bluuebunny/crossref_metadata_2025 huggingface dataset:
Ribociclib enhances infigratinib‐induced cancer cell differentiation and delays resistance in FGFR‐driven hepatocellular carcinoma
Authors: Prawira Aldo , Le Thi Bich Uyen , Vu Thanh Chung , Huynh Hung
Published: November 2020

Background & Aims

Infigratinib is a pan‐FGFR (fibroblast growth factor receptor) inhibitor that has shown encouraging activity in FGFR‐dependent hepatocellular carcinoma (HCC) models. However, long‐term treatment results in the emergence of resistant colonies. We sought to understand the mechanisms behind infigratinib‐induced tumour cell differentiation and resistance and to explore the potential of adding the CDK4/6 inhibitor ribociclib to prolong cell differentiation.

Methods

Nine high and three low FGFR1‐3‐expressing HCC patient‐derived xenograft (PDX) tumours were subcutaneously implanted into SCID mice and subsequently treated with either infigratinib alone or in combination with ribociclib. Tumour tissues were then subjected to immunohistochemistry to assess cell differentiation, as indicated by the cytoplasmic‐to‐nuclear ratio and markers such as CYP3A4, HNF4α and albumin. Western blot analyses were performed to investigate the signalling pathways involved.

Results

Infigratinib induced cell differentiation in FGFR1‐3‐dependent HCC PDX models, as indicated by an increase in the cytoplasmic/nuclear ratio and an increase in CYP3A4, HNF4α and albumin. Resistant colonies emerged in long‐term treatment, characterised by a reversal of differentiated cell morphology, a reduction in the cytoplasmic‐to‐nuclear ratio and a loss of differentiation markers. Western blot analyses identified an increase in the CDK4/Cdc2/Rb pathway. The addition of ribociclib effectively blocked this pathway and reversed resistance to infigratinib, resulting in prolonged cell differentiation and growth inhibition.

Conclusions

Our findings demonstrate that the combined inhibition of FGFR/CDK4/6 pathways is highly effective in providing long‐lasting tumour growth inhibition and cell differentiation and reducing drug resistance. Therefore, further clinical investigations in patients with FGFR1‐3‐dependant HCC are warranted.
Maintenance of normal fusion in intermittent exotropia
Authors: Ma Martin Ming‐Leung , Kang Ying , Scheiman Mitchell , Chen Qiwen , Ye Xuelian , Chen Xiang
Published: November 2020

Purpose

To evaluate the reliability of the Bagolini filter bar and striated lenses for measuring the fusion maintenance score, which is the ability of participants with intermittent exotropia to maintain normal sensorimotor fusion.

Methods

Thirty‐two Chinese participants aged 7–20 years with intermittent exotropia (excluding the convergence insufficiency type) were enrolled in this prospective study. At the eligibility screening, visual acuity, cover test and assessment of the office control score were performed. At study visit 1, eligible participants underwent negative and positive fusional vergence tests at far and near, eye dominance test and the fusion maintenance test. All eligible participants returned for study visit 2 on the same day (2–4 h later) and the testing was repeated. The primary outcome measure was the intra‐class correlation coefficient of the fusion maintenance score between the two study visits.

Results

The intra‐class correlation coefficient of the fusion maintenance score was 0.84, indicating good reliability. There was no significant difference (mean difference = 0.05, p = 0.95) between the fusion maintenance scores for the first (5.62) and second study visits (5.57). The coefficient of repeatability and the smallest detectable change for the fusion maintenance scores were 7.6 and 6.3, respectively. The fusion maintenance score was significantly associated with the distance (Spearman correlation −0.57, p < 0.001) and near (Spearman correlation −0.4, p = 0.02) office control scores.

Conclusion

These data demonstrate that the fusion maintenance score is a reliable tool to evaluate sensorimotor fusion in intermittent exotropia. These results suggest that the fusion maintenance score may be a useful outcome measure in future clinical trials to evaluate the effectiveness of treatments for intermittent exotropia.
Naturally occurring circadian rhythm variation associated with clock gene loci in Swedish Arabidopsis accessions
Authors: Rees Hannah , Joynson Ryan , Brown James K. M. , Hall Anthony
Published: November 2020

Circadian clocks have evolved to resonate with external day and night cycles. However, these entrainment signals are not consistent everywhere and vary with latitude, climate and seasonality. This leads to divergent selection for clocks which are locally adapted. To investigate the genetic basis for this circadian variation, we used a delayed fluorescence imaging assay to screen 191 naturally occurring Swedish Arabidopsis accessions for their circadian phenotypes. We demonstrate that the period length co‐varies with both geography and population sub‐structure. Several candidate loci linked to period, phase and relative amplitude error (RAE) were revealed by genome‐wide association mapping and candidate genes were investigated using TDNA mutants. We show that natural variation in a single non‐synonymous substitution within COR28 is associated with a long‐period and late‐flowering phenotype similar to that seen in TDNA knock‐out mutants. COR28 is a known coordinator of flowering time, freezing tolerance and the circadian clock; all of which may form selective pressure gradients across Sweden. We demonstrate the effect of the COR28‐58S SNP in increasing period length through a co‐segregation analysis. Finally, we show that period phenotypic tails remain diverged under lower temperatures and follow a distinctive “arrow‐shaped” trend indicative of selection for a cold‐biased temperature compensation response.
Neural and self‐reported reward responsiveness are associated with dispositional affectivity and emotion dysregulation in adolescents with evidence for convergent and incremental validity
Authors: Zubovics Evelin A. , Fiáth Richárd , Rádosi Alexandra , Pászthy Bea , Réthelyi János M. , Ulbert István , Bunford Nóra
Published: November 2020

Adolescence is a developmental period characterized by heightened reward sensitivity which, in turn, confers risk for pertinent negative outcomes, underscoring the need to better understand biological bases and behavioral correlates of reward responsiveness during this developmental phase. Our goals in the current study were to examine, in a sample of 43 typically developing adolescents (Mage = 15.67 years; SD = 1.01; 32.6% boys), (1) evidence of convergent validity between neural and self‐report reward responsiveness, (2) associations between neural reward responsiveness and self‐report dispositional affectivity and emotion dysregulation (ED) and (3) evidence of incremental validity of self‐report beyond neural reward responsiveness in predicting affectivity and ED. During electroencephalography (EEG), adolescents completed two experimental paradigms probing event‐related potential (ERP) indices of reward anticipation and initial responsiveness to reward attainment. Following EEG, they completed self‐report measures of reward responsiveness, affectivity, and ED. Findings indicated some evidence of convergent validity between enhanced ERP indices of reward anticipation and initial response to reward and greater reinforcement sensitivity; that ERP indices of both reward responsiveness aspects predicted lower negative affectivity and less ED; and evidence of incremental validity of self‐report beyond neural reward responsiveness in predicting outcomes. Results underscore the utility of a multi‐method framework in assessing adolescent reward responsiveness and support the relevance of reward responsiveness in explaining individual differences in dispositional affectivity and ED.
Phylogenetics, historical biogeography and molecular species delimitation of Gnaptorina Reitter (Coleoptera: Tenebrionidae: Blaptini)
Authors: Li Xiu‐Min , Bai Xing‐Long , Kergoat Gael J. , Pan Zhao , Ren Guo‐Dong
Published: November 2020

With 38 described species or subspecies, Gnaptorina Reitter is the second‐most species‐rich genus in the darkling beetle subtribe Gnaptorinina (Tenebrionidae: Tenebrioninae). In this study, we reconstructed a phylogeny of the genus based on one nuclear and three mitochondrial genes and used this phylogeny to explore the historical biography and diversification of Gnaptorina species. We implemented multiple molecular species delimitation approaches to reassess the status of Gnaptorina species and taxonomic subdivisions of the genus. Dating and historical biogeography analyses suggest an early Eocene origin of the genus, with the southeastern regions of the Tibetan Plateau most likely as areas of origin. Based on these results, we propose a new classification for Gnaptorina with three major clades identified. Consequently, the monotypic subgenus Boreoptorina is newly synonymized with the more species‐rich subgenus Hesperoptorina, and G. dongdashanensis Shi is transferred from Hesperoptorina to the subgenus Gnaptorina. In addition, G. minxiana Medvedev, formerly treated as a subspecies of G. potanini Reitter, is elevated to species. Results of molecular species delimitation analyses are largely congruent and confirm the status of most morphological species.
Evolutionary expansion and functional divergence of sugar transporters in Saccharum (S. spontaneum and S. officinarum)
Authors: Zhang Qing , Hua Xiuting , Liu Hong , Yuan Yuan , Shi Yan , Wang Zhengchao , Zhang Muqing , Ming Ray , Zhang Jisen
Published: November 2020

The sugar transporter (ST) family is considered to be the most important gene family for sugar accumulation, but limited information about the ST family in the important sugar‐yielding crop Saccharum is available due to its complex genetic background. Here, 105 ST genes were identified and clustered into eight subfamilies in Saccharum spontaneum. Comparative genomics revealed that tandem duplication events contributed to ST gene expansions of two subfamilies, PLT and STP, in S. spontaneum, indicating an early evolutionary step towards high sugar content in Saccharum. The analyses of expression patterns were based on four large datasets with a total of 226 RNA sequencing samples from S. spontaneum and Saccharum officinarum. The results clearly demonstrated 50 ST genes had different spatiotemporal expression patterns in leaf tissues, 10 STs were specifically expressed in the stem, and 10 STs responded to the diurnal rhythm. Heterologous expression experiments in the defective yeast strain EBY.VW4000 indicated STP13, pGlcT2, VGT3, and TMT4 are the STs with most affinity for glucose/fructose and SUT1_T1 has the highest affinity to sucrose. Furthermore, metabolomics analysis suggested STP7 is a sugar starvation‐induced gene and STP13 has a function in retrieving sugar in senescent tissues. PLT11, PLT11_T1, TMT3, and TMT4 contributed to breaking the limitations of the storage sink. SUT1, SUT1_T1, PLT11, TMT4, pGlcT2, and VGT3 responded for different functions in these two Saccharum species. This study demonstrated the evolutionary expansion and functional divergence of the ST gene family and will enable the further investigation of the molecular mechanism of sugar metabolism in Saccharum.
Historical biogeography of Heteropterinae skippers via Beringian and post‐Tethyan corridors
Authors: Toussaint Emmanuel F. A. , Ellis Emily A. , Gott Riley J. , Warren Andrew D. , Dexter Kelly M. , Storer Caroline , Lohman David J. , Kawahara Akito Y.
Published: November 2020

Skippers are a species rich and widespread group of butterflies with evolutionary patterns and processes largely unstudied despite some recent efforts. Among Hesperiidae, the subfamily Heteropterinae is a moderately diverse clade comprising ca. 200 species distributed from North to South America and from Africa to the Palearctic region. While some regions are species rich, others are far less diverse. Using anchored phylogenomics, we infer a robust timetree and estimate ancestral ranges to understand the biogeographic history of these skippers. Inferences based on up to 383 exons recover a robust backbone for the subfamily along with the monophyly of all genera. Bayesian divergence time estimates suggest an origin of Heteropterinae in the late Eocene, ca. 40 million years ago. Maximum likelihood ancestral range estimates indicate an origin of the group in the New World. The eastern Palearctic was likely colonized via a Beringian route and a reverse colonization event resulted in two independent and extant American clades. We estimate a vicariant event between Central and South America that significantly predates estimates of the proto‐Caribbean seaway closure, indicating active overwater dispersal in the Oligocene. The colonization of Africa from the east Palearctic is synchronous with the closure of the Tethys Ocean, while the colonization of Madagascar appears to be comparatively recent. Our results shed light on the systematics and biogeography of Heteropterinae skippers and unveil the evolutionary history of a new leaf in the skipper tree‐of‐life.
Pelvic Response of a Total Human Body Finite Element Model During Simulated Injurious Under Body Blast Impacts
Authors: Weaver Caitlin M. , Guleyupoglu Berkan , Miller Anna N. , Kleinberger Michael , Stitzel Joel D.
Published: November 2020

Military operations in Iraq and Afghanistan have resulted in the increased exposure of military personnel to explosive threats. Combat-related pelvic fractures are a relatively new battlefield injury that poses a serious threat to military personnel. Injury prediction for these events continues to be a challenge due to the limited availability of blast-specific test studies and the use of established automotive-based injury criteria that do not directly translate to combat-related exposures. The objective of this study is to evaluate the pelvic response of the global human body models consortium (GHBMC) 50th percentile detailed male model (v4.3) in under body blast (UBB) loading scenarios. Nine simulations were conducted with mild or enhanced threat levels, and nominal or obtuse occupant positions. Cross-sectional force outputs from the superior pubic ramus (SPR), ilium, and sacroiliac (SI) regions were evaluated using previously developed injury risk curves (IRC). Additionally, maximum principal strain (MPS) data were extracted from the pelvic cortical bone elements. Results showed that shear force was the best predictor of fracture for the ischial and SI regions, while axial force was the best predictor for the SPR region. These outcomes were consistent with the load path of the simulated UBB events. The obtuse posture had higher peak force values for injurious and noninjurious outcomes for the SPR and SI region. The nominal posture had higher peak force values for noninjurious outcomes in the ischial region. These outcomes were supported by the MPS response present in these postures.
What's next for COVID-19 apps? Governance and oversight
Authors: Blasimme Alessandro , Vayena Effy
Published: November 2020

Adaptive governance can help earn social license
Cooling our insatiable demand for data
Authors: Fleischer Amy S.
Published: November 2020

Hyperscale data centers provide challenges and opportunities for energy use
Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma
Authors: Stokholm Jakob , Thorsen Jonathan , Blaser Martin J. , Rasmussen Morten A. , Hjelmsø Mathis , Shah Shiraz , Christensen Emil D. , Chawes Bo L. , Bønnelykke Klaus , Brix Susanne , Mortensen Martin S. , Brejnrod Asker , Vestergaard Gisle , Trivedi Urvish , Sørensen Søren J. , Bisgaard Hans
Published: November 2020

Cesarean section delivery is associated with gut microbiota differences and an increased risk of asthma by age six.
MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates
Authors: Hordeaux Juliette , Buza Elizabeth L. , Jeffrey Brianne , Song Chunjuan , Jahan Tahsin , Yuan Yuan , Zhu Yanqing , Bell Peter , Li Mingyao , Chichester Jessica A. , Calcedo Roberto , Wilson James M.
Published: November 2020

Inhibiting transgene expression with a tissue-specific microRNA target ameliorates AAV vector toxicity in NHPs.
Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens
Authors: Pybus Christine A. , Felder-Scott Christina , Obuekwe Victor , Greenberg David E.
Published: November 2020

Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane.
Population Pharmacokinetics and Pharmacodynamics of Meropenem in Critically Ill Pediatric Patients
Authors: Saito Jumpei , Shoji Kensuke , Oho Yusuke , Kato Hiroki , Matsumoto Shotaro , Aoki Satoshi , Nakamura Hidefumi , Ogawa Takanori , Hasegawa Mayumi , Yamatani Akimasa , Miyairi Isao
Published: November 2020

This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM.
Deep Gene Sequence Cluster Analyses of Multi-Virus-Infected Mucosal Tissue Reveal Enhanced Transmission of Acute HIV-1
Authors: Klein Katja , Nankya Immaculate , Nickel Gabrielle , Ratcliff Annette N. , Meadows Adam A. J. , Hathaway Nicholas , Bailey Jeffrey A. , Stieh Daniel J. , Cheeseman Hannah M. , Carias Ann M. , Lobritz Michael A. , Mann Jamie F. S. , Gao Yong , Hope Thomas J. , Shattock Robin J. , Arts Eric J.
Published: November 2020

During heterosexual HIV-1 transmission, a genetic bottleneck occurs in the newly infected individual as the virus passes from the mucosa, leading to systemic infection with a single transmitted HIV-1 clone in the recipient. This bottleneck in the recipient has just been described, and the mechanisms involved in this selection process have not been elucidated.
Influenza Virus Neuraminidase Engages CD83 and Promotes Pulmonary Injury
Authors: Ma Ning , Li Xingjie , Jiang Hongyu , Dai Yulong , Xu Guofeng , Zhang Zongde
Published: November 2020

The massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon is referred to as the “cytokine storm.” However, the mechanism by which influenza induces the cytokine storm is not fully understood.
Haemophagocytic lymphohistiocytosis that spontaneously resolved: a case of EBV
Authors: Chahine Zena , Jayakrishnan Thejus , Samhouri Yazan , Fazal Salman
Published: November 2020

A 23-year-old Caucasian woman, presented with recurrent fevers, elevated liver function tests and pancytopenia. Her labs at presentation were white blood cells 1.5 ×109/L, haemoglobin 8 g/L, platelets 59 k/mcl, lactate dehydrogenase (LDH) over 2000 U/L, aspartate aminotransferase 593 U/L, alanine aminotransferase 1321 U/L, alkaline phosphatase 223 U/L and ferritin 7665 µg/L. Epstein-Barr virus (EBV) IgM and IgG antibodies were positive in serum. A soluble interleukin 2 receptor was elevated at 2458. A bone marrow biopsy revealed scattered macrophages containing erythrocytes and other cellular elements. Immunohistochemistry for CD68 highlighted macrophages with erythrophagocytosis and in situ hybridisation was positive for EBV. She met the diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH). She was initially treated with broad spectrum antibiotics which were eventually discontinued once the diagnosis was established. Over a period of 2–3 weeks her fever, transaminitis, ferritin and LDH improved spontaneously. She continued to improve clinically and was subsequently discharged. HLH is an aggressive, life-threatening hyper-inflammatory syndrome which, if not promptly recognised and treated, can be fatal. Treatment involves etoposide-based chemotherapy and possible stem-cell transplantation. This patient showed signs of improvement spontaneously and a decision was made to not treat her. This was a rare case of EBV-associated HLH which resolved spontaneously without any intervention. This young patient was not subjected to unnecessary chemotherapy. So far only few cases of spontaneous resolution of EBV-associated HLH have been reported.
Reduction in healthcare services during the COVID-19 pandemic in China
Authors: Zhang Yi-Na , Chen Yun , Wang Ying , Li Fan , Pender Michelle , Wang Na , Yan Fei , Ying Xiao-Hua , Tang Sheng-Lan , Fu Chao-Wei
Published: November 2020

Introduction

The COVID-19 pandemic caused a healthcare crisis in China and continues to wreak havoc across the world. This paper evaluated COVID-19’s impact on national and regional healthcare service utilisation and expenditure in China.

Methods

Using a big data approach, we collected data from 300 million bank card transactions to measure individual healthcare expenditure and utilisation in mainland China. Since the outbreak coincided with the 2020 Chinese Spring Festival holiday, a difference-in-difference (DID) method was employed to compare changes in healthcare utilisation before, during and after the Spring Festival in 2020 and 2019. We also tracked healthcare utilisation before, during and after the outbreak.

Results

Healthcare utilisation declined overall, especially during the post-festival period in 2020. Total healthcare expenditure and utilisation declined by 37.8% and 40.8%, respectively, while per capita expenditure increased by 3.3%. In a subgroup analysis, we found that the outbreak had a greater impact on healthcare utilisation in cities at higher risk of COVID-19, with stricter lockdown measures and those located in the western region. The DID results suggest that, compared with low-risk cities, the pandemic induced a 14.8%, 26.4% and 27.5% reduction in total healthcare expenditure in medium-risk and high-risk cities, and in cities located in Hubei province during the post-festival period in 2020 relative to 2019, an 8.6%, 15.9% and 24.4% reduction in utilisation services; and a 7.3% and 18.4% reduction in per capita expenditure in medium-risk and high-risk cities, respectively. By the last week of April 2020, as the outbreak came under control, healthcare utilisation gradually recovered, but only to 79.9%–89.3% of its pre-outbreak levels.

Conclusion

The COVID-19 pandemic had a significantly negative effect on healthcare utilisation in China, evident by a dramatic decline in healthcare expenditure. While the utilisation level has gradually increased post-outbreak, it has yet to return to normal levels.
Treatment with the anti-IgE monoclonal antibody omalizumab in women with asthma undergoing fertility treatment: a proof-of-concept study—The PRO-ART study protocol
Authors: Tidemandsen Casper , Juul Gade Elisabeth , Ulrik Charlotte Suppli , Nielsen Henriette Svarre , Oxlund-Mariegaard Birgitte Sophie , Kristiansen Karsten , Freiesleben Nina La Cour , Nøhr Bugge , Udengaard Hanne , Backer Vibeke
Published: November 2020

Introduction

Asthma is associated with prolonged time to pregnancy and a higher need for fertility treatment. However, the mechanism underlying this association remains incompletely understood. Previous research points to asthma-driven systemic inflammation also affecting the reproductive organs and thereby fertility. The aim of this study was to determine if treatment with omalizumab prior to fertility treatment will increase pregnancy rate among women with asthma by decreasing the systemic asthma-related inflammation and, by that, to provide insight into the underlying mechanisms.

Methods and analysis

This is an ongoing prospective multicentre randomised controlled trial planned to enrol 180 women with asthma recruited from fertility clinics in Denmark. The patients are randomised 1:1 to either omalizumab or placebo. The primary endpoint is the difference in pregnancy rate confirmed with ultrasound at gestational week 7 of pregnancy. The secondary endpoints are change in sputum and blood eosinophil cell count, change in biomarkers, change in microbiota, together with rate of pregnancy loss, frequency of malformations, pre-eclampsia, preterm birth, birth weight, small for gestational age and perinatal death between groups.

Ethics and dissemination

The methods used in this study are of low risk, but if successful, our findings will have a large impact on a large group of patients as infertility and asthma are the most common chronic diseases among the young population. The study has been approved by the Ethics Committee–Danish national research ethics committee (H-18016605) and the Danish Medicines Agency (EudraCT no: 2018-001137-41) and the Danish Data Protection Agency (journal number: VD-2018486 and I-Suite number 6745). The test results will be published regardless of whether they are positive, negative or inconclusive. Publication in international peer-reviewed scientific journals is planned.

Trial registration number

NCT03727971.
Translating the Symptom Screening in Paediatrics Tool (SSPedi) into North American Spanish and Among Spanish-speaking children receiving cancer treatments: evaluating understandability and cultural relevance in a multiple-phase descriptive study
Authors: Plenert Erin , Grimes Allison , Sugalski Aaron , Langevin Anne-Marie , Nieto Dominica , Salaverria Carmen , Gomez Sergio , Gonzalez Gisela , D'Angelo Gisela , Dupuis Lee , Sung Lillian
Published: November 2020

Objectives

Symptom screening is important to achieving symptom control. Symptom Screening in Paediatrics Tool (SSPedi) is validated for English-speaking children. Objectives were to translate SSPedi into Spanish, and to evaluate the understandability and cultural relevance of the translated version among Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplant recipients.

Methods

We conducted a multiphase, descriptive study to translate SSPedi into Spanish. The first step was to determine whether one Spanish version would be appropriate for both North America and Argentina. Once this decision was made, forward and backward translations were performed. The translated version was evaluated by Spanish-speaking children 8–18 years of age receiving cancer treatments.

Primary and secondary outcome measures

Primary outcome was child self-reported difficulty with understanding of the entire instrument and each symptom using a 5-point Likert scale. Secondary outcomes were incorrect understanding of SSPedi items identified by cognitive interviews with the children using a 4-point Likert scale and cultural relevance, which was assessed qualitatively.

Results

This report focuses on North American Spanish as a separate version will be required for Argentinian Spanish SSPedi based on different common vocabulary and grammatical structure. There were 20 children from Toronto and San Antonio included in cognitive interviews. The most common types of Spanish spoken were Mexican (13, 65%), Central American (2, 10%) and South American (2, 10%). No child reported that it was hard or very hard to complete Spanish SSPedi. Changes to the instrument itself were not required based on understanding or cultural relevance.

Conclusions

We translated and finalised Spanish SSPedi appropriate for use in North America. Future research will translate and evaluate SSPedi for use in Argentina and other Spanish-speaking countries.
Which moral barriers and facilitators do physicians encounter in advance care planning conversations about the end of life of persons with dementia? A meta-review of systematic reviews and primary studies
Authors: Keijzer-van Laarhoven Angela JJM , Touwen Dorothea P , Tilburgs Bram , van Tilborg-den Boeft Madelon , Pees Claudia , Achterberg Wilco P , van der Steen Jenny T
Published: November 2020

Importance and objective

Conducting advance care planning (ACP) conversations with people with dementia and their relatives contributes to providing care according to their preferences. In this review, we identify moral considerations which may hinder or facilitate physicians in conducting ACP in dementia.

Design

For this meta-review of systematic reviews and primary studies, we searched the PubMed, Web of Science and PsycINFO databases between 2005 and 30 August 2019. We included empirical studies concerning physicians’ moral barriers and facilitators of conversations about end-of-life preferences in dementia care. The protocol was registered at Prospero (CRD42019123308).

Setting and participants

Physicians and nurse practitioners providing medical care to people with dementia in long-term and primary care settings. We also include observations from patients or family caregivers witnessing physicians’ moral considerations.

Main outcomes

Physicians’ moral considerations involving ethical dilemmas for ACP. We define moral considerations as the weighing by the professional caregiver of values and norms aimed at providing good care that promotes the fundamental interests of the people involved and which possibly ensues dilemmas.

Results

Of 1347 studies, we assessed 22 systematic reviews and 51 primary studies as full texts. We included 11 systematic reviews and 13 primary studies. Themes included: (1) beneficence and non-maleficence; (2) respecting dignity; (3) responsibility and ownership; (4) relationship and (5) courage. Moral dilemmas related to the physician as a professional and as a person. For most themes, there were considerations that either facilitated or hindered ACP, depending on physician’s interpretation or the context.

Conclusions

Physicians feel a responsibility to provide high-quality end-of-life care to patients with dementia. However, the moral dilemmas this may involve, can lead to avoidant behaviour concerning ACP. If these dilemmas are not recognised, discussed and taken into account, implementation of ACP as a process between physicians, persons with dementia and their family caregivers may fail.
Protocol for a case–control study of vitamin D status, adult multidrug-resistant tuberculosis disease and tuberculosis infection in Mumbai, India
Authors: Mistry Nerges , Hemler Elena C. , Dholakia Yatin , Bromage Sabri , Shukla Anupam , Dev Prachi , Govekar Laxmi , Tipre Pranita , Shah Daksha , Keshavjee Salmaan A. , Fawzi Wafaie W.
Published: November 2020

Introduction

Vitamin D status may be an important determinant of multidrug-resistant tuberculosis (MDR-TB) infection, progression to disease and treatment outcomes. Novel and potentially cost-effective therapies such as vitamin D supplementation are needed to stem the tide of TB and MDR-TB globally, particularly in India, a country that accounts for the largest fraction of the world’s TB incidence and MDR-TB incidence, and where vitamin D deficiency is endemic. While vitamin D has shown some promise in the treatment of MDR-TB, its role in the context of MDR-TB infection and progression to disease is largely unknown.

Methods and analysis

Through a case–control study in Mumbai, India, we aim to examine associations between vitamin D status and active MDR-TB and to investigate vitamin D status and TB infection among controls. Cases are adult outpatient pulmonary patients with MDR-TB recruited from two public TB clinics. Controls are recruited from the cases’ household contacts and from non-respiratory departments of the facilities where cases were recruited. Cases and controls are assessed for serum 25-hydroxyvitamin D concentration, nutrient intake, diet quality, anthropometry and other relevant clinical and sociodemographic parameters. Controls undergo additional clinical assessments to rule out active TB and laboratory assessments to determine presence of TB infection. Statistical analysis investigates associations between vitamin D status and active MDR-TB and between vitamin D status and TB infection among controls, accounting for potential confounding effects of diet, anthropometry and other covariates.

Ethics and dissemination

This study has been approved by Harvard T.H. Chan School of Public Health Institutional Review Board; Foundation for Medical Research Institutional Research Ethics Committee and Health Ministry’s Screening Committee of the Indian Council for Medical Research. Permission was granted by the Municipal Corporation of Greater Mumbai, India, a collaborating partner on this research. Outcomes will be disseminated through publication and scientific presentation.

Trial registration number

NCT04342598.
Fibrosis-4 index as a predictor for mortality in hospitalised patients with COVID-19: a retrospective multicentre cohort study
Authors: Park Jung Gil , Kang Min Kyu , Lee Yu Rim , Song Jeong Eun , Kim Na Young , Kweon Young Oh , Tak Won Young , Jang Se Young , Lee Changhyeong , Kim Byung Seok , Hwang Jae Seok , Jang Byoung Kuk , Bae Jinmok , Lee Ji Yeon , Suh Jeong Ill , Park Soo Young , Chung Woo Jin
Published: November 2020

Objective

The reliable risk factors for mortality of COVID-19 has not evaluated in well-characterised cohort. This study aimed to identify risk factors for in-hospital mortality within 56 days in patients with severe infection of COVID-19.

Design

Retrospective multicentre cohort study.

Setting

Five tertiary hospitals of Daegu, South Korea.

Participants

1005 participants over 19 years old confirmed COVID-19 using real-time PCR from nasopharyngeal and oropharyngeal swabs.

Methods

The clinical and laboratory features of patients with COVID-19 receiving respiratory support were analysed to ascertain the risk factors for mortality using the Cox proportional hazards regression model. The relationship between overall survival and risk factors was analysed using the Kaplan-Meier method.

Outcome

In-hospital mortality for any reason within 56 days.

Results

Of the 1005 patients, 289 (28.8%) received respiratory support, and of these, 70 patients (24.2%) died. In multivariate analysis, high fibrosis-4 index (FIB-4; HR 2.784), low lymphocyte count (HR 0.480), diabetes (HR 1.917) and systemic inflammatory response syndrome (HR 1.714) were found to be independent risk factors for mortality in patients with COVID-19 receiving respiratory support (all p<0.05). Regardless of respiratory support, survival in the high FIB-4 group was significantly lower than in the low FIB-4 group (28.8 days vs 44.0 days, respectively, p<0.001). A number of risk factors were also significantly related to survival in patients with COVID-19 regardless of respiratory support (0–4 risk factors, 50.2 days; 49.7 days; 44.4 days; 32.0 days; 25.0 days, respectively, p<0.001).

Conclusion

FIB-4 index is a useful predictive marker for mortality in patients with COVID-19 regardless of its severity.
Thromboelastography-guided blood transfusion during cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a prospective randomised controlled trial
Authors: Wang Shaoheng , Zhang Qing , Chen Linfeng , Liu Gang , Liu Peng fei
Published: November 2020

Introduction

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a well-established treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high incidence of complications. Moreover, relative studies have indicated that traditional laboratory testing is insufficient to demonstrate the overall haemostatic physiology of CRS/HIPEC. Thromboelastography (TEG), administered by monitoring dynamic changes in haemostasis, has been shown to contribute to reducing transfusion requirements and improving survival. However, there is no evidence to verify whether TEG can be applied to guide transfusion strategies during CRS/HIPEC. Therefore, we aim to investigate whether TEG-guided blood product transfusion (TEG-BT) therapy is superior to traditional blood product transfusion (T-BT) therapy for guiding perioperative blood transfusion treatment and improving the prognosis of patients undergoing CRS/HIPEC.

Methods and analysis

The TEG-BT versus T-BT study is a single-centre, randomised, blinded outcome assessment clinical trial of 162 patients with PC, aged 18–64 years and undergoing CRS/HIPEC. Participants will be randomly allocated to receive TEG-BT or T-BT. The primary outcome will be the evaluation of perioperative blood transfusion, which refers to the total amount of blood transfusion given from the time patients enter the operating room up to 72 hours postoperatively. The secondary outcomes will include the transfusion volume during surgery, total amount of intraoperative infusion, amount of blood lost during the operation, total blood transfusion between 0 and 72 hours after surgery, lowest haemoglobin level within 72 hours after surgery, intensive care unit duration, overall length of stay, total cost of hospitalisation and adverse events. Data will be analysed according to the intention-to-treat principle.

Ethics and dissemination

The study protocol has been approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2020-3). The results will be published in peer-reviewed journals.

Trial registration number

Chinese Clinical Trial Registry (ChiCTR2000028835).
Mapping mental health recovery tools developed by mental health service users and ex-users: protocol for a scoping review
Authors: Sampietro Hernán María , Carmona Viviana R , Rojo J Emilio , Gómez-Benito Juana
Published: November 2020

Introduction

Since the emergence in 1997 of the Wellness Recovery Action Plan, a number of other tools developed by users and/or ex-users of mental health services have been published and implemented. All these tools aim to promote self-determination in mental health recovery processes. A scoping review will be carried out in order to (1) identify existing tools, (2) describe their distinctive characteristics and (3) examine how they have been implemented and evaluated.

Methods and analysis

The scoping review will be guided by the methodological framework proposed by Arksey and O’Malley and expanded by Levacet al. It will involve, primarily, a literature search of the following electronic databases: Cochrane database, Cumulative Index to Nursing and Allied Health Literature, PsycInfo, PsycArticles, Scopus, PubMed and Web of Science. In addition, the search process will consider grey literature databases. Users, ex-users and survivors organisations and networks will be contacted in order to identify any relevant material. The reference lists of the articles identified through the literature search will be inspected. Finally, hand searches of journals will be conducted in order to increase the confidence in the search. Two main approaches will be used to present the charted data: a descriptive analysis and a thematic analysis. The study will be performed between April and December 2020. The results will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.

Ethics and dissemination

This study does not require ethical approval because the data used are from publicly available materials. The study results will be disseminated through an article submitted for publication to a scientific journal and presented at relevant conferences. The results will also be shared in future workshops and seminars as part of continuing education programmes for mental health professionals.
Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial
Authors: Schuhmacher Juliane , Heidu Sonja , Balchen Torben , Richardson Jennifer Rebecca , Schmeltz Camilla , Sonne Jesper , Schweiker Jonas , Rammensee Hans-Georg , Thor Straten Per , Røder Martin Andreas , Brasso Klaus , Gouttefangeas Cécile
Published: November 2020

Background

Peptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells.

Methods

Twenty-two patients who had previously undergone radical prostatectomy received subcutaneous injections of 0.1 mg of a single RhoC-derived 20mer peptide emulsified in Montanide ISA-51 every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. The drug safety and vaccine-specific immune responses were assessed during treatment and thereafter within a 13-month follow-up period. Serum level of prostate-specific antigen was measured up to 26 months postvaccination.

Results

Most patients (18 of 21 evaluable) developed a strong CD4 T cell response against the vaccine, which lasted at least 10 months following the last vaccination. Three promiscuouslypresented HLA-class II epitopes were identified. Vaccine-specific CD4 T cells were polyfunctional and effector memory T cells that stably expressed PD-1 (CD279) and OX-40 (CD134), but not LAG-3 (CD223). One CD8 T cell response was detected in addition. The vaccine was well tolerated and no treatment-related adverse events of grade ≥3 were observed.

Conclusion

Targeting of RhoC induced a potent and long-lasting T cell immunity in the majority of the patients. The study demonstrates an excellent safety and tolerability profile. Vaccination against RhoC could potentially delay or prevent tumor recurrence and metastasis formation.

Trial registration number

NCT03199872.
Racial and gender disparities in neurology
Authors: Saleem Sidra , Naveed Sadiq , Mohyud Din Chaudhary Amna , Zeshan Muhammad , Hafeez Dawood , Siddiqi Javed , Khosa Faisal
Published: November 2020

Introduction

The USA is a diverse society with representation from different ethnic and racial backgrounds, resulting in under-represented minorities (URMs) in various specialties of medicine. Our objective was to find the statistical ratio of URMs in the academic faculty of neurology.

Methods

This was a retrospective analysis of the American Association of Medical College database. The database covered neurology faculty members from 2006 to 2017.

Results

This study shows a significant change in racial representation in faculty ranks over the last 12 years. At chairperson rank, white people decreased from 86.4% to 79.8% whereas Asian, Hispanic and multiple races (non-Hispanic) simultaneously increased from 6.4% to 9.3%, 0.9% to 3.1% and 1.8% to 4.7%, respectively. At the professor rank, white people decreased from 87.4% to 81.6%, while Asians and Hispanics increased from 7.1% to 10.5% and from 0.7% to 2.1%, respectively. At the rank of associate professor, white people decreased from 81.1% to 68.3% whereas Asians, Hispanics and unknown races increased from 10.3% to 19.0%, 1.6% to 3.1% and from 2.1% to 3.5%, respectively. For the rank of assistant professor, white people decreased from 64.7% to 56.9% and Asians increased from 20.5% to 25.9%. Gender differences (men vs women) for the ranks of chairperson, professor, associate professor, assistant professor and instructors were 90.3% and 9.7%, 83.1% and 16.9%, 67.1% and 32.9%, 56.8% and 43.2%, and 48.1% and 51.9%, respectively.

Conclusion

Over a period of 12 years the racial proportion in academic neurology has changed, but it is not proportionate to their respective increase in the population of the USA. Moreover, the portion of female faculty increased, but they are still under-represented in leadership roles. This racial and gender disparity can be addressed by well-planned interventions.
Caudal inferior alveolar nerve block in a Bennett’s wallaby (Macropus rufogriseus)
Authors: Ho Nicola Tian Zhi , Morgan Rhiannon Emma , Bolt David M , Hawkins Alexander Eric , Veres‐Nyéki Kata Orsolya
Published: November 2020

A Bennett’s wallaby (Macropus rufogriseus) was referred for diagnostic imaging and further investigation into suspected progressive pyogranulomatous osteomyelitis of the mandible. This diagnosis was confirmed via CT and CT‐guided fine‐needle biopsies of the right mandible, and surgery was performed to remove the affected teeth and treat the associated bone.

The right inferior alveolar nerve was targeted using a lateral approach with the needle directed medially in a rostro‐ventral direction into the masseteric foramen using bupivacaine hydrochloride 0.6 mg/kg.

To the authors’ knowledge, the inferior alveolar nerve block has never been reported in this species, and the lateral approach via the masseteric foramen is novel, considering that the nerve is usually targeted at the medial aspect of the mandible.

Surgical treatment of pyogranulomatous osteomyelitis is likely to be associated with significant pain, and the use of a locoregional technique to provide regional anaesthesia would complement the provision of balanced, multimodal anaesthesia.
Low-pressure superconductivity in lithium-doped methane predicted by first principles
Authors: Lu Ning , Hai Yu-Long , Lv Hai-Yan , Li Wen-Jie , Yang Chun-Lei , Zhong Guo-Hua
Published: November 2020

To explore the high-temperature superconductor at low pressures, we have investigated the crystal structures, electronic properties, and possible superconductivity in the case of methane (CH4) doped by lithium in the pressure range of [Formula: see text][Formula: see text]GPa, based on the first-principles calculations. The results show that Li-intercalated CH4 (Lix(CH4)[Formula: see text]) can realize metallization and superconductivity at low pressures, even 5[Formula: see text]GPa. We find that there is a charge transfer between Li and CH4, but the metallization is driven by the change of crystal field induce by doping instead of charge transfer. The critical temperture is predicted from 3.8[Formula: see text]K at 5[Formula: see text]GPa for LiCH4 to 12.1[Formula: see text]K at 100[Formula: see text]GPa for Li(CH4)4. The low-pressure superconductivity of Lix(CH4)[Formula: see text] can be further optimized by adjusting component and pressure.
Optimal control of a rumor model with group propagation over complex networks
Authors: Myilsamy Kalaiselvi , Kumar Muthukrishnan Senthil , Kumar Athira Satheesh
Published: November 2020

Rumor is an unauthenticated statement that gives significant changes in the social life of the people, financial markets (stocks and trades), etc. By incorporating the dissemination of rumor through groups in social, mobile networks and by considering the people’s cognitive factor (hesitate and forget), a new model on the rumor spreading process is presented in this paper. The spreading dynamics of rumor in homogeneous and heterogeneous networks is analyzed by using mean-field theory. The reproduction number is obtained by using the next-generation matrix. The global stability of the rumor-free equilibrium for the homogeneous and heterogeneous model is proved elaborately. An optimal control problem is developed to minimize the hesitators and infected persons and the existence of optimality is shown using Pontryagin’s Minimum Principle. The hesitating and forgetting mechanism has a great impact on the model and is similar to the real-life. Further, the control parameters work superior in controlling the spreading of rumors. Finally, the numerical results are verified by the analytical results.
SOCIAL PREFERENCES OF YOUNG ADULTS IN JAPAN: THE ROLES OF AGE AND GENDER
Authors: KAWASE AKIHIRO
Published: November 2020

Deviations from self-interest in economic behavior have recently been featured in models of “social preferences.” This study examines the social preferences of Japanese university students using Charness and Rabin ’s [( 2002 ). Understanding social preferences with simple tests. Quarterly Journal of Economics, 117, 817–869] experimental design and Martinsson et al. ’s [( 2011 ). Social preferences during childhood and the role of gender and age: An experiment in Austria and Sweden. Economics Letters, 110, 248–251] empirical methodology. The obtained distributions of preference types are as follows: self-interest — 14%, competitive — 23%, difference aversion — 73% and social-welfare — 22%. I find a significant age effect for the self-interest preference alone, and a gender difference for the self-interest, difference aversion and social-welfare preferences.