bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust segmentation of lung in chest x-ray: applications in analysis of acute respiratory distress syndrome
Authors: Reamaroon Narathip , Sjoding Michael W. , Derksen Harm , Sabeti Elyas , Gryak Jonathan , Barbaro Ryan P. , Athey Brian D. , Najarian Kayvan
Published: October 2020

Background

This study outlines an image processing algorithm for accurate and consistent lung segmentation in chest radiographs of critically ill adults and children typically obscured by medical equipment. In particular, this work focuses on applications in analysis of acute respiratory distress syndrome – a critical illness with a mortality rate of 40% that affects 200,000 patients in the United States and 3 million globally each year.

Methods

Chest radiographs were obtained from critically ill adults (n = 100), adults diagnosed with acute respiratory distress syndrome (ARDS) (n = 25), and children (n = 100) hospitalized at Michigan Medicine. Physicians annotated the lung field of each radiograph to establish the ground truth. A Total Variation-based Active Contour (TVAC) lung segmentation algorithm was developed and compared to multiple state-of-the-art methods including a deep learning model (U-Net), a random walker algorithm, and an active spline model, using the Sørensen–Dice coefficient to measure segmentation accuracy.

Results

The TVAC algorithm accurately segmented lung fields in all patients in the study. For the adult cohort, an averaged Dice coefficient of 0.86 ±0.04 (min: 0.76) was reported for TVAC, 0.89 ±0.12 (min: 0.01) for U-Net, 0.74 ±0.19 (min: 0.15) for the random walker algorithm, and 0.64 ±0.17 (min: 0.20) for the active spline model. For the pediatric cohort, a Dice coefficient of 0.85 ±0.04 (min: 0.75) was reported for TVAC, 0.87 ±0.09 (min: 0.56) for U-Net, 0.67 ±0.18 (min: 0.18) for the random walker algorithm, and 0.61 ±0.18 (min: 0.18) for the active spline model.

Conclusion

The proposed algorithm demonstrates the most consistent performance of all segmentation methods tested. These results suggest that TVAC can accurately identify lung fields in chest radiographs in critically ill adults and children.
Use of patient derived urine renal epithelial cells to confirm pathogenicity of PKHD1 alleles
Authors: Molinari Elisa , Srivastava Shalabh , Dewhurst Rebecca M. , Sayer John A.
Published: October 2020

Background

PKHD1 is the main genetic cause of autosomal recessive polycystic kidney disease (ARPKD), a hereditary hepato-renal fibrocystic disorder which is the most important cause of end-stage renal disease during early childhood. ARPKD can also present in adulthood with milder phenotypes. In this study, we describe a 24-year-old woman with atypical polycystic kidney, no family history of renal disease and no obvious extra-renal manifestations who was referred for genetic investigation.

Methods

We used a combination of next generation sequencing, Sanger sequencing and RNA and microscopy studies performed on urine-derived renal epithelial cells (URECs) to provide a genetic diagnosis of ARPKD.

Results

A next generation sequencing panel of cystic ciliopathy genes allowed the identification of two heterozygous sequence changes in PKHD1 (c.6900C > T; p.(Asn2300=) and c.7964A > C; p.(His2655Pro)). The pathogenicity of the synonymous PKHD1 variant is not clear and requires RNA studies, which cannot be carried out efficiently on RNA extracted from proband blood, due to the low expression levels of PKHD1 in lymphocytes.

Using URECs as a source of kidney-specific RNA, we show that PKHD1 is alternatively spliced around exon 43, both in control and proband URECs. The variant p.(Asn2300=) shifts the expression ratio in favour of a shorter, out-of-frame transcript. To further study the phenotypic consequence of these variants, we investigated the ciliary phenotype of patient URECs, which were abnormally elongated and presented multiple blebs along the axoneme.

Conclusions

We confirm the power of URECs as a tool for functional studies on candidate variants in inherited renal disease, especially when the expression of the gene of interest is restricted to the kidney and we describe, for the first time, ciliary abnormalities in ARPKD patient cells.
Effects of prenatal mindfulness-based childbirth education on child-bearers’ trajectories of distress: a randomized control trial
Authors: Sbrilli Marissa D. , Duncan Larissa G. , Laurent Heidemarie K.
Published: October 2020

Background

The perinatal period is a time of immense change, which can be a period of stress and vulnerability for mental health difficulties. Mindfulness-based interventions have shown promise for reducing distress, but further research is needed to identify long-term effects and moderators of mindfulness training in the perinatal period.

Methods

The current study used data from a pilot randomized control trial (RCT) comparing a condensed mindfulness-based childbirth preparation program—the Mind in Labor (MIL)—to treatment as usual (TAU) to examine whether prenatal mindfulness training results in lower distress across the perinatal period, and whether the degree of benefit depends on child-bearers’ initial levels of risk (i.e., depression and anxiety symptoms) and protective (i.e., mindfulness) characteristics. Child-bearers (N = 30) in their third trimester were randomized to MIL or TAU and completed assessments of distress—perceived stress, anxiety, and depressive symptoms—at pre-intervention, post-intervention, six-weeks post-birth, and one-year postpartum.

Results

Multilevel modeling of distress trajectories revealed greater decreases from pre-intervention to 12-months postpartum for those in MIL compared to TAU, especially among child-bearers who were higher in anxiety and/or lower in dispositional mindfulness at baseline.

Conclusions

The current study offers preliminary evidence for durable perinatal mental health benefits following a brief mindfulness-based program and suggests further investigation of these effects in larger samples is warranted.

Trial registration

The ClinicalTrials.gov identifier for the study is: NCT02327559. The study was retrospectively registered on June 23, 2014.
Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours
Authors: Stockley J. , Akhand R. , Kennedy A. , Nyberg C. , Crosbie E. J. , Edmondson R. J.
Published: October 2020

Background

MCM5 is a protein involved in DNA replication, facilitating cell proliferation. In normal epithelium MCM5 expression is restricted to the cells in the basal proliferative compartments, however in the presence of a tumour MCM5 positive cells are present at the surface epithelium and are shed into bodily fluids. The aim of this study was to determine the sensitivity of MCM5 as a biomarker for the detection of endometrial and ovarian cancer.

Methods

Patients with known ovarian or endometrial cancers, or known benign gynaecological conditions, were enrolled. Informed consent was obtained prior to the collection of full void urine, and either a vaginal tampon (worn for 6–8 h), or a vaginal swab. Vaginal secretions were extracted from the tampon or swab, centrifuged and lysed. Urine samples were centrifuged and lysed. MCM5 levels were determined by MCM5-ELISA (Arquer Diagnostics Ltd).

Results

125 patients completed the study protocol, 41 patients had endometrial cancer, 26 ovarian cancer, and 58 benign controls. All patients provided a urine sample and either a tampon or vaginal swab sample. Urine MCM5 levels were higher in cancer patients than controls (p < 0.0001), there was no significant difference in levels between tampon samples or vaginal swab samples in cancer patients when compared to controls.

Performance of MCM5 to discriminate cancer from benign disease was high with an area under the ROC curve of 0.83 for endometrial cancer and 0.68 for ovarian cancer. Using a cut off of 12 pg/mL, overall sensitivity for endometrial cancer was 87.8, and 61.5% for ovarian cancer with a specificity of 75.9%.

Conclusions

MCM5 is a novel sensitive and specific biomarker for the detection of ovarian and endometrial tumours in urine samples, which is likely to have clinical utility as a diagnostic aid.
Prevalence of intimate partner violence in Malaysia and its associated factors: a systematic review
Authors: Kadir Shahar Hayati , Jafri Faridah , Mohd Zulkefli Nor Afiah , Ahmad Norliza
Published: October 2020

Background

Intimate partner violence (IPV) is any behaviour within an intimate relationship that causes physical, psychological or sexual harm to those in the relationship. IPV is an important public health problem with substantial consequences on physical, mental, sexual, and reproductive health. Data on the systematic review of IPV are vital as basis for policy and program recommendations. The purpose of this systematic review was to ascertain the prevalence of IPV and its associated factors in Malaysia.

Materials and methods

A systematic review was conducted on published research studies from four databases which included Scopus, Medline, Sage and Google Scholar using keywords of intimate partner violence OR IPV AND associated factors OR risk factors OR protective factors AND Malaysia. Articles included were either cross-sectional, cohort or case-control studies which were published between the year 2005 till present. Excluded articles were the non-Malaysian origin, irrelevant topics being studied and articles not written in English.

Results and discussion

Out of 1983 records identified and screened, five were included for the analysis and interpretation of the data. All of the included studies were of cross-sectional design in which one of the studies was secondary data. IPV prevalence in Malaysia has a wide range between 4.94 and 35.9%. Two studies reported emotional or psychological abuse as the most common form of IPV (13% out of 22%) and (29.8%; CI = [0.27, 0.32]). Significant factors associated with IPV were lower education background, lower socio-economic status, history/ current substance abuse, exposure to prior abuse or violence, violence-condoning attitude; husbands or partners controlling behaviour, substance abuse and involvement in fights and lack of social support.

Conclusion

Specific IPV intervention should focus on lower socio-economic groups, high-risk institutionalised groups, the involvement of partners or husband and addressing issues of substance abuse.
Elevated MTA1 induced the migration and invasion of renal cell carcinoma through the NF-κB pathway
Authors: Lv Cai , Huang Yuan , Lei Qingqing , Liu Zhenxiang , Shen Shixing , Si Wenxia
Published: October 2020

Background

The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC.

Methods

109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65.

Results

Herein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs.

Conclusions

MTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.
How do genes flow? Identifying potential dispersal mode for the semi-aquatic lichen Dermatocarpon luridum using spatial modelling and photobiont markers
Authors: Doering Jennifer A. , Booth Tom , Wiersma Yolanda F. , Piercey-Normore Michele D.
Published: October 2020

Background

Landscape genetics is an interdisciplinary field that combines tools and techniques from population genetics with the spatially explicit principles from landscape ecology. Spatial variation in genotypes is used to test hypotheses about how landscape pattern affects dispersal in a wide range of taxa. Lichens, symbiotic associations between mycobionts and photobionts, are an entity for which little is known about their dispersal mechanism. Our objective was to infer the dispersal mechanism in the semi-aquatic lichenDermatocarpon luridumusing spatial models and the spatial variation of the photobiont,Diplosphaera chodatii. We sequenced the ITS rDNA and the β-actin gene regions of the photobiont and mapped the haplotype spatial distribution in Payuk Lake. We subdivided Payuk Lake into subpopulations and applied four spatial models based on the topography and hydrology to infer the dispersal mechanism.

Results

Genetic variation corresponded with the topography of the lake and the net flow of water through the waterbody. A lack of isolation-by-distance suggests high gene flow or dispersal within the lake. We infer the dispersal mechanism inD. luridumcould either be by wind and/or water based on the haplotype spatial distribution of its photobiont using the ITS rDNA and β-actin markers.

Conclusions

We inferred that the dispersal mechanism could be either wind and/or water dispersed due to the conflicting interpretations of our landscape hypotheses. This is the first study to use spatial modelling to infer dispersal in semi-aquatic lichens. The results of this study may help to understand lichen dispersal within aquatic landscapes, which can have implications in the conservation of rare or threatened lichens.
Impact on place of death in cancer patients: a causal exploration in southern Switzerland
Authors: Kern Heidi , Corani Giorgio , Huber David , Vermes Nicola , Zaffalon Marco , Varini Marco , Wenzel Claudia , Fringer André
Published: October 2020

Background

Most terminally ill cancer patients prefer to die at home, but a majority die in institutional settings. Research questions about this discrepancy have not been fully answered. This study applies artificial intelligence and machine learning techniques to explore the complex network of factors and the cause-effect relationships affecting the place of death, with the ultimate aim of developing policies favouring home-based end-of-life care.

Methods

A data mining algorithm and a causal probabilistic model for data analysis were developed with information derived from expert knowledge that was merged with data from 116 deceased cancer patients in southern Switzerland. This data set was obtained via a retrospective clinical chart review.

Results

Dependencies of disease and treatment-related decisions demonstrate an influence on the place of death of 13%. Anticancer treatment in advanced disease prevents or delays communication about the end of life between oncologists, patients and families. Unknown preferences for the place of death represent a great barrier to a home death. A further barrier is the limited availability of family caregivers for terminal home care. The family’s preference for the last place of care has a high impact on the place of death of 51%, while the influence of the patient’s preference is low, at 14%. Approximately one-third of family systems can be empowered by health care professionals to provide home care through open end-of-life communication and good symptom management. Such intervention has an influence on the place of death of 17%. If families express a convincing preference for home care, the involvement of a specialist palliative home care service can increase the probability of home deaths by 24%.

Conclusion

Concerning death at home, open communication about death and dying is essential. Furthermore, for the patient preference for home care to be respected, the family’s decision for the last place of care seems to be key. The early initiation of family-centred palliative care and the provision of specialist palliative home care for patients who wish to die at home are suggested.
Optimizing of a question prompt list to improve communication about the heart failure trajectory in patients, families, and health care professionals
Authors: Hjelmfors Lisa , van der Wal Martje H. L. , Friedrichsen Maria , Milberg Anna , Mårtensson Jan , Sandgren Anna , Strömberg Anna , Jaarsma Tiny
Published: October 2020

Background

The aim of this study was to optimize a Question Prompt List which is designed to improve communication about the heart failure trajectory among patients, family members, and health care professionals.

Methods

Data were collected in a two-round Delphi survey and a cross-sectional survey, including patients with heart failure, their family members, and health care professionals working in heart failure care in Sweden and the Netherlands. Acceptability for and demand of the Question Prompt List were assessed.

Results

A total of 96 patients, 63 family members and 26 health care professionals participated in the study. Regarding acceptability, most of the original questions were found to be relevant by the participants for inclusion in the Question Prompt List but some cultural differences exist, which resulted in two versions of the list: a Swedish version including 33 questions and a Dutch version including 38 questions. Concerning demand, participants reported that they were interested in discussing the questions in the revised Question Prompt List with a physician or a nurse. Few patients and family members reported that they were worried by the questions in the Question Prompt List and hence did not want to discuss the questions.

Conclusions

This Question Prompt List has successfully been adapted into a Swedish version and a Dutch version and includes questions about the HF trajectory which patients, their families, and health care professionals perceived to be relevant for discussion in clinical practice. Overall, patients and family members were not worried about the content in the Question Prompt List and if used in accordance with patients’ and family members’ preferences, the Question Prompt List can help to improve communication about the heart failure trajectory.
The social paradoxes of commercial surrogacy in developing countries: India before the new law of 2018
Authors: Rozée Virginie , Unisa Sayeed , de La Rochebrochard Elise
Published: October 2020

Background

Commercial surrogacy is a highly controversial issue that leads to heated debates in the feminist literature, especially when surrogacy takes place in developing countries and when it is performed by local women for wealthy international individuals. The objective of this article is to confront common assumptions with the narratives and experiences described by Indian surrogates themselves.

Methods

This qualitative study included 33 surrogates interviewed in India (Mumbai, Chennai and New Delhi) who were at different stages of the surrogacy process. They were recruited through five clinics and agencies. This 2-year field study was conducted before the 2018 surrogacy law.

Results

Surrogates met the criteria fixed by the national guidelines in terms of age and marital and family situation. The commitment to surrogacy had generally been decided with the husband. Its aim was above all to improve the socioeconomic condition of the family. Women described surrogacy as offering better conditions than their previous paid activity. They had clear views on the child and their work. However, they declared that they faced difficulties and social condemnation as surrogacy is associated with extra-marital relationships. They also described a medical process in which they had no autonomy although they did not express complaints. Overall, surrogates did not portray themselves as vulnerable women and victims, but rather as mothers and spouses taking control of their destiny.

Conclusions

The reality of surrogacy in India embraces antagonistic features that we analyze in this paper as “paradoxes”. First, while women have become surrogates in response to gender constraints as mothers and wives, yet in so doing they have gone against gender norms. Secondly, while surrogacy was socially perceived as dirty work undertaken in order to survive, surrogates used surrogacy as a means to upward mobility for themselves and their children. Finally, while surrogacy was organized to counteract accusations of exploitation, surrogates were under constant domination by the medical system and had no decision-making power in the surrogacy process. This echoes their daily life as women. Although the Indian legal framework has changed, surrogacy still challenges gender norms, particularly in other developing countries where the practice is emerging.
Violence detection explanation via semantic roles embeddings
Authors: Mensa Enrico , Colla Davide , Dalmasso Marco , Giustini Marco , Mamo Carlo , Pitidis Alessio , Radicioni Daniele P.
Published: October 2020

Background

Emergency room reports pose specific challenges to natural language processing techniques. In this setting, violence episodes on women, elderly and children are often under-reported. Categorizing textual descriptions as containing violence-related injuries (V)vs. non-violence-related injuries (NV) is thus a relevant task to the ends of devising alerting mechanisms to track (and prevent) violence episodes.

Methods

We presentViDeS(so dubbed afterViolence Detection System), a system to detect episodes of violence from narrative texts in emergency room reports. It employs a deep neural network for categorizing textual ER reports data, and complements such output by making explicit which elements corroborate the interpretation of the record as reporting about violence-related injuries. To these ends we designed a novel hybrid technique for filling semantic frames that employs distributed representations of terms herein, along with syntactic and semantic information. The system has been validated on real data annotated with two sorts of information: about the presence vs. absence of violence-related injuries, and about some semantic roles that can be interpreted as major cues for violent episodes, such as the agent that committed violence, the victim, the body district involved, etc.. The employed dataset contains over 150K records annotated with class (V,NV) information, and 200 records with finer-grained information on the aforementioned semantic roles.

Results

We used data coming from an Italian branch of the EU-Injury Database (EU-IDB) project, compiled by hospital staff. Categorization figures approach full precision and recall for negative cases and.97 precision and.94 recall on positive cases. As regards as the recognition of semantic roles, we recorded an accuracy varying from.28 to.90 according to the semantic roles involved. Moreover, the system allowed unveiling annotation errors committed by hospital staff.

Conclusions

Explaining systems’ results, so to make their output more comprehensible and convincing, is today necessary for AI systems. Our proposal is to combine distributed and symbolic (frame-like) representations as a possible answer to such pressing request for interpretability. Although presently focused on the medical domain, the proposed methodology is general and, in principle, it can be extended to further application areas and categorization tasks.
Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross-clade protection against different H5N1 viruses in chickens
Authors: Lei Han , Gao Tong , Cen Qianhong , Peng Xiaojue
Published: October 2020

Background

The highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry. The currently available avian influenza H5N1 vaccines for poultry are clade-specific. Therefore, an effective vaccine for preventing and controlling H5N1 viruses belonging to different clades needs to be developed.

Results

Recombinant L. lactis/pNZ8148-Spax-HA was generated, and the influenza virus haemagglutinin (HA) protein of A/Vietnam/1203/2004 (H5N1) was displayed on the surface of Lactococcus lactis (L. lactis). Spax was used as an anchor protein. Chickens vaccinated orally with unadjuvanted L. lactis/pNZ8148-Spax-HA could produce significant humoral and mucosal responses and neutralizing activities against H5N1 viruses belonging to different clades. Importantly, unadjuvanted L. lactis/pNZ8148-Spax-HA conferred cross-clade protection against lethal challenge with different H5N1 viruses in the chicken model.

Conclusion

This study provides insights into the cross-clade protection conferred by unadjuvanted L. lactis/pNZ8148-Spax-HA, and the results might help the establishment of a promising platform for the development of a safe and effective H5N1 cross-clade vaccine for poultry.
Item analysis of the KIDSCREEN-10 using Rasch modelling
Authors: Müller Marianne , Haenni Hoti Andrea
Published: October 2020

Aim

To test the psychometric properties of the KIDSCREEN-10.

Background

It is important to assess mental health and well-being in children for an early detection of psychological problems or hidden morbidities. There is limited knowledge about the psychometric quality of the reduced version of the KIDSCREEN questionnaire with only 10 items.

Methods

Analysis of psychometric properties was done by fitting Rasch models and graphical loglinear Rasch models to data collected in a study on acculturation of primary school children and their teachers in 2017.

Results

The data did not fit a Rasch model but did fit a graphical loglinear Rasch model. There was local dependence for four item pairs and differential item functioning for gender and citizenship.

Conclusions

The KIDSCREEN-10 provides essentially valid measurements of health-related quality of life in children if local dependency and dif ferential item functioning are taken into account. Reliability and targeting were less than satisfactory, especially for certain subgroups but reliability was adequate for most groups.
TAM family receptors in conjunction with MAPK signalling are involved in acquired resistance to PI3Kα inhibition in head and neck squamous cell carcinoma
Authors: Ruicci Kara M. , Meens Jalna , Plantinga Paul , Stecho William , Pinto Nicole , Yoo John , Fung Kevin , MacNeil Danielle , Mymryk Joe S. , Barrett John W. , Howlett Christopher J. , Boutros Paul C. , Ailles Laurie , Nichols Anthony C.
Published: October 2020

Background

Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway is common in many malignancies, including head and neck squamous cell carcinoma (HNSCC). Despite pre-clinical and clinical studies, outcomes from targeting the PI3K pathway have been underwhelming and the development of drug resistance poses a significant barrier to patient treatment. In the present study, we examined mechanisms of acquired resistance to the PI3Kα inhibitor alpelisib (formerly BYL719) in HNSCC cell lines and patient-derived xenografts (PDXs).

Methods

Five unique PDX mouse models and three HNSCC cell lines were used. All cell lines and xenografts underwent genomic characterization prior to study. Serial drug treatment was conducted in vitro and in vivo to develop multiple, clinically-significant models of resistance to alpelisib. We then used reverse phase protein arrays (RPPAs) to profile the expression of proteins in parental and drug-resistant models. Top hits were validated by immunoblotting and immunohistochemistry. Flow cytometric analysis and RNA interference studies were then used to interrogate the molecular mechanisms underlying acquired drug resistance.

Results

Prolonged treatment with alpelisib led to upregulation of TAM family receptor tyrosine kinases TYRO3 and AXL. Importantly, a significant shift in expression of both TYRO3 and AXL to the cell surface was detected in drug-resistant cells. Targeted knockdown of TYRO3 and AXL effectively re-sensitized resistant cells to PI3Kα inhibition. In vivo, resistance to alpelisib emerged following 20–35 days of treatment in all five PDX models. Elevated TYRO3 expression was detected in drug-resistant PDX tissues. Downstream of TYRO3 and AXL, we identified activation of intracellular MAPK signalling. Inhibition of MAPK signalling also re-sensitized drug-resistant cells to alpelisib.

Conclusions

We have identified TYRO3 and AXL receptors to be key mediators of resistance to alpelisib, both in vitro and in vivo. Our findings suggest that pan-TAM inhibition is a promising avenue for combinatorial or second-line therapy alongside PI3Kα inhibition. These findings advance our understanding of the role TAM receptors play in modulating the response of HNSCC to PI3Kα inhibition and suggest a means to prevent, or at least delay, resistance to PI3Kα inhibition in order to improve outcomes for HNSCC patients.
Autosomal recessive polycystic kidney disease: case report of a newborn with rare PKHD1 mutation, rapid renal enlargement and early fatal outcome
Authors: Serra Gregorio , Corsello Giovanni , Antona Vincenzo , D’Alessandro Maria Michela , Cassata Nicola , Cimador Marcello , Giuffrè Mario , Schierz Ingrid Anne Mandy , Piro Ettore
Published: October 2020

Introduction

Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center.

Patient presentation

We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency.

Conclusions

This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.
Frailty, delirium and hospital mortality of older adults admitted to intensive care: the Delirium (Deli) in ICU study
Authors: Sanchez David , Brennan Kathleen , Al Sayfe Masar , Shunker Sharon-Ann , Bogdanoski Tony , Hedges Sonja , Hou Yu Chin , Lynch Joan , Hunt Leanne , Alexandrou Evan , Saxena Manoj , Abel Simon , Lakshmanan Ramanathan , Bhonagiri Deepak , Parr Michael J. , Aneman Anders , Chroinin Danielle Ni , Hillman Kenneth M. , Frost Steven A.
Published: October 2020

Background

Clinical frailty among older adults admitted to intensive care has been proposed as an important determinant of patient outcomes. Among this group of patients, an acute episode of delirium is also common, but its relationship to frailty and increased risk of mortality has not been extensively explored. Therefore, the aim of this study was to explore the relationship between clinical frailty, delirium and hospital mortality of older adults admitted to intensive care.

Methods

This study is part of a Delirium in Intensive Care (Deli) Study. During the initial 6-month baseline period, clinical frailty status on admission to intensive care, among adults aged 50 years or more; acute episodes of delirium; and the outcomes of intensive care and hospital stay were explored.

Results

During the 6-month baseline period, 997 patients, aged 50 years or more, were included in this study. The average age was 71 years (IQR, 63–79); 55% were male (n = 537). Among these patients, 39.2% (95% CI 36.1–42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more, and 13.0% (n = 127) had at least one acute episode of delirium. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted rate ratio (adjRR) = 1.71, 95% confidence interval (CI) 1.20–2.43, p = 0.003), had a longer hospital stay (2.6 days, 95% CI 1–7 days, p = 0.009) and had a higher risk of hospital mortality (19% versus 7%, adjRR = 2.54, 95% CI 1.72–3.75, p < 0.001), when compared to non-frail patients. Patients who were frail and experienced an acute episode of delirium in the intensive care had a 35% rate of hospital mortality versus 10% among non-frail patients who also experienced delirium in the ICU.

Conclusion

Frailty and delirium significantly increase the risk of hospital mortality. Therefore, it is important to identify patients who are frail and institute measures to reduce the risk of adverse events in the ICU such as delirium and, importantly, to discuss these issues in an open and empathetic way with the patient and their families.
Inter-tumor genomic heterogeneity of breast cancers: comprehensive genomic profile of primary early breast cancers and relapses
Authors: Fumagalli Caterina , Ranghiero Alberto , Gandini Sara , Corso Federica , Taormina Sergio , De Camilli Elisa , Rappa Alessandra , Vacirca Davide , Viale Giuseppe , Guerini-Rocco Elena , Barberis Massimo
Published: October 2020

Background

The breast cancer genome dynamically evolves during malignant progression and recurrence. We investigated the genomic profiles of primary early-stage breast cancers and matched relapses to elucidate the molecular underpinnings of the metastatic process, focusing on potentially actionable alterations in the recurrences.

Methods

A mono-institutional cohort of 128 patients with breast cancers (n = 68 luminal B HER2, n = 6 luminal B HER2+, n = 1 HER2+ non-luminal, n = 56 triple negative) and at least one recurrence in a timeframe of 17 years was evaluated. Next-generation sequencing comprehensive genomic profiling was performed on 289 formalin-fixed paraffin-embedded (FFPE) samples, including primary tumors and matched relapses. Correlations of genomic aberrations with clinicopathologic factors and time to breast cancer relapse were analyzed.

Results

Genomic data were available for 188 of 289 FFPE samples that achieved the sequencing quality parameters (failure rate 34.9%), including 106 primary tumors and 82 relapses. All primary and relapse samples harbored at least one genomic alteration, with a median number of six alterations per sample (range 1–16). The most frequent somatic genomic alterations were mutations of TP53 (primary tumors = 49%, relapses = 49%) and PIK3CA (primary tumors = 33%, relapses = 30%). Distinctive genomic alterations of primary tumors were significantly associated with molecular subtypes. TP53, PIK3R1, and NF1 somatic alterations were more frequently detected in triple negative tumors (p value < 0.05); CCND1, FGF3, and FGFR1 copy number gains were recurrently identified in luminal cases (p value < 0.05). Moreover, TP53 mutations and MYC amplification were significantly and independently associated with a shorter time to relapse (p value < 0.05). Molecular subtype changes between primary tumors and relapses were seen in 10 of 128 (7.8%) cases. Most driver genomic alterations (55.8%) were shared between primary tumors and matched recurrences. However, in 39 of 61 cases (63.9%), additional private alterations were detected in the relapse samples only, including 12 patients with potentially actionable aberrations.

Conclusions

Specific genomic aberrations of primary breast cancers were associated with time to relapse. Primary tumors and matched recurrences showed a core of shared driver genomic aberrations but private actionable alterations have been identified in the relapses.
Use of ICD-10 diagnosis codes to identify seropositive and seronegative rheumatoid arthritis when lab results are not available
Authors: Curtis Jeffrey R. , Xie Fenglong , Zhou Hong , Salchert David , Yun Huifeng
Published: October 2020

Background

Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody tests are often measured at the time of rheumatoid arthritis (RA) diagnosis but may not be repeated and therefore not available in electronic health record (EHR) data; lab test results are unavailable in most administrative claims databases. ICD10 coding allows discrimination between rheumatoid factor positive (M05) (“seropositive”) and seronegative (M06) patients, but the validity of these codes has not been examined.

Methods

Using the ACR’s Rheumatology Informatics System for Effectiveness (RISE) EHR-based registry and U.S. MarketScan data where some patients have lab test results, we assembled two cohorts. Seropositive RA was defined having a M05 diagnosis code on the second rheumatologist encounter, M06 similarly identified seronegative RA, and RF and anti-CCP lab test results were the gold standard. We calculated sensitivity (Se) and positive predicted value (PPV) of the M05/M06 diagnosis codes.

Results

We identified 43,581 eligible RA patients (RISE) and 1185 (MarketScan) with RF or anti-CCP lab test results available. Using M05 as the proxy for seropositive RA, sensitivity = 0.76, PPV = 0.82 in RISE, and Se = 0.73, PPV = 0.84 in MarketScan. Results for M06 as a proxy for seronegative RA were comparable in RISE, albeit somewhat lower in MarketScan. Over 3 consecutive visits, approximately 90% of RA patients were coded consistently using either M05 or M06 at each visit.

Conclusion

Under ICD10, M05 and M06 diagnosis codes are reasonable proxies to identify seropositive and seronegative RA with high sensitivity and positive predictive values if lab test results are not available.
Persistent left superior vena cava: clinical importance and differential diagnoses
Authors: Azizova Aynur , Onder Omer , Arslan Sevtap , Ardali Selin , Hazirolan Tuncay
Published: October 2020

Persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly and may be a component of the complex cardiac pathologies. While it is often asymptomatic, it can lead to significant problems such as arrhythmias and cyanosis. Besides, it can cause serious complications during vascular interventional procedures or the surgical treatment of cardiac anomalies (CA). The clinical significance of PLSVC depends on the drainage site and the accompanying CA. In this article, we will describe the epidemiology, embryology, and anatomic variations of PLSVC. Possible accompanying CA and heterotaxy spectrum will be reviewed with the help of multidetector computed tomography (MDCT) images. Radiological pitfalls, differential diagnoses, and the clinical importance of PLSVC will be highlighted.
Research on sports fitness management based on blockchain and Internet of Things
Authors: Shan Yu , Mai Yuehui
Published: October 2020

The amount of exercise and fitness level of sports athletes can be quantitatively evaluated through the measurement of health and sports information, thereby ensuring effective fitness effects. The development of blockchain and Internet of Things technology provides a new perspective and technical means for fitness management technology. In view of the current problems in the field of sports fitness, this paper designs and implements a dynamic management technology for sports fitness based on the concept of Internet of Things and blockchain. First, based on an in-depth analysis of the current status of theoretical research and application of the Internet of health at home and abroad, the theories and methods of sports information and health information collection are studied. A temperature sensor and an acceleration sensor are used to collect human body temperature and exercise steps, respectively, and then estimate human health and exercise conditions. Second, solve the privacy problem in the collection and transmission of the Internet of Things by adding blockchain technology. Finally, the machine-learning method is used to clean and manage the information and data to realize the real-time detection and management of the athlete’s fitness status. The actual case test shows that the functions and technical performance indicators of the dynamic fitness management technology can meet the needs of users in indoor and outdoor fitness management, and promote the development of the sports industry and provide a scientific reference.
Goal-directed haemodynamic therapy (GDHT) in surgical patients: systematic review and meta-analysis of the impact of GDHT on post-operative pulmonary complications
Authors: Dushianthan Ahilanandan , Knight Martin , Russell Peter , Grocott Michael PW
Published: October 2020

Background

Perioperative goal-directed haemodynamic therapy (GDHT), defined as the administration of fluids with or without inotropes or vasoactive agents against explicit measured goals to augment blood flow, has been evaluated in many randomised controlled trials (RCTs) over the past four decades. Reported post-operative pulmonary complications commonly include chest infection or pneumonia, atelectasis, acute respiratory distress syndrome or acute lung injury, aspiration pneumonitis, pulmonary embolism, and pulmonary oedema. Despite the substantial clinical literature in this area, it remains unclear whether their incidence is reduced by GDHT. This systematic review aims to determine the effect of GDHT on the respiratory outcomes listed above, in surgical patients.

Methods

We searched the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, EMBASE, and clinical trial registries up until January 2020. We included all RCTs reporting pulmonary outcomes. The primary outcome was post-operative pulmonary complications and secondary outcomes were specific pulmonary complications and intra-operative fluid input. Data synthesis was performed on Review Manager and heterogeneity was assessed using I2 statistics.

Results

We identified 66 studies with 9548 participants reporting pulmonary complications. GDHT resulted in a significant reduction in total pulmonary complications (OR 0.74, 95% CI 0.59 to 0.92). The incidence of pulmonary infections, reported in 45 studies with 6969 participants, was significantly lower in the GDHT group (OR 0.72, CI 0.60 to 0.86). Pulmonary oedema was recorded in 23 studies with 3205 participants and was less common in the GDHT group (OR 0.47, CI 0.30 to 0.73). There were no differences in the incidences of pulmonary embolism or acute respiratory distress syndrome. Sub-group analyses demonstrated: (i) benefit from GDHT in general/abdominal/mixed and cardiothoracic surgery but not in orthopaedic or vascular surgery; and (ii) benefit from fluids with inotropes and/or vasopressors in combination but not from fluids alone. Overall, the GDHT group received more colloid (+280 ml) and less crystalloid (−375 ml) solutions than the control group. Due to clinical and statistical heterogeneity, we downgraded this evidence to moderate.

Conclusions

This systematic review and meta-analysis suggests that the use of GDHT using fluids with inotropes and/or vasopressors, but not fluids alone, reduces the development of post-operative pulmonary infections and pulmonary oedema in general, abdominal and cardiothoracic surgical patients. This evidence was graded as moderate.

PROSPERO registry reference: CRD42020170361
A miR-182 variant and risk of hepatocellular carcinoma in a southern Chinese population
Authors: Qiu Moqin , Liu Yingchun , Lin Qiuling , Zhou Zihan , Jiang Yanji , Huo Rongrui , Liang Xiumei , Yu Xiangyuan , Cao Ji , Zhou Xianguo , Yu Hongping
Published: October 2020

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the posttranscriptional level and are involved in human carcinogenesis. The aim of the current study was to investigate the associations between miR-182 single nucleotide polymorphisms and HCC risk in a southern Chinese population. In this case-control study of 863 HCC patients and 908 cancer-free controls, we performed genotyping of miR-182 rs4541843 and assessed its association with HCC risk. We found that individuals carrying the AG/AA genotypes of miR-182 rs4541843 were significantly associated with an increased risk of HCC compared with those carrying the GG genotype (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.07–2.76, P = 0.026). In the stratified analysis, this increased risk was more pronounced in the subgroups of older individuals (adjusted OR = 1.98, 95% CI = 1.04–3.76, P = 0.037), males (adjusted OR = 1.81, 95% CI = 1.09–2.99, P = 0.021), and never drinkers (adjusted OR = 1.84, 95% CI = 1.03–3.30, P = 0.041). Our results suggested that miR-182 polymorphism rs4541843 may contribute to the susceptibility to HCC. Our findings require validation in further studies with larger sample sizes.
Dipolar elementary current systems for ionospheric current reconstruction at low and middle latitudes
Authors: Vanhamäki Heikki , Maute Astrid , Alken Patrick , Liu Huixin
Published: October 2020

The technique of spherical elementary current systems (SECS) is a powerful way to determine ionospheric and field-aligned currents (FAC) from magnetic field measurements made by low-Earth-orbiting satellites, possibly in combination with magnetometer arrays on the ground. The SECS method consists of two sets of basis functions for the ionospheric currents: divergence-free (DF) and curl-free (CF) components, which produce poloidal and toroidal magnetic fields, respectively. The original CF SECS are only applicable at high latitudes, as they build on the assumption that the FAC flow radially into or out of the ionosphere. The FAC at low and middle latitudes are far from radial, which renders the method inapplicable at these latitudes. In this study, we modify the original CF SECS by including FAC that flow along dipolar field lines. This allows the method to be applied at all latitudes. We name this method dipolar elementary current systems (DECS). Application of the DECS to synthetic data, as well as Swarm satellite measurements are carried out, demonstrating the good performance of this method, and its applicability to studies of ionospheric current systems at low and middle latitudes.
Locomotion approach of bipedal robot utilizing passive wheel without swing leg based on stability margin maximization and fall prevention functions
Authors: Kimura Kohei , Imaoka Noriaki , Noda Shintaro , Kakiuchi Yohei , Okada Kei , Inaba Masayuki
Published: October 2020

This paper proposes a locomotion approach of leg-wheel robot utilizing passive wheel attached to the foot of bipedal robot. The key feature of this approach is bipedal mobility without swing leg. This mobility contributes the stability based on expansion of support polygon during locomotion, the robustness for obstacles and stopping to prevent fall, and the adaptability by prevention of body swing sideways. To achieve these, we propose the stability margin maximization to optimize center of gravity projection for support polygon and the fall prevention functions for real environment that is a difficult situation to prevent unexpected fall by the only planning. Finally, we apply the proposed methods to leg-wheel phases through locomotion and verify the contribution by experiments using real bipedal robot.