bluuebunny/crossref_metadata_2025 huggingface dataset:
Length of stay and cost of care associated with admissions for atrial fibrillation among patients with cancer
Authors: Guha Avirup , Jain Anubhav , Aggarwal Ankita , Dey Amit K. , Dani Sourbha , Ganatra Sarju , Marchlinski Francis E. , Addison Daniel , Fradley Michael G.
Published: June 2022

Background

The aim of this study is to assess the burden of AF-related hospitalizations inclusive of inflation-adjusted cost-of-care and length-of-stay (LOS) among cancer patients and the impact of direct current cardioversion (DCCV) on these outcomes.

Methods

Using the National Inpatient Sample (NIS), patients hospitalized with either a primary or secondary diagnosis of AF and comorbid cancer were identified and both cost of hospitalization and LOS were evaluated for each group. Subgroup analyses were performed for specific cancer types (breast, lung, colon, prostate and lymphoma), and those receiving DCCV.

Results

The prevalence of co-morbid AF was 8.2 million (16%) and 35.5 million (10%) among those with vs. those without cancer, respectively (odds ratio = 1.6, 95% confidence interval = 1.5–1.7; P < 0.001). Over time, both primary and prevalent AF admissions among those with comorbid cancer increased from 1.1% and 12.3% in 2003 to 1.5% and 21% in 2015, respectively. The total cost of hospitalization increased 94.4% among those with AF and comorbid cancer compared to 23.9% among those without cancer. Among the subgroup of patients with comorbid cancer and primary admission for AF undergoing DCCV, length of stay (2.7 vs. 2.2 days; P < 0.001, model 1) and cost of care ($7,093 vs. 6,152; P < 0.001) were both significantly higher.

Conclusions

AF related admissions are increasing for all populations especially amongst those patients with a comorbid diagnosis of cancer, including all cancer subtypes evaluated. Among those patients who underwent DCCV, cancer patients had longer length of stay and increased health care costs.
Standard of care for COVID-19 in randomized clinical trials registered in trial registries and published in preprint servers and scholarly journals: a cross-sectional study
Authors: Fidahic Mahir , Nujic Danijela , Civljak Marta , Runjic Renata , Markotic Filipa , Vidak Marin , Puljak Livia
Published: June 2022

Background

The concept of standard of care (SoC) treatment is commonly utilized in clinical trials. However, in a setting of an emergent disease, such as COVID-19, where there is no established effective treatment, it is unclear what the investigators considered as the SoC in early clinical trials. The aim of this study was to analyze and classify SoC reported in randomized controlled trial (RCT) registrations and RCTs published in scholarly journals and on preprint servers about treatment interventions for COVID-19.

Methods

We conducted a cross-sectional study. We included RCTs registered in a trial registry, and/or published in a scholarly journal, and/or published on preprint servers medRxiv and bioRxiv (any phase; any recruitment status; any language) that aim to compare treatment interventions related to COVID-19 and SoC, available from January 1, 2020, to October 8, 2020. Studies using „standard“ treatment were eligible for inclusion if they reported they used standard, usual, conventional, or routine treatment. When we found such multiple reports of an RCT, we treated those multiple sources as one unit of analysis.

Results

Among 737 unique trials included in the analysis, 152 (21%) reported that SoC was proposed by the institutional or national authority. There were 129 (18%) trials that reported component(s) of SoC; the remaining trials simply reported that they used SoC, with no further detail. Among those 129 trials, the number of components of SoC ranged from 1 to 10. The most commonly used groups of interventions in the SoC were antiparasitics (62% of the trials), antivirals (57%), antibiotics (31%), oxygen (17%), antithrombotics/anticoagulants (14%), vitamins (13%), immunomodulatory agents (13%), corticosteroids (12%), analgesics/antipyretics (12%). Various combinations of those interventions were used in the SoC, with up to 7 different types of interventions combined. Posology, timing, and method of administration were frequently not reported for SoC components.

Conclusion

Most RCTs (82%) about treatment for COVID-19 that were registered or published in the first 9 months of the pandemic did not describe the “standard of care” they used. Many of those interventions have, by now, been shown as ineffective or even detrimental.
Predictors of time to recovery from postpartum hemorrhage in Debre Markos comprehensive specialized hospital, Northwest, Ethiopia, 2020/21
Authors: Kassie Bekalu , Ahmed Beker , Degu Genet
Published: June 2022

Background

Postpartum hemorrhage is one of the leading causes of maternal deaths worldwide. Early recovery is a performance indicator and better health outcome of patients with postpartum hemorrhage. Therefore, this study aimed to assess time to recovery from postpartum hemorrhage and its predictors in Debre Markos Comprehensive Specialized Hospital, Ethiopia, 2020.

Methods

A retrospective follow-up study was conducted among 302 women who were diagnosed with postpartum hemorrhage from January 1, 2016 to December 31, 2020 at Debre Markos Comprehensive Specialized Hospital. Consecutive sampling technique was employed. To show the statistical significant difference between each group of variables, log rank test was used. Kaplan Meier analysis to estimate time to recovery and cox proportional-hazard regression analysis to determine independent predictors were carried out cautiously. Adjusted hazard ratio used to determine the strength of association.

Result

The median recovery time from postpartum hemorrhage was 13 h with range of (10 to 17 h). Blood transfusion (AHR: 1.8, 95% CI (1.39, 2.57)), NASG utilization (AHR: 6.5, 95% CI (4.58, 9.42)) fluid resuscitation (AHR 2.9, 95% CI (1.48, 5.54)), active management of third stage of labor (AHR: 1.7, 95% CI (1.18, 2.45)) and history of antenatal care follow-up (AHR: 2.6, 95% CI (1.91, 3.56)) were the predictors, which shorten the recovery time. Comorbidities like anemia at the time of admission (AHR: 0.62 95% CI (0.44, 0.89)), retroviral infection (AHR: 0.33, 95% CI (0.16, 0.67)) and Hepatitis B-Virus infection (AHR: 0.52, 95% CI (0.32, 0.82)) delay the recovery rate from postpartum hemorrhage.

Conclusion

Mothers in North-West Ethiopia stays morbid from postpartum hemorrhage for more than half a day. Their recovery time was affected by Non-Pneumatic Anti-Shock Garment utilization, implementation of emergency management components like blood transfusion and fluid resuscitation, history of antenatal care follow up, and being comorbid with viral infections. Non-pneumatic anti-shock garment application to every mother with postpartum hemorrhage and implementation of proper emergency management approach are vital for rapid recovery from postpartum hemorrhage.
MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment
Authors: Garcia-Gerique Laura , García Marta , Garrido-Garcia Alícia , Gómez-González Soledad , Torrebadell Montserrat , Prada Estela , Pascual-Pasto Guillem , Muñoz Oscar , Perez-Jaume Sara , Lemos Isadora , Salvador Noelia , Vila-Ubach Monica , Doncel-Requena Ana , Suñol Mariona , Carcaboso Angel M. , Mora Jaume , Lavarino Cinzia
Published: June 2022

Background

The bone marrow (BM) is the most common site of dissemination in patients with aggressive, metastatic neuroblastoma (NB). However, the molecular mechanisms underlying the aggressive behavior of NB cells in the BM niche are still greatly unknown. In the present study, we explored biological mechanisms that play a critical role in NB cell survival and progression in the BM and investigated potential therapeutic targets.

Methods

Patient-derived bone marrow (BM) primary cultures were generated using fresh BM aspirates obtained from NB patients. NB cell lines were cultured in the presence of BM conditioned media containing cell-secreted factors, and under low oxygen levels (1% O2) to mimic specific features of the BM microenvironment of high-risk NB patients. The BM niche was explored using cytokine profiling assays, cell migration-invasion and viability assays, flow cytometry and analysis of RNA-sequencing data. Selective pharmacological inhibition of factors identified as potential mediators of NB progression within the BM niche was performed in vitro and in vivo.

Results

We identified macrophage migration inhibitory factor (MIF) as a key inflammatory cytokine involved in BM infiltration. Cytokine profiling and RNA-sequencing data analysis revealed NB cells as the main source of MIF in the BM, suggesting a potential role of MIF in tumor invasion. Exposure of NB cells to BM-conditions increased NB cell-surface expression of the MIF receptor CXCR4, which was associated with increased cell viability, enhanced migration-invasion, and activation of PI3K/AKT and MAPK/ERK signaling pathways. Moreover, subcutaneous co-injection of NB and BM cells enhanced tumor engraftment in mice. MIF inhibition with 4-IPP impaired in vitro NB aggressiveness, and improved drug response while delayed NB growth, improving survival of the NB xenograft model.

Conclusions

Our findings suggest that BM infiltration by NB cells may be mediated, in part, by MIF-CXCR4 signaling. We demonstrate the antitumor efficacy of MIF targeting in vitro and in vivo that could represent a novel therapeutic target for patients with disseminated high-risk NB.
The effect of implants loaded with stem cells from human exfoliated deciduous teeth on early osseointegration in a canine model
Authors: Cao Xu , Wang Caiyun , Yuan Dingxiang , Chen Su , Wang Xin
Published: June 2022

Background

This in vivo experimental study investigated the effect of stem cells from human exfoliated deciduous teeth (SHEDs) on early osteogenesis around implants.

Methods

In four healthy adult male Beagle dogs, the left mandibular received implants and SHED as the experimental group, and the right mandibular received implants and phosphate-buffered saline as the control group. The Beagle dogs were randomly divided into groups A and B, which were sacrificed at 2 and 4 weeks after implantation. Micro-computed tomography and histological analysis were used to investigate the effect of SHED-loading on the early osseointegration around the implants.

Results

The total bone-to-implant contact (BIC%) and interthread bone improved significantly. The analysis of the bone volume fraction and trabecular thickness showed that the bone trabecula around the implants in the SHEDs group was thicker and denser than that in the control group, suggesting a better osseointegration.

Conclusions

The application of implants pre-adhered with SHEDs improved and accelerated early osseointegration around the implant, resulting in thicker and denser trabecular bone.
Intimate partner violence and associated factors among reproductive age women in Liberia: a cross-sectional study using a recent Liberian demographic and health survey
Authors: Tsegaw Menen , Mulat Bezawit , Shitu Kegnie
Published: June 2022

Background

Intimate partner violence (IPV) is a major public health problem and a violation of women's human rights. Almost one third of women aged 15–49 years who have been in a relationship have experienced to some form of physical and/or sexual violence by their intimate partner worldwide.

Objective

The study aimed to assess the prevalence of intimate partner violence within the last 12 months and associated factors among reproductive aged women in Liberia.

Method

This study was based on a large community-based cross-sectional survey, Liberia Demographic Health Survey (LDHS), conducted From October 16, 2019, to February 12, 2020, in Liberia. The 2019–20 LDHS used a stratified two-stage cluster design. Multivariable logistic regression was used to identify independent intimate partner violence among reproductive age women in Liberia and to control confounders. Adjusted odds ratio and confidence interval (CI) were used to declare statistical significance in the final model. Those variables with p value < 0.05 were considered as statistically significant.

Result

The overall prevalence of IPV within the last 12 months was 44.74% (42.73–46.77). age of the women 41% (AOR = 0.59, 95%CI 0.37–0.93), 42% (AOR = 0.58, 95%CI 0.35–0.94), and 59% (AOR = 0.41, 95%CI 0.25–0.68) among women with in the age group of 35–39, 40–44 and 45–49 respectively, south central region (AOR = 0.71, 95%CI 0.52–0.96), women’s primary education (AOR = 1.28, 95%CI 1.01–1.63), female household head (AOR = 0.77, 95%CI 0.61–0.97), husbands higher education (AOR = 0.62, 95%CI 0.39–0.99), positive wife beating attitude (AOR = 1.57, 95%CI 1.29–1.90), husband drinks (AOR = 2.59, 95%CI 2.14–3.15) and Women’s decision making autonomy (AOR = 0.75, 95%CI 0.61–0.93) were significantly associated with IPV.

Conclusion

The prevalence of IPV in Liberia was high. Socio-demographic characteristics of women, husbands education, sex of household head, having a positive attitude towards wife-beating, partner’s alcohol drinking habit and women empowerment was significantly associated with IPV in Liberia. Policymakers and program designers have to take into account those factors when they design interventions to reduce IPV in Liberia.
Nurse preceptors’ perceptions of benefits, rewards, support, and commitment to the preceptor role in a new preceptorship program
Authors: Gholizadeh Leila , Shahbazi Shahla , Valizadeh Sousan , Mohammadzad Masoumeh , Ghahramanian Akram , Shohani Masoumeh
Published: June 2022

Background

Nurse preceptorship is a new concept emerging in the Iranian health care system. The purpose of this research was to assess preceptor nurses’ perceived benefits, rewards, support, and commitment to the role in a new nurse preceptorship program in Iran and to examine the relationships between these concepts.

Methods

A descriptive correlational study was employed, and using total population sampling method, 45 preceptor nurses were recruited from a tertiary referral teaching hospital in Iran. Data were collected using the Preceptor’s Perception of Benefits and Rewards Scale, the Preceptor’s Perception of Support Scale, and the Commitment to the Preceptor Role Scale. Descriptive statistics and correlational analysis were used to analyse data.

Results

Preceptors’ commitment to their role was positively and moderately associated with their perceived benefits and rewards (r = 0.503,p = 0.001) and perceived support (r = 0.430,p = 0.003). None of the examined demographic and practice variables showed statistically significant association with commitment to the preceptor role.

Conclusions

Commitment to the preceptor role was associated with benefits, rewards and support that preceptor nurses perceive in relation to their role. To optimise the effectiveness of nurse preceptorship programs, benefits, rewards, recognition, and support should be integral to planning of these programs.
Changes in the quality of cancer care as assessed through performance indicators during the first wave of the COVID-19 pandemic in 2020: a scoping review
Authors: Carvalho Ana Sofia , Brito Fernandes Óscar , de Lange Mats , Lingsma Hester , Klazinga Niek , Kringos Dionne
Published: June 2022

Background

Cancer comprises a high burden on health systems. Performance indicators monitoring cancer outcomes are routinely used in OECD countries. However, the development of process and cancer-pathway based information is essential to guide health care delivery, allowing for better monitoring of changes in the quality of care provided. Assessing the changes in the quality of cancer care during the COVID-19 pandemic requires a structured approach considering the high volume of publications. This study aims to summarize performance indicators used in the literature to evaluate the impact of the COVID-19 pandemic on cancer care (January-June 2020) in OECD countries and to assess changes in the quality of care as reported via selected indicators.

Methods

Search conducted in MEDLINE and Embase databases. Performance indicators and their trends were collated according to the cancer care pathway.

Results

This study included 135 articles, from which 1013 indicators were retrieved. Indicators assessing the diagnostic process showed a decreasing trend: from 33 indicators reporting on screening, 30 (91%) signalled a decrease during the pandemic (n = 30 indicators, 91%). A reduction was also observed in the number of diagnostic procedures (n = 64, 58%) and diagnoses (n = 130, 89%). The proportion of diagnoses in the emergency setting and waiting times showed increasing trends (n = 8, 89% and n = 14, 56%, respectively). A decreasing trend in the proportion of earliest stage cancers was reported by 63% of indicators (n = 9), and 70% (n = 43) of indicators showed an increasing trend in the proportion of advanced-stage cancers. Indicators reflecting the treatment process signalled a reduction in the number of procedures: 79%(n = 82) of indicators concerning surgeries, 72%(n = 41) of indicators assessing radiotherapy, and 93%(n = 40) of indicators related to systemic therapies. Modifications in cancer treatment were frequently reported: 64%(n = 195) of indicators revealed changes in treatment.

Conclusions

This study provides a summary of performance indicators used in the literature to assess the cancer care pathway from January 2020 to June 2020 in OECD countries, and the changes in the quality of care signalled by these indicators. The trends reported inform on potential bottlenecks of the cancer care pathway. Monitoring this information closely could contribute to identifying moments for intervention during crises.
Long non-coding RNA MIR4435-2HG: a key molecule in progression of cancer and non-cancerous disorders
Authors: Ghasemian Majid , Rajabibazl Masoumeh , Sahebi Unes , Sadeghi Samira , Maleki Reza , Hashemnia Veys , Mirfakhraie Reza
Published: June 2022

MIR4435-2HG (LINC00978) is a long non-coding RNA (lncRNA) that acts as an oncogene in almost all cancers. This lncRNA participates in the molecular cascades involved in other disorders such as coronary artery diseases, osteonecrosis, osteoarthritis, osteoporosis, and periodontitis. MIR4435-2HG exerts its functions via the spectrum of different mechanisms, including inhibition of apoptosis, sponging microRNAs (miRNAs), promoting cell proliferation, increasing cell invasion and migration, and enhancing epithelial to mesenchymal transition (EMT). MIR4435-2HG can regulate several signaling pathways, including Wnt, TGF-β/SMAD, Nrf2/HO-1, PI3K/AKT, MAPK/ERK, and FAK/AKT/β‑catenin signaling pathways; therefore, it can lead to tumor progression. In the present review, we aimed to discuss the potential roles of lncRNA MIR4435-2HG in developing cancerous and non-cancerous conditions. Due to its pivotal role in different disorders, this lncRNA can serve as a potential biomarker in future investigations. Moreover, it may serve as a potential therapeutic target for the treatment of various diseases.
Retraction Note to: LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis
Authors: Liang Yiran , Song Xiaojin , Li Yaming , Chen Bing , Zhao Wenjing , Wang Lijuan , Zhang Hanwen , Liu Ying , Han Dianwen , Zhang Ning , Ma Tingting , Wang Yajie , Ye Fangzhou , Luo Dan , Li Xiaoyan , Yang Qifeng
Published: June 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-020-01206-5
CCL7 playing a dominant role in recruiting early OCPs to facilitate osteolysis at metastatic site of colorectal cancer
Authors: Yang He , Jian Li , Jin Qian , Xia Kang , Cai-ru Wang , Jun Sheng , Chen Huang , Wei Wang , Ben-jing Song , Shi-hong Li , Shi-wei Long , Juan Wu , Wei Zheng
Published: June 2022

Background

Chemoattractant is critical to recruitment of osteoclast precursors and stimulates tumor bone metastasis. However, the role of chemoattractant in bone metastasis of colorectal cancer (CRC) is still unclear.

Methods

Histochemistry analysis and TRAP staining were utilized to detect the bone resorption and activation of osteoclasts (OCs) after administration of CCL7 neutralizing antibody or CCR1 siRNA. qRT-PCR analysis and ELISA assay were performed to detect the mRNA level and protein level of chemoattractant. BrdU assay and Tunel assay were used to detect the proliferation and apoptosis of osteoclast precursors (OCPs). The migration of OCPs was detected by Transwell assay. Western blots assay was performed to examine the protein levels of pathways regulating the expression of CCL7 or CCR1.

Results

OCPs-derived CCL7 was significantly upregulated in bone marrow after bone metastasis of CRC. Blockage of CCL7 efficiently prevented bone resorption. Administration of CCL7 promoted the migration of OCPs. Lactate promoted the expression of CCL7 through JNK pathway. In addition, CCR1 was the most important receptor of CCL7.

Conclusion

Our study indicates the essential role of CCL7-CCR1 signaling for recruitment of OCPs in early bone metastasis of CRC. Targeting CCL7 or CCR1 could restore the bone volume, which could be a potential therapeutical target.
Tumor-associated macrophages promote epithelial–mesenchymal transition and the cancer stem cell properties in triple-negative breast cancer through CCL2/AKT/β-catenin signaling
Authors: Chen Xiangzhou , Yang Mingqiang , Yin Jiang , Li Pan , Zeng Shanshan , Zheng Guopei , He Zhimin , Liu Hao , Wang Qian , Zhang Fan , Chen Danyang
Published: June 2022

Background

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis and limited treatment. As a major component of the tumor microenvironment, tumor-associated macrophages (TAMs) play an important role in facilitating the aggressive behavior of TNBC. This study aimed to explore the novel mechanism of TAMs in the regulation of epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties in TNBC.

Methods

Expression of the M2-like macrophage marker CD163 was evaluated by immunohistochemistry in human breast cancer tissues. The phenotype of M2 macrophages polarized from Tohoku-Hospital-Pediatrics-1 (THP1) cells was verified by flow cytometry. Transwell assays, wound healing assays, western blotting, flow cytometry, ELISA, quantitative polymerase chain reaction (qPCR), luciferase reporter gene assays, and immunofluorescence assays were conducted to investigate the mechanism by which TAMs regulate EMT and CSC properties in BT549 and HCC1937 cells.

Results

Clinically, we observed a high infiltration of M2-like tumor-associated macrophages in TNBC tissues and confirmed that TAMs were associated with unfavorable prognosis in TNBC patients. Moreover, we found that conditioned medium from M2 macrophages (M2-CM) markedly promoted EMT and CSC properties in BT549 and HCC1937 cells. Mechanistically, we demonstrated that chemokine (C–C motif) ligand 2 (CCL2) secretion by TAMs activated Akt signaling, which in turn increased the expression and nuclear localization of β-catenin. Furthermore, β-catenin knockdown reversed TAM-induced EMT and CSC properties.

Conclusions

This study provides a novel mechanism by which TAMs promote EMT and enhance CSC properties in TNBC via activation of CCL2/AKT/β-catenin signaling, which may offer new strategies for the diagnosis and treatment of TNBC.
Identification of characteristic metabolic panels for different stages of prostate cancer by 1H NMR-based metabolomics analysis
Authors: Zhang Xi , Xia Binbin , Zheng Hong , Ning Jie , Zhu Yinjie , Shao Xiaoguang , Liu Binrui , Dong Baijun , Gao Hongchang
Published: June 2022

Background

Prostate cancer (PCa) is the second most prevalent cancer in males worldwide, yet detecting PCa and its metastases remains a major challenging task in clinical research setups. The present study aimed to characterize the metabolic changes underlying the PCa progression and investigate the efficacy of related metabolic panels for an accurate PCa assessment.

Methods

In the present study, 75 PCa subjects, 62 PCa patients with bone metastasis (PCaB), and 50 benign prostatic hyperplasia (BPH) patients were enrolled, and we performed a cross-sectional metabolomics analysis of serum samples collected from these subjects using a1H nuclear magnetic resonance (NMR)-based metabolomics approach.

Results

Multivariate analysis revealed that BPH, PCa, and PCaB groups showed distinct metabolic divisions, while univariate statistics integrated with variable importance in the projection (VIP) scores identified a differential metabolite series, which included energy, amino acid, and ketone body metabolism. Herein, we identified a series of characteristic serum metabolic changes, including decreased trends of 3-HB and acetone as well as elevated trends of alanine in PCa patients compared with BPH subjects, while increased levels of 3-HB and acetone as well as decreased levels of alanine in PCaB patients compared with PCa. Additionally, our results also revealed the metabolic panels of discriminant metabolites coupled with the clinical parameters (age and body mass index) for discrimination between PCa and BPH, PCaB and BPH, PCaB and PCa achieved the AUC values of 0.828, 0.917, and 0.872, respectively.

Conclusions

Overall, our study gave successful discrimination of BPH, PCa and PCaB, and we characterized the potential metabolic alterations involved in the PCa progression and its metastases, including 3-HB, acetone and alanine. The defined biomarker panels could be employed to aid in the diagnosis and classification of PCa in clinical practice.
Targeting choroid plexus epithelium as a novel therapeutic strategy for hydrocephalus
Authors: Yang Yijian , He Jian , Wang Yuchang , Wang Chuansen , Tan Changwu , Liao Junbo , Tong Lei , Xiao Gelei
Published: June 2022

The choroid plexus is a tissue located in the lateral ventricles of the brain and is composed mainly of choroid plexus epithelium cells. The main function is currently thought to be the secretion of cerebrospinal fluid and the regulation of its pH, and more functions are gradually being demonstrated. Assistance in the removal of metabolic waste and participation in the apoptotic pathway are also the functions of choroid plexus. Besides, it helps to repair the brain by regulating the secretion of neuropeptides and the delivery of drugs. It is involved in the immune response to assist in the clearance of infections in the central nervous system. It is now believed that the choroid plexus is in an inflammatory state after damage to the brain. This state, along with changes in the cilia, is thought to be an abnormal physiological state of the choroid plexus, which in turn leads to abnormal conditions in cerebrospinal fluid and triggers hydrocephalus. This review describes the pathophysiological mechanism of hydrocephalus following choroid plexus epithelium cell abnormalities based on the normal physiological functions of choroid plexus epithelium cells, and analyzes the attempts and future developments of using choroid plexus epithelium cells as a therapeutic target for hydrocephalus.
Wearable airbag technology and machine learned models to mitigate falls after stroke
Authors: Botonis Olivia K. , Harari Yaar , Embry Kyle R. , Mummidisetty Chaithanya K. , Riopelle David , Giffhorn Matt , Albert Mark V. , Heike Vallery , Jayaraman Arun
Published: June 2022

Background

Falls are a common complication experienced after a stroke and can cause serious detriments to physical health and social mobility, necessitating a dire need for intervention. Among recent advancements, wearable airbag technology has been designed to detect and mitigate fall impact. However, these devices have not been designed nor validated for the stroke population and thus, may inadequately detect falls in individuals with stroke-related motor impairments. To address this gap, we investigated whether population-specific training data and modeling parameters are required to pre-detect falls in a chronic stroke population.

Methods

We collected data from a wearable airbag’s inertial measurement units (IMUs) from individuals with (n = 20 stroke) and without (n = 15 control) history of stroke while performing a series of falls (842 falls total) and non-falls (961 non-falls total) in a laboratory setting. A leave-one-subject-out crossvalidation was used to compare the performance of two identical machine learned models (adaptive boosting classifier) trained on cohort-dependent data (control or stroke) to pre-detect falls in the stroke cohort.

Results

The average performance of the model trained on stroke data (recall = 0.905, precision = 0.900) had statistically significantly better recall (P = 0.0035) than the model trained on control data (recall = 0.800, precision = 0.944), while precision was not statistically significantly different. Stratifying models trained on specific fall types revealed differences in pre-detecting anterior–posterior (AP) falls (stroke-trained model’s F1-score was 35% higher, P = 0.019). Using activities of daily living as non-falls training data (compared to near-falls) significantly increased the AUC (Area under the receiver operating characteristic) for classifying AP falls for both models (P < 0.04). Preliminary analysis suggests that users with more severe stroke impairments benefit further from a stroke-trained model. The optimal lead time (time interval pre-impact to detect falls) differed between control- and stroke-trained models.

Conclusions

These results demonstrate the importance of population sensitivity, non-falls data, and optimal lead time for machine learned pre-impact fall detection specific to stroke. Existing fall mitigation technologies should be challenged to include data of neurologically impaired individuals in model development to adequately detect falls in other high fall risk populations.

Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05076565; Unique Identifier: NCT05076565. Retrospectively registered on 13 October 2021
“No Regrets” Purchasing in a pandemic: making the most of advance purchase agreements
Authors: Thornton Ian , Wilson Paul , Gandhi Gian
Published: June 2022

“No regrets” buying – using Advance Purchase Agreements (APAs) – has characterized the response to recent pandemics such as Avian flu, Zika Virus, and now COVID-19. APAs are used to reduce demand uncertainty for product developers and manufacturers; to hedge against R&D and manufacturing risks; and to secure availability of products in the face of spiking demand. Evidence on the use of APAs to buy vaccines, medicines, diagnostics, and personal protective equipment during recent pandemics illustrates how these contracts can achieve their intended objectives for buyers. But, transferring risk from suppliers to buyers - as APAs do - can have consequences, including overbuying and overpaying. Furthermore, the widespread use of APAs by high-income countries has contributed to the striking inequities that have characterized the Swine flu and COVID-19 responses, delaying access to vaccines and other supplies for low- and middle-income countries (L&MICs).

We identify seven ways to address some of the risks and disadvantages of APAs, including adoption of a global framework governing how countries enter into APAs and share any resulting supplies; voluntary pooling through joint or coordinated APAs; a concessional-capital-backed facility to allow international buyers and L&MICs to place options on products as an alternative to full purchase commitments; greater collection and sharing of market information to help buyers place smarter APAs; support for a resale market; building in mechanisms for donation from the outset; and transitioning away from APAs as markets mature. While a binding global framework could in theory prevent the competitive buying and hoarding that have characterized country/state responses to pandemics, it will be very challenging to put in place. The other solutions, while less sweeping, can nonetheless mitigate both the inequities associated with the current uncoordinated use of APAs and also some of the risks to individual buyers.

Analysis of recent experiences can provide useful lessons on APAs for the next pandemic. It will be important to keep in mind, however, that these contractual instruments work by transferring risk to the buyer, and that buyers must therefore accept the consequences. In the spirit of “no regrets” purchasing, having bought what hindsight suggests was too much is generally preferable to having bought not enough.
Mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder: case report and literature review
Authors: Ren Xu , Jiang Hong , Sun Kan , Qin Xufu , Qu Yongping , Xia Tian , Chen Yan
Published: June 2022

Background

Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) of the gallbladder are rare malignancies. Here we presented two cases and reviewed the related literature.

Case presentation

Our two patients were postoperatively diagnosed with gallbladder MiNENs, which pathologically consisted of a large cell neuroendocrine carcinoma and papillary adenocarcinoma. After cholecystectomy, one patient had a survival time of 30 months, while the other remained alive through 12 months of follow-up. In the literature, a total of 72 cases of gallbladder MiNENs were identified, and with our two patients included, we calculated a male-to-female ratio of 0.22 and a mean age of 64.5 years for the 74 reported cases. About one-half of these patients were found to have gallstones and presented with abdominal pain or discomfort in a relatively early stage. The preoperative diagnosis of these 74 cases mainly relied on abdominal ultrasound, contrast-enhanced computed tomography (CT) scanning, and magnetic resonance imaging or positron emission tomography/CT. However, the final diagnosis was established based upon the pathological evidence and expression of synaptophysin (Syn) and/or chromogranin A identified by immunohistochemical staining or neurosecretory granules detected by electron microscopy. Fifty-eight patients (78.4%) underwent various operations including simple cholecystectomy (n = 14), en bloc cholecystectomy (n = 9), standard or non-standard radical cholecystectomy (n = 25), or extended radical cholecystectomy (n = 6). The mean size of the resected gallbladder masses was 50.8 ± 36.1 mm (n = 63) with regional lymph node metastasis in 37 patients (52.1%), liver invasion or staging greater than T3 in 33 patients (45.8%), and hepatic metastasis in 26 patients (35.1%). The postoperative median survival time was 36 ± 11.42 months (95% confidence interval, 13.62 to 58.38 months). The log-rank analysis did not find that postoperative adjuvant chemotherapy contributed to a longer survival time relative to that among the patients who did not receive chemotherapy (numbers of patients, 15 versus 43; survival times, 36 months versus 30 months, p > 0.05).

Conclusions

Our two cases and the cases in the literature suggest that MiNENs of the gallbladder predominantly occur in women; are associated with early lymph node metastasis, local hepatic invasion, and hepatic metastasis; and can be managed by various surgeries as well as chemotherapy combined with somatostatin analogs.
Green pharmacy at the tips of your toes: medicinal plants used by Setos and Russians of Pechorsky District, Pskov Oblast (NW Russia)
Authors: Belichenko Olga , Kolosova Valeria , Kalle Raivo , Sõukand Renata
Published: June 2022

Background

While the hybridization of ecological knowledge has attracted substantial attention from researchers, the coexistence of local and allopathic medicinal traditions in literate societies widely exposed to centralized schooling and medical services has not yet been investigated. To this end, we studied the current and remembered local ethnomedical practices of Setos and neighboring Russians at the border with Estonia.

Methods

During 2018–2019, we carried out 62 semi-structured interviews in the Pechorsky District of Pskov Oblast, NW Russia. For cross-border comparison, we utilized the data from 71 interviews carried out at the same time among Setos in Estonia. The Jaccard Similarity Index and qualitative comparison were used to analyze the data.

Results

The study participants mentioned 819 uses of 112 taxa belonging to 54 families. More than two-thirds of the uses (565) were quoted by 36 Russian interviewees, while the remaining third (254) were quoted by 26 Seto interviewees, with the top 3 in both groups beingViburnum opulus,Rubus idaeus, andPlantago major. The Seto intraethnic similarity index was lower (0.43) than the interethnic similarity in Estonia (0.52) and comparable to the interethnic similarity in Russia (0.43). Setos in Russia and local Russians rely more on wild plants (86% and 80% of medicinal plants, respectively), while Setos in Estonia and Estonians show less preference to them (63% and 61%, respectively). Nevertheless, Setos tend to source wild plants available in their gardens (33% of plants for Setos in Estonia and 38% in Russia), while Russians prefer to source them in the wild (38%).

Conclusions

The preference of both groups in Russia for wild plants over cultivated and purchased plants was inspired by the overall plant literacy, access to nature, and one-to-many knowledge transfer favoring wild plants. Setos in Russia reported a narrower and more homogenous set of plants transferred vertically. However, due to atomization and the erosion of horizontal connections, there are singular plant uses among Setos that overlap with the local Russian set of medicinal plants and differ qualitatively from that of Setos in Estonia.
Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury
Authors: Li Haiyan , Yang Dong-Hua , Zhang Yanmei , Zheng Fuchun , Gao Fenfei , Sun Jiajia , Shi Ganggang
Published: June 2022

Background

NLRP3 inflammasome activation and pyroptosis play a significant role in myocardial ischemia reperfusion injury (MI/RI). Geniposide was reported to show potential therapeutic use for MI/RI with its anti-inflammatory and anti-oxidative properties. However, research on the specific mechanism of geniposide has not been reported.

Methods

The MIRI model of animal was created in male C57BL/6J mice and the hypoxia reoxygenation (H/R) model was established for the in vitro experiments. Neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown of TXNIP or NLRP3 were used. Geniposide was administered to mice before vascular ligation. HE staining, 2,3,5-triphenyltetrazolium chloride (TTC) staining, echocardiography, oxidative stress and myocardial enzyme detection were used to evaluate the cardioprotective effect of geniposide. Meanwhile, pharmacological approaches of agonist and inhibitor were used to observe potential pathway for geniposide cardioprotective in vitro and in vivo. Moreover, ELISA kits were adopted to detect the levels of inflammatory factors, such as IL-1β and IL-18. The gene and protein expression of NLRP3 and pyroptosis-related factors in heart tissue were performed by RT-PCR, western blotting and immunofluorescence in vivo and in vitro, respectively.

Results

Our results indicate that geniposide can reduce the area of myocardial infarction, improve heart function, and inhibit the inflammatory response in mice after MI/RI. In addition, RT-PCR and western blotting shown geniposide promoting AMPK phosphorylation to activate myocardium energy metabolism and reducing the levels of genes and proteins expression of NLRP3, ASC, N-GSDMD and cleaved caspase-1, IL-1β, IL-18. Meanwhile, geniposide improved NRVMs energy metabolism, which decreased ROS levels and the protein expression of TXNIP and thus suppressed the expression of NLRP3. AMPK antagonist or agonist and siRNA downregulation of TXNIP or NLRP3 were also verify the effect of geniposide against H/R injury. Further research found that geniposide promoted the translocation of TXNIP and reduce the binding of TXNIP and NLRP3.

Conclusions

In our study, geniposide can significantly inhibit NLRP3 inflammasome activation via the AMPK signaling pathway and inhibit pyroptosis of cardiomyocytes in myocardial tissues.
Retraction Note: Knockdown of FOXO3a induces epithelialmesenchymal transition and promotes metastasis of pancreatic ductal adenocarcinoma by activation of the βcatenin/TCF4 pathway through SPRY2
Authors: Li Jun , Yang Rumeng , Dong Yuting , Chen Manyao , Wang Yu , Wang Guoping
Published: June 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-019-1046-x.
Reappraising the clinical usability of consolidation-to-tumor ratio on CT in clinical stage IA lung cancer
Authors: Yoon Dong Woog , Kim Chu Hyun , Hwang Soohyun , Choi Yoon-La , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Kim Jhingook , Shim Young Mog , Shin Sumin , Lee Ho Yun
Published: June 2022

Objectives

Ground-glass opacity (GGO) on computed tomography is associated with prognosis in early-stage non-small cell lung cancer (NSCLC) patients. However, the stratification of the prognostic value of GGO is controversial. We aimed to evaluate clinicopathologic characteristics of early-stage NSCLC based on the consolidation-to-tumor ratio (CTR), conduct multi-pronged analysis, and stratify prognosis accordingly.

Methods

We retrospectively investigated 944 patients with clinical stage IA NSCLC, who underwent curative-intent lung resection between August 2018 and January 2020. The CTR was measured and used to categorize patients into six groups (1, 0%; 2, 0–25%; 3, 25–50%; 4, 50–75%; 5, 75–100%; and 6, 100%).

Results

Pathologic nodal upstaging was found in 1.8% (group 4), 9.0% (group 5), and 17.4% (group 6), respectively. The proportion of patients with a high grade of tumor-infiltrating lymphocytes tended to decrease as the CTR increased. In a subtype analysis of patients with adenocarcinoma, all of the patients with predominant micro-papillary patterns were in the CTR > 50% groups, and most of the patients with predominant solid patterns were in group 6 (47/50, 94%). The multivariate analysis demonstrated that CTR 75–100% (hazard ratio [HR], 3.85; 95% confidence interval [CI], 1.58–9.36) and CTR 100% (HR, 5.58; 95% CI, 2.45–12.72) were independent prognostic factors for DFS, regardless of tumor size.

Conclusion

We demonstrated that the CTR could provide various noninvasive clinicopathological information. A CTR of more than 75% is the factor associated with a poor prognosis and should be considered when making therapeutic plans for patients with early-stage NSCLC.
Radiomic assessment of oesophageal adenocarcinoma: a critical review of 18F-FDG PET/CT, PET/MRI and CT
Authors: O’Shea Robert J. , Rookyard Chris , Withey Sam , Cook Gary J. R. , Tsoka Sophia , Goh Vicky
Published: June 2022

Objectives

Radiomic models present an avenue to improve oesophageal adenocarcinoma assessment through quantitative medical image analysis. However, model selection is complicated by the abundance of available predictors and the uncertainty of their relevance and reproducibility. This analysis reviews recent research to facilitate precedent-based model selection for prospective validation studies.

Methods

This analysis reviews research on 18F-FDG PET/CT, PET/MRI and CT radiomics in oesophageal adenocarcinoma between 2016 and 2021. Model design, testing and reporting are evaluated according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) score and Radiomics Quality Score (RQS). Key results and limitations are analysed to identify opportunities for future research in the area.

Results

Radiomic models of stage and therapeutic response demonstrated discriminative capacity, though clinical applications require greater sensitivity. Although radiomic models predict survival within institutions, generalisability is limited. Few radiomic features have been recommended independently by multiple studies.

Conclusions

Future research must prioritise prospective validation of previously proposed models to further clinical translation.
Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial
Authors: Valenzuela Michael , Duncan T. , Abey A. , Johnson A. , Boulamatsis C. , Dalton M. A. , Jacobson E. , Brunel L. , Child G. , Simpson D. , Buckland M. , Lowe A. , Siette J. , Westbrook F. , McGreevy P.
Published: June 2022

Background

Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD). Given there has been no new safe, clinically effective and widely accessible treatment for AD for almost 20 years, an all-new cell therapeutic approach was trialled in canine veterinary patients, and further modelled in aged rats for more detailed neurobiological analysis.

Methods

A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD). Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis. Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment. Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia. Three dog brains were donated following natural death and histology carried out to quantify Alzheimer pathology as well as immature neurons and synapses; these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD. Further, an age-related memory dysfunction rat model (N = 16) was used to more closely evaluate intrahippocampal engraftment of canine SKN cells, focusing on mnemonic and synaptic effects as well as donor cell survival, neurodifferentation and electrophysiologic circuit integration in a live hippocampal slice preparation.

Results

Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years. At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher. There was no impact on AD pathology or long-term safety signals. Modelling in aged rats replicated the main canine trial findings: hippocampally-dependent place memory deficits were reversed and synaptic depletion rescued. In addition, this model confirmed donor cell survival and migration throughout the hippocampus, neuronal differentiation in situ, and physiologically-correct integration into pyramidal layer circuits.

Conclusions

With further development, SKN cell therapy may have potential for treating carefully chosen AD patients based on neurosynaptic restoration in the hippocampus.