bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale part mutual information for quantifying nonlinear direct associations in networks
Authors: Shang Junliang , Wang Jing , Sun Yan , Li Feng , Liu Jin-Xing , Zhang Honghai 
Published: March 2021

Abstract

Motivation
For network-assisted analysis, which has become a popular method of data mining, network construction is a crucial task. Network construction relies on the accurate quantification of direct associations among variables. The existence of multiscale associations among variables presents several quantification challenges, especially when quantifying nonlinear direct interactions.

Results
In this study, the multiscale part mutual information (MPMI), based on part mutual information (PMI) and nonlinear partial association (NPA), was developed for effectively quantifying nonlinear direct associations among variables in networks with multiscale associations. First, we defined the MPMI in theory and derived its five important properties. Second, an experiment in a three-node network was carried out to numerically estimate its quantification ability under two cases of strong associations. Third, experiments of the MPMI and comparisons with the PMI, NPA and conditional mutual information were performed on simulated datasets and on datasets from DREAM challenge project. Finally, the MPMI was applied to real datasets of glioblastoma and lung adenocarcinoma to validate its effectiveness. Results showed that the MPMI is an effective alternative measure for quantifying nonlinear direct associations in networks, especially those with multiscale associations.

Availability and implementation
The source code of MPMI is available online at https://github.com/CDMB-lab/MPMI.

Supplementary information
Supplementary data are available at Bioinformatics online.
Brain size evolution in whales and dolphins: new data from fossil mysticetes
Authors: Mccurry Matthew R , Marx Felix G , Evans Alistair R , Park Travis , Pyenson Nicholas D , Kohno Naoki , Castiglione Silvia , Fitzgerald Erich M G 
Published: March 2021

AbstractCetaceans (whales and dolphins) have some of the largest and most complex brains in the animal kingdom. When and why this trait evolved remains controversial, with proposed drivers ranging from echolocation to foraging complexity and high-level sociality. This uncertainty partially reflects a lack of data on extinct baleen whales (mysticetes), which has obscured deep-time patterns of brain size evolution in non-echolocating cetaceans. Building on new measurements from mysticete fossils, we show that the evolution of large brains preceded that of echolocation, and subsequently followed a complex trajectory involving several independent increases (e.g. in rorquals and oceanic dolphins) and decreases (e.g. in right whales and ‘river dolphins’). Echolocating whales show a greater tendency towards large brain size, thus reaffirming cognitive demands associated with sound processing as a plausible driver of cetacean encephalization. Nevertheless, our results suggest that other factors such as sociality were also important.
Activation of the basal ganglia and indirect pathway neurons during frontal lobe seizures
Authors: Brodovskaya Anastasia , Shiono Shinnosuke , Kapur Jaideep 
Published: March 2021

AbstractThere are no detailed descriptions of neuronal circuit active during frontal lobe motor seizures. Using activity reporter mice, local field potential recordings, tissue clearing, viral tracing, and super-resolution microscopy, we found neuronal activation after focal motor to bilateral tonic-clonic seizures in the striatum, globus pallidus externus, subthalamic nucleus, substantia nigra pars reticulata and neurons of the indirect pathway. Seizures preferentially activated dopamine D2 receptor-expressing neurons over D1 in the striatum, which have different projections. Furthermore, the D2 receptor agonist infused into the striatum exerted an anticonvulsant effect. Seizures activate structures via short and long latency loops, and anatomical connections of the seizure focus determine the seizure circuit. These studies, for the first time, show activation of neurons in the striatum, globus pallidus, subthalamic nucleus, and substantia nigra during frontal lobe motor seizures on the cellular level, revealing a complex neuronal activation circuit subject to modulation by the basal ganglia.
Severe hypercalcaemia early after kidney transplantation in two patients with severe secondary hyperparathyroidism previously treated with etelcalcetide
Authors: Dachy Guillaume , Pochet Jean-Michel , Labriola Laura , Buemi Antoine , Gillion Valentine , Jadoul Michel , Kanaan Nada , Devresse Arnaud 
Published: March 2021

Abstract
Cinacalcet and, more recently, etelcalcetide revolutionized the treatment of chronic kidney disease–mineral and bone disorder (CKD–MBD). Kidney transplant (KT) usually improves CKD–MBD. However, a significant proportion of KT recipients have high serum calcium levels, not requiring any treatment. We report two patients previously treated with etelcalcetide who developed severe (&gt;3.3 mmol/L) hypercalcaemia in the early post-KT course, requiring parathyroidectomy. Pathological studies showed parathyroid adenomas and hyperplasia. One patient had a graft biopsy showing numerous intratubular calcium phosphate crystals. These observations should prompt pharmacovigilance studies and careful follow-up of KT recipients previously treated with etelcalcetide.
Hormonal modulation of reproduction and fertility signaling in polistine wasps
Authors: Oi Cintia Akemi , da Silva Rafael Carvalho , Stevens Ian , Ferreira Helena Mendes , Nascimento Fabio Santos , Wenseleers Tom 
Published: March 2021

AbstractIn social insects, it has been suggested that reproduction and the production of particular fertility-linked cuticular hydrocarbons (CHC) may be under shared juvenile hormone (JH) control, and this could have been key in predisposing such cues to later evolve into full-fledged queen pheromone signals. However, to date, only few studies have experimentally tested this “hormonal pleiotropy” hypothesis. Here, we formally test this hypothesis using data from four species of Polistine wasps, Polistes dominula, Polistes satan, Mischocyttarus metathoracicus, and Mischocyttarus cassununga, and experimental treatments with JH using the JH analogue methoprene and the anti-JH precocene. In line with reproduction being under JH control, our results show that across these four species, precocene significantly decreased ovary development when compared with both the acetone solvent-only control and the methoprene treatment. Consistent with the hormonal pleiotropy hypothesis, these effects on reproduction were further matched by subtle shifts in the CHC profiles, with univariate analyses showing that in P. dominula and P. satan the abundance of particular linear alkanes and mono-methylated alkanes were affected by ovary development and our hormonal treatments. The results indicate that in primitively eusocial wasps, and particularly in Polistes, reproduction and the production of some CHC cues are under joint JH control. We suggest that pleiotropic links between reproduction and the production of such hydrocarbon cues have been key enablers for the origin of true fertility and queen signals in more derived, advanced eusocial insects.
Myocardial infarction secondary to coronary embolus in a patient with left ventricular non-compaction cardiomyopathy: a case report
Authors: Dhawan Rahul , Kadir Sajid , Barton David E , Stone Jeremy R , Chatzizisis Yiannis S 
Published: March 2021

Abstract

Background
Coronary embolism is a rare cause of myocardial infarction (MI). We present a case report which emphasizes the importance of intracoronary imaging in these cases to identify the pathophysiological mechanism of MI.

Case summary
A 53-year-old male with no past medical history presented to the hospital with typical angina. Electrocardiogram and serum troponin I level trend confirmed non-ST-elevation myocardial infarction. Coronary angiography showed no evidence of any obstructive coronary artery disease, but two small thrombi were noted in the distal first obtuse marginal branch. Optical coherence tomography imaging confirmed this finding in absence of any underlying atherosclerotic plaque rupture or erosion. Cardiac magnetic resonance imaging revealed the diagnosis of non-compaction cardiomyopathy with severely depressed left ventricular function. Transmural MI was revealed by late gadolinium enhancement in the mid-lateral wall. Based on the pathophysiology of the MI confirmed by intracoronary imaging, antiplatelet medications were discontinued, and the patient was discharged on warfarin. Medical therapy was initiated for his cardiomyopathy. The patient recovered well and was asymptomatic at 1-year follow-up visit.

Discussion
Intracoronary imaging plays an important role to supplement coronary angiography to confirm the pathophysiology of MI in coronary embolism cases. This is important as it alters management in these patients.
The association between cardiovascular disease admission rates and the coronavirus disease 2019 lockdown and reopening of a nation: a Danish nationwide cohort study
Authors: Butt Jawad H , Østergaard Lauge , Gerds Thomas A , Lauridsen Marie D , Kragholm Kristian , Schou Morten , Phelps Matthew , Gislason Gunnar H , Torp-Pedersen Christian , Køber Lars , Fosbøl Emil L 
Published: March 2021

AbstractAimsTo investigate the admission rates of cardiovascular diseases, overall and according to subgroups, and subsequent mortality rates during the coronavirus disease 2019 societal lockdown (12 March 2020) and reopening phase (15 April 2020) in Denmark.Methods and resultsUsing Danish nationwide registries, we identified patients with a first-time acute cardiovascular admission in two periods: (i) 2 January–16 October 2019 and (ii) 2 January–15 October 2020. Weekly incidence rates of a first-time cardiovascular admission, overall and according to subtypes, in the two periods were calculated. The incidence rate of first-time cardiovascular admissions overall was significantly lower during the first weeks of lockdown in 2020 compared with a similar period in 2019 but increased after the gradual reopening of the Danish society. A similar trend was observed for all subgroups of cardiovascular diseases. The mortality rate among patients admitted after March 12 was not significantly different in 2020 compared with 2019 [mortality rate ratio 0.98; 95% confidence interval (CI) 0.91–1.06)].ConclusionIn Denmark, we observed a substantial decrease in the rate of acute cardiovascular admissions, overall and according to subtypes, during the first weeks of lockdown. However, after the gradual reopening of the Danish society, the admission rates for acute cardiovascular diseases increased and returned to rates similar to those observed in 2019. The mortality rate in patients admitted with cardiovascular diseases during lockdown was similar to that of patients during the same period in 2019.
Older Adults Demonstrate Biomarker Evidence of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) After Sepsis
Authors: Mankowski Robert T , Anton Stephen D , Ghita Gabriela L , Brumback Babette , Darden Dijoia B , Bihorac Azra , Leeuwenburgh Christiaan , Moldawer Lyle L , Efron Philip A , Brakenridge Scott C , Moore Frederick A 
Published: March 2021

Abstract

Background
Hospital deaths after sepsis have decreased substantially and most young adult survivors rapidly recover (RAP). However, many older survivors develop chronic critical illness (CCI) with poor long-term outcomes. The etiology of CCI is multifactorial and the relative importance remains unclear. Sepsis is caused by a dysregulated immune response and biomarkers reflecting a persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have been observed in CCI after sepsis. Therefore, the purpose of this study was to compare serial PICS biomarkers in (i) older (vs young) adults and (ii) older CCI (vs older RAP) patients to gain insight into underlying pathobiology of CCI in older adults.

Method
Prospective longitudinal study with young (≤45 years) and older (≥65 years) septic adults, who were characterized by (i) baseline predisposition, (ii) hospital outcomes, (iii) serial Sequential Organ Failure Assessment (SOFA) organ dysfunction scores over 14 days, (iv) Zubrod Performance status at 3-, 6-, and 12-month follow-up, and (v) mortality over 12 months, was conducted. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS.

Results
Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status, and mortality over 12 months. Additionally, older (vs young) and older CCI (vs older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism, and antiangiogenesis over 14 days after sepsis.

Conclusion
Older (vs young) and older CCI (vs older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS.
Frailty, With or Without Cognitive Impairment, Is a Strong Predictor of Recurrent Falls in a US Population-Representative Sample of Older Adults
Authors: Ge Mei-Ling , Simonsick Eleanor M , Dong Bi-Rong , Kasper Judith D , Xue Qian-Li 
Published: March 2021

Abstract

Background
Physical frailty and cognitive impairment have been separately associated with falls. The purpose of the study is to examine the associations of physical frailty and cognitive impairment separately and jointly with incident recurrent falls among older adults.

Methods
The analysis included 6000 older adults in community or non-nursing home residential care settings who were at least 65 years old and participated in the National Health and Aging Trends Study. Frailty was assessed using the physical frailty phenotype; cognitive impairment was defined by bottom quintile of the clock-drawing test or immediate and delayed 10-word recall, or self/proxy-report of diagnosis of dementia, or AD8 score at least 2. The marginal means/rates models were used to analyze the associations of frailty and cognitive impairment with recurrent falls over 6 years of follow-up between 2011 and 2017.

Results
Of the 6000 older adults, 1787 (29.8%) had cognitive impairment only, 334 (5.6%) had frailty only, 615 (10.3%) had both, and 3264 (54.4%) had neither. After adjusting for age, sex, race, education, living alone, obesity, disease burden, and mobility disability, those with frailty (with or without cognitive impairment) at baseline had higher rates of recurrent falls than those without cognitive impairment and frailty (frailty only: rate ratio [RR] = 1.31, 95% confidence interval [CI] = 1.18–1.44; both: RR = 1.28, 95% CI = 1.17–1.40). The association was marginally significant for those with cognitive impairment only (RR = 1.07, 95% CI = 1.00–1.13).

Conclusions
Frailty and cognitive impairment were independently associated with recurrent falls in noninstitutionalized older adults. There was a lack of synergistic effect between frailty and cognitive impairment.
Chromosome-level genome assemblies of the malaria vectors Anopheles coluzzii and Anopheles arabiensis
Authors: Zamyatin Anton , Avdeyev Pavel , Liang Jiangtao , Sharma Atashi , Chen Chujia , Lukyanchikova Varvara , Alexeev Nikita , Tu Zhijian , Alekseyev Max A , Sharakhov Igor V 
Published: March 2021

Abstract

Background
Anopheles coluzzii and Anopheles arabiensis belong to the Anopheles gambiae complex and are among the major malaria vectors in sub-Saharan Africa. However, chromosome-level reference genome assemblies are still lacking for these medically important mosquito species.

Findings
In this study, we produced de novo chromosome-level genome assemblies for A. coluzzii and A. arabiensis using the long-read Oxford Nanopore sequencing technology and the Hi-C scaffolding approach. We obtained 273.4 and 256.8 Mb of the total assemblies for A. coluzzii and A. arabiensis, respectively. Each assembly consists of 3 chromosome-scale scaffolds (X, 2, 3), complete mitochondrion, and unordered contigs identified as autosomal pericentromeric DNA, X pericentromeric DNA, and Y sequences. Comparison of these assemblies with the existing assemblies for these species demonstrated that we obtained improved reference-quality genomes. The new assemblies allowed us to identify genomic coordinates for the breakpoint regions of fixed and polymorphic chromosomal inversions in A. coluzzii and A. arabiensis.

Conclusion
The new chromosome-level assemblies will facilitate functional and population genomic studies in A. coluzzii and A. arabiensis. The presented assembly pipeline will accelerate progress toward creating high-quality genome references for other disease vectors.
The role of religion in mitigating the COVID-19 pandemic: the Malaysian multi-faith perspectives
Authors: Tan Min Min , Musa Ahmad Farouk , Su Tin Tin 
Published: March 2021

Abstract
Social distancing is crucial in breaking the cycle of transmission of COVID-19. However, many religions require the faithful to congregate. In Malaysia, the number of COVID-19 cases spiked up from below 30 in February 2020 to more than a thousand a month later. The sudden increase was mostly linked to a large Islamic gathering attended by 16,000 near the capital, Kuala Lumpur. Another large COVID-19 cluster was from a church gathering in Kuching, Sarawak. Within a few weeks, Malaysia became the worst hit country by COVID-19 in Southeast Asia. While religious leaders have advised social distancing among their congregants, the belief that “God is our shield” is often cited for gathering. There is a need to promote sound decision-making among religious adherents so that they will not prioritize their loyalty to the subjective interpretation of religion over evidence-based medicine. Malaysia, a multi-cultural and multi-faith country, is an example of how religious beliefs could strongly influence health behaviours at individual and community levels. In this article, we detail the religious aspects of COVID-19 prevention and control in Malaysia and discuss the possible role of religious organizations in encouraging sound decision-making among religious adherents in mitigating this crisis. We make recommendations on how to promote a partnership between the healthcare system and religious organizations, and how religion and faith could be integrated into health promotion channels and resources in the response of COVID-19 and future communicable diseases.
The Arab Court of Human Rights and the Enforcement of the Arab Charter on Human Rights
Authors: Almutawa Ahmed 
Published: March 2021

Abstract
Under the League of Arab States’ human rights regime, Arab countries are governed by the Arab Charter of Human Rights 2004. The Charter, however, lacks an enforcement mechanism. The Statute of the Arab Court of Human Rights 2014 aims to fill this enforcement void. This article addresses the criticism that, because it fails to provide for a direct right of individual petition, the Statute is not fit for purpose. It is argued contrarily that, within the context of an Arab human rights system, the Court should be welcomed as an important step in the process of establishing an effective regime.
HOSTED—England’s Household Transmission Evaluation Dataset: preliminary findings from a novel passive surveillance system of COVID-19
Authors: Hall JA , Harris RJ , Zaidi A , Woodhall SC , Dabrera G , Dunbar JK 
Published: March 2021

Abstract

Background
Household transmission of SARS-CoV-2 is an important component of the community spread of the pandemic. Little is known about the factors associated with household transmission, at the level of the case, contact or household, or how these have varied over the course of the pandemic.

Methods
The Household Transmission Evaluation Dataset (HOSTED) is a passive surveillance system linking laboratory-confirmed COVID-19 cases to individuals living in the same household in England. We explored the risk of household transmission according to: age of case and contact, sex, region, deprivation, month and household composition between April and September 2020, building a multivariate model.

Results
In the period studied, on average, 5.5% of household contacts in England were diagnosed as cases. Household transmission was most common between adult cases and contacts of a similar age. There was some evidence of lower transmission rates to under-16s [adjusted odds ratios (aOR) 0.70, 95% confidence interval (CI) 0.66–0.74). There were clear regional differences, with higher rates of household transmission in the north of England and the Midlands. Less deprived areas had a lower risk of household transmission. After controlling for region, there was no effect of deprivation, but houses of multiple occupancy had lower rates of household transmission [aOR 0.74 (0.66–0.83)].

Conclusions
Children are less likely to acquire SARS-CoV-2 via household transmission, and consequently there was no difference in the risk of transmission in households with children. Households in which cases could isolate effectively, such as houses of multiple occupancy, had lower rates of household transmission. Policies to support the effective isolation of cases from their household contacts could lower the level of household transmission.
A novel osimertinib-resistant human lung adenocarcinoma cell line harbouring mutant EGFR and activated IGF1R
Authors: Makimoto Go , Ninomiya Kiichiro , Kubo Toshio , Sunami Ryota , Kato Yuka , Ichihara Eiki , Ohashi Kadoaki , Rai Kammei , Hotta Katsuyuki , Tabata Masahiro , Maeda Yoshinobu , Kiura Katsuyuki 
Published: March 2021

Abstract

Objective
A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is the standard treatment for patients with non-small cell lung cancer harbouring mutant EGFR. Unfortunately, these patients inevitably acquire resistance to EGFR-TKI therapies, including osimertinib. However, the mechanism associated with this resistance remains unclear.

Methods
A 63-year-old Japanese female with lung adenocarcinoma underwent right upper lobectomy (pT1bN2M0 pStage IIIA, EGFR Ex21 L858R). She manifested post-operative tumour recurrence with multiple lung metastases 8 months later and began gefitinib treatment. The lung lesions re-grew 15 months later, and EGFR T790M mutation was detected in the lung metastasis re-biopsy. She was administered osimertinib; however, it relapsed with pleural effusion 16 months later. We isolated cells from the osimertinib-resistant pleural effusion to establish a novel cell line, ABC-31.

Results
Although the EGFR L858R mutation was detected in ABC-31 cells, the T790M mutation was lost. ABC-31 cells were resistant to EGFR-TKIs, including osimertinib. Phospho-receptor tyrosine kinase array revealed activation of the insulin-like growth factor 1 receptor (IGF1R), whereas overexpression of the IGF1R ligand, IGF2, induced IGF1R activation in ABC-31 cells. Combination therapy using EGFR-TKIs and IGF1R inhibitor acted synergistically in vitro. She was re-administered osimertinib since EGFR-TKIs and IGF1R inhibitor combination therapy was impossible in clinical practice. This had a slight and short-lived effect.

Conclusions
Taken together, we have successfully established a new osimertinib-resistant lung adenocarcinoma cell line with activated IGF1R. These ABC-31 cells will help develop novel therapeutic strategies for patients with lung adenocarcinoma resistant to specific treatment via IGF1R activation.