bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered amygdala effective connectivity in migraine without aura: evidence from resting‐state fMRI with Granger causality analysis
Authors: Huang Xiaobin , Zhang Di , Wang Peng , Mao Cunnan , Miao Zhengfei , Liu Chunmei , Xu Chenjie , Yin Xindao , Wu Xinying
Published: April 2021

Background

Granger causality analysis (GCA) has been used to investigate the pathophysiology of migraine. Amygdala plays a key role in pain modulation of migraine attack. However, the detailed neuromechanism remained to be elucidated. We applied GCA to explore the amygdala-based directional effective connectivity in migraine without aura (MwoA) and to determine the relation with clinical characteristics.

Methods

Forty-five MwoA patients and forty age-, sex-, and years of education-matched healthy controls(HCs) underwent resting-state functional magnetic resonance imaging (fMRI). Bilateral amygdala were used as seed regions in GCA to investigate directional effective connectivity and relation with migraine duration or attack frequency.

Results

MwoA patients showed significantly decreased effective connectivity from right amygdala to right superior temporal gyrus, left superior temporal gyrus and right precentral gyrus compared with HCs. Furthermore, MwoA patients demonstrated significantly decreased effective connectivity from the left amygdala to the ipsilateral superior temporal gyrus. Also, MwoA patients showed enhanced effective connectivity from left inferior frontal gyrus to left amygdala. Effective connectivity outflow from right amygdala to right precentral gyrus was negatively correlated to disease duration.

Conclusions

Altered directional effective connectivity of amygdala demonstrated that neurolimbic pain networks contribute to multisensory integration abnormalities and deficits in pain modulation of MwoA patients.
Popularity and performance of bioinformatics software: the case of gene set analysis
Authors: Xie Chengshu , Jauhari Shaurya , Mora Antonio
Published: April 2021

Background

Gene Set Analysis (GSA) is arguably the method of choice for the functional interpretation of omics results. The following paper explores the popularity and the performance of all the GSA methodologies and software published during the 20 years since its inception. "Popularity" is estimated according to each paper's citation counts, while "performance" is based on a comprehensive evaluation of the validation strategies used by papers in the field, as well as the consolidated results from the existing benchmark studies.

Results

Regarding popularity, data is collected into an online open database ("GSARefDB") which allows browsing bibliographic and method-descriptive information from 503 GSA paper references; regarding performance, we introduce a repository of jupyter workflows and shiny apps for automated benchmarking of GSA methods (“GSA-BenchmarKING”). After comparing popularity versus performance, results show discrepancies between the most popular and the best performing GSA methods.

Conclusions

The above-mentioned results call our attention towards the nature of the tool selection procedures followed by researchers and raise doubts regarding the quality of the functional interpretation of biological datasets in current biomedical studies. Suggestions for the future of the functional interpretation field are made, including strategies for education and discussion of GSA tools, better validation and benchmarking practices, reproducibility, and functional re-analysis of previously reported data.
Case report and review of literature of a rare congenital disorder: Adams-Oliver syndrome
Authors: Suarez Edwin , Bertoli Mia J. , Eloy Jean Daniel , Shah Shridevi Pandya
Published: April 2021

Background

Adams-Oliver syndrome is characterized by the combination of congenital scalp defects and terminal transverse limb defects. In some instances, cardiovascular malformations and orofacial malformations have been observed. Little is written with regards to the anesthetic management and airway concerns of patients with Adams-Oliver syndrome.

Case presentation

A five-year-old female with Adams-Oliver syndrome presented for repeat lower extremity surgery. Airway exam was significant for dysmorphic features, such as hypertelorism, deviated jaw, and retrognathia. Video laryngoscope was utilized for intubation due to the patients retrognathic jaw, cranial deformities, and facial dysmorphism. A vein finder with ultrasound guidance was needed to place the peripheral intravenous line due to her history of difficult intravenous access. The patient was successfully intubated with slight cricoid pressure applied to direct the endotracheal tube smoothly. Surgery and recovery were both unremarkable.

Conclusions

Due to varying presentations of Adams-Oliver syndrome, anesthetic and airway management considerations should be carefully assessed prior to surgery. Anesthesiologists must take into consideration possible orofacial abnormalities that may make intubation difficult. Amniotic band syndrome and other limb defects could potentially impact intravenous access as well.
Definition of acute kidney injury impacts prevalence and prognosis in ACS patients undergoing coronary angiography
Authors: Weferling Maren , Liebetrau Christoph , Kraus Daniel , Zierentz Philipp , von Jeinsen Beatrice , Dörr Oliver , Weber Michael , Nef Holger , Hamm Christian W. , Keller Till
Published: April 2021

Background

Development of acute kidney injury (AKI) in invasively managed patients with acute coronary syndrome (ACS) is associated with a markedly increased mortality risk. Different definitions of AKI are in use, leading to varying prevalence and outcome measurements. The aim of the present study is to analyze an ACS population undergoing coronary angiography for differences in AKI prevalence and outcome using four established AKI definitions.

Methods

944 patients (30% female) were enrolled in a prospective registry between 2003 and 2005 with 6-month all-cause mortality as outcome measure. Four established AKI definitions were used: an increase in serum creatinine (sCR) ≥ 1.5 fold, ≥ 0.3 mg/dl, and ≥ 0.5 mg/dl and a decrease in eGFR > 25% from baseline (AKIN 1, AKIN 2, CIN, and RIFLE definition groups, respectively).

Results

AKI rates varied widely between the different groups. Using the CIN definition, AKI frequency was lowest (4.4%), whereas it was highest if the RIFLE definition was applied (13.2%). AKIN 2 displayed a twofold higher AKI prevalence compared with AKIN 1 (10.2% vs. 5.3% (p < 0.001)). AKI was a strong risk factor for mid-term mortality, with distinctive variability between the definitions. The lowest mortality risk was found in the RIFLE group (HR 6.0; 95% CI 3.7–10.0; p < 0.001), whereas CIN revealed the highest risk (HR 16.7; 95% CI 9.9–28.1; p < 0.001).

Conclusion

Prevalence and outcome in ACS patients varied considerably depending on the AKI definition applied. To define patients with highest renal function-associated mortality risk, use of the CIN definition seems to have the highest prognostic relevance.
Three‐month outcomes of aortic valve reconstruction using collagenous membranes (biosheets) produced by in‐body tissue architecture in a goat model: a preliminary study
Authors: Okamoto Keitaro , Umeno Tadashi , Shuto Takashi , Wada Tomoyuki , Anai Hirofumi , Nishida Haruto , Nakayama Yasuhide , Miyamoto Shinji
Published: April 2021

Background

Autologous pericardium is widely used as a plastic material in intracardiac structures, in the pulmonary artery, and in aortic valve leaflets. For aortic valve reconstruction (AVRec) using the Ozaki procedure, it has produced excellent clinical results over a 10-year period. In-body tissue architecture (iBTA), which is based on the phenomenon of tissue encapsulation of foreign materials, can be used to prepare autologous prosthetic tissues. In this preliminary study, we examined whether biosheets can be used as valve leaflet material for glutaraldehyde-free AVRec by subchronic implantation experiments in goats and evaluated its performance compared with glutaraldehyde-treated autologous pericardium for AVRec.

Methods

Biosheets were prepared by embedding molds for two months into the dorsal subcutaneous spaces of goats. Autogenic biosheets (n = 4) cut into the shape of the valve were then implanted to the aortic valve annulus of four goats for three months without glutaraldehyde treatment. Autologous pericardium (n = 4) was used in four goats as a control. Valve function was observed using echocardiography.

Results

All goats survived the three-month study period. With biosheets, the leaflet surfaces were very smooth and, on histology, partially covered with a thin neointima (including endothelial cells). Biosheets were more thoroughly assimilated into the aortic root compared with autologous pericardium.

Conclusions

For the first time, biosheets were used for large animal AVRec. Biosheets could function as leaflets in the aortic position and may have the ability to assimilate into native valves.
Endocarditis with spondylodiscitis: clinical characteristics and prognosis
Authors: Del Pace Stefano , Scheggi Valentina , Virgili Giacomo , Caciolli Sabina , Olivotto Iacopo , Zoppetti Nicola , Merilli Irene , Ceschia Nicole , Andrei Valentina , Alterini Bruno , Stefàno Pier Luigi , Marchionni Niccolò
Published: April 2021

Background

The association of infective endocarditis (IE) with spondylodiscitis (SD) was first reported in 1965, but few data are available about this issue. This study aimed to evaluate the prevalence of SD in patients with IE, and to determine the clinical features and the prognostic impact of this association.

Methods

We retrospectively analysed 363 consecutive patients admitted to our Department with non-device-related IE. Radiologically confirmed SD was revealed in 29 patients (8%). Long-term follow-up (average: 3 years) was obtained by structured telephone interviews; in 95 cases (13 of whom had been affected by SD), follow-up echocardiographic evaluation was also available.

Results

At univariable analysis, the combination of IE with SD was associated with male gender (p = 0.017), diabetes (p = 0.028), drug abuse (p = 0.009), Streptococcus Viridans (p = 0.009) and Enterococcus (p = 0.015) infections. At multivariable analysis, all these factors independently correlated with presence of SD in patients with IE. Mortality was similar in patients with and without SD. IE relapses at 3 years were associated with the presence of SD (p = 0.003), Staphylococcus aureus infection (p < 0.001), and drug abuse (p < 0.001) but, at multivariable analysis, only drug abuse was an independent predictor of IE relapses (p < 0.001; HR 6.8, 95% CI 1.6–29). At echocardiographic follow-up, SD was not associated with worsening left ventricular systolic function or valvular dysfunction.

Conclusions

The association of IE with SD is not rare. Hence, patients with IE should be screened for metastatic infection of the vertebral column, especially if they have risk factors for it. However, SD does not appear to worsen the prognosis of patients with IE, either in-hospital or long-term.
Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis
Authors: Dein Eric J. , Wigley Fredrick M. , McMahan Zsuzsanna H.
Published: April 2021

Background

Lower gastrointestinal (GI) tract involvement can affect up to 50% of systemic sclerosis (SSc) patients, and may result in malabsorption, pseudo-obstruction, hospitalization, and death. We report our experience with linaclotide, a selective agonist of guanylate cyclase C (GC-C), for SSc patients with refractory lower GI disease.

Methods

We performed an analysis of patients seen at the Johns Hopkins Scleroderma Center and identified patients prescribed linaclotide for refractory lower GI manifestations. Patients had clinical data collected in our longitudinal database. Linaclotide responders were on medication for at least 12 months with documented effectiveness by the treating physician.

Results

Thirty-one patients with SSc were treated with linaclotide. At the time of linaclotide initiation, 23 of these patients (74%) were classified as having severe GI disease, as defined by recurrent pseudo-obstruction, malabsorption, and/or need for artificial nutrition (Medsger GI severity score ≥ 3). The majority of patients (90.3%; 28/31) had a treatment response, while only three patients (9.7%) reported ineffectiveness or intolerable side effects. Low-dose linaclotide (≤ 145 mcg daily) was used in 18 patients and was effective in 94%. High-dose therapy (> 145 mcg daily) was effective in 11 of 13 patients (85%). Common side effects were diarrhea, cramping, or bloating (11/31, 35%). Ineffectiveness, cost, and abdominal pain were complaints cited among those who discontinued therapy.

Conclusion

Linaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.
Social engagement and physical frailty in later life: does marital status matter?
Authors: Wang Yi , Chen Zhuo , Zhou Chengchao
Published: April 2021

Background

Physical frailty is a common characteristic of older people with the ageing process and has been viewed as a major public health issue. The longitudinal association between different social engagement and physical frailty among older people has not been explored adequately in China. Marital status forms a critical context for the link between social engagement and frailty among older people, which might constitute a moderating process. The purpose of the present study is to investigate the longitudinal association between social engagement and the changes in physical frailty among Chinese older adults, and to examine whether the association between social engagement and frailty differs by marital status.

Methods

The data use in this study were from the data from the China Health and Retirement Longitudinal Study aged 60+ years from 2011 to 2015. A total of 6575 respondents who participated in at least one follow-up wave were included in the analysis. The relationship between social engagement and changes in frailty over time, and the moderating role of marital status were estimated using individual fixed-effects models. Sensitive analyses were conducted to test the robustness of the results.

Results

After adjusting the confounders, participants who interact with friends (Coef: -1.309, P < 0.001), engaging in hobby groups (Coef: -1.189, P < 0.001), engaging in sports groups (Coef: -0.945, P = 0.001), and volunteering (Coef: -1.957, P = 0.001) with a frequency of almost daily had a significantly lower frailty risk than participants who never engaging in those activities. The association between frequent engaging in hobby groups and physical frailty was strongest for unmarried than married older adults (Coef: -1.325, P = 0.031).

Conclusions

Frequent social engagement might help to decrease the risk of frailty in the Chinese older population. This finding has important implications for public health policy and encourages the incorporation of a broad range of social engagement into the daily lives of older individuals. Specially, encouraging unmarried older adults to engage in intellectual activities, such as playing chess or Mahjong with others, may be an effective way to reduce physical frailty.
Effect of various dialysis modalities on intradialytic hemodynamics, tissue injury and patient discomfort in chronic dialysis patients: design of a randomized cross-over study (HOLLANT)
Authors: Rootjes Paul A. , Nubé Menso J. , de Roij van Zuijdewijn Camiel L. M. , Wijngaarden Gertrude , Grooteman Muriel P. C.
Published: April 2021

Background

From a recent meta-analysis it appeared that online post-dilution hemodiafiltration (HDF), especially with a high convection volume (HV-HDF), is associated with superior overall and cardiovascular survival, if compared to standard hemodialysis (HD). The mechanism(s) behind this effect, however, is (are) still unclear. In this respect, a lower incidence of intradialytic hypotension (IDH), and hence less tissue injury, may play a role. To address these items, the HOLLANT study was designed.

Methods

HOLLANT is a Dutch multicentre randomized controlled cross-over trial. In total, 40 prevalent dialysis patients will be included and, after a run-in phase, exposed to standard HD, HD with cooled dialysate, low-volume HDF and high-volume HDF (Dialog iQ® machine) in a randomized fashion. The primary endpoint is an intradialytic nadir in systolic blood pressure (SBP) of < 90 and < 100 mmHg for patients with predialysis SBP < 159 and ≥ 160 mmHg, respectively. The main secondary outcomes are 1) intradialytic left ventricle (LV) chamber quantification and deformation, 2) intradialytic hemodynamic profile of SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), 3) organ and tissue damage, such as the release of specific cellular components, and 4) patient reported symptoms and thermal perceptions during each modality.

Discussion

The current trial is primarily designed to test the hypothesis that a lower incidence of intradialytic hypotension contributes to the superior survival of (HV)-HDF. A secondary objective of this investigation is the question whether changes in the intradialytic blood pressure profile correlate with organ dysfunction and tissue damage, and/or patient discomfort.

Trial registration

Registered Report Identifier:NCT03249532# (ClinicalTrials.gov). Date of registration: 2017/08/15.
Molecular response to induction chemotherapy and its correlation with treatment outcome in head and neck cancer patients by means of NMR-based metabolomics
Authors: Boguszewicz Łukasz , Bieleń Agata , Jarczewski Jarosław Dawid , Ciszek Mateusz , Skorupa Agnieszka , Składowski Krzysztof , Sokół Maria
Published: April 2021

Background

The aim of this prospective study is to identify the biomarkers associated with the effects of induction chemotherapy (iCHT) in terms of the favorable/weaker response to the treatment in locally advanced head and neck squamous cells carcinomas (LA-HNSCC).

Methods

The studied group consisted of 53 LA-HNSCC patients treated with iCHT. The treatment tolerance was measured by the Common Terminology Criteria for Adverse Events (CTCAE). The response to the treatment was evaluated by the clinical, fiberoptic and radiological examinations made before and after iCHT (the TNM Classification of Malignant Tumors was used for classifying the extent of cancer spread). Proton nuclear magnetic resonance (1H NMR) serum spectra of the samples collected before and after iCHT were acquired with a 400 MHz spectrometer and analyzed using the multivariate and univariate statistical methods.

Results

The molecular response to iCHT involves an increase of the serum lipids which is accompanied by the simultaneous decrease of alanine, glucose and N-acetyl-glycoprotein (NAG). Furthermore, in males, the iCHT induced changes in the lipid signals and NAG significantly correlate with the regression of the primary tumor. The OPLS-DA multivariate model identified two subgroups of the patients with a weaker metabolic and clinical response. The first one consisted of the patients with a significantly lower initial nodal stage, the second one showed no differences in the initial clinical and metabolic statuses.

Conclusions

The NMR-based metabolomic study of the serum spectra revealed that iCHT induces the marked changes in the LA-HNSCC patients’ metabolic profiles and makes it possible to stratify the patients according to their response to iCHT. These effects are sex dependent. Further studies on a larger scale accounting for sex and the clinical and metabolic factors are warranted.
Correction to: Co-expression of SOX2 and HR-HPV RISH predicts poor prognosis in small cell neuroendocrine carcinoma of the uterine cervix
Authors: Zhang Shi-Wen , Luo Rong-Zhen , Sun Xiao-Ying , Yang Xia , Yang Hai-Xia , Xiong Si-Ping , Liu Li-Li
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Association between alcohol consumption status and obesity-related comorbidities in men: data from the 2016 Korean community health survey
Authors: Kim Bo-Yeon , Nam Hyewon , Yoo Jeong-Ju , Cho Yoon-Young , Choi Dug-Hyun , Jung Chan-Hee , Mok Ji-Oh , Kim Chul-Hee
Published: April 2021

Background

This study was performed to investigate the association between the amount of alcohol consumption or binge drinking and obesity-related comorbidities in Korean men.

Methods

A total of 103,048 men aged 19 years or older were investigated in the 2016 Korean Community Health Survey. The participants were divided into five groups according to the standard number of alcoholic drinks consumed per week.

Results

Of the total participants, 20.7% were in the high alcohol consumption group, consuming more than 28 drinks per week. After adjustment for clinical factors, high alcohol consumption was significantly associated with higher odds ratios (ORs) of obesity (OR, 1.449; 95% confidence interval [CI], 1.412 to 1.591; P < 0.0001), hypertension (OR, 1.76; 95% CI, 1.636 to 1.894; P < 0.0001), and dyslipidemia (OR, 1.356; 95% CI, 1.247 to 1.474; P < 0.0001). In contrast, mild to moderate alcohol consumption was associated with a lower risk of diabetes (OR, 0.799; 95% CI, 0.726 to 0.88; P = 0.0015) and high alcohol consumption was not associated with a higher risk of diabetes (OR, 0.945; 95% CI, 0.86 to 1.039; P = 0.0662). Among drinkers, except for social drinkers, binge drinking was significantly associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia.

Conclusions

High alcohol consumption was associated with higher risks of obesity, hypertension, and dyslipidemia in Korean men. In contrast, high consumption was not associated with a higher risk of diabetes. In particular, binge drinkers were associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia compared to non-binge drinkers.
Low back pain as an initial symptom of pregnancy‐associated breast cancer: a case report
Authors: Sugai Shunya , Sakata Eiko , Kurabayashi Takumi
Published: April 2021

Background

Low back pain during pregnancy and postpartum is common and might not arouse clinical interest. Pregnancy-associated breast cancer is often found as a breast mass, but its diagnosis is difficult during pregnancy and postpartum. As more women delay their first pregnancies, its incidence may increase in the future.

Case presentation

The patient was a 30-year-old gravida 3, para 3. She had low back pain from the second trimester of her previous two pregnancies, which improved spontaneously after delivery. In her third pregnancy, she again developed low back pain in the second trimester. Her delivery was normal. However, her low back pain continued for up to 7 months postpartum and then worsened sharply. A whole-body scan revealed a compression fracture due to multiple spinal metastases of breast cancer. As she had not complained about her breasts, they had not been closely examined.

Conclusions

This case shows the importance of considering bone metastases from breast cancer in the differential diagnosis of patients with low back pain during pregnancy and postpartum.
The effect of a supportive home care program on caregiver burden with stroke patients in Iran: an experimental study
Authors: Ashghali Farahani Mansoureh , Najafi Ghezeljeh Tahereh , Haghani Shima , Alazmani-Noodeh Farshid
Published: April 2021

Background

Stroke can impose a heavy burden on caregivers. Caring for stroke patients at home is more challenging than in hospitals with facilities. The purpose of this study was to evaluate the effect of a supportive home care program on caregiver burden with stroke patients.

Methods

This was an experimental study. One hundred sixteen caregivers of stroke patients were recruited using convenience sampling from two university-affiliated hospitals in Tehran from June 2019 to February 2020. They were randomly allocated into two groups (supportive home care program and routine hospital education program) using a randomized block design. The supportive home care program included eight educational sessions delivered in the hospital before discharge, and with home visits after hospital discharge. Caregiver burden was measured using Caregiver Burden Inventory. The data were analyzed using independent samples t-test and Analysis of Covariance.

Results

Caregiver burden in the routine education group increased significantly after 2 weeks, from 52.27 ± 23.95 to 62.63 ± 22.68. The mean of caregiver burden scores in the supportive home care program decreased from 44.75 ± 17.21 to 40.46 ± 17.28. The difference between the scores of the two groups before the intervention was not significantly different (t = 1.941, df = 114, p = 0.055). There was a significant difference between the two groups regarding caregiver burden scores after the intervention period (η2 = 0.305, P < 0.001).

Conclusions

Caregiver burden increased significantly after the discharge without proper interventions in the caregivers of stroke patients. Providing support for home care providers can help to decrease or prevent the intensification of caregiver burden.
What makes a “successful” or “unsuccessful” discharge letter? Hospital clinician and General Practitioner assessments of the quality of discharge letters
Authors: Weetman Katharine , Spencer Rachel , Dale Jeremy , Scott Emma , Schnurr Stephanie
Published: April 2021

Background

Sharing information about hospital care with primary care in the form of a discharge summary is essential to patient safety. In the United Kingdom, although discharge summary targets on timeliness have been achieved, the quality of discharge summaries’ content remains variable.

Methods

Mixed methods study in West Midlands, England with three parts: 1. General Practitioners (GPs) sampling discharge summaries they assessed to be “successful” or “unsuccessful” exemplars, 2. GPs commenting on the reasons for their letter assessment, and 3. surveying the hospital clinicians who wrote the sampled letters for their views. Letters were examined using content analysis; we coded 15 features (e.g. “diagnosis”, “GP plan”) based on relevant guidelines and standards. Free text comments were analysed using corpus linguistics, and survey data were analysed using descriptive statistics.

Results

Fifty-three GPs participated in selecting discharge letters; 46 clinicians responded to the hospital survey. There were statistically significant differences between “successful” and “unsuccessful” inpatient letters (n = 375) in relation to inclusion of the following elements: reason for admission (99.1% vs 86.5%); diagnosis (97.4% vs 74.5%), medication changes (61.5% vs 48.9%); reasons for medication changes (32.1% vs 18.4%); hospital plan/actions (70.5% vs 50.4%); GP plan (69.7% vs 53.2%); information to patient (38.5% vs 24.8%); tests/procedures performed (97.0% vs 74.5%), and test/examination results (96.2% vs 77.3%). Unexplained acronyms and jargon were identified in the majority of the sample (≥70% of letters). Analysis of GP comments highlighted that the overall clarity of discharge letters is important for effective and safe care transitions and that they should be relevant, concise, and comprehensible. Hospital clinicians identified several barriers to producing “successful” letters, including: juniors writing letters, time limitations, writing letters retrospectively from patient notes, and template restrictions.

Conclusions

The failure to uniformly implement national discharge letter guidance into practice is continuing to contribute to unsuccessful communication between hospital and general practice. While the study highlighted barriers to producing high quality discharge summaries which may be addressed through training and organisational initiatives, it also indicates a need for ongoing audit to ensure the quality of letters and so reduce patient risk at the point of hospital discharge.
MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells
Authors: Zangouei Amir Sadra , Alimardani Maliheh , Moghbeli Meysam
Published: April 2021

Background

Chemotherapy is one of the most common treatment options for breast cancer (BC) patients. However, about half of the BC patients are chemotherapeutic resistant. Doxorubicin (DOX) is considered as one of the first line drugs in the treatment of BC patients whose function is negatively affected by multi drug resistance. Due to the severe side effects of DOX, it is very important to diagnose the DOX resistant BC patients. Therefore, assessment of molecular mechanisms involved in DOX resistance can improve the clinical outcomes in BC patients by introducing the novel therapeutic and diagnostic molecular markers. MicroRNAs (miRNAs) as members of the non-coding RNAs family have pivotal roles in various cellular processes including cell proliferation and apoptosis. Therefore, aberrant miRNAs functions and expressions can be associated with tumor progression, metastasis, and drug resistance. Moreover, due to miRNAs stability in body fluids, they can be considered as non-invasive diagnostic markers for the DOX response in BC patients.

Main body

In the present review, we have summarized all of the miRNAs that have been reported to be associated with DOX resistance in BC for the first time in the world.

Conclusions

Since, DOX has severe side effects; it is required to distinguish the non DOX-responders from responders to improve the clinical outcomes of BC patients. This review highlights the miRNAs as pivotal regulators of DOX resistance in breast tumor cells. Moreover, the present review paves the way of introducing a non-invasive panel of prediction markers for DOX response among BC patients.
Agent-based modelling of complex factors impacting malaria prevalence
Authors: Amadi Miracle , Shcherbacheva Anna , Haario Heikki
Published: April 2021

Background

Increasingly complex models have been developed to characterize the transmission dynamics of malaria. The multiplicity of malaria transmission factors calls for a realistic modelling approach that incorporates various complex factors such as the effect of control measures, behavioural impacts of the parasites to the vector, or socio-economic variables. Indeed, the crucial impact of household size in eliminating malaria has been emphasized in previous studies. However, increasing complexity also increases the difficulty of calibrating model parameters. Moreover, despite the availability of much field data, a common pitfall in malaria transmission modelling is to obtain data that could be directly used for model calibration.

Methods

In this work, an approach that provides a way to combine in situ field data with the parameters of malaria transmission models is presented. This is achieved by agent-based stochastic simulations, initially calibrated with hut-level experimental data. The simulation results provide synthetic data for regression analysis that enable the calibration of key parameters of classical models, such as biting rates and vector mortality. In lieu of developing complex dynamical models, the approach is demonstrated using most classical malaria models, but with the model parameters calibrated to account for such complex factors. The performance of the approach is tested against a wide range of field data for Entomological Inoculation Rate (EIR) values.

Results

The overall transmission characteristics can be estimated by including various features that impact EIR and malaria incidence, for instance by reducing the mosquito–human contact rates and increasing the mortality through control measures or socio-economic factors.

Conclusion

Complex phenomena such as the impact of the coverage of the population with long-lasting insecticidal nets (LLINs), changes in behaviour of the infected vector and the impact of socio-economic factors can be included in continuous level modelling. Though the present work should be interpreted as a proof of concept, based on one set of field data only, certain interesting conclusions can already be drawn. While the present work focuses on malaria, the computational approach is generic, and can be applied to other cases where suitable in situ data is available.
Malaria in pregnancy complications in Southern Venezuela
Authors: Romero Mariestéfany , Leiba Elízabeth , Carrión-Nessi Fhabián S. , Freitas-De Nobrega Diana C. , Kaid-Bay Serris , Gamardo Ángel F. , Chavero Melynar , Figuera Luisamy , Camejo-Ávila Natasha A. , Marcano María V. , Lopez-Perez Mary , Forero-Peña David A.
Published: April 2021

Background

Pregnant women are particularly vulnerable to malaria infections, increasing the risk of maternal–fetal complications, mainly in high-endemicity areas. However, few studies of malaria in pregnancy (MiP) have been carried out in Latin America, a region with low endemicity and transmission of both,Plasmodium falciparumandPlasmodium vivax. Despite the high malaria burden in Venezuela in the last years, no recent studies of MiP have been conducted. Hence, epidemiological and clinical characteristics of pregnant women with malaria in southern Venezuela are described herein.

Methods

A retrospective study in pregnant women attending at the “Ruíz y Páez” University Hospital Complex, Bolivar state, Venezuela, was carried out between February and October, 2019. Epidemiological, clinical, and laboratory information was analysed.

Results

Thirty-seven out of 52 pregnant women analysed were infected withP. vivax. Age ranged between 15 and 39 years, and adolescent pregnancies were common. Malaria infection was diagnosed mainly during the third trimester of pregnancy (63.4%). The distribution of symptoms and signs as well as clinical laboratory values was similar amongPlasmodiumspp. Although uncomplicated malaria was most frequent, 30% (13/52) had severe anaemia. A high proportion of studied women (44%) presented at least one complication during the pregnancy or delivery. Spontaneous abortion was recorded in four women, and three fetal deaths were observed. Six women had preterm delivery without any further complication.

Conclusions

A high prevalence of maternal–fetal complications was found in the studied population, highlighting the requirement for a careful medical follow up during the prenatal check-ups, which should include routinary malaria tests. Preventive measures as distribution of insecticide-treated mosquito net for pregnant women at risk should also be implemented. Those measures can help to reduce the negative impact of malaria on the newborn and mother.
The impact of urine microbiota in patients with lower urinary tract symptoms
Authors: Lee Hsiang-Ying , Wang Jiunn‐Wei , Juan Yung-Shun , Li Ching-Chia , Liu Chung-Jung , Cho Sung Yong , Yeh Hsin-Chih , Chueh Kuang-Shun , Wu Wen-Jeng , Wu Deng‐Chyang
Published: April 2021

Introduction

Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS).

Materials and methods

We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at − 80 °C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson’s correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples.

Results

We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman’s correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P < 0.05).

Conclusion

Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.
mRNA therapeutics in cancer immunotherapy
Authors: Beck Jan D. , Reidenbach Daniel , Salomon Nadja , Sahin Ugur , Türeci Özlem , Vormehr Mathias , Kranz Lena M.
Published: April 2021

Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Nucleoside modification and elimination of double-stranded RNA can reduce the immunomodulatory activity of mRNA and increase and prolong protein production. In combination with nanoparticle-based formulations that increase transfection efficiency and facilitate lymphatic system targeting, nucleoside-modified mRNA enables efficient delivery of cytokines, costimulatory receptors, or therapeutic antibodies. Steady but transient production of the encoded bioactive molecule from the mRNA template can improve the pharmacokinetic, pharmacodynamic and safety properties as compared to the respective recombinant proteins. This may be harnessed for applications that benefit from a higher level of expression control, such as chimeric antigen receptor (CAR)-modified adoptive T-cell therapies. This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.
Determining the psychometric properties of a novel questionnaire to measure “preparedness for the future” (Prep FQ)
Authors: Heyland Daren K. , Pope J. Paige , Jiang Xuran , Day Andrew G.
Published: April 2021

Background

People are living longer than ever before. However, with living longer comes increased problems that negatively impact on quality of life and the quality of death. Tools are needed to help individuals assess whether they are practicing the best attitudes and behaviors that are associated with a future long life, high quality of life, high quality of death and a satisfying post-death legacy. The purpose of paper is to describe the process we used to develop a novel questionnaire (“Preparedness for the Future Questionnaire™ or Prep FQ”) and to define its psychometric properties.

Methods

Using a multi-step development procedure, items were generated, for the new questionnaire after which the psychometric properties were tested with a heterogeneous sample of 502 Canadians. Using an online polling panel, respondents were asked to complete demographic questions as well as the Prep-FQ, Global Rating of Life Satisfaction, the Keyes Psychological Well-Being scale and the Short-Form 12.

Results

The final version of the questionnaire contains 34 items in 8 distinct domains (“Medico-legal”, “Social”, “Psychological Well-being”, “Planning”, “Enrichment”, “Positive Health Behaviors”, “Negative Health Behaviors”, and “Late-life Planning”). We observed minimum missing data and good usage of all response options. The average overall Prep FQ score is 51.2 (SD = 13.3). The Cronbach alphas assessing internal reliability for the Prep FQ domains ranged from 0.33 to 0.88. The intra-class correlation coefficient (ICC) used to assess the test–retest reliability had an overall score of 0.87. For the purposes of establishing construct validity, all the pre-specified relationships between Prep FQ and the other questionnaires were met.

Conclusion

Analyses of this novel measure offered support for its face validity, construct validity, test–retest reliability, and internal consistency. With the development of this useful and valid scale, future research can utilize this measure to engage people in the process of comprehensively assessing and improving their state of preparedness for the future, tracking their progress along the way. Ultimately, this program of research aims to improve the quality and quantity of peoples live by helping them ‘think ahead’ and ‘plan ahead’ on the aspects of their daily life that matter to their future.
Current status and recent advances in resection cavity irradiation of brain metastases
Authors: Minniti Giuseppe , Niyazi Maximilian , Andratschke Nicolaus , Guckenberger Matthias , Palmer Joshua D. , Shih Helen A. , Lo Simon S. , Soltys Scott , Russo Ivana , Brown Paul D. , Belka Claus
Published: April 2021

Despite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there are several issues that need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity.
Risk factors associated with surgical site infections after thoracic or lumbar surgery: a 6-year single centre prospective cohort study
Authors: Spatenkova Vera , Bradac Ondrej , Jindrisek Zdenek , Hradil Jan , Fackova Daniela , Halacova Milada
Published: April 2021

Background

Surgical site infection (SSI) is a risk in every operation. Infections negatively impact patient morbidity and mortality and increase financial demands. The aim of this study was to analyse SSI and its risk factors in patients after thoracic or lumbar spine surgery.

Methods

A six-year single-centre prospective observational cohort study monitored the incidence of SSI in 274 patients who received planned thoracic or lumbar spinal surgery for degenerative disease, trauma, or tumour. They were monitored for up to 30 days postoperatively and again after 1 year. All patients received short antibiotic prophylaxis and stayed in the eight-bed neurointensive care unit (NICU) during the immediate postoperative period. Risk factors for SSI were sought using multivariate logistic regression analysis.

Results

We recorded 22 incidences of SSI (8.03%; superficial 5.84%, deep 1.82%, and organ 0.36%). Comparing patients with and without SSI, there were no differences in age (p=0.374), gender (p=0.545), body mass index (p=0.878), spine diagnosis (p=0.745), number of vertebrae (p=0.786), spine localization (p=0.808), implant use (p=0.428), American Society of Anesthesiologists (ASA) Score (p=0.752), urine catheterization (p=0.423), drainage (p=0.498), corticosteroid use (p=0.409), transfusion (p=0.262), ulcer prophylaxis (p=0.409) and diabetes mellitus (p=0.811). The SSI group had longer NICU stays (p=0.043) and more non-infectious hospital wound complications (p<0.001). SSI risk factors according to our multivariate logistic regression analysis were hospital wound complications (OR 20.40, 95% CI 7.32–56.85, p<0.001) and warm season (OR 2.92, 95% CI 1.03–8.27, p=0.044).

Conclusions

Contrary to the prevailing literature, our study did not identify corticosteroids, diabetes mellitus, or transfusions as risk factors for the development of SSI. Only wound complications and warm seasons were significantly associated with SSI development according to our multivariate regression analysis.