bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal sleep duration and neonatal birth weight: the Japan Environment and Children’s Study
Authors:   The Japan Environment and Children’s Study (JECS) Group, Murata Tsuyoshi , Kyozuka Hyo , Fukuda Toma , Yasuda Shun , Yamaguchi Akiko , Morokuma Seiichi , Sato Akiko , Ogata Yuka , Shinoki Kosei , Hosoya Mitsuaki , Yasumura Seiji , Hashimoto Koichi , Nishigori Hidekazu , Fujimori Keiya
Published: April 2021

Background

The adequate maternal sleep duration required for favorable obstetric outcomes is unknown. We evaluated the association between maternal sleep duration and low birth weight infants, small for gestational age infants, and macrosomia.

Methods

Participants enrolled in the Japan Environment and Children’s Study, a nationwide birth cohort study, with singleton pregnancies after 22 weeks, who gave birth between 2011 and 2014 were enrolled and categorized into five groups according to maternal sleep duration during pregnancy: < 6.0 h, 6.0–7.9 h, 8.0–8.9 h, 9.0–9.9 h, and 10.0–12.0 h. We evaluated the association between maternal sleep duration and the incidence of low birth weight infants (< 2500 g), very low birth weight infants (< 1500 g), small for gestational age infants, and macrosomia (> 4000 g), with women with maternal sleep duration of 6.0–7.9 h as the reference, using a multiple logistic regression model.

Results

In total, 82,171 participants were analyzed. The adjusted odds ratios (95% confidence intervals) for low birth weight infants in women with maternal sleep duration of 9.0–9.9 h and 10.0–12.0 h and for small for gestational age infants in women with maternal sleep duration of 9.0–9.9 h were 0.90 (0.83–0.99), 0.86 (0.76–0.99), and 0.91 (0.82–0.99), respectively, before adjusting for excessive gestational weight gain. No significant association was observed between maternal sleep duration and these outcomes after adjusting for excessive gestational weight gain. Among women with appropriate gestational weight gain, the adjusted odds ratios (95% confidence intervals) for low birth weight infants and for small for gestational age infants with sleep duration of 9.0–9.9 h were 0.88 (0.80–0.97) and 0.87 (0.78–0.97), respectively.

Conclusions

Maternal sleep duration of 9.0–9.9 h was significantly associated with the decreased incidence of low birth weight infants and small for gestational age infants in pregnant women with appropriate gestational weight gain, compared with that of 6.0–7.9 h. Care providers should provide proper counseling regarding the association between maternal sleep duration and neonatal birth weight and suggest comprehensive maternal lifestyle modifications to prevent low birth weight and small for gestational age infants.
Comparison of maternal and neonatal outcomes between acute fatty liver of pregnancy and hemolysis, elevated liver enzymes and low platelets syndrome: a retrospective cohort study
Authors: Ang Sau Xiong , Chen Chie-Pein , Sun Fang-Ju , Chen Chen-Yu
Published: April 2021

Background

Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome are two uncommon disorders that mimic each other clinically, but are distinct pathophysiologically. This study aimed to compare maternal and neonatal outcomes between AFLP and HELLP syndrome.

Methods

This retrospective cohort study was performed at a tertiary referral center in Taiwan between June 2004 and April 2020. We used the Swansea Criteria to diagnose AFLP, and the Tennessee Classification System to diagnose HELLP syndrome. Maternal characteristics, laboratory data, complications, and neonatal outcomes were compared. We analyzed the categorical variables with Chi-square test or Fisher’s exact test and continuous variables with Student’s t test or Mann-Whitney U test. Subsequent logistic regression analyses adjusting by potential confounding factors with significant difference were analyzed.

Results

During the study period, 21 women had AFLP and 80 women had HELLP syndrome. There was a higher rate of preeclampsia (95.0 % versus 23.8 %) in the HELLP syndrome group compared to the AFLP group. However, the AFLP group had more other maternal complications including jaundice (85.7 % versus 13.8 %), acute kidney injury (61.9 % versus 15.0 %), disseminated intravascular coagulopathy (66.7 % versus 8.8 %), and sepsis (47.6 % versus 10.0 %) compared to the HELLP syndrome group. Nevertheless, higher rates of small for gestational age neonates (57.1 % versus 33.3 %), neonatal respiratory distress syndrome (39.2 % versus 8.3 %) and neonatal sepsis (34.2 % versus 12.5 %) were noted in the HELLP syndrome group.

Conclusions

AFLP is associated with a higher rate of multiple organ dysfunction in mothers, whereas HELLP syndrome is associated with a higher rate of neonatal morbidity.
Reference-free transcriptome signatures for prostate cancer prognosis
Authors: Nguyen Ha T.N. , Xue Haoliang , Firlej Virginie , Ponty Yann , Gallopin Melina , Gautheret Daniel
Published: April 2021

Background

RNA-seq data are increasingly used to derive prognostic signatures for cancer outcome prediction. A limitation of current predictors is their reliance on reference gene annotations, which amounts to ignoring large numbers of non-canonical RNAs produced in disease tissues. A recently introduced kind of transcriptome classifier operates entirely in a reference-free manner, relying on k-mers extracted from patient RNA-seq data.

Methods

In this paper, we set out to compare conventional and reference-free signatures in risk and relapse prediction of prostate cancer. To compare the two approaches as fairly as possible, we set up a common procedure that takes as input either a k-mer count matrix or a gene expression matrix, extracts a signature and evaluates this signature in an independent dataset.

Results

We find that both gene-based and k-mer based classifiers had similarly high performances for risk prediction and a markedly lower performance for relapse prediction. Interestingly, the reference-free signatures included a set of sequences mapping to novel lncRNAs or variable regions of cancer driver genes that were not part of gene-based signatures.

Conclusions

Reference-free classifiers are thus a promising strategy for the identification of novel prognostic RNA biomarkers.
When lockdown policies amplify social inequalities in COVID-19 infections: evidence from a cross-sectional population-based survey in France
Authors:   for the SAPRIS study group, Bajos Nathalie , Jusot Florence , Pailhé Ariane , Spire Alexis , Martin Claude , Meyer Laurence , Lydié Nathalie , Franck Jeanna-Eve , Zins Marie , Carrat Fabrice
Published: April 2021

Background

Significant differences in COVID-19 incidence by gender, class and race/ethnicity are recorded in many countries in the world. Lockdown measures, shown to be effective in reducing the number of new cases, may not have been effective in the same way for all, failing to protect the most vulnerable populations. This survey aims to assess social inequalities in the trends in COVID-19 infections following lockdown.

Methods

A cross-sectional survey conducted among the general population in France in April 2020, during COVID-19 lockdown.

Ten thousand one hundred one participants aged 18–64, from a national cohort who lived in the three metropolitan French regions most affected by the first wave of COVID-19.

The main outcome was occurrence of possible COVID-19 symptoms, defined as the occurrence of sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days in the 15 days before the survey. We used multinomial regression models to identify social and health factors related to possible COVID-19 before and during the lockdown.

Results

In all, 1304 (13.0%; 95% CI: 12.0–14.0%) reported cases of possible COVID-19. The effect of lockdown on the occurrence of possible COVID-19 was different across social hierarchies. The most privileged class individuals saw a significant decline in possible COVID-19 infections between the period prior to lockdown and during the lockdown (from 8.8 to 4.3%,P = 0.0001) while the decline was less pronounced among working class individuals (6.9% before lockdown and 5.5% during lockdown,P = 0.03). This differential effect of lockdown remained significant after adjusting for other factors including history of chronic disease. The odds of being infected during lockdown as opposed to the prior period increased by 57% among working class individuals (OR = 1.57; 95% CI: 1.00–2.48). The same was true for those engaged in in-person professional activities during lockdown (OR = 1.53; 95% CI: 1.03–2.29).

Conclusions

Lockdown was associated with social inequalities in the decline in COVID-19 infections, calling for the adoption of preventive policies to account for living and working conditions. Such adoptions are critical to reduce social inequalities related to COVID-19, as working-class individuals also have the highest COVID-19 related mortality, due to higher prevalence of comorbidities.
Age-dependence of healthcare interventions for COVID-19 in Ontario, Canada
Authors: Papst Irena , Li Michael , Champredon David , Bolker Benjamin M. , Dushoff Jonathan , D. Earn David J.
Published: April 2021

Background

Patient age is one of the most salient clinical indicators of risk from COVID-19. Age-specific distributions of known SARS-CoV-2 infections and COVID-19-related deaths are available for many regions. Less attention has been given to the age distributions of serious medical interventions administered to COVID-19 patients, which could reveal sources of potential pressure on the healthcare system should SARS-CoV-2 prevalence increase, and could inform mass vaccination strategies. The aim of this study is to quantify the relationship between COVID-19 patient age and serious outcomes of the disease, beyond fatalities alone.

Methods

We analysed 277,555 known SARS-CoV-2 infection records for Ontario, Canada, from 23 January 2020 to 16 February 2021 and estimated the age distributions of hospitalizations, Intensive Care Unit admissions, intubations, and ventilations. We quantified the probability of hospitalization given known SARS-CoV-2 infection, and of survival given COVID-19-related hospitalization.

Results

The distribution of hospitalizations peaks with a wide plateau covering ages 60–90, whereas deaths are concentrated in ages 80+. The estimated probability of hospitalization given known infection reaches a maximum of 27.8% at age 80 (95% CI 26.0%–29.7%). The probability of survival given hospitalization is nearly 100% for adults younger than 40, but declines substantially after this age; for example, a hospitalized 54-year-old patient has a 91.7% chance of surviving COVID-19 (95% CI 88.3%–94.4%).

Conclusions

Our study demonstrates a significant need for hospitalization in middle-aged individuals and young seniors. This need is not captured by the distribution of deaths, which is heavily concentrated in very old ages. The probability of survival given hospitalization for COVID-19 is lower than is generally perceived for patients over 40. If acute care capacity is exceeded due to an increase in COVID-19 prevalence, the distribution of deaths could expand toward younger ages. These results suggest that vaccine programs should aim to prevent infection not only in old seniors, but also in young seniors and middle-aged individuals, to protect them from serious illness and to limit stress on the healthcare system.
En bloc resection and reconstruction of a huge chondrosarcoma involving multilevel upper thoracic spine and chest wall: case report
Authors: Tang Xiaodong , Cai Zhenyu , Wang Ruifeng , Ji Tao , Guo Wei
Published: April 2021

Background

En bloc resection of malignant tumors involving upper thoracic spine is technically difficult. We surgically treated a patient with grade 2 chondrosarcoma involving T1–5, left upper thoracic cavity, and chest wall.

Case presentation

A 37 years old, male patient was referred to our hospital for a huge lump involved left shoulder and chest wall. In order to achieve satisfied surgical margins, anterior approach, posterior approach, and lateral approach were carried out sequentially. After en bloc tumor resection, the upper thoracic spine was reconstructed with a 3D-printed modular vertebral prosthesis, and the huge chest wall defect was repaired by a methyl methacrylate layer between 2 pieces of polypropylene mesh. Postoperatively, the patient suffered from pneumonia and neurological deterioration which fully recovered eventfully. At 24 months after operation, the vertebral prosthesis and internal fixation were intact; there was no tumor local recurrence, and the patient was alive with stable pulmonary metastases.

Conclusion

This case report describes resection of a huge chondrosarcoma involving not only multilevel upper thoracic spine, but also entire left upper thoracic cavity and chest wall. Although with complications, en bloc tumor resection with combined surgical approach and effective reconstructions could improve oncologic and functional prognosis in carefully selected spinal tumor patients.
Transforaminal epidural steroid injection combined with radio frequency for the treatment of lumbar disc herniation: a 2-year follow-up
Authors: Wei Wen-Bo , Dang Sha-Jie , Wei Ling , Liu Tian , Wang Jue
Published: April 2021

Background

To assess the therapeutic efficacy of transforaminal epidural steroid injection (TFESI) combined with radio frequency (RF) for the treatment of lumbar disc herniation (LDH).

Methods

A total of 230 patients participated in the study: TFESI (Group T, n = 110), TFESI combined with RF (Group TR, n = 120). Visual analogue scale (VAS), Oswestry disability index (ODI) and Global perceived effect (GPE) scale were measured pre-operation, 1, 3, 6, 12 and 24 months after the operation. Hospitalization time, treatment time, complications, and recurrence were compared between the two groups.

Results

The VAS and ODI at each observation point of the post-operation were significantly decreased compared with the pre-operation in both groups (P < 0.05). There was no statistically difference of VAS and ODI between the two groups at 1 and 3 months of the post-operation (P > 0.05). However, The VAS and ODI scores in Group TR were significantly lower than that in Group T at 6, 12 and 24 months of the post-operation (P < 0.05). The GPE in group TR was high in the early days, while that at 1 and 3 months after treatment was significantly higher than that in group T (P < 0.05). The recurrence rate in Group TR was lower than that in Group T (P = 0.002). There was no significant difference in hospitalization time, complications, VAS and ODI score at the pre-operation between the two groups (P > 0.05).

Conclusion

These findings suggest that TFESI combined with RF could effectively improve the pain and function, and had a long-term satisfactory effect for the treatment of LDH.
The use of BokaFlo™ instrument to measure salivary flow
Authors: Fallon Braden S. , Chase Trevor J. , Cooke Elaine M. , Ghazitabatabaei Amir , Naylor Nathan O. , Cutshall Jordan J. , Trump Bryan G. , Weller Melodie L.
Published: April 2021

Background

Dry mouth currently affects roughly 20% of the population and is a condition characterized by chronic hyposalivation and/or subjective reports of xerostomia. Low saliva flow can be indicative of other undiagnosed diseases, such as primary Sjogren’s syndrome, and may contribute to difficulty chewing, increased caries susceptibility and infection. The passive drool test (PDT) is the primary method used to evaluate patients for hyposalivation but it is time-consuming and inconvenient. New methodology is needed to facilitate increased testing for hyposalivation in the dental clinic. The aim of this study was to evaluate an alternative method to measure salivary flow in dental offices.

Methods

In this study, we tested a new biomedical device, the BokaFlo™, to measure salivary flow in subjects in comparison to the current PDT standard. Participants completed an oral health questionnaire and saliva flow was evaluated by the PDT and the BokaFlo™ system.

Results

Saliva flow as measured by the BokaFlo™ positively correlated with the saliva flow measured by the PDT methodology (r = 0.22, p < 0.05). The device predicted low saliva flow in subjects with a sensitivity of 0.76 and specificity of 0.84 for subjects with hyposalivation, defined as a saliva flow rate of ≤ 0.1 ml/min. A significant negative correlation between the total oral health questionnaire score and the likelihood of participant exhibiting low salivary flow was observed (r = − 0.31, p < 0.006).

Conclusion

The BokaFlo™ was effectively able to measure low saliva flow correlating with the PDT methodology and may provide more efficient testing of saliva flow in the dental office.
Stainless-steel crowns in children: Norwegian and Finnish dentists’ knowledge, practice and challenges
Authors: Uhlen M. M. , Tseveenjav B. , Wuollet E. , Furuholm J. , Ansteinsson V. , Mulic A. , Valen H.
Published: April 2021

Background

Stainless-steel crowns (SSCs) are recommended for restorative treatment of young teeth severely affected by caries, fractures or dental developmental disorders (DDDs). However, despite recommendations and clinical evidence, SSCs are not widely used by general dentists, who favour extraction and more conventional restorations. The present study aimed to investigate the views of and use of SSCs among Norwegian and Finnish dentists.

Methods

The present study was a cross-sectional survey among Norwegian and Finnish dentists. An electronic questionnaire was sent to Norwegian and Finnish dentists asking whether they used SSCs and on which indications. In addition, the questionnaire assessed reasons for non-use and dentists’ perceptions regarding advantages and challenges in the use of SSCs, as well as the need for additional training. Distributions of background characteristics, use of and views on SSCs were calculated, and statistical significance of the associations between respondents’ background and their answers were evaluated.

Results

Of the 574 Norwegian and 765 Finnish respondents, only 12.0% and 12.9% reported to use SSCs, respectively. The most frequently reported barrier reported by those who did not use SSCs was lack of practical training. The most frequent challenge reported by those using SSCs was difficulties in crown adjustment followed by aesthetic issues, and the most frequently reported advantage was that SSCs maintain the function and occlusion. The majority of respondents reported a need for more information and practical training in the use of SSCs, with hands-on course as their most frequently preferred education type.

Conclusion

Although the value of SSCs for restoring young molars is recognized by Norwegian and Finnish dentists, SSCs are rarely used by general dentists. The majority of the respondents reported lack of training and materials and was interested in receiving more information and education.
Hospice care providers experiences of grappling with medical assistance in dying in a hospice setting: a qualitative descriptive study
Authors: Freeman Shannon , Banner Davina , Ward Valerie
Published: April 2021

Background

Rapid implementation of Medical Assistance in Dying (MAiD) across care settings has challenged providers and organizations, including hospices, to develop and implement new modes of practice. The aim of this study was to examine the effects that legalization of MAiD has had on hospice care provider roles within the non-provider context.

Methods

Eight in-depth semi-structured interviews were conducted and a qualitative descriptive approach used to examine hospice care providers experiences in a small western Canadian city. In the study context, patients who choose MAiD are cared for until immediately prior to the procedure when they are transferred off-site to undergo MAiD. Inductive and thematic analyses were undertaken.

Results

Participants experienced practical, philosophical, and professional challenges. Despite the overwhelming desire to support patient autonomy and decision-making, some interpreted patient choice for MAiD as rejection of the natural death experience at the hospice. Patient choice for MAiD initiated a new and different pathway of end-of-life care. While participants felt uncertain how best to support patients undergoing MAiD, they shared mixed optimism on how their care provider roles were evolving as their level of experience broadened. While implementation of MAiD was rapid, the introduction of practical and professional supports has remained slow to materialize, leaving many providers to navigate their own personal and professional positions and practices.

Conclusion

Care providers require a multi-faceted range of clinical, legal, and logistical supports at the practice, organizational, and health system levels, to facilitate care delivery to those requesting and undergoing MAiD and to promote coordinated and holistic patient-centered care. The different pathway for those who chose MAiD may lead care providers to struggle with relational challenges and interpersonal unease. Further research may address how to support those undergoing MAiD within the hospice context.
An emergency care research course for healthcare career preparation
Authors: Miller Karen F. , Das Rishub K. , Majors Ciera D. , Paz Hadassah H. , Robinson Ayana N. , Hamilton Veronica F. , Jackson Brittney E. , Collins Sean P. , Storrow Alan B.
Published: April 2021

Background

University students have limited opportunities to gain healthcare clinical exposure within an academic curriculum. Furthermore, traditional pre-medical clinical experiences like shadowing lack active learning components. This may make it difficult for students to make an informed decision about pursuing biomedical professions. An academic university level research course with bedside experience provides students direct clinical participation in the healthcare setting.

Methods

Described is a research immersion course for senior university students (3rd to 5th year) interested in healthcare and reported study enrollment with final course evaluations. The setting was an adult, academic, urban, level 1 trauma center emergency department (ED) within a tertiary-care, 1000-bed, medical center. Our course, “Immersion in Emergency Care Research”, was offered as a university senior level class delivered consecutively over 16-weeks for students interested in healthcare careers. Faculty and staff from the Department of Emergency Medicine provided a classroom lecture program and extensive bedside, hands-on clinical research experience. Students enrolled patients in a survey study requiring informed consent, interviews, data abstraction and data entry. Additionally, they were required to write and present a mock emergency care research proposal inspired by their clinical experience. The course evaluations from students’ ordinal rankings and blinded text responses report possible career impact.

Results

Thirty-two students, completed the 16-week, 6–9 h per week, course from August to December in 1 of 4 years (2016 to 2019). Collectively, students enrolled 759 ED patients in the 4 survey studies and reported increased confidence in the clinical research process as each week progressed. Ranked evaluations were extremely positive, with many students describing how the course significantly impacted their career pathways and addressed an unmet need in biomedical education. Six students continued the research experience from the course through independent study using the survey data to develop 3 manuscripts for submission to peer-reviewed journals.

Conclusions

A bedside emergency care research course for students with pre-healthcare career aspirations can successfully provide early exposure to patients and emergency care, allow direct experience with clinical bedside research, research data collection, and may impact biomedical science career choices.
Validity evidence for a novel instrument assessing medical student attitudes toward instruction in implicit bias recognition and management
Authors: Gonzalez Cristina M. , Grochowalski Joseph H. , Garba Ramya J. , Bonner Shacelles , Marantz Paul R.
Published: April 2021

Background

Implicit bias instruction is becoming more prevalent in health professions education, with calls for skills-based curricula moving from awareness and recognition to management of implicit bias. Evidence suggests that health professionals and students learning about implicit bias (“learners”) have varying attitudes about instruction in implicit bias, including the concept of implicit bias itself. Assessing learner attitudes could inform curriculum development and enable instructional designs that optimize learner engagement. To date, there are no instruments with evidence for construct validity that assess learner attitudes about implicit bias instruction and its relevance to clinical care.

Methods

The authors developed a novel instrument, the Attitude Towards Implicit Bias Instrument (ATIBI) and gathered evidence for three types of construct validity- content, internal consistency, and relationship to other variables.

Results

Authors utilized a modified Delphi technique with an interprofessional team of experts, as well as cognitive interviews with medical students leading to item refinement to improve content validity. Seven cohorts of medical students, N = 1072 completed the ATIBI. Psychometric analysis demonstrated high internal consistency (α = 0.90). Exploratory factor analysis resulted in five factors. Analysis of a subset of 100 medical students demonstrated a moderate correlation with similar instruments, the Integrative Medicine Attitude Questionnaire (r = 0.63, 95% CI: [0.59, 0.66]) and the Internal Motivation to Respond Without Prejudice Scale (r = 0.36, 95% CI: [0.32, 0.40]), providing evidence for convergent validity. Scores on our instrument had low correlation to the External Motivation to Respond Without Prejudice Scale (r = 0.15, 95% CI: [0.09, 0.19]) and the Groningen Reflection Ability Scale (r = 0.12, 95% CI: [0.06, 0.17]) providing evidence for discriminant validity. Analysis resulted in eighteen items in the final instrument; it is easy to administer, both on paper form and online.

Conclusion

The Attitudes Toward Implicit Bias Instrument is a novel instrument that produces reliable and valid scores and may be used to measure medical student attitudes related to implicit bias recognition and management, including attitudes toward acceptance of bias in oneself, implicit bias instruction, and its relevance to clinical care.
Serial serum creatinine, SDMA and urinary acute kidney injury biomarker measurements in dogs envenomated by the European adder (Vipera berus)
Authors: Harjen Hannah J. , Nicolaysen Tove V. , Negard Tale , Lund Hege , Sævik Bente K. , Anfinsen Kristin P. , Moldal Elena R. , Zimmer Karin E. , Rørtveit Runa
Published: April 2021

Background

Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated byV. berusat 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs.

Results

Thirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 μmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P <  0.0001,P <  0.0001,P = 0.01), 24 h (P <  0.001,P <  0.001,P = 0.002) and 36 h (P <  0.001,P <  0.001,P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003,P = 0.0005,P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls.

Conclusion

Urinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated byV. berus.
NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer
Authors: Faria Sara Socorro , Costantini Susan , de Lima Vladmir Cláudio Cordeiro , de Andrade Victor Pianna , Rialland Mickaël , Cedric Rebe , Budillon Alfredo , Magalhães Kelly Grace
Published: April 2021

Breast cancer is the most diagnosed malignancy in women. Increasing evidence has highlighted the importance of chronic inflammation at the local and/or systemic level in breast cancer pathobiology, influencing its progression, metastatic potential and therapeutic outcome by altering the tumor immune microenvironment. These processes are mediated by a variety of cytokines, chemokines and growth factors that exert their biological functions either locally or distantly. Inflammasomes are protein signaling complexes that form in response to damage- and pathogen-associated molecular patterns (DAMPS and PAMPS), triggering the release of pro-inflammatory cytokines. The dysregulation of inflammasome activation can lead to the development of inflammatory diseases, neurodegeneration, and cancer. A crucial signaling pathway leading to acute and chronic inflammation occurs through the activation of NLRP3 inflammasome followed by caspase 1-dependent release of IL-1β and IL-18 pro-inflammatory cytokines, as well as, by gasdermin D-mediated pyroptotic cell death. In this review we focus on the role of NLRP3 inflammasome and its components in breast cancer signaling, highlighting that a more detailed understanding of the clinical relevance of these pathways could significantly contribute to the development of novel therapeutic strategies for breast cancer.
Gene coexpression network approach to develop an immune prognostic model for pancreatic adenocarcinoma
Authors: Gu Xiaoqiang , Zhang Qiqi , Wu Xueying , Fan Yue , Qian Jianxin
Published: April 2021

Background

Pancreatic adenocarcinoma (PAAD) is a nonimmunogenic tumor, and very little is known about the relationship between the host immune response and patient survival. We aimed to develop an immune prognostic model (IPM) and analyze its relevance to the tumor immune profiles of patients with PAAD.

Methods

We investigated differentially expressed genes between tumor and normal tissues in the TCGA PAAD cohort. Immune-related genes were screened from highly variably expressed genes with weighted gene correlation network analysis (WGCNA) to construct an IPM. Then, the influence of IPM on the PAAD immune profile was comprehensively analyzed.

Results

A total of 4902 genes highly variably expressed among primary tumors were used to construct a weighted gene coexpression network. One hundred seventy-five hub genes in the immune-related module were used for machine learning. Then, we established an IPM with four core genes (FCGR2B, IL10RA, and HLA-DRA) to evaluate the prognosis. The risk score predicted by IPM was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. Moreover, we found that the patients in the low-risk group had higher cytolytic activity and lower innate anti-PD-1 resistance (IPRES) signatures than patients in the high-risk group.

Conclusions

Unlike the traditional methods that use immune-related genes listed in public databases to screen prognostic genes, we constructed an IPM through WGCNA to predict the prognosis of PAAD patients. In addition, an IPM prediction of low risk indicated enhanced immune activity and a decreased anti-PD-1 therapeutic response.
High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke
Authors: Hu Mengyan , Lin Yinyao , Men Xuejiao , Wang Shisi , Sun Xiaobo , Zhu Qiang , Lu Danli , Liu Sanxin , Zhang Bingjun , Cai Wei , Lu Zhengqi
Published: April 2021

Background

A high-salt diet (HSD) is one of the major risk factors for acute ischemic stroke (AIS). As a potential mechanism, surplus salt intake primes macrophages towards a proinflammatory phenotype. In this study, whether HSD could blunt the efferocytic capability of macrophages after ischemic stroke, thus exacerbating post-stroke neural inflammation, was investigated.

Methods

Wild-type male C57BL/6 mice were fed with fodder containing 8% sodium chloride for 4 weeks and subjected to transient middle cerebral occlusion (tMCAO). Disease severity, macrophage polarization as well as efferocytic capability were evaluated. Bone marrow-derived macrophages were cultured in vitro, and the impact of high salinity on their efferocytic activity, as well as their expression of phagocytic molecules, were analyzed. The relationships among sodium concentration, macrophage phenotype, and disease severity in AIS patients were explored.

Results

HSD-fed mice displayed increased infarct volume and aggravated neurological deficiency. Mice fed with HSD suffered exacerbated neural inflammation as shown by higher inflammatory mediator expression and immune cell infiltration levels. Infiltrated macrophages within stroke lesions in HSD-fed mice exhibited a shift towards proinflammatory phenotype and impaired efferocytic capability. As assessed with a PCR array, the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a receptor relevant to phagocytosis, was downregulated in high-salt-treated bone marrow-derived macrophages. Enhancement of TREM2 signaling restored the efferocytic capacity and cellular inflammation resolution of macrophages in a high salinity environment in vitro and in vivo. A high concentration of urine sodium in AIS patients was found to be correlated with lower TREM2 expression and detrimental stroke outcomes.

Conclusions

HSD inhibited the efferocytic capacity of macrophages by downregulating TREM2 expression, thus impeding inflammation resolution after ischemic stroke. Enhancing TREM2 signaling in monocytes/macrophages could be a promising therapeutic strategy to enhance efferocytosis and promote post-stroke inflammation resolution.
Alcohol marketing versus public health: David and Goliath?
Authors: Madden Mary , McCambridge Jim
Published: April 2021

Background

Alcohol harms are rising globally, and alcohol policies, where they exist, are weak or under-developed. Limited progress has been made since the formulation of the World Health Organisation (WHO) Global Strategy in 2010. WHO is seeking to accelerate progress in implementing international efforts to reduce the harmful use of alcohol. The threat to global health posed by tobacco is well understood by policy communities and populations globally; by contrast alcohol is much less so, despite available evidence.

The competition for epistemic authority

Global alcohol corporations have sought to become trusted sources of advice for policy makers and consumers, while continuing to grow their markets. Evidence-informed public health messaging faces formidable competition from transnational corporations as the worlds of corporate and political communications, social and mainstream media become increasingly linked, presenting new opportunities for corporate actors to shape global health governance. Alcohol messaging that uses means of persuasion tied to industry agendas does not tell a clear story about commercial determinants of health, and does not contribute to health improvement. On the contrary, the basic tenets of an evidence-informed population-based approach are denied and the policy measures supported by high quality evidence are being opposed, because they are inimical to commercial interests. A David and Goliath metaphor for this state of affairs, which seems to fit at first glance, may unwittingly reinforce the status quo.

Conclusion

Public opinion on alcohol and policy issues varies across time and place and can be influenced by dedicated public health interventions. Alcohol marketing dominates people’s thinking about alcohol because we currently allow this to happen. Greater ambition is needed in developing countermarketing and other interventions to promote evidence-informed ideas with the public. Alcohol policies need to be further developed, and implemented more widely, in order to arrest the growing burden of alcohol harms across the world.
Decision-making process for introduction of maternal vaccines in Kenya, 2017–2018
Authors: Otieno Nancy A. , Malik Fauzia A. , Nganga Stacy W. , Wairimu Winnie N. , Ouma Dominic O. , Bigogo Godfrey M. , Chaves Sandra S. , Verani Jennifer R. , Widdowson Marc-Alain , Wilson Andrew D. , Bergenfeld Irina , Gonzalez-Casanova Ines , Omer Saad B.
Published: April 2021

Background

Maternal immunization is a key strategy for reducing morbidity and mortality associated with infectious diseases in mothers and their newborns. Recent developments in the science and safety of maternal vaccinations have made possible development of new maternal vaccines ready for introduction in low- and middle-income countries. Decisions at the policy level remain the entry point for maternal immunization programs. We describe the policy and decision-making process in Kenya for the introduction of new vaccines, with particular emphasis on maternal vaccines, and identify opportunities to improve vaccine policy formulation and implementation process.

Methods

We conducted 29 formal interviews with government officials and policy makers, including high-level officials at the Kenya National Immunization Technical Advisory Group, and Ministry of Health officials at national and county levels. All interviews were recorded and transcribed. We analyzed the qualitative data using NVivo 11.0 software.

Results

All key informants understood the vaccine policy formulation and implementation processes, although national officials appeared more informed compared to county officials. County officials reported feeling left out of policy development. The recent health system decentralization had both positive and negative impacts on the policy process; however, the negative impacts outweighed the positive impacts. Other factors outside vaccine policy environment such as rumours, sociocultural practices, and anti-vaccine campaigns influenced the policy development and implementation process.

Conclusions

Public policy development process is complex and multifaceted by its nature. As Kenya prepares for introduction of other maternal vaccines, it is important that the identified policy gaps and challenges are addressed.
Resolvin D1 reduces cancer growth stimulating a protective neutrophil-dependent recruitment of anti-tumor monocytes
Authors: Mattoscio Domenico , Isopi Elisa , Lamolinara Alessia , Patruno Sara , Medda Alessandro , De Cecco Federica , Chiocca Susanna , Iezzi Manuela , Romano Mario , Recchiuti Antonio
Published: April 2021

Background

Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression.

Methods

Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients.

Results

RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration.

Conclusions

RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.
Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome
Authors:   the RICO study group, Venet Fabienne , Cour Martin , Rimmelé Thomas , Viel Sebastien , Yonis Hodane , Coudereau Remy , Amaz Camille , Abraham Paul , Monard Céline , Casalegno Jean-Sebastien , Brengel-Pesce Karen , Lukaszewicz Anne-Claire , Argaud Laurent , Monneret Guillaume
Published: April 2021

Background

Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved.

Methods

We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements.

Results

ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS.

Conclusions

Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.
Computational methods for chromosome-scale haplotype reconstruction
Authors: Garg Shilpa
Published: April 2021

High-quality chromosome-scale haplotype sequences of diploid genomes, polyploid genomes, and metagenomes provide important insights into genetic variation associated with disease and biodiversity. However, whole-genome short read sequencing does not yield haplotype information spanning whole chromosomes directly. Computational assembly of shorter haplotype fragments is required for haplotype reconstruction, which can be challenging owing to limited fragment lengths and high haplotype and repeat variability across genomes. Recent advancements in long-read and chromosome-scale sequencing technologies, alongside computational innovations, are improving the reconstruction of haplotypes at the level of whole chromosomes. Here, we review recent and discuss methodological progress and perspectives in these areas.
Impact of early detection and vaccination strategy in COVID-19 eradication program in Jakarta, Indonesia
Authors: Aldila Dipo , Samiadji Brenda M. , Simorangkir Gracia M. , Khosnaw Sarbaz H. A. , Shahzad Muhammad
Published: April 2021

Objective

Several essential factors have played a crucial role in the spreading mechanism of COVID-19 (Coronavirus disease 2019) in the human population. These factors include undetected cases, asymptomatic cases, and several non-pharmaceutical interventions. Because of the rapid spread of COVID-19 worldwide, understanding the significance of these factors is crucial in determining whether COVID-19 will be eradicated or persist in the population. Hence, in this study, we establish a new mathematical model to predict the spread of COVID-19 considering mentioned factors.

Results

Infection detection and vaccination have the potential to eradicate COVID-19 from Jakarta. From the sensitivity analysis, we find that rapid testing is crucial in reducing the basic reproduction number when COVID-19 is endemic in the population rather than contact trace. Furthermore, our results indicate that a vaccination strategy has the potential to relax social distancing rules, while maintaining the basic reproduction number at the minimum possible, and also eradicate COVID-19 from the population with a higher vaccination rate. In conclusion, our model proposed a mathematical model that can be used by Jakarta’s government to relax social distancing policy by relying on future COVID-19 vaccine potential.