < 0.001). Compared to the control group, LV PS-circumferential, PSSR-radial and PDSR-circumferential were decreased in the T2DM(AF+) group (all p < 0.001) but preserved in the T2DM(AF−) group. Among all clinical indices, AF was independently associated with worsening LV PS-longitudinal (β = 2.218, p < 0.001), PS-circumferential (β = 3.948, p < 0.001), PS-radial (β = − 8.40, p < 0.001), PSSR-radial and -circumferential (β = − 0.345 and 0.101, p = 0.002 and 0.014, respectively), PDSR-radial and -circumferential (β = 0.359 and − 0.14, p = 0.022 and 0.003, respectively).

Conclusions

In patients with T2DM, the presence of paroxysmal AF further exacerbates LV function and deformation. Proactive prevention, regular detection and early intervention of AF could potentially benefit T2DM patients.
Designing and validating an experimental protocol to induce airway narrowing in older adults with and without asthma
Authors: Chavoshian Shaghayegh , Cao Xiaoshu , Thommandram Anirudh , Stanbrook Matthew B. , Tarlo Susan M. , Fossat Yan , Yadollahi Azadeh
Published: March 2024

Background

Persons with asthma may experience excessive airway narrowing due to exercise or exposure to cold air, worsening their daily functionality. Exercise has several benefits for asthma control, but it may induce airway narrowing in some persons with asthma. When combined with cold temperatures, it introduces another layer of challenges. Therefore, managing this interaction is crucial to increase the quality of life in individuals with asthma. The purpose of this study was to develop a reliable experimental protocol to assess the effects of exercise and cold air on airway narrowing in adults with asthma in a controlled and safe environment.

Methods

This study was a randomized cross-over study in adults with and without asthma. Participants underwent a protocol involving a 10-min seated rest, followed by a 10-min cycling on a stationary bike in different temperatures of 0, 10, or 20 $$^{\circ }$$

∘

C. The sequence of room temperatures was randomized, and there was a 30-min interval for recovery between each temperature transition. In each temperature, to measure lung function and respiratory symptoms, oscillometry and a questionnaire were used at 0 min (baseline), after 10 min of sitting and before starting biking (pre-exercise), and after 10 min of biking (post-exercise). At each room temperature, the changes in airway mechanics and asthma symptoms among baseline, pre-exercise, and post-exercise were compared with one-way repeated measures ANOVA or Friedman Rank Test. Within each arm, cardiac and thoraco-abdominal motion respiration signals were also measured continuously using electrodes and calibrated respiratory inductance plethysmographs, respectively.

Results

A total of 23 persons with asthma (11 females, age: 56.3 ± 10.9 years, BMI: 27.4 ± 5.7 kg/m2) and 6 healthy subjects (3 females, age: 61.8 ± 9.1 years, BMI: 28.5 ± 3.1 kg/m2) were enrolled in the study. Cold temperature of 0 $$^{\circ }$$

∘

C induced airway narrowing in those with and without asthma after 10 and 20 min, respectively. Exercise intervention had significant changes in airway narrowing in participants with asthma in the range of 10–20 $$^{\circ }$$

∘

C. Our results showed that in asthma, changes in subjective respiratory symptoms were due to both cold temperatures of 0 and 10 $$^{\circ }$$

∘

C and exercise in the 0–20 $$^{\circ }$$

∘

C range. Respiratory symptoms were not noticed among the healthy participants.

Conclusion

In conclusion, our findings suggest that exposure to cold temperatures of 0 $$^{\circ }$$

∘

C could serve as a reliable method in the experimental protocol for inducing airway narrowing in asthma. The impact of exercise on airway narrowing was more variable among participants. Understanding these triggers in the experimental protocol is essential for the successful management of asthma in future studies.
Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway
Authors: Yang Shi-Yuan , Hu Yue , Zhao Ran , Zhou Yu-Ning , Zhuang Yu , Zhu Yan , Ge Xiao-Li , Lu Ting-Wei , Lin Kai-Li , Xu Yuan-Jin
Published: March 2024

Background

Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin’s clinical application is limited due to its poor water solubility and low bioavailability.

Results

In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA——miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway.

Conclusion

In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Graphical Abstract
Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells
Authors: Gagliardi Sinforosa , Mitruccio Marco , Di Corato Riccardo , Romano Roberta , Aloisi Alessandra , Rinaldi Rosaria , Alifano Pietro , Guerra Flora , Bucci Cecilia
Published: March 2024

Background

Among the mechanisms of mitochondrial quality control (MQC), generation of mitochondria-derived vesicles (MDVs) is a process to avoid complete failure of mitochondria determining lysosomal degradation of mitochondrial damaged proteins. In this context, RAB7, a late endocytic small GTPase, controls delivery of MDVs to late endosomes for subsequent lysosomal degradation. We previously demonstrated that RAB7 has a pivotal role in response to cisplatin (CDDP) regulating resistance to the drug by extracellular vesicle (EVs) secretion.

Methods

Western blot and immunofluorescence analysis were used to analyze structure and function of endosomes and lysosomes in CDDP chemosensitive and chemoresistant ovarian cancer cell lines. EVs were purified from chemosensitive and chemoresistant cells by ultracentrifugation or immunoisolation to analyze their mitochondrial DNA and protein content. Treatment with cyanide m-chlorophenylhydrazone (CCCP) and RAB7 modulation were used, respectively, to understand the role of mitochondrial and late endosomal/lysosomal alterations on MDV secretion. Using conditioned media from chemoresistant cells the effect of MDVs on the viability after CDDP treatment was determined. Seahorse assays and immunofluorescence analysis were used to study the biochemical role of MDVs and the uptake and intracellular localization of MDVs, respectively.

Results

We observed that CDDP-chemoresistant cells are characterized by increased MDV secretion, impairment of late endocytic traffic, RAB7 downregulation, an increase of RAB7 in EVs, compared to chemosensitive cells, and downregulation of the TFEB-mTOR pathway overseeing lysosomal and mitochondrial biogenesis and turnover. We established that MDVs can be secreted rather than delivered to lysosomes and are able to deliver CDDP outside the cells. We showed increased secretion of MDVs by chemoresistant cells ultimately caused by the extrusion of RAB7 in EVs, resulting in a dramatic drop in its intracellular content, as a novel mechanism to regulate RAB7 levels. We demonstrated that MDVs purified from chemoresistant cells induce chemoresistance in RAB7-modulated process, and, after uptake from recipient cells, MDVs localize to mitochondria and slow down mitochondrial activity.

Conclusions

Dysfunctional MQC in chemoresistant cells determines a block in lysosomal degradation of MDVs and their consequent secretion, suggesting that MQC is not able to eliminate damaged mitochondria whose components are secreted becoming effectors and potential markers of chemoresistance.
Dysregulated Gab1 signalling in triple negative breast cancer
Authors: Bongartz Hannes , Mehwald Nora , Seiß Elena A. , Schumertl Tim , Naß Norbert , Dittrich Anna
Published: March 2024

Background

Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is especially aggressive and associated with high metastasis. The aetiology of TNBC is heterogeneous and characterised by multiple different mutations that amongst others cause constitutive and dysregulated MAPK and PI3K signalling. Additionally, in more than 50% of TNBC patients, the epidermal growth factor receptor (EGFR) is overexpressed and constitutively active. The multi-site docking protein Grb2-associated binder 1 (Gab1) is a central signalling hub that connects MAPK and PI3K signalling.

Methods

Expression and activation of members of the Gab1/PI3K/MAPK signalling network were assessed in cells from different breast cancer subtypes. Influence of short- and long-term inhibition of EGFR, MAPK and PI3K on the activation of the Gab1/PI3K/MAPK signalling network as well as on cell viability, proliferation and migration was determined. Additionally, cellular localisation of Gab1 and Gab1 variants in naive cells and cells treated with the above-mentioned inhibitors was investigated.

Results

We show that, activation of the Gab1/PI3K/MAPK signalling network is heterogeneous between different breast cancer subtypes. Gab1 phosphorylation and plasma membrane recruitment of Gab1 are dysregulated in the EGFRhigh TNBC cell line MDA-MB-468. While the Gab1/MAPK/PI3K signalling network follows canonical Gab1 signalling in naive MDA-MB-468 cells, Gab1 signalling is changed in cells that acquired resistance towards MAPK and PI3K inhibition. In resistant cells, Gab1 is not located at the plasma membrane despite strong activation of PI3K and MAPK. Furthermore, Gab1 tyrosine phosphorylation is uncoupled from plasma membrane recruitment.

Conclusion

Our study indicates that Gab1 signalling changes fundamentally during the acquisition of resistance to pharmacological inhibitors. Given the molecular heterogeneity between breast cancer subtypes, the detailed understanding of dysregulated and aberrant signalling is an absolute necessity in order to develop personalised therapies for patients with TNBC.
WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy
Authors: Chen Bolin , Zou Jing , Xie Lihui , Cai Yinjun , Li Bowen , Tan Wei , Huang Jinhaohao , Li Fangling , Xu Huizhuo
Published: March 2024

Background

In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR.

Method

Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting.

Result

Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability.

Conclusions

WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.

Graphical Abstract
Resisting stigma: the role of online communities in young mothers’ successful breastfeeding
Authors: Severinsen Christina , Neely Eva , Hutson Rochelle
Published: March 2024

Background

Breastfeeding initiation and continuation rates are shaped by complex and interrelated determinants across individual, interpersonal, community, organisational, and policy spheres. Young mothers, however, face a double burden of stigma, being perceived as immature and incompetent in their mothering and breastfeeding abilities. In this study, we aimed to understand the experiences of young mothers who exclusively breastfed for six months and beyond and explore their experiences of stigma and active resistance through social media.

Methods

In 2020, in-depth telephone interviews about breastfeeding experiences were conducted with 44 young mothers under age 25 in Aotearoa New Zealand who breastfed for six months or longer. Participants were recruited via social media. Interviews were audio-recorded, transcribed and analysed thematically.

Results

Analysis yielded four themes on young mothers’ negotiation of breastfeeding and support. The first three themes revealed young mothers’ encounters with socio-cultural contexts. They faced negative judgments about maturity and competence, adverse guidance to supplement or cease breastfeeding, and an undermining of their breastfeeding efforts. The fourth theme showed how young mothers sought alternative support in online environments to avoid negative interactions. Online spaces provided anonymity, convenience, experiential knowledge and social connections with shared values. This facilitated identity strengthening, empowerment and stigma resistance.

Conclusion

Our research highlights the importance of online communities as a tool for young mothers to navigate and resist the societal stigmas surrounding breastfeeding. Online spaces can provide a unique structure that can help counteract the adverse effects of social and historical determinants on breastfeeding rates by fostering a sense of inclusion and support. These findings have implications for the development of breastfeeding promotion strategies for young mothers and highlight the potential of peer support in counteracting the negative impacts of stigma. The research also sheds light on the experiences of young mothers within the health professional relationship and the effects of stigma and cultural health capital on their engagement and withdrawal from services. Further research should examine how sociocultural barriers to breastfeeding stigmatise and marginalise young mothers and continue to reflect on their socio-political and economic positioning and how it can exacerbate inequities.
Comparison of surgical and conservative treatment outcomes for type a aortic intramural hematoma
Authors: Yin Li , Wang Jiankai , Qiu Zhibing , Chen Xin , Su Cunhua
Published: March 2024

Objective

This study aimed to compare hospital and long-term clinical outcomes associated with various treatment methods for Stanford A type aortic intramural hematoma (IMH) to provide a reference for clinical decision-making.

Methods

In this single-center cohort study, we retrospectively analyzed 73 patients with Type A IMH treated at our center from August 1, 2018 to August 1, 2021. Among these patients, 26 were treated conservatively, and 47 underwent surgical intervention. We next compared this IMH cohort with 154 patients with acute type A aortic dissection (AD) who were treated surgically during the same study period.

Results

Computed tomography angiography revealed that the diameter of the ascending aorta of IMH patients treated with surgery was higher than IMH patients treated with conservative therapy (44.92 ± 7.58 mm vs. 51.22 ± 11.85 mm, P < 0.05), while there was no significant difference in other clinical parameters. The in-hospital mortality of patients with IMH who underwent surgical treatment was lower than those undergoing conservative treatment (0% vs. 11.5%, P < 0.05). The long-term mortality of the conservative IMH group was higher than the surgical IMH group (26.1% vs. 8.5%, P < 0.05). There was no significant difference in the surgical parameters and postoperative complications between AD and IMH surgery patients. The proportion of circulatory arrest time in the lower body (19.98 ± 9.39 min vs. 17.51 ± 3.97 min) and arch involvement (98 (63.6%) vs. 22 (46.8%)) in the IMH surgery group was lower than in the AD surgery group (P < 0.05).

Conclusions

Compared with conservative treatment, surgical treatment of IMH significantly improves the survival rate of patients. Thus, surgical intervention should be considered the primary treatment option if feasible. Furthermore, The safety of IMH surgery can be guaranteed just like AD. But we still need in the future evidence on bigger samples.

Graphical abstract
Ginsenosides as dietary supplements with immunomodulatory effects: a review
Authors: Tang Ping , Liu Sitong , Zhang Junshun , Ai Zhiyi , Hu Yue , Cui Linlin , Zou Hongyang , Li Xia , Wang Yu , Nan Bo , Wang Yuhua
Published: March 2024

Immune disorders have become one of the public health problems and imposes a serious economic and social burden worldwide. Ginsenosides, the main active constituents of ginseng, are regarded as a novel supplementary strategy for preventing and improving immune disorders and related diseases. This review summarized the recent research progress of ginsenosides in immunomodulation and proposed future directions to promote the development and application of ginsenosides. After critically reviewing the immunomodulatory potential of ginsenosides both in vitro and in vivo and even in clinical data of humans, we provided a perspective that ginsenosides regulated the immune system through activation of immune cells, cytokines, and signaling pathways such as MAPK, PI3K/Akt, STAT, and AMPK, as well as positively affected immune organs, gut flora structure, and systemic inflammatory responses. However, the evidence for the safety and efficacy of ginsenosides is insufficient, and the immune pathways of ginsenosides remain incompletely characterized. We believe that this review will provide a valuable reference for further research on ginsenosides as dietary supplements with immunomodulatory effects.
CD133 significance in glioblastoma development: in silico and in vitro study
Authors: Abdoli Shadbad Mahdi , Nejadi Orang Fatemeh , Baradaran Behzad
Published: March 2024

Background

Glioblastoma multiform (GBM) is among the commonly diagnosed brain malignancies with poor prognosis. CD133 has been introduced as an oncogene in various cancers, like GBM. This study aimed to investigate the significance of CD133 in GBM development using in silico and in vitro techniques.

Method

The TCGA-GBM database was analyzed for the correlational and comparative studies. After selecting the U87MG cell line, CD133-siRNA was transfected into U87MG cells and treated with temozolomide. The cell viability, cell cycle, migration, clonogenicity, and apoptosis of groups were investigated using MTT, flow cytometry, wound-healing, colony formation, and annexin V/PI assays. Using qRT-PCR method, the mRNA expression levels of MMP16, SOX2, RAF1, MAP2K1, MAPK3, PIK3CA, AKT3, mTOR, CDK4, and BCL2 were studied.

Results

CD133 silencing improves apoptosis rate, arrests the cell cycle at the sub-G1 phase, suppresses the clonogenicity of U87MG cells, and inhibits the PI3K/Akt and MAPK pathways via downregulating the RAF1, MAP2K1, MAPK3, PIK3CA, AKT3, and mTOR expression. Besides, combining CD133 silencing with temozolomide treatment considerably inhibits the migration of U87MG cells compared to temozolomide monotherapy.

Conclusion

CD133 can regulate the PI3K/Akt and MAPK pathways and modulate the clonogenicity, apoptosis, and cell cycle of GBM. Combining CD133 silencing with temozolomide treatment considerably increases apoptosis, arrests the cell cycle at the sub-G1, and suppresses migration of U87MG cells compared to temozolomide monotherapy.

Graphical Abstract
Torso hemorrhage: noncompressible? never say never
Authors: Zhang Lian-Yang , Zhang Hua-Yu
Published: March 2024

Since limb bleeding has been well managed by extremity tourniquets, the management of exsanguinating torso hemorrhage (TH) has become a hot issue both in military and civilian medicine. Conventional hemostatic techniques are ineffective for managing traumatic bleeding of organs and vessels within the torso due to the anatomical features. The designation of noncompressible torso hemorrhage (NCTH) marks a significant step in investigating the injury mechanisms and developing effective methods for bleeding control. Special tourniquets such as abdominal aortic and junctional tourniquet and SAM junctional tourniquet designed for NCTH have been approved by FDA for clinical use. Combat ready clamp and junctional emergency treatment tool also exhibit potential for external NCTH control. In addition, resuscitative endovascular balloon occlusion of the aorta (REBOA) further provides an endovascular solution to alleviate the challenges of NCTH treatment. Notably, NCTH cognitive surveys have revealed that medical staff have deficiencies in understanding relevant concepts and treatment abilities. The stereotypical interpretation of NCTH naming, particularly the term noncompressible, is the root cause of this issue. This review discusses the dynamic relationship between TH and NCTH by tracing the development of external NCTH control techniques. The authors propose to further subdivide the existing NCTH into compressible torso hemorrhage and NCTH’ (noncompressible but REBOA controllable) based on whether hemostasis is available via external compression. Finally, due to the irreplaceability of special tourniquets during the prehospital stage, the authors emphasize the importance of a package program to improve the efficacy and safety of external NCTH control. This program includes the promotion of tourniquet redesign and hemostatic strategies, personnel reeducation, and complications prevention.
Why consumers have impulsive purchase behavior in live streaming: the role of the streamer
Authors: LI Xiaolin , Huang Dunhu , Dong Guofeng , Wang Bing
Published: March 2024

To explore the influencing factors of consumers’ impulsive purchase behavior in live streaming, based on the Stimulus-Organism-Response framework, we construct the model of how streamers influence consumers’ impulsive purchase behavior by consulting literature. Collected data by means of a questionnaire, and made an empirical study by using the structural equation model to explore the mechanism of streamer affecting consumers’ impulsive purchase behavior. The results show that streamer characteristics (personal charisma, professionalism) and streamer performance (interactivity, entertainment) affect consumers’ impulsive purchase behavior by affecting consumers’ trust and flow experience. The empirical results have important theoretical and practical significance.
Perception of affordable diet is associated with pre-school children’s diet diversity in Addis Ababa, Ethiopia: the EAT Addis survey
Authors: Abdelmenan Semira , Berhane Hanna Y. , Turner Christopher , Worku Alemayehu , Selling Katarina , Ekström Eva-Charlotte , Berhane Yemane
Published: March 2024

Background

Despite improvements in food access and nutrition security over the last few decades, malnutrition remains a major public health problem. One of the significant contributors to these problems is affordability of nutritious food. This study aimed to examine the association between perceived food affordability and pre-school children’s diet diversity in Addis Ababa, Ethiopia.

Methods

Cross-sectional data from 2017 to 18 were used for the analysis. A 24-hour dietary recall assessment was done to assess children’s dietary diversity (DD). We used a modified operational definition of affordability indicator called perceived affordability of dietary diversity (afford-DD) to evaluate the impact of the food environment in terms of affordability at the household level. A sample (n 4,898) of children aged 6–59 months representative of households in Addis Ababa was randomly selected using a multistage sampling procedure including all districts in the city. Mixed-effects linear regression models were used to assess the association between children’s DD and afford-DD.

Results

The survey revealed that the mean (standard deviation [SD]) of children’s DD was 3.9 [± 1.4] while the mean [SD] of afford-DD was 4.6 [± 2.1]. Overall, 59.8% of children met the minimum dietary diversity (≥ 4 food groups). White roots and tubers were the most commonly consumed food groups regardless of their affordability. Considerable variations were observed between households that reported the food item affordable and not affordable in consumption of Vitamin A rich vegetables and fruits, meat and fish, egg, and dairy. The children’s DD was positively associated with afford-DD after adjusting for maternal education, household wealth status and other relevant confounding. Higher maternal education modified the association between affordability and children’s diet diversity.

Conclusions

This study suggests higher perceived food affordability was associated with better diet diversity in children. A higher level of maternal education had the potential to mitigate affordability challenges in meeting the children’s dietary diversity needs. Our study emphasizes the need for inclusive food programs and nutrition interventions addressing social differences, intensifying efforts to make nutrient-rich diets affordable for the less privileged, and highlights the potential benefits of targeting maternal education in addressing child dietary diversity.