bluuebunny/crossref_metadata_2025 huggingface dataset:
EIF4A inhibition targets bioenergetic homeostasis in AML MOLM-14 cells in vitro and in vivo and synergizes with cytarabine and venetoclax
Authors: Fooks Katie , Galicia-Vazquez Gabriela , Gife Victor , Schcolnik-Cabrera Alejandro , Nouhi Zaynab , Poon William W. L. , Luo Vincent , Rys Ryan N. , Aloyz Raquel , Orthwein Alexandre , Johnson Nathalie A. , Hulea Laura , Mercier Francois E.
Published: December 2022

Background

Acute myeloid leukemia (AML) is an aggressive hematological cancer resulting from uncontrolled proliferation of differentiation-blocked myeloid cells. Seventy percent of AML patients are currently not cured with available treatments, highlighting the need of novel therapeutic strategies. A promising target in AML is the mammalian target of rapamycin complex 1 (mTORC1). Clinical inhibition of mTORC1 is limited by its reactivation through compensatory and regulatory feedback loops. Here, we explored a strategy to curtail these drawbacks through inhibition of an important effector of the mTORC1signaling pathway, the eukaryotic initiation factor 4A (eIF4A).

Methods

We tested the anti-leukemic effect of a potent and specific eIF4A inhibitor (eIF4Ai), CR-1-31-B, in combination with cytosine arabinoside (araC) or the BCL2 inhibitor venetoclax. We utilized the MOLM-14 human AML cell line to model chemoresistant disease both in vitro and in vivo. In eIF4Ai-treated cells, we assessed for changes in survival, apoptotic priming, de novo protein synthesis, targeted intracellular metabolite content, bioenergetic profile, mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP).

Results

eIF4Ai exhibits anti-leukemia activity in vivo while sparing non-malignant myeloid cells. In vitro, eIF4Ai synergizes with two therapeutic agents in AML, araC and venetoclax. EIF4Ai reduces mitochondrial membrane potential (MMP) and the rate of ATP synthesis from mitochondrial respiration and glycolysis. Furthermore, eIF4i enhanced apoptotic priming while reducing the expression levels of the antiapoptotic factors BCL2, BCL-XL and MCL1. Concomitantly, eIF4Ai decreases intracellular levels of specific metabolic intermediates of the tricarboxylic acid cycle (TCA cycle) and glucose metabolism, while enhancing mtROS. In vitro redox stress contributes to eIF4Ai cytotoxicity, as treatment with a ROS scavenger partially rescued the viability of eIF4A inhibition.

Conclusions

We discovered that chemoresistant MOLM-14 cells rely on eIF4A-dependent cap translation for survival in vitro and in vivo. EIF4A drives an intrinsic metabolic program sustaining bioenergetic and redox homeostasis and regulates the expression of anti-apoptotic proteins. Overall, our work suggests that eIF4A-dependent cap translation contributes to adaptive processes involved in resistance to relevant therapeutic agents in AML.
Incorporating ‘Green Podiatry’ into your clinic, and into your life
Authors: Evans AM Angela Margaret
Published: December 2022

Background

This commentary outlines practical ways of positively incorporating green podiatry, foot health, physical activity benefits, and relevance to climate change into the clinical setting as Conference of Parties (COP27) approaches. Recent reports from the Intergovernmental Panel on Climate Change, the World Economic Forum, and undergraduate curricula concerns, are presented.

Main body

Climate change is irrefutable, and as health professionals, podiatrists can discuss the benefits and principles of green podiatry with patients of all ages in their clinics, appreciating that people are increasingly worried about the climate crisis.

Feet as fundamental for independent, healthy, and carbon–neutral active transport, needs to become a key message. The three pillars for green podiatry are exercise, evidence, and the everyday changes that all podiatrists can make. Likewise, podiatrists can encourage their patients, and in doing so, join with community leadership, alongside other allied health and medical peers.

Conclusion

Podiatrists have a shared responsibility to work and live as ‘green’ as possible, and to share this message with patients. Reducing waste, physically and in the form of unnecessary treatment, and supporting a review of supply chains, are important aspects of reducing health care emissions.

Promoting feet as carbon–neutral transport, and physical activity as evidence based and health enhancing, are a sound contribution to twenty‐first century public health. Podiatry has a great opportunity for positive legacy.
The epidemiology of and management of pediatric patients with head trauma: a hospital-based study from Southern Sweden
Authors: Al Mukhtar Ali , Bergenfeldt Henrik , Edelhamre Marcus , Vedin Tomas , Larsson Per-Anders , Öberg Stefan
Published: December 2022

Background

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children worldwide. In Scandinavia, the epidemiology of pediatric head trauma is poorly documented. This study aimed to investigate and compare the epidemiology and management of pediatric patients with isolated head trauma (IHT) and head trauma in connection with multitrauma (MHT).

Methods

We conducted a retrospective review of medical records of patients < 18 years of age who attended any of the five emergency departments (ED) in Scania County in Sweden in 2016 due to head trauma. Clinical data of patients with IHT were analyzed and compared with those of patients with MHT.

Results

We identified 5046 pediatric patients with head trauma, 4874 with IHT and 186 with MHT, yielding an incidence of ED visits due to head trauma of 1815/100,000 children/year. There was male predominance, and the median age was four years. Falls were the dominating trauma mechanism in IHT patients, while motor vehicle accidents dominated in MHT patients. The frequencies of CT head-scans, ward admissions and intracranial injuries (ICI) were 5.4%, 11.1% and 0.7%, respectively. Four patients (0.08%) required neurosurgical intervention. The relative risks for CT-scans and admissions to a hospital ward and ICI were 10, 4.5 and 19 times higher for MHT compared with IHT patients.

Conclusion

Head trauma is a common cause of ED visits in our study. Head-CTs and ICIs were less frequent than in previous studies. MHT patients had higher rates of CT-scans, admissions, and ICIs than IHT patients, suggesting that they are separate entities that should ideally be managed using different guidelines to optimize the use of CT-scans of the head.
Risk for mental illness following exposure to violence and threats among newly arrived refugees
Authors: Mangrio Elisabeth , Zdravkovic Slobodan , Ivert Anna-Karin
Published: December 2022

Objective

There is an association between pre-migration exposure to threats and violence, and the risk for mental illness among newly arrived refugees (NAR). The aim of this study is therefore to investigate the effect of pre-migration violent and threatening experiences on the mental health of NAR in Sweden. The participants were recruited between February 2015 and February 2016, undergoing the naturalisation process in Sweden. In total, 681 questionnaires were returned (response rate of 39.5%).

Results

The results showed that almost 50% of the sample were at risk for mental illness. Analysis of pre-migration exposure to violence or threats, and risk for mental illness, showed a significant odds ratio for violence as well as for threats. Analysing men and women separately resulted in a significant odds ratio for women for pre-migration threats. For men, pre-migration violence and threats were significantly associated with the risk for mental illness.

The host society receiving NAR must screen for mental illness and be prepared to provide support and care for refugees who were exposed to violence or threats, and who are subsequently at risk for mental illness. This must be considered in order to improve health and subsequently the social integration of refugees.
The hibernation-derived compound SUL-138 shifts the mitochondrial proteome towards fatty acid metabolism and prevents cognitive decline and amyloid plaque formation in an Alzheimer’s disease mouse model
Authors: de Veij Mestdagh Christina F. , Koopmans Frank , Breiter Jonathan C. , Timmerman Jaap A. , Vogelaar Pieter C. , Krenning Guido , Mansvelder Huibert D. , Smit August B. , Henning Robert H. , van Kesteren Ronald E.
Published: December 2022

Background

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide and remains without effective cure. Increasing evidence is supporting the mitochondrial cascade hypothesis, proposing that loss of mitochondrial fitness and subsequent ROS and ATP imbalance are important contributors to AD pathophysiology.

Methods

Here, we tested the effects of SUL-138, a small hibernation-derived molecule that supports mitochondrial bioenergetics via complex I/IV activation, on molecular, physiological, behavioral, and pathological outcomes in APP/PS1 and wildtype mice.

Results

SUL-138 treatment rescued long-term potentiation and hippocampal memory impairments and decreased beta-amyloid plaque load in APP/PS1 mice. This was paralleled by a partial rescue of dysregulated protein expression in APP/PS1 mice as assessed by mass spectrometry-based proteomics. In-depth analysis of protein expression revealed a prominent effect of SUL-138 in APP/PS1 mice on mitochondrial protein expression. SUL-138 increased the levels of proteins involved in fatty acid metabolism in both wildtype and APP/PS1 mice. Additionally, in APP/PS1 mice only, SUL-138 increased the levels of proteins involved in glycolysis and amino acid metabolism pathways, indicating that SUL-138 rescues mitochondrial impairments that are typically observed in AD.

Conclusion

Our study demonstrates a SUL-138-induced shift in metabolic input towards the electron transport chain in synaptic mitochondria, coinciding with increased synaptic plasticity and memory. In conclusion, targeting mitochondrial bioenergetics might provide a promising new way to treat cognitive impairments in AD and reduce disease progression.
A systematic review and meta-analysis of unmet needs for healthcare and long-term care among older people
Authors: Rahman Md. Mizanur , Rosenberg Megumi , Flores Gabriela , Parsell Nadia , Akter Shamima , Alam Md Ashraful , Rahman Md. Mahfuzur , Edejer Tessa
Published: December 2022

Background

The absolute number of older individuals needing medical care and long-term care (LTC) is increasing globally due to the growing ageing population. However, it is uncertain who and what proportion of the population has access to care. Therefore, a systematic review and meta-analysis of the prevalence and reasons for unmet needs for healthcare and long-term care among older people, 65 years old and above, across countries was conducted.

Methods

An information specialist performed a comprehensive search of four major databases (PubMed, EMBASE, Web of Science, and CINAHL) from inception to June 2020 without restrictions on language and date. We did random-effects meta-analysis to obtain pooled prevalence. We stratified the meta-analysis by reasons for unmet need categorized by barrier dimension (availability, accessibility, affordability, and acceptability), survey year, geographic location, and socio-demographic characteristics of the older individual.

Results

After screening 3912 articles, we included 101 studies published between 1996 and 2020. Of the 101 studies, 87 studies reported unmet healthcare needs and 14 studies reported unmet LTC needs. Overall, 10.4% (95% CI, 7.3–13.9) of the older population had unmet needs for healthcare. The common reasons for unmet healthcare needs were cost of treatment, lack of health facilities, lack of/conflicting time, health problem not viewed as serious, and mistrust/fear of provider. A significant variation in pooled prevalence of unmet healthcare needs due to cost was found by gender (male [10.9, 95% CI, 8.9–13.1] vs female [14.4, 95% CI, 11.8–17.3]), educational level (primary or less [13.3, 95% CI, 9.6–17.6] vs higher [7.5, 95% CI, 5.9–9.3]), self-reported health (poor [23.2, 95% CI, 18.8–27.8] vs good [4.4, 95% CI, 3.4–5.5]), insurance status (insured [9.0, 95% CI, 7.5–10.6] vs uninsured [27.7, 95% CI, 24.0–31.5]), and economic status of population (poorest [28.2, 95% CI, 14.1–44.9] vs richest [7.1, 95% CI, 3.8–11.3]). One in four (25.1, 95% CI, 17.1–34.2) older people had unmet needs in LTC. Rural residents had a higher prevalence of unmet needs in LTC compared to their urban counterparts.

Conclusion

With the population ageing globally, it is necessary to improve access to health care and LTC for older people. Ensuring affordability of health services, reducing geographical barriers, and improving acceptability, will be critical in reducing unmet need. Unmet needs for healthcare were concentrated in population with no education, poor economic group, outpatient health facility user, and uninsured group. With education and economic-based inequalities at the forefront, all countries should focus on improving access to health services by reducing the burden related to healthcare costs.
Preparing for participation in the centers for Medicare and Medicaid Services’ bundle care payment initiative—advanced for major bowel surgery
Authors: Collins Caitlin R. , Abel Mary Kathryn , Shui Amy , Intinarelli Gina , Sosa Julie Ann , Wick Elizabeth C.
Published: December 2022

Background

As healthcare costs rise, there is an increasing emphasis on alternative payment models to improve care efficiency. The bundled payment represents an alternative reimbursement model gaining popularity within the surgical sphere. We aimed to assess where the largest opportunities for care improvement lay and how best to identify patients at high risk of suffering costly complications.

Methods

We utilized itemized CMS claims data for a retrospective cohort of patients between 2014 and 2016 who met inclusion criteria for the Major Bowel Bundled Payment Program and performed a cost analysis to identify opportunities for improved care efficiency. Based on the results of this cost analysis, we identified readmissions as a target for improvement. We then assessed whether the American College of Surgeons’ National Surgical Quality Improvement Program surgical risk calculator (ACS NSQIP SRC) could accurately identify patients within our bundled payment population who were at high risk of readmission using a logistic regression model.

Results

Our study cohort included 252 patients. Readmissions accounted for 12.8% of the average total care episode cost with a coefficient of variation of 2.72, thereby representing the most substantial, non-fixed cost for our bundled payment patients. Patients readmitted within their 90-day care episode were 2.53 times more likely to be high-cost (>$60,000) than patients not readmitted. However, the ACS NSQIP SRC did not accurately predict patients at high risk of readmission within the first 30 days with an AUROC of 0.58.

Conclusions

Our study highlights the importance of reducing readmissions as a central component of improving care for bowel surgery bundled payment patients. Preventing such readmissions requires accurate identification of patients at high risk of readmission; however, current risk prediction models lack the adaptability necessary for this task.
Perioperative factors related to the prognosis of elderly patients with hepatocellular carcinoma
Authors: Xu Lining , Xu Yingying , Li Guiping , Yang Bo
Published: December 2022

Background

Hepatic resection is a potentially curative treatment for patients with hepatocellular carcinoma (HCC). The treatment of elderly patients with HCC has always been difficult. With the development of geriatrics and geriatric surgery, the number of elderly patients with HCC undergoing hepatectomy has gradually increased. To further improve the long-term prognosis of elderly patients with hepatocellular carcinoma undergoing surgery, it is necessary to study the related perioperative factors. Our aim was to study the impact of preoperative and intraoperative factors on the long-term survival of elderly patients with HCC who underwent hepatectomy.

Methods

A total of 151 elderly patients with HCC who underwent hepatectomy were retrospectively studied. Univariate and multivariate Cox regression analyses were performed for preoperative- and intraoperative-related prognostic factors.

Results

The 1-, 3-, 5- and 10-year overall survival rates of elderly patients with HCC who underwent resection were 79.5%, 60.8%, 46.6%, and 25.4%, respectively. Multivariate analyses identified four independent predictors of long-term prognosis: Child–Pugh grade (B/C versus A: HR[hazard ratio] = 2.318, P = 0.019), alpha-fetoprotein value (> 20 ng/ml versus ≤ 20 ng/ml: HR = 1.972, P = 0.005), resection style (anatomical versus no anatomical: HR = 1.976, P = 0.006), and intraoperative blood loss (> 400 ml versus ≤ 400 ml: HR = 2.008, P = 0.003).

Conclusions

Poor survival of elderly patients with HCC who underwent hepatectomy was correlated with the preoperative and intraoperative factors of Child–Pugh grade, Alpha-fetoprotein value, resection style, and intraoperative blood loss.
The moderating effect of emotion regulation in the association between coping strategies and resilience in Lebanese adults
Authors: Awad Emmanuelle , Fawaz Mirna , Hallit Souheil , Obeid Sahar
Published: December 2022

Objectives

To evaluate the psychometric properties of the Coping Strategies Inventory–Short Form and investigate the relationship between coping strategies and resilience, taking into consideration the moderating role of emotion regulation.

Methods

This cross-sectional study was carried out between May and July 2022. A total of 387 participants was recruited through convenience sampling through several areas in Lebanon governorates. The data was collected through an online questionnaire containing the following sections: sociodemographic information about the participants, Connor-Davidson Resilience Scale (CD-RISC), Emotion Regulation Questionnaire and Coping Strategies Inventory–Short Form.

Results

The confirmatory factor analysis results confirmed the four-factor structure of the Coping Strategies Inventory–Short Form, with no measurement invariance across gender. In individuals with high problem-focused engagement and emotion-focused engagement, lower expressive suppression was significantly associated with more resilience. In individuals with high problem-focused disengagement, having high expressive suppression was significantly associated with less resilience.

Conclusion

The current study provides novel and distinct findings regarding the relationship between emotion regulation, coping strategies and resilience in all of their dimensions. Furthermore, the present results provide insight on how a population under extreme stress receives and reacts to its reality.
Self-assessed visual function outcome in cataract surgery: minimum important difference of the Catquest-9SF questionnaire
Authors: Grimfors Magnus , Lundström Mats , Kugelberg Maria
Published: December 2022

Background

The purpose of this study was to study the minimum important difference (MID) of the Catquest-9SF questionnaire in cataract surgery.

Methods

A nationwide multi-center prospective randomized study was conducted using the Swedish National Cataract Register and the Catquest-9SF questionnaire. Randomized patients (n = 400) who had completed the Catquest-9SF before surgery and three months after surgery were sent an anchor question on self-assessed change in visual function after cataract surgery 14 days after the postoperative Catquest-9SF. Rasch analysis was performed on the preoperative and postoperative Catquest-9SF questionnaires, and the patients were dichotomized with regard to their preoperative Rasch score. The MID range of the two groups was calculated based on the anchor question, and the anchor question based MID was then estimated in a scatter plot. The MID was also estimated based on distribution by calculating Cohen’s effect size.

Results

The analyses included 231 patients who had completed the Catquest-9SF on both occasions as well as the questionnaire with the anchor question. The group with better preoperative visual function had an anchor question based MID of − 0.5 and a Cohen’s effect size based MID of − 1.07. The group with worse preoperative visual function had an anchor question based MID of − 1.80 and a Cohen’s effect size based MID of − 1.46.

Conclusion

This article contributes detailed knowledge of the MID of Catquest-9SF, enabling even more accurate high-quality evaluation of the outcome and benefit of cataract surgery worldwide.
Epstein–Barr virus-associated inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver: a case report and review of the literature
Authors: Abe K. , Kitago M. , Matsuda S. , Shinoda M. , Yagi H. , Abe Y. , Oshima G. , Hori S. , Endo Y. , Yokose T. , Miura E. , Kubota N. , Ueno A. , Masugi Y. , Ojima H. , Sakamoto M. , Kitagawa Y.
Published: December 2022

Background

Follicular dendritic cell sarcoma is a rare stromal tumor with no standard treatment. However, some reports have revealed that follicular dendritic cell sarcoma has an inflammatory pseudotumor variant associated with Epstein–Barr virus infection that has a relatively good prognosis. In this report, we present a case of a resected inflammatory pseudotumor variant of follicular dendritic cell sarcoma of the liver, and have reviewed the literature on the clinicopathological, molecular, and genomic features of this tumor.

Case presentation

The inflammatory pseudotumor variant of follicular dendritic cell sarcoma originates only in the liver or spleen, causes no symptoms, and is more common in middle-aged Asian women. It has no characteristic imaging features, which partially explains why the inflammatory pseudotumor variant of follicular dendritic cell sarcoma is difficult to diagnose. Pathologically, the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has spindle cells mixed with inflammatory cells and is variably positive for follicular dendritic cell markers (CD21, CD23, and CD35) and Epstein–Barr virus-encoded RNA. On genetic analysis, patients with this tumor high levels of latent membrane protein 1 gene expression and extremely low levels of host C–X–C Chemokine Receptor type 7 gene expression, indicating that the inflammatory pseudotumor variant of follicular dendritic cell sarcoma has a latent Epstein–Barr virus type 2 infection.

Conclusions

The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is an Epstein–Barr virus-associated tumor and a favorable prognosis by surgical resection, similar to Epstein–Barr virus-associated gastric cancer.
Pacing Behaviour Development and Acquisition: A Systematic Review
Authors: Menting Stein Gerrit Paul , Edwards Andrew Mark , Hettinga Florentina Johanna , Elferink-Gemser Marije Titia
Published: December 2022

Background

The goal-directed decision-making process of effort distribution (i.e. pacing) allows individuals to efficiently use energy resources as well as to manage the impact of fatigue on performance during exercise. Given the shared characteristics between pacing behaviour and other skilled behaviour, it was hypothesized that pacing behaviour would adhere to the same processes associated with skill acquisition and development.

Methods

PubMed, Web of Science and PsycINFO databases between January 1995 and January 2022 were searched for articles relating to the pacing behaviour of individuals (1) younger than 18 years of age, or (2) repeatedly performing the same exercise task, or (3) with different levels of experience.

Results

The search resulted in 64 articles reporting on the effect of age (n = 33), repeated task exposure (n = 29) or differing levels of experience (n = 13) on pacing behaviour. Empirical evidence identifies the development of pacing behaviour starts during childhood (~ 10 years old) and continues throughout adolescence. This development is characterized by an increasingly better fit to the task demands, encompassing the task characteristics (e.g. duration) and environment factors (e.g. opponents). Gaining task experience leads to an increased capability to attain a predetermined pace and results in pacing behaviour that better fits task demands.

Conclusions

Similar to skilled behaviour, physical maturation and cognitive development likely drive the development of pacing behaviour. Pacing behaviour follows established processes of skill acquisition, as repeated task execution improves the match between stimuli (e.g. task demands and afferent signals) and actions (i.e. continuing, increasing or decreasing the exerted effort) with the resulting exercise task performance. Furthermore, with increased task experience attentional capacity is freed for secondary tasks (e.g. incorporating opponents) and the goal selection is changed from achieving task completion to optimizing task performance. As the development and acquisition of pacing resemble that of other skills, established concepts in the literature (e.g. intervention-induced variability and augmented feedback) could enrich pacing research and be the basis for practical applications in physical education, healthcare, and sports.
Exploring right ventricular function applicability in a prediction model to identify preterm infants with early bronchopulmonary dysplasia (REPORT-BPD study): a mixed-methods observational cohort feasibility study protocol
Authors: Muhsen Wisam S. , Nestaas Eirik , Hosking Joanne , Latour Jos
Published: December 2022

Background

Bronchopulmonary dysplasia (BPD) is a chronic disease that affects the immature lungs of preterm infants. Infants born before 32 weeks of gestation are at a greater risk of developing BPD due to the need for respiratory support with higher oxygen requirement.

Pulmonary vascular remodelling in early BPD can impose an additional burden on the right ventricle (RV) and RV dysfunction.

This protocol outlines the study design and aims to formulate a prediction model to identify early BPD through the data generated from echo scans analysis.

Methods

The mixed-methods observational cohort feasibility study, which comprises three work-packages (WPs), will be conducted at the regional neonatal unit, University Hospital Plymouth, Plymouth, UK. WP-I will recruit 40 preterm infants; each participant will have two heart scans performed in the first ten days after birth (DABs).

WP-II will collect the documentation of the participating preterm infants’ parents in the study neonatal unit diaries in the first 10 DABs. WP-III will involve semi-structured interviews of 10–15 parents of participating preterm infants and 10–15 health professionals who participated in WP-I.

The study recruitment will be conducted over 18-months. The start date is 01 June 2022. WP-I and WP-II recruitment will occur during this period, while WP-III recruitment will occur during the second half. The results are expected to be submitted for publication by mid-2024.

Discussion

This paper outlines the study design. If the study successfully identifies the most sensitive echo parameter in recognising the RV dysfunction associated with early BPD, it will be an important finding in constructing an early BPD prediction model.

Trial registration

ClinicalTrials.gov Identifier is NCT05235399
Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody
Authors: Wu Hao , Wei Guoli , Luo Lixia , Li Lingchang , Gao Yibo , Tan Xiaobin , Wang Sen , Chang Haoxiao , Liu Yuxi , Wei Yingjie , Song Jie , Zhang Zhenhai , Huo Jiege
Published: December 2022

Background

Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response.

Methods

In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological.

Results

Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment.

Conclusion

The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.
Deep learning tomographic reconstruction through hierarchical decomposition of domain transforms
Authors: Fu Lin , De Man Bruno
Published: December 2022

Deep learning (DL) has shown unprecedented performance for many image analysis and image enhancement tasks. Yet, solving large-scale inverse problems like tomographic reconstruction remains challenging for DL. These problems involve non-local and space-variant integral transforms between the input and output domains, for which no efficient neural network models are readily available. A prior attempt to solve tomographic reconstruction problems with supervised learning relied on a brute-force fully connected network and only allowed reconstruction with a 1284 system matrix size. This cannot practically scale to realistic data sizes such as 5124 and 5126 for three-dimensional datasets. Here we present a novel framework to solve such problems with DL by casting the original problem as a continuum of intermediate representations between the input and output domains. The original problem is broken down into a sequence of simpler transformations that can be well mapped onto an efficient hierarchical network architecture, with exponentially fewer parameters than a fully connected network would need. We applied the approach to computed tomography (CT) image reconstruction for a 5124 system matrix size. This work introduces a new kind of data-driven DL solver for full-size CT reconstruction without relying on the structure of direct (analytical) or iterative (numerical) inversion techniques. This work presents a feasibility demonstration of full-scale learnt reconstruction, whereas more developments will be needed to demonstrate superiority relative to traditional reconstruction approaches. The proposed approach is also extendable to other imaging problems such as emission and magnetic resonance reconstruction. More broadly, hierarchical DL opens the door to a new class of solvers for general inverse problems, which could potentially lead to improved signal-to-noise ratio, spatial resolution and computational efficiency in various areas.
Improving access to highly effective emergency contraception: an assessment of barriers and facilitators to integrating the levonorgestrel IUD as emergency contraception using two applications of the Consolidated Framework for Implementation Research
Authors: Simmons Rebecca G. , Baayd Jami , Elliott Sarah , Cohen Susanna R. , Turok David K.
Published: December 2022

Background

Emergency contraception prevents unwanted pregnancy after sexual intercourse. New evidence has demonstrated that the levonorgestrel 52 mg IUD is a highly effective method of emergency contraception. However, translating this research finding into clinical practice faces existing barriers to IUD access, including costs and provider training, novel barriers of providing IUDs for emergency contraception at unscheduled appointments. The purpose of this study was to identify barriers and facilitators to the utilization of the levonorgestrel IUD as emergency contraception from client, provider, and health systems perspectives.

Methods

We conducted English and Spanish-speaking focus groups (n=5) of both contraceptive users (n=22) and providers (n=13) to examine how the levonorgestrel IUD as EC was perceived and understood by these populations and to determine barriers and facilitators of utilization. We used findings from our focus groups to design a high-fidelity in-situ simulation scenario around EC that we pilot tested with clinical teams in three settings (a county health department, a community clinic, and a midwifery clinic), to further explore structural and health systems barriers to care. Simulation scenarios examined health system barriers to the provision of the levonorgestrel IUD as EC. We coded both focus groups and in-clinic simulations using the modified Consolidated Framework for Implementation Research (CFIR). We then applied our findings to the CFIR-Expert Recommendations for Implementing Change (ERIC) Barrier Busting Tool and mapped results to implement recommendations provided by participants.

Results

Ultimately, 9 constructs from the CFIR were consistently identified across focus groups and simulations. Main barriers included suboptimal knowledge and acceptability of the intervention itself, appropriately addressing knowledge and education needs among both providers and contraceptive clients, and adequately accounting for structural barriers inherent in the health system. The CFIR-ERIC Barrier Busting Tool identified eight strategies to improve levonorgestrel IUD as EC access: identifying implementation champions, conducting educational meetings, preparing educational toolkits, involving patients and their partners in implementation, conducting a local needs assessment, distributing educational materials, and obtaining patient feedback.

Conclusions

To sustainably incorporate the levonorgestrel IUD as EC into clinical practice, education, health systems strengthening, and policy changes will be necessary.
Finding more than what you are looking for: a retrospective study of incidental findings in magnetic resonance imaging (MRI) scans performed for patients suspicious of vestibular schwannoma
Authors: Pratap Deepika , Warner Giles Christian , Hanasoge Raveesh
Published: December 2022

Background

Nearly 20% of the patients presenting to ENT department with audiovestibular symptoms are considered potential candidates for vestibular schwannoma screening. MRI scan done on these patients can also detect a large number of incidental findings. We did a retrospective descriptive study of incidental findings identified on MRI scans done on patients presenting to the ENT department in a county hospital in United Kingdom from April 2020 to April 2021. All MRI reports were scrutinised and various incidental findings tabulated. The further management of patients with these findings were also analysed.

Results

A total of 159 MRIs were reviewed. The most common incidental finding was small vessel disease followed by old infarcts. Fifteen patients were found to have significant incidental findings. The detection rate of vestibular schwannoma was 3.1%.

Conclusion

With the increased use of imaging technology, the incidence of incidental findings has risen. Understanding the significance of these findings is important so that clinicians can counsel their patients and make appropriate management plans. Categorising the incidental findings into groups based on their level of significance may help in making these clinical decisions.
Gene expression of programmed cell death ligand-1 (PDL-1) and vitamin D receptor (VDR) with the serum vitamin D3 in lung cancer
Authors: Salama Ragaa H. M. , Faied Soad M. A. , ELkholy Maha , Abd-Elmawgoud Norhan S. , Alsanory Tasneem A. , Alsanory Aya A. , Abd-Elmoniem Ahmed A. , Abd-Elmawgoud Mohamed S. , Mahmoud Hemat A. , Abdel-Qawy Abdel-Rahman H. , Dahpy Marwa A.
Published: December 2022

Background

Lung cancer (LC) is one of the leading causes of death worldwide. Programmed cell death receptor 1 (PD-1) interacts with its ligand (PDL-1) on T cells inhibiting its functioning which may affect the patient's immunological response.

Aim

Investigate if there is a link between smoking and tissue expression of PDL-1 and vitamin D receptor (VDR) in lung cancer patients. In addition, the relation of vitamin D with smoking and these biochemical markers.

Methods

PDL-1 and VDR expressions were evaluated by real-time PCR in 54 lung cancer biopsy samples and 36 controls to prove this hypothesis. Vitamin D levels in the blood were measured using an ELISA.

Results

Expressions of PDL-1 were significantly upregulated in LC patients than in controls. The highest expression was in stage II and in squamous cell carcinoma followed by small cell carcinoma then adenocarcinoma. However, VDR expressions and vitamin D levels in serum were significantly downregulating in LC patients than in controls. There was a positive correlation between PDL-1expression and duration of smoking but not smoking index. Also, there is an inverse correlation between duration of smoking, smoking index, and VDR.

Conclusion

Expression of PDL-1 in LC was significantly upregulated and correlated with staging. Interestingly, our current study for the first time explained the role of duration of smoking on PDL-1 and VDR in the pathogenesis of LC. As PDL-1 expression increased with duration of smoking whereas VDR decreased, this novel findings may provide a possible link between the cumulative effect of smoking and the level of expressions of these biomarkers.
Is there a hierarchy in mental health stigma?
Authors: Mula Marco
Published: December 2022

People with mental illness fight not just against their condition but also against stigma, discrimination and inequalities. Research into stigma in mental illness has increased over time, but data on transdiagnostic stigma are still very limited. This commentary focuses on this topic alongside a recently published article in BJPsych Open.
Fishing the waves: comparing GAMs and random forest to evaluate the effect of changing marine conditions on the energy performance of vessels
Authors: COLOMBELLI ALESSANDRO , PULCINELLA JACOPO , BONANOMI SARA , NOTTI EMILIO , MORO FABRIZIO , SALA ANTONELLO
Published: December 2022

The optimization of consumption and the reduction of gas emissions in fisheries rely on a thorough examination of all factors affecting the energy balance of fishing vessels. Engines, propellers, or the hydrodynamic characteristics of vessels and gears are unquestionably the primary factors affecting this balance, and an improvement in energy efficiency based on these factors is typically attained through technical modifications to existing technologies. Behavioral modifications, such as a reduction in operational speeds or the selection of closer fishing grounds, are another option. There may still be room for improvement in behavioral responses, for instance by adapting fishing strategies in response to changing weather and sea conditions. As far as the authors are aware, the influence of varying sea state and wind conditions on the energy expenditure of fishing vessels has not yet been investigated and is the focus of this research. In this study, wind and wave actions were associated with the observed activity of three fishing vessels operating in the northern Adriatic Sea: an OTB, a PTM, and a TBB trawler. The analysis made use of a comparison between two different approaches, generalized additive models (GAMs) and random forest, in order to quantify the significance of each variable on the response and generate consumption forecasts. In our analysis, the observed influence of predictors was significant albeit occasionally ambiguous. Wave height had the most obvious impact on energy expenditure, with the towing and gear handling phases being the most affected by wave action. Conversely, navigation seemed to be mostly unaffected by significant wave heights up to 1.5 meters, with unclear effects on consumption estimated above this threshold. The relationship between winds and fuel consumption was found to be nonlinear and ambiguous; hence, its significance should be investigated further.
Κριτική θεώρηση των κοινωνιολογικών προσεγγίσεων για τις ανισότητες στην εκπαίδευση
Authors: Ζέρβα Ευδοκία
Published: December 2022

Η παρούσα μελέτη αφορά στην κριτική προσπέλαση των κοινωνιολογικών προσεγγίσεων των ανισοτήτων στην εκπαίδευση.

Η πεποίθηση πως οι κοινωνικές ανισότητες αποτελούν προϊόν των επιδόσεων και των δυνατοτήτων του/της εκάστοτε μαθητή/τριας βασίζεται στον προβληματισμό για ίσες ευκαιρίες πρόσβασης στη γνώση που αναπτύχθηκε από τον 18ο αιώνα. Ενώ ο δομικός  λειτουργισμός διακρίνει τις κοινωνικές ανισότητες σε ενδογενείς και σε εξωγενείς, και οι  φονξιοναλιστές αντιλαμβάνονταν τα εκπαιδευτικά συστήματα ως συστήματα κατάληψης θέσεων της κοινωνικής ελίτ και αποδοχής της αποτυχίας όσων αποκλείονται από αυτές, οι μαρξιστές ανακαλύπτουν μια αντιστοιχία μεταξύ εκπαίδευσης και απασχόλησης. Ο Althusser αντιλαμβάνεται την εκπαίδευση σαν κυρίαρχο Ιδεολογικό Μηχανισμό του Κράτους που συντελεί καθοριστικά στην ιδεολογική αναπαραγωγή του καπιταλιστικού συστήματος, άρα και των κοινωνικών ανισοτήτων.

Στη νεώτερη μαρξιστική οπτική οι θεωρίες της αντίστασης αντιλαμβάνονται το σχολείο ως πεδίο ανταγωνισμού, πάλης και διακήρυξης δημοκρατικών ιδεωδών. Οι θεωρητικοί της κριτικής παιδαγωγικής προτείνουν μια παιδαγωγική της αντίστασης και της διαφοράς που θα εναντιώνεται στη λογική ενός σχολείου όπου αναπαράγονται η ανισότητα, ο ρατσισμός και ο σεξισμός

Στη σύζευξη των αρχών της φονξιοναλιστικής και της μαρξιστικής θεωρίας η θεωρία του «μορφωτικού κεφαλαίου» αποδίδει  τις κοινωνικές ανισότητες μέσω της εκπαίδευσης στα επικρατούντα καπιταλιστικά πρότυπα και ιδεώδη. Αντίθετα, οι κοινωνιολόγοι της μικρο-ερμηνευτικής  οπτικής ισχυρίζονται ότι το σχολείο σαν κοινωνική κατάσταση συγκροτείται κατά τη διαδικασία μέσω της αλληλενέργειας (ή διαντίδρασης) μαθητών και δασκάλων, όπου συναντώνται και συμφύρονται τα πολιτιστικά τους χαρακτηριστικά και όπου οι μαθητές διαμορφώνουν στρατηγικές αντιμετώπισης των καθημερινών προβλημάτων και, τελικά, αποκτούν κοινωνικές ταυτότητες.

Η μακρο-κοινωνιολογική και η μικρο-κοινωνιολογική ανάλυση συνδυάζονται στη δομοποίηση του Giddens, ο οποίος  χρησιμοποιεί τη θεσμική ανάλυση με την οποία αντιλαμβάνεται τις δομικές ιδιότητες των κοινωνικών συστημάτων ως αναπαραγόμενα χαρακτηριστικά τους και την ανάλυση της στρατηγικής συμπεριφοράς σύμφωνα την οποία τα δρώντα πρόσωπα συγκροτούν κοινωνικές σχέσεις αντλώντας δεδομένα από τις ίδιες δομικές ιδιότητες. Παρά την πληθώρα ερευνών και μελετών στο πεδίο των εκπαιδευτικών ανισοτήτων η μεγαλύτερη μερίδα του κοινωνικού συνόλου αγνοεί, και θα εξακολουθεί να αγνοεί, πως η πρόοδος και η επιτυχία συγκεκριμένων ανθρώπων δεν αποτελεί απόρροια της αξίας τους αλλά συνδέονται με ένα πλέγμα πολιτιστικών συνιστωσών, των κοινωνικών αλληλεπιδράσεων και των οικονομικών πόρων και εξαρτώνται από το επίπεδο πρόσβασης και διάθεσης αυτών.
Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study
Authors: González Natalia , Elise Laumen Jolein Gyonne , Abdellati Saïd , de Block Tessa , De Baetselier Irith , Van Dijck Christophe , Kenyon Chris , S. Manoharan–Basil Sheeba
Published: December 2022

Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics.

Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO–F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO–F WT and WHO–F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence.

Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance.

Conclusions:  We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions.
The cocktail infection: anaerobic and aerobic co-Infections in tubercular vertebral osteomyelitis
Authors: Bhat Shyamasunder N , Kundangar Raghuraj , Ampar Nishanth , Sait Anika , Shenoy Padmaja Ananth , Sukumar Cynthia Amrutha , Saravu Kavitha
Published: December 2022

Background: Anaerobic organisms have been known to have an association with dental infections, bacteremia, endocarditis and soft tissue infections. However, anaerobic isolation from bone and joint infections are relatively rare. Sparse literature has been found on reports of anaerobic osteomyelitis. There is no literature reported on anaerobic osteomyelitis complicating Tuberculosis of spine.

Case Report: We report two cases of tuberculosis of spine complicated by aerobic and anerobic infections. The first is a case of a young female who presented with chronic lower backache and fever. Examination revealed a lumbar scoliosis with paraspinal tenderness. Magnetic resonance imaging (MRI) of the spine showed lumbar spondylodiscitis with multiple abscesses. There were air-fluid levels noted in the abscesses. The pus sent for CBNAAT (cartridge based nucleic acid amplification test) was positive. Further the cultures also grew Escherichia coli (aerobic) Bacteroids fragilis and Peptoniphilus asachrolyticus (anaerobic) organisms. She improved with a course of intravenous antibiotics and decompression surgery.

The second case is a middle aged man who presented with chronic neck pain and fever. Examination revealed kyphosis of the neck with spasm of the neck muscles and midline tenderness. MRI showed C4-5 cervical spondylodiscitis with parapharyngeal collections showing air-fluid levels. The pus culture showed Streptococcus constellatus (aerobic) and  Prevotella sps. (anaerobic). The CBNAAT report was positive for Mycobacterium tuberculosis. The patient was treated with intravenous antibiotics and cervical decompression.

Conclusion: Though tubercular vertebral osteomyelitis (TVO) is usually a diagnosis in itself, it should not hinder us from considering secondary infections (both aerobic and anaerobic) complicating the osteomyelitis. Further, the presence of air-fluid levels on imaging studies and the presence of foul smell during operative exploration of the spine must arouse the suspicion of an anaerobic co-infection. Isolation and treatment of these organisms are crucial as they may hamper the clinical outcome of the primary TVO.