bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative dynamic quantitative sensory testing in remote pain-free areas is associated with axial pain after posterior cervical spinal surgeries
Authors: Chen Kaiwen , Yu Jie , Nie Cong , Zhu Yu , Jiang Jianyuan , Lei Wei , Xia Xinlei , Zheng Chaojun
Published: May 2022

Background

Postoperative axial pain (PAP), characterized by pain and/or stiffness around the posterior neck, periscapular areas and/or shoulder region, is a vexing complication affecting 5–60% of patients undergoing posterior cervical decompression. Given its relatively high frequency and negative impact on patients’ physical and mental status, efforts preoperatively to confirm patients at risk of developing PAP to offer more efficient pain management to minimize this complication have a high priority. The aim of this study is to investigate the role of preoperative dynamic quantitative sensory testing (QST) in predicting the PAP after posterior cervical decompression.

Methods

This longitudinal observational study included 122 patients with degenerative cervical myelopathy undergoing laminoplasty or laminectomy. Preoperatively, all patients underwent the assessment of pressure pain thresholds (PPTs) at local and remote pain-free areas and both temporal summation (TS) and conditioned pain modulation (CPM) at remote pain free-areas. These patients underwent further pain-related, psychosocial and clinical function assessments before and/or after operation.

Results

In the present study, 21 patients (21/122, 17.2%) developed PAP, and the 6-month postoperative follow-up demonstrated that 8 of these 21 patients developed chronic PAP (CPAP). All preoperative covariates with significant differences between the PAP and non-PAP groups were subjected to multivariate logistic regression, and the presence of preoperative axial pain, surgical plan including C2 decompression, total international physical activity questionnaire score (cutoff value [CV]: 2205.5, sensitivity: 82.4%; specificity: 61.1%) and TS value (CV: 2.5, sensitivity: 42.9%; specificity: 83.2%) were independently associated with PAP (P < 0.05). Logistic regression further revealed that the presence of preoperative axial pain, TS value (CV: 2.5, sensitivity: 62.5%; specificity: 83.2%) and CPM value (CV: 0.65, sensitivity: 87.5%; specificity: 61.4%) were significant predictors of CPAP (P < 0.05).

Conclusions

The findings of this study support the hypothesis that preoperative endogenous pain modulation efficiency may be associated with axial pain after posterior cervical decompression. Clinically, preoperative estimation of both TS and CPM in remote pain-free areas may provide additional useful information for identifying patients who may be at risk of developing both PAP and CPAP, which may be beneficial in enabling stratification in the perioperative period of patients based on individual vulnerabilities to avoid/reduce this complication.
Comparison of the serum brain-derived neurotrophic factor (BDNF) between fibromyalgia and nociceptive pain groups; and effect of duloxetine on the BDNF level
Authors: Bidari Ali , Ghavidel-Parsa Banafsheh , Gharibpoor Faeze
Published: May 2022

Background

The primary objective was to compare the serum brain-derived neurotrophic factor (BDNF) level in the patients with two types of pain: fibromyalgia (FM) and non-FM nociceptive pain (non-FM NP). The secondary objective was to investigate the effect of duloxetine on serum BDNF in FM patients and assess the direction of BDNF changes’ relation to clinical parameters’ alterations.

Methods: This is a study on 73 patients (50 FM and 23 non-FM chronic non-inflammatory pain patients). Serum BDNF was first compared between both groups. Patients with FM, then prospectively, underwent standardized FM treatment with duloxetine maximized to 60 mg/day. The Revised Fibromyalgia Impact Questionnaire (FIQR), Short-Form Health Survey (SF-12), pain visualized analog scale (pain VAS), Beck Depression Inventory-II (BDI-II), polysymptomatic distress scale (PSD) and serum BDNF were measured and compared at baseline and 4 weeks after treatment in FM group.

Results

The mean of adjusted BDNF level in the FM group had no significant difference than the non-FM NP group ((5293.5 ± 2676.3 vs. 6136.3 ± 4037.6; P value = 0.77). Using linear mixed model, we showed that duloxetine reduced BDNF level significantly in FM patients, even after adjusting for depression, pain and severity of the disease (P < 0.01). The FIQR, BDI-II, PSD, and pain VAS improved significantly after duloxetine treatment.

Conclusions

Non-significant BDNF level difference between FM and non-FM nociceptive pain suggested that peripheral BDNF is not a pathophysiological feature of FM. The decreased BDNF level parallel with improvement of PSD/pain scores after duloxetine treatment indicates BDNF alteration in the pain modulation process, regardless of cause and effect.
An evaluation of three-dimensional facial changes after surgically assisted rapid maxillary expansion (SARME): an observational study
Authors: Zupan Jurij , Ihan Hren Nataša , Verdenik Miha
Published: May 2022

Background

The abnormal facial features in maxillary transverse deficiency (MTD) are minimal and limited to a deficiency of the middle facial third, narrow nares and nasal base, and deepened nasolabial folds. The surgical expansion of the narrow maxilla has most obvious effects on widening of the maxillary dental arch and expansion of the maxillary and palatal structures in the transverse plane, however sagittal changes also occurs. The purpose of this observational study was to evaluate the three-dimensional (3D) facial soft tissue changes following surgically assisted rapid maxillary expansion (SARME).

Methods

In 15 skeletally mature patients with severe maxillary transverse deficiency, the planned maxillary expansion (on average 8.8 mm ± 2.3 mm) was achieved with a bone-borne palatal distractor. The 3D optical scans of the facial surface were obtained before and six months after SARME. In the first part, we defined different anatomical landmarks on both scans and compared cephalometric measurements. In the second part, we registered both 3D scans in the same workplace using the regional best-fit method (forehead, supraorbital and nasal root regions were selected for the superimposition) and conducted surface analysis.

Results

The largest differences between the pre- and post-operation scans were observed in the paranasal and cheek area (1.4 ± 1.0 mm). Significant differences occurred for an increased nasal width, a decreased upper-face height with an unchanged lower height, an increased vertical philtrum height and an increased nasolabial angle. A significant increase in the facial profile angle was also observed, resulting in an increased facial convexity and anterior displacement of the upper-lip area.

Conclusions

The widening of the nose and increased projection in the cheek and paranasal area in the lateral direction after maxillary expansion were confirmed; moreover, facial convexity increases, reflecting the underlying advancement of the maxilla.
Cancer patients spend more time at home and more often die at home with advance care planning conversations in primary health care: a retrospective observational cohort study
Authors: Driller Bardo , Talseth-Palmer Bente , Hole Torstein , Strømskag Kjell Erik , Brenne Anne-Tove
Published: May 2022

Background

Spending time at home and dying at home is advocated to be a desirable outcome in palliative care (PC). In Norway, home deaths among cancer patients are rare compared to other European countries. Advance care planning (ACP) conversations enable patients to define goals and preferences, reflecting a person’s wishes and current medical condition.

Method

The study included 250 cancer patients in the Romsdal region with or without an ACP conversation in primary health care who died between September 2018 and August 2020. The patients were identified through their contact with the local hospital, cancer outpatient clinic or hospital-based PC team.

Results

During the last 90 days of life, patients who had an ACP conversation in primary health care (N=125) were mean 9.8 more days at home, 4.5 less days in nursing home and 5.3 less days in hospital. Having an ACP conversation in primary health care, being male or having a lower age significantly predicted more days at home at the end of life (p< .001). Patients with an ACP conversation in primary health care where significantly more likely to die at home (p< .001) with a four times higher probability (RR=4.5). Contact with the hospital-based PC team was not associated with more days at home or death at home. Patients with contact with the hospital-based PC team were more likely to have an ACP conversation in primary health care.

Conclusion

Palliative cancer patients with an ACP conversation in primary health care spent more days at home and more frequently died at home. Data suggest it is important that ACP conversations are conducted in primary health care setting.
A case management model for patients with granulomatous mastitis: a prospective study
Authors: Deng Yuan , Xiong Ying , Ning Ping , Wang Xin , Han Xiao-Rong , Tu Guo-Fang , He Pei-Yu
Published: May 2022

Background

Granulomatous mastitis (GM) is a chronic inflammatory mastitis disease that requires long-term treatment and has a high recurrence rate. Case management has been proven to be an effective mechanism in assisting patients with chronic illness to receive regular and targeted disease monitoring and health care service. The aim of this study was to investigate the application of a hospital-to-community model of case management for granulomatous mastitis and explore the related factors associated with its recurrence.

Methods

This was a prospective study on patients with granulomatous mastitis based on a case management model. Data on demographic, clinical and laboratory information, treatment methods, follow-up time, and recurrence were collected and analyzed. The eight-item Morisky Medication Adherence Scale (MMAS-8) was used to investigate patients' adherence to medications. Logistic regression models were built for analysis of risk factors for the recurrence of granulomatous mastitis.

Results

By October 2021, a total of 152 female patients with a mean age of 32 years had undergone the entire case management process. The mean total course of case management was 24.54 (range 15–45) months. Almost all the patients received medication treatment, except for one pregnant patient who received observation therapy, and approximately 53.9% of the patients received medication and surgery. The overall recurrence rate was 11.2%, and “high” medication adherence (RR = 0.428, 95% CI 0.224–0.867, P = 0.015) was significantly associated with a lower rate of recurrence, while the rate of recurrence with a surgical procedure + medication was higher than that with medication alone (RR = 4.128, 95% CI 1.026–16.610, P = 0.046).

Conclusion

A case management model for patients with granulomatous mastitis was applied to effectively monitor changes in the disease and to identify factors associated with disease recurrence. “Low” medication adherence was a significant risk factor for the recurrence of granulomatous mastitis. Patients treated with medication and surgery were more likely to experience recurrence than those treated with medication alone. The optimal treatment approach should be planned for granulomatous mastitis patients, and patient medication adherence should be of concern to medical staff.
Factors influencing medical students’ attitudes towards substance use during pregnancy
Authors: Richelle Lou , Dramaix-Wilmet Michèle , Roland Michel , Kacenelenbogen Nadine
Published: May 2022

Background

People with substance use disorder, and pregnant women especially, are subject to a lot of stigmas, which can prevent optimal accessibility and quality of care. In this survey, we investigated attitudes of final year medical students regarding substance use during pregnancy and identified the factors that influence these attitudes.

Method

This cross-sectional study was conducted in 2019 and 2020 in Belgium using the short version of the “Substance Abuse Attitude Survey” questionnaire. We focused on two items regarding punishment of substance use during pregnancy. We analysed the concordance between these two, their correlation with other items (e.g. stereotyping, morality, forced withdrawal, low treatment optimism) and the association between respondents’ opinion on punishment and their sociodemographic data.

Results

The response rate was 65.2% (370/567 online and face-to face questionnaires). 19.2% of respondents were in favour of punishment for alcohol use (n = 353) and 15.1% for drug use (n = 356) during pregnancy. The agreement analysis between the two items showed that 14.3% of students were in favour of punishing both pregnant women who use drugs and those using alcohol. Respondents tended to be more in favour of punishment if they were male students, older, their mothers’ had a lower education level or had no personal or family history of substance use. Attitudes appeared to be more punitive among students with limited contact with people with substance use disorder (i.e. none or limited to hospital). Students intending to specialise in internal medicine were more in favour of punishment of women whereas none of those intending to specialise in psychiatry were in favour.

Conclusion

Our study shows that about 20% of surveyed medical students favoured punishing substance-using pregnant women. Awareness and training work seems to be necessary to ensure adequate care and support for this already vulnerable population.
Travelling to die: views, attitudes and end-of-life preferences of Israelis considering receiving aid-in-dying in Switzerland
Authors: Sperling Daniel
Published: May 2022

Background

Following the increased presence of the Right-to-Die Movement, improved end-of-life options, and the political and legal status of aid-in-dying around the globe, suicide tourism has become a promising alternative for individuals who wish to end their lives. Yet, little is known about this from the perspective of those who engage in the phenomenon.

Methods

This study applied the qualitative research approach, following the grounded theory tradition. It includes 11 in-depth semi-structured interviews with Israeli members of the Swiss non-profit Dignitas who contemplated traveling to Switzerland for aid-in-dying.

Results

Seven themes emerged from the data analysis, including health and functioning; feelings regarding survivorship and existence; interacting with the health sector; attitudes regarding death and dying; suicide; choosing death; and choosing suicide tourism. A significant portion of the participants had experienced suicidal thoughts and had even previously attempted suicide, some more than once. Most of them referred to chronic illnesses, functional disability, and social isolation. They understand suffering within the subjective dimension, namely only by the person who is actually subjected to the disease, ailments, and disability. Participants regarded aid-in-dying in Switzerland as positive thanks to its guaranteed outcome: "beautiful death", compared to "disadvantaged dying" which places a burden on the participants' loved ones throughout the prolonged dying. Most of them do not necessarily want to have their loved ones beside them when they die, and they see no significant meaning in dying in a foreign country to which they have no emotional or civil attachment.

Conclusion

The desirable approval or tragic refusal by Dignitas to participants' requests for suicide tourism enhances the paradox between the perception of aid-in-dying as a mechanism for fulfilling controlled death and its bureaucratic and materialistic characteristics specifically reflected in a paid, formalized approach to aid-in-dying that cultivate dependency and collaboration.
Smartphone-based mobile applications for adverse drug reactions reporting: global status and country experience
Authors: Fukushima Ayako , Iessa Noha , Balakrishnan Madhava Ram , Pal Shanthi Narayan
Published: May 2022

Background

Smartphone technology can support paperless reporting of adverse drug reactions (ADRs). The aims of this study were to systematically assess smartphone ADR-reporting applications, understand their qualitative and quantitative impact on ADR reporting, and garner key lessons from owners and developers.

Methods

This study had three components: (1) An assessment of ADR-reporting apps, (2) an online survey on the impact of app implementation on ADR reporting and the experiences of app developers and owners, and (3) a search of VigiBase, the World Health Organization global database of individual case safety reports (ICSRs), to observe trends in the number of ADR reports targeting countries where the apps were implemented.

Results

Twenty-two apps were included. Eight out of the 22 apps were for countries in the WHO African region. Features observed included E2B data elements (E stands for efficacy) and functions supporting reporting and user engagement. Seventeen app developers and owners answered to the survey and reported overall positive experiences with app features, and post-launch increases in the total number of ICSRs. User type and user environment were cited as factors influencing app use: Respondents said younger people and/or those with an inclination to use technology were more likely to use apps compared to older or more technology-averse people, while respondents in countries with limited internet connectivity reported persistent difficulties in app use.

Conclusions

Smartphone apps for reporting ADRs offer added value compared to conventional reporting tools. Reporting tools should be selected based on interface features and factors that may influence app usage.
Prediction of unplanned 30-day readmission for ICU patients with heart failure
Authors: Pishgar M. , Theis J. , Del Rios M. , Ardati A. , Anahideh H. , Darabi H.
Published: May 2022

Background

Intensive Care Unit (ICU) readmissions in patients with heart failure (HF) result in a significant risk of death and financial burden for patients and healthcare systems. Prediction of at-risk patients for readmission allows for targeted interventions that reduce morbidity and mortality.

Methods and results

We presented a process mining/deep learning approach for the prediction of unplanned 30-day readmission of ICU patients with HF. A patient’s health records can be understood as a sequence of observations called event logs; used to discover a process model. Time information was extracted using the DREAM (Decay Replay Mining) algorithm. Demographic information and severity scores upon admission were then combined with the time information and fed to a neural network (NN) model to further enhance the prediction efficiency. Additionally, several machine learning (ML) algorithms were developed to be used as the baseline models for the comparison of the results.

Results

By using the Medical Information Mart for Intensive Care III (MIMIC-III) dataset of 3411 ICU patients with HF, our proposed model yielded an area under the receiver operating characteristics (AUROC) of 0.930, 95% confidence interval of [0.898–0.960], the precision of 0.886, sensitivity of 0.805, accuracy of 0.841, and F-score of 0.800 which were far better than the results of the best baseline model and the existing literature.

Conclusions

The proposed approach was capable of modeling the time-related variables and incorporating the medical history of patients from prior hospital visits for prediction. Thus, our approach significantly improved the outcome prediction compared to that of other ML-based models and health calculators.
Cost of illness of chronic kidney disease in Lebanon: from the societal and third-party payer perspectives
Authors: Aoun Mabel , Helou Elie , Sleilaty Ghassan , Zeenny Rony M. , Chelala Dania
Published: May 2022

Background

Chronic kidney disease (CKD) is the 12th leading cause of death worldwide. Cost-of-illness studies of CKD are scarce in developing countries. This study aims to estimate the cost of illness of all stages of CKD in Lebanon, from early stages until dialysis and kidney transplantation. The secondary objective is to identify factors related to the highest financial burden.

Methods

This is a cross-sectional study of CKD patients who presented to two nephrology clinics during November 2020. Their medical and administrative records were reviewed for collection of demographics, CKD characteristics, direct medical costs (medications, diagnostic tests, hospitalizations, inpatient care, outpatient care), direct non-medical costs (transportation) and indirect costs (productivity losses) for one year. Kruskal Wallis test was used to compare the costs between different CKD stages and categories. Logistic regression analysis was used to evaluate risk factors associated with costs.

Results

The sample included 102 non-dialysis CKD patients, 40 hemodialysis, 8 peritoneal dialysis and 10 transplant patients. Their mean age was 66.74 ± 15.36 years, 57.5% were males and 42.5% diabetics. The total median cost per year of CKD across all categories was assessed to be 7,217,500 Lebanese Pounds (3,750,000–35,535,250; 1 $USD = 1515 LBP in 2019) from the societal perspective and 5,685,500 LBP (2,281,750- 32,386,500) from the third-party payer perspective. Statistical analysis showed a higher total cost in hemodialysis (p < 0.001), higher cost of medications in transplant (p < 0.001) and higher cost in technique modality in peritoneal dialysis (p < 0.001). In a sub-analysis of hemodialysis patients, dialysis vintage negatively correlated with total societal cost (r = -0.391, p = 0.013); the regression analysis found diabetes as a risk factor for higher cost (OR = 2.3; 95%CI: 0.638,8.538; p = 0.201). In the subcategory of CKD-ND patients, age correlated with total societal cost (r = 0.323, p = 0.001); diabetes and coronary artery disease were significantly associated with higher total cost (OR = 2.4; 95%CI: 1.083,5.396; p = 0.031; OR = 3.7; 95%CI: 1.535,8.938; p = 0.004).

Conclusions

This cost of illness study showed a high burden of hemodialysis and peritoneal dialysis cost compared to transplant and non-dialysis CKD patients. It revealed a significantly higher cost of medications in transplant patients. Health policies should target interventions that prevent end-stage kidney disease and encourage kidney transplantation.
The steroid hormone estriol (E3) regulates epigenetic programming of fetal mouse brain and reproductive tract
Authors: Zhou Yuping , Gu Baoxia , Brichant Geraldine , Singh Jay Prakash , Yang Huan , Chang Hao , Zhao Yanding , Cheng Chao , Liu Zhong-Wu , Alderman Myles H. , Lu Lingeng , Yang Xiaoyong , Gao Xiao-Bing , Taylor Hugh S.
Published: May 2022

Background

Estriol (E3) is a steroid hormone formed only during pregnancy in primates including humans. Although E3 is synthesized at large amounts through a complex pathway involving the fetus and placenta, it is not required for the maintenance of pregnancy and has classically been considered virtually inactive due to associated very weak canonical estrogen signaling. However, estrogen exposure during pregnancy may have an effect on organs both within and outside the reproductive system, and compounds with binding affinity for estrogen receptors weaker than E3 have been found to impact reproductive organs and the brain. Here, we explore potential effects of E3 on fetal development using mouse as a model system.

Results

We administered E3 to pregnant mice, exposing the fetus to E3. Adult females exposed to E3 in utero (E3-mice) had increased fertility and superior pregnancy outcomes. Female and male E3-mice showed decreased anxiety and increased exploratory behavior. The expression levels and DNA methylation patterns of multiple genes in the uteri and brains of E3-mice were distinct from controls. E3 promoted complexing of estrogen receptors with several DNA/histone modifiers and their binding to target genes. E3 functions by driving epigenetic change, mediated through epigenetic modifier interactions with estrogen receptors rather than through canonical nuclear transcriptional activation.

Conclusions

We identify an unexpected functional role for E3 in fetal reproductive system and brain. We further identify a novel mechanism of estrogen action, through recruitment of epigenetic modifiers to estrogen receptors and their target genes, which is not correlated with the traditional view of estrogen potency.
Associations of face-to-face and non-face-to-face social isolation with all-cause and cause-specific mortality: 13-year follow-up of the Guangzhou Biobank Cohort study
Authors: Wang Jiao , Zhang Wei Sen , Jiang Chao Qiang , Zhu Feng , Jin Ya Li , Cheng Kar Keung , Lam Tai Hing , Xu Lin
Published: May 2022

Background

Although social isolation has been associated with a higher mortality risk, little is known about the potential different impacts of face-to-face and non-face-to-face isolation on mortality. We examined the prospective associations of four types of social isolation, including face-to-face isolation with co-inhabitants and non-co-inhabitants, non-face-to-face isolation, and club/organization isolation, with all-cause and cause-specific mortality separately.

Methods

This prospective cohort study included 30,430 adults in Guangzhou Biobank Cohort Study (GBCS), who were recruited during 2003–2008 and followed up till Dec 2019.

Results

During an average of 13.2 years of follow-up, 4933 deaths occurred during 396,466 person-years. Participants who lived alone had higher risks of all-cause (adjusted hazard ratio (AHR) 1.24; 95% confidence interval (CI) 1.04-1.49) and cardiovascular disease (CVD) (1.61; 1.20–2.03) mortality than those who had ≥ 3 co-habitant contact after adjustment for thirteen potential confounders. Compared with those who had ≥ 1 time/month non-co-inhabitant contact, those without such contact had higher risks of all-cause (1.60; 1.20–2.00) and CVD (1.91; 1.20–2.62) mortality. The corresponding AHR (95% CI) in participants without telephone/mail contact were 1.27 (1.14–1.42) for all-cause, 1.30 (1.08–1.56) for CVD, and 1.37 (1.12–1.67) for other-cause mortality. However, no association of club/organization contact with the above mortality and no association of all four types of isolation with cancer mortality were found.

Conclusions

In this cohort study, face-to-face and non-face-to-face isolation were both positively associated with all-cause, CVD-, and other-cause (but not cancer) mortality. Our finding suggests a need to promote non-face-to-face contact among middle-aged and older adults.
Prevalence and molecular characterization of Dirofilaria immitis in road killed canids of northern Iran
Authors: Sharifdini Meysam , Karimi Mahan , Ashrafi Keyhan , Soleimani Mostafa , Mirjalali Hamed
Published: May 2022

Background

Dirofilaria immitisis a mosquito-borne filarial nematode, which infects primarily wild and domestic canids, causing cardiopulmonary dirofilariasis. The aim of the present study was to determine the prevalence and characterize molecular features ofD. immitisin road killed canids, northern Iran.

Methods

The carcasses of 53 road killed canids including 18 dogs (Canis familiaris), and 35 golden jackals (C. aureus) were necropsied in both Mazanderan and Guilan provinces, northern Iran. The molecular analyses were conducted based on the cytochrome oxidase (Cox) 1 and 18S ribosomal RNA (rRNA) genes.

Results

The heartworm infection was found in 55.6% of dogs and 22.9% of jackals. Our study revealed significantly higher prevalence ofD. immitisin dogs compared to jackals (P = 0.031). The prevalence ofD. immitiswas no statistically significant between males and females in both dogs and jackal (P > 0.05). Comparison of theCox1 gene sequences with available data in the GenBank illustrated 100% similarity withD. immitisisolates from different hosts in European, Asian, and South American continents. Moreover, the 18S rRNA gene sequences showed 100% identity with dog isolates from Japan and French Guiana.

Conclusions

This study confirms the high prevalence ofD. immitisin dogs and jackals of northern Iran. Developing control programs to prevent transmission of the disease is necessary for dogs and humans in the study areas.
Stratification of lncRNA modulation networks in breast cancer
Authors: Yu Wen-Hsuan , Hsu Chia-Lang , Lin Chen-Ching , Oyang Yen-Jen , Juan Hsueh-Fen , Huang Hsuan-Cheng
Published: May 2022

Background

Recently, non-coding RNAs are of growing interest, and more scientists attach importance to research on their functions. Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts longer than 200 nucleotides. We already knew that lncRNAs are related to cancers and will be dysregulated in them. But most of their functions are still left to further study. A mechanism of RNA regulation, known as competing endogenous RNAs (ceRNAs), has been proposed to explain the complex relationships among mRNAs and lncRNAs by competing for binding with shared microRNAs (miRNAs).

Methods

We proposed an analysis framework to construct the association networks among lncRNA, mRNA, and miRNAs based on their expression patterns and decipher their network modules.

Results

We collected a large-scale gene expression dataset of 1,061 samples from breast invasive carcinoma (BRCA) patients, each consisted of the expression profiles of 4,359 lncRNAs, 16,517 mRNAs, and 534 miRNAs, and applied the proposed analysis approach to interrogate them. We have uncovered the underlying ceRNA modules and the key modulatory lncRNAs for different subtypes of breast cancer.

Conclusions

We proposed a modulatory analysis to infer the ceRNA effects among mRNAs and lncRNAs and performed functional analysis to reveal the plausible mechanisms of lncRNA modulation in the four breast cancer subtypes. Our results might provide new directions for breast cancer therapeutics and the proposed method could be readily applied to other diseases.
A systematic analysis of gene–gene interaction in multiple sclerosis
Authors: Slim Lotfi , Chatelain Clément , Foucauld Hélène de , Azencott Chloé-Agathe
Published: May 2022

Background

For the most part, genome-wide association studies (GWAS) have only partially explained the heritability of complex diseases. One of their limitations is to assume independent contributions of individual variants to the phenotype. Many tools have therefore been developed to investigate the interactions between distant loci, or epistasis. Among them, the recently proposed EpiGWAS models the interactions between a target variant and the rest of the genome. However, applying this approach to studying interactions along all genes of a disease map is not straightforward. Here, we propose a pipeline to that effect, which we illustrate by investigating a multiple sclerosis GWAS dataset from the Wellcome Trust Case Control Consortium 2 through 19 disease maps from the MetaCore pathway database.

Results

For each disease map, we build an epistatic network by connecting the genes that are deemed to interact. These networks tend to be connected, complementary to the disease maps and contain hubs. In addition, we report 4 epistatic gene pairs involving missense variants, and 25 gene pairs with a deleterious epistatic effect mediated by eQTLs. Among these, we highlight the interaction of GLI-1 and SUFU, and of IP10 and NF-$$\kappa$$
κ
B, as they both match known biological interactions. The latter pair is particularly promising for therapeutic development, as both genes have known inhibitors.

Conclusions

Our study showcases the ability of EpiGWAS to uncover biologically interpretable epistatic interactions that are potentially actionable for the development of combination therapy.
Systematic analysis of prognostic significance, functional enrichment and immune implication of STK10 in acute myeloid leukemia
Authors: Bi Lei , Jia Shuangshuang , Hu Wuyue , Su Xiaoli , Chen Xiequn , Tang Hailong
Published: May 2022

Background

Despite deeper understanding of the genetic landscape of acute myeloid leukemia (AML), the improvement of survival is still a great challenge. STK10 is overexpressed in several cancers with functions varying according to cancer types. But the functions of STK10 in AML has never been reported.

Methods

We analyzed the expression, prognosis and potential functions of STK10 utilizing public web servers. Metascape and the String database were used for functional and protein–protein interaction analyses.

Results

We found STK10 was enriched in blood & immune cells and overexpressed in AML. High STK10 expression was associated with poor overall survival, which was also identified in the subgroups of patients ≤ 60 years old and patients with non-high-risk cytogenetics. We demonstrated genes associated with STK10 were enriched in blood, spleen and bone marrow, influencing the immune function and biological process of AML. ITGB2 and ITGAM might directly interact with STK10 and were associated with poor prognosis. Besides, STK10 was associated with the infiltration of immune cells and immune checkpoints, like HLA-E, CD274 and GAL-9.

Conclusions

The present study was the original description of STK10 in AML and set the stage for developing STK10 as a new prognostic marker or therapeutic target for AML.
Melanin biopolymer synthesis using a new melanogenic strain of Flavobacterium kingsejongi and a recombinant strain of Escherichia coli expressing 4-hydroxyphenylpyruvate dioxygenase from F. kingsejongi
Authors: Lee Han Sae , Choi Jun Young , Kwon Soon Jae , Park Eun Seo , Oh Byeong M. , Kim Jong H. , Lee Pyung Cheon
Published: May 2022

Background

Melanins are a heterologous group of biopolymeric pigments synthesized by diverse prokaryotes and eukaryotes and are widely utilized as bioactive materials and functional polymers in the biotechnology industry. Here, we report the high-level melanin production using a new melanogenic Flavobacterium kingsejongi strain and a recombinant Escherichia coli overexpressing F. kingsejongi 4-hydroxyphenylpyruvate dioxygenase (HPPD).

Results

Melanin synthesis of F. kingsejongi strain was confirmed via melanin synthesis inhibition test, melanin solubility test, genome analysis, and structural analysis of purified melanin from both wild-type F. kingsejongi and recombinant E. coli expressing F. kingsejongi HPPD. The activity of F. kingsejongi HPPD was demonstrated via in vitro assays with 6 × His-tagged and native forms of HPPD. The specific activity of F. kingsejongi HPPD was 1.2 ± 0.03 μmol homogentisate/min/mg-protein. Bioreactor fermentation of F. kingsejongi produced a large amount of melanin with a titer of 6.07 ± 0.32 g/L, a conversion yield of 60% (0.6 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.03 g/L·h, indicating its potential for industrial melanin production. Additionally, bioreactor fermentation of recombinant E. coli expressing F. kingsejongi HPPD produced melanin at a titer of 3.76 ± 0.30 g/L, a conversion yield of 38% (0.38 ± 0.03 g melanin per gram tyrosine), and a productivity of 0.04 g/L·h.

Conclusions

Both strains showed sufficiently high fermentation capability to indicate their potential as platform strains for large-scale bacterial melanin production. Furthermore, F. kingsejongi strain could serve as a model to elucidate the regulation of melanin biosynthesis pathway and its networks with other cellular pathways, and to understand the cellular responses of melanin-producing bacteria to environmental changes, including nutrient starvation and other stresses.
PICALM exerts a role in promoting CRC progression through ERK/MAPK signaling pathway
Authors: Zhang Xitao , Liu Tianlai , Huang Jinlin , He Jianping
Published: May 2022

Background

Colorectal cancer (CRC) is a common malignant tumor in gastrointestinal tract with high incidence and mortality. In this study, the functions and potential mechanism of phosphatidylinositol-binding clathrin assembly protein (PICALM) in CRC were preliminarily explored.

Methods

Based on the Cancer Genome Atlas database and immunohistochemistry staining, revealing that the expression level of PICALM in CRC tissues was higher than that in adjacent normal tissues.

Results

Moreover, loss-of-function and gain-of-function assays in HCT 116 and RKO cells found that PICALM promotes proliferation and migration of CRC cells and inhibits apoptosis. Consistently, knockdown of PICALM inhibited tumorigenicity of CRC cells in vivo. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that knockdown of PICALM resulted in the enrichment of MAPK signaling pathway. Treatment of CRC cells with MAPK inhibitor reversed the effects of PICALM overexpression on proliferation and apoptosis. In addition, overexpression of PICALM upregulated the protein levels of ERK1/2 (p-ERK1/2), MEK1/2 (p-MEK1/2), p38 (p-p38) and JNK (p-JNK), and these effects were partially alleviated by the treatment of MAPK inhibitor.

Conclusions

In summary, the study presented the new discovery that PICALM promoted CRC progression through ERK/MAPK signaling pathway, which drew further interest regarding its clinical application as a promising therapeutic target.
ncRNAs-mediated high expression of TIMM8A correlates with poor prognosis and act as an oncogene in breast cancer
Authors: Wang Zhonglin , Li Shuqin , Xu Feng , Fu Jingyue , Sun Jie , Gan XinLi , Yang Chuang , Mao Zhongqi
Published: May 2022

Background

Breast cancer is notorious for its increasing incidence for decades. Ascending evidence has demonstrated that translocase of inner mitochondrial membrane (TIMM) proteins play vital roles in progression of several types of human cancer. However, the biological behaviors and molecular mechanisms of TIMM8A in breast cancer remain not fully illustrated.

Methods

Pan-cancer analysis was firstly performed for TIMM8A’s expression and prognosis by Oncomine database. Subsequently, TIMM8A-related noncoding RNAs (ncRNAs) were identified by a series of bioinformatics analyses and dual-luciferase reporter assay, including expression analysis, correlation analysis, and survival analysis. Moreover, the effect of TIMM8A on breast cancer proliferation and apoptosis was evaluated in vitro by CCK-8 assays, EdU cell proliferation assays, JC-1 mitochondrial membrane potential detection assays and Western blot assays and the in vivo effect was revealed through a patient-derived xenograft mouse model.

Results

We found that TIMM8A showed higher expression level in breast cancer and the higher TIMM8A mRNA expression group had a poorer prognosis than the lower TIMM8A group. hsa-circ-0107314/hsa-circ-0021867/hsa-circ-0122013 might be the three most potential upstream circRNAs of hsa-miR-34c-5p/hsa-miR-449a-TIMM8A axis in breast cancer. TIMM8A promotes proliferation of breast cancer cells in vitro and tumor growth in vivo.

Conclusion

Our results confirmed that ncRNAs-mediated upregulation of TIMM8A correlated with poor prognosis and act as an oncogene in breast cancer.
ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression
Authors: Liu Junqiang , Chou Zhiyuan , Li Chun , Huang Kai , Wang Xuejian , Li Xiunan , Han Chuanchun , Al-Danakh Abdullah , Li Xiaodong , Song Xishuang
Published: May 2022

Background

Zinc finger and BTB domain-containing 7A (ZBTB7A) is a member of the POK family of transcription factors that plays an oncogenic or tumor-suppressive role in different cancers depending on the type and genetic context of cancer. However, the function and molecular mechanism of ZBTB7A in bladder cancer (BC) remain elusive.

Methods

The role of ZBTB7A in bladder cancer was detected by colony formation, transwell, and tumor formation assays. The expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed by qRT-PCR and Western blot. Bioinformatics analysis and a dual-luciferase reporter assay were used to assess the effect of ZBTB7A on the promoter activity of HIC1.

Results

The present study revealed that knockdown of ZBTB7A suppressed BC cell growth and migration, as indicated by an approximately 50% reduction in the number of colonies and an approximately 70% reduction in the number of migrated cells. Loss of ZBTB7A inhibited tumor growth in vivo, resulting in a 75% decrease in tumor volume and an 80% decrease in tumor weight. Further mechanistic studies revealed that ZBTB7A bound to the hypermethylated in cancer 1 (HIC1) promoter and downregulated HIC1 expression, accelerating the malignant behavior of BC. Increased expression of ZBTB7A in BC tissues was negatively corrected with the expression of HIC1. Moreover, ZBTB7A was a target of miR-144-3p, which decreased ZBTB7A expression in BC.

Conclusion

Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.
DNA repair and damage pathways in mesothelioma development and therapy
Authors: Malakoti Faezeh , Targhazeh Niloufar , Abadifard Erfan , Zarezadeh Reza , Samemaleki Sahar , Asemi Zatollah , Younesi Simin , Mohammadnejad Reza , Hadi Hossini Seyed , Karimian Ansar , Alemi Forough , Yousefi Bahman
Published: May 2022

Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.
Exploring theoretical mechanisms of community-engaged research: a multilevel cross-sectional national study of structural and relational practices in community-academic partnerships
Authors: Oetzel John G. , Boursaw Blake , Magarati Maya , Dickson Elizabeth , Sanchez-Youngman Shannon , Morales Leo , Kastelic Sarah , Eder Milton “Mickey” , Wallerstein Nina
Published: May 2022

Background

Community-Based Participatory Research (CBPR) is often used to address health inequities due to structural racism. However, much of the existing literature emphasizes relationships and synergy rather than structural components of CBPR. This study introduces and tests new theoretical mechanisms of the CBPR Conceptual Model to address this limitation.

Methods

Three-stage online cross-sectional survey administered from 2016 to 2018 with 165 community-engaged research projects identified through federal databases or training grants. Participants (N = 453) were principal investigators and project team members (both academic and community partners) who provided project-level details and perceived contexts, processes, and outcomes. Data were analyzed through structural equation modeling and fuzzy-set qualitative comparison analysis.

Results

Commitment to Collective Empowerment was a key mediating variable between context and intervention activities. Synergy and Community Engagement in Research Actions were mediating variables between context/partnership process and outcomes. Collective Empowerment was most strongly aligned with Synergy, while higher levels of Structural Governance and lower levels of Relationships were most consistent with higher Community Engagement in Research Actions.

Conclusions

The CBPR Conceptual Model identifies key theoretical mechanisms for explaining health equity and health outcomes in community-academic partnerships. The scholarly literature’s preoccupation with synergy and relationships overlooks two promising practices—Structural Governance and Collective Empowerment—that interact from contexts through mechanisms to influence outcomes. These results also expand expectations beyond a “one size fits all” for reliably producing positive outcomes.
Two-dimensional metal-organic frameworks: from synthesis to bioapplications
Authors: Wang Weiqi , Yu Yuting , Jin Yilan , Liu Xiao , Shang Min , Zheng Xiaohua , Liu Tingting , Xie Zhigang
Published: May 2022

As a typical class of crystalline porous materials, metal–organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.

Graphical Abstract
Nanozyme-natural enzymes cascade catalyze cholesterol consumption and reverse cancer multidrug resistance
Authors: Du Bin , Zheng Mei , Ma Huizhen , Huang Jingshu , Jiao Qingqing , Bai Yimeng , Zhao Mengmeng , Zhou Jie
Published: May 2022

Multidrug resistance is still a major obstacle to cancer treatment. The most studies are to inhibit the activity of the drug transporter P-glycoprotein (P-gp), but the effect is not ideal. Herein, a nanosystem was built based on cascade catalytic consumption of cholesterol. Cholesterol oxidase (natural enzyme, COD) was immobilized on the carrier (NH2-MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H2O2 was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (•OH) with killing effect. Due to the high expression of CD44 receptor on the surface of tumor cells, we encapsulated chondroitin sulfate gel shell (CS-shell) with CD44 targeting and apoptosis promoting effect on the surface of DOX@MOF-COD nanoparticles, which can accurately and efficiently deliver the drugs to the tumor site and improve the effect of reversing drug resistance. Taking drug-resistant cell membrane as "breakthrough", this paper will provide a new idea for reversing multidrug resistance of tumor.

Graphical Abstract