bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between RT-PCR Ct Values and COVID-19 New Daily Cases: A Multicenter Cross-Sectional Study
Authors: Abdulrahman Abdulkarim , Mallah Saad , AlAwadhi Abdulla Ismael , Perna Simone , Janahi Essam , AlQahtani Manaf
Published: December 2020

Introduction: Proactive prediction of the epidemiologic dynamics of viral diseases and outbreaks of the likes of COVID-19 has remained a difficult pursuit for scientists, public health researchers, and policymakers. It is unclear whether RT-PCR Cycle Threshold (Ct) values of COVID-19 (or any other virus) as indicator of viral load, could represent a possible predictor for underlying epidemiological changes on a population level.

Objectives: To investigate whether population-wide changes in SARS-CoV-2 RT-PCR Ct values over time are associated with the daily fraction of positive COVID-19 tests. In addition, this study analyses the factors that could influence the RT-PCR Ct values.

Method: A retrospective cross-sectional study was conducted on 63,879 patients from May 4, 2020 to September 30, 2020, in all COVID-19 facilities in the Kingdom of Bahrain. Data collected included number of tests and newly diagnosed cases, as well as Ct values, age, gender nationality, and symptomatic status.

Results: Ct values were found to be negatively and very weakly correlated with the fraction of daily positive cases in the population r = -0.06 (CI95%: -0.06; -0.05; p=0.001). The R-squared for the regression model (adjusting for age and number of daily tests) showed an accuracy of 45.3%. Ct Values showed an association with nationality (p=0.012). After the stratification, the association between Ct values and the fraction of daily positive cases was only maintained for the female gender and Bahraini-nationality. Symptomatic presentation was significantly associated with lower Ct values (higher viral loads). Ct values do not show any correlation with age (p=0.333) or gender (p=0.522).

Conclusion: We report one of the first and largest studies to investigate the epidemiological associations of Ct values with COVID-19. Ct values offer a potentially simple and widely accessible tool to predict and model epidemiological dynamics on a population level. More population studies and predictive models from global cohorts are necessary.
Plasma S1P links to hypertension and biomarkers of inflammation and cardiovascular disease – findings from a translational investigation
Authors: Jujic Amra , Matthes Frank , Vanherle Lotte , Petzka Henning , Orho-Melander Marju , Nilsson Peter M , Magnusson Martin , Meissner Anja
Published: December 2020

Sphingosine-1-phosphate (S1P) is an important regulator of immune cell trafficking and vascular dysfunction contributing to the development and progression of overt hypertension. Although targeting S1P signaling revealed therapeutic potential in different experimental hypertension studies, validations of S1P-blood pressure (BP) associations in humans are lacking. In a translational approach, we explored the associations between plasma S1P and BP in a family-based study cohort (Malmö Offspring (MOS) study; N=1026), and in a longitudinally conducted murine hypertension cohort.

In MOS, linear multivariate regression analyses showed that plasma S1P associates with increased systolic BP (β=1.06, P=0.015). Study subjects with systolic BP ≥140 mmHg presented with significantly higher S1P plasma concentrations compared to subjects with BP <120 mmHg independent of age and sex. The S1P-BP association was validated in a murine model where plasma S1P increased with systolic BP (r=0.7018, R2=0.4925; P<0.0001). In a sub-sample of MOS (N=444), proteomic profiling for markers of inflammation, metabolism and cardiovascular disease using proximity Extension Assays revealed multiple significant S1P associations, some of them with marked sex-specificity.In vitroandex vivovalidation of identified S1P associations disclosed augmented expression of different vascular dysfunction and inflammation markers in response to S1P.

Our translational findings show a link between plasma S1P and systolic BP as well as several inflammation and cardiovascular disease markers and suggest S1P’s biomarker potential. This encourages further studies to investigate its predictive capacity for hypertensive disease or the therapeutic potential of its signaling axis.
Evolution during primary HIV infection does not require adaptive immune selection
Authors: Swan David A , Rolland Morgane , Herbeck Joshua , Schiffer Joshua T , Reeves Daniel B
Published: December 2020

Modern HIV research depends crucially on both viral sequencing and population measurements. To directly link mechanistic biological processes and evolutionary dynamics during HIV infection, we developed multiple within-host phylodynamic (wi-phy) models of HIV primary infection for comparative validation against viral load and evolutionary dynamics data. The most parsimonious and accurate model required no positive selection, suggesting that the host adaptive immune system reduces viral load, but does not drive observed viral evolution. Rather, random genetic drift primarily dictates fitness changes. These results hold during early infection, and even during chronic infection when selection has been observed, viral fitness distributions are not largely different from in vitro distributions that emerge without adaptive immunity. These results highlight how phylogenetic inference must consider complex viral and immune-cell population dynamics to gain accurate mechanistic insights.

One sentence summary

Through the lens of a unified population and phylodynamic model, current data show the first wave of HIV mutations are not driven by selection by the adaptive immune system.
Evolutionary loss of inflammasomes in carnivores to facilitate carriage of zoonotic infections
Authors: Digby Z. , Rooney J. , Boyle J.P. , Bibo-Verdugo B. , Pickering R. , Webster S.J. , Monie T.P. , Hopkins L.J. , Kayagaki N. , Salvesen G.S. , Warming S. , Weinert L. , Bryant C.E.
Published: December 2020

Zoonotic infections, such as COVID-19, reside in animal hosts before jumping species to humans. The Carnivora, like mink, carry many zoonoses yet how diversity in host immune genes across species impact upon pathogen carriage are poorly understood. Here we describe a progressive evolutionary downregulation of pathogen sensing inflammasome pathways in Carnivora. This includes the loss of nucleotide-oligomerisation domain leucine rich repeat receptors (NLRs), acquisition of a unique caspase−1/−4 effector fusion protein that processes gasdermin D pore formation without inducing lytic cell death and the formation of an NLRP3-caspase-8 containing inflammasome that inefficiently processes interleukin-1β (IL-1β). Inflammasomes regulate gut immunity, but the carnivorous diet is antimicrobial suggesting a tolerance to the loss of these immune pathways. The consequences of systemic inflammasome downregulation, however, can reduce the host sensing of specific pathogens such that they can reside undetected in the Carnivora.
Following The Niche: Reconstructing 32,000 Years Of Niche Dynamics In Four European Ungulate Species
Authors: Leonardi Michela , Boschin Francesco , Boscato Paolo , Manica Andrea
Published: December 2020

An understanding of how ecological niches can change through time is key to predicting the effect of future global change. Past climatic fluctuations provide a natural experiment to assess the extent to which species can change their niche. Here we use an extensive archaeological database to formally test whether the niche of four European ungulates changed between 40 and 8 kya (i.e. before major anthropogenic habitat modification and excluding the confounding effect of domestication). We find that niche change depended on habitat. Horse and aurochs, which are adapted to open environment, changed their niche after the Last Glacial Maximum, and it is unclear whether this was the result of adaptation, or an expansion of the realized niche as a response to the extinction of other megafauna (competitors and predators) that shared the same habitat preferences. On the other hand, red deer and wild boar, which prefer close and semi-close habitats, did not change their niche during the same period; possibly because these habitats have experienced fewer extinctions. Irrespective of the mechanism that might have led to the observed niche changes, the fact that large mammals with long generation times can change their niche over the time period of thousands of years cautions against assuming a constant niche when predicting the future.

Significance statement

When predicting species responses to future change, it is often assumed that their habitat preferences (i.e. their niche) will not change. However, it is strongly debated whether this is reasonable. Here we show that two out of four species of large European ungulates changed their niche following the Last Glacial Maximum, possibly as a response to the reorganization of animal communities that resulted from numerous megafauna extinctions. This finding cautions against the assumption of a constant niche, highlighting that, to predict the future, we will ultimately need to understand the mechanisms that underpin the success of a given species under different climatic conditions.
Robo2 drives target selective peripheral nerve regeneration in response to glia derived signals
Authors: Murphy Patricia L. , Isaacman-Beck Jesse , Granato Michael
Published: December 2020

Peripheral nerves are divided into multiple branches leading to divergent synaptic targets. This poses a remarkable challenge for regenerating axons as they select their original trajectory at nerve branch-points. Despite implications for functional regeneration, the molecular mechanisms underlying target selectivity are not well characterized. Zebrafish motor nerves are composed of a ventral and a dorsal branch that diverge at a choice point, and we have previously shown that regenerating axons faithfully select their original branch and targets. Here we identify Robo2 as a key regulator of target selective regeneration. We demonstrate that Robo2 function in regenerating axons is required and sufficient to drive target selective regeneration, and that Robo2 acts in response to glia located precisely where regenerating axons select the branch-specific trajectory to prevent and correct axonal errors. Combined our results reveal a glia derived mechanism that acts locally via axonal Robo2 to promote target selective regeneration.
Adverse Social Experiences in Adolescent Rats Results in Persisting Sex-Dependent Effects on Alcohol-Seeking Behavior
Authors: Surakka Akseli , Vengeliene Valentina , Skorodumov Ivan , Meinhardt Marcus , Hansson Anita C. , Spanagel Rainer
Published: December 2020

Background

Accumulating clinical evidence suggests women with prior exposure to adverse childhood experiences are more susceptible to alcohol relapse and other health-related issues. Yet, preclinical studies investigating sex-dependent effects of adolescent adverse social experiences (ASEs) on later alcohol-seeking behavior are lacking. This is mainly due to a lack of valid animal models and a shortage of studies comparing sexes. Therefore, we sought to investigate the sex-dependent effects of ASE on adult alcohol-seeking behavior, locomotion and reward sensitivity in both male and female rats.

Methods

We recently developed a rat model for adolescent peer-rejection which allows us to study the long-term consequences of ASEs. Peer-rejection interferes with adolescent rats‘ability to engage in adequate and reciprocal play behaviors that result in persistent dysregulation of social and pain-related behavior. Adolescent Wistar rats were reared from postnatal day (pd) 21 to pd 50 either within a group of Fischer 344 rats (ASE) or with Wistar rats (control). Adult male and female rats were tested in the reinstatement paradigm for cue-induced alcohol-seeking behavior, circadian locomotor activity, and sucrose consumption in adulthood long-after the termination of the peer-rejection condition.

Results

Peer-rejection induced persistent sex-dependent changes to cue-induced reinstatement. Females showed an increased reinstatement effect while peer-rejected males demonstrated a decrease. No differences were observed in circadian locomotor activity or reward sensitivity to sucrose.

Conclusions

Peer-rejection has lasting sex-dependent consequences on alcohol-seeking behavior without affecting locomotion or sweet reward sensitivity. Our results suggest that peer-rejected female rats represent a vulnerable population to study relapse-like behaviors similar to clinical findings. While males seem to buffer the peer-rejection effect and demonstrate resilience to later-life alcohol-seeking behaviors, measured by the reinstatement effect. Finally, we provide a novel approach to investigate the molecular and neurobiological underpinnings of ASEs on alcohol and other drug-seeking behaviors.
Evolution-inspired dissection of caspase activities enables the redesign of caspase-4 into an LPS sensing interleukin-1 converting enzyme
Authors: Devant Pascal , Cao Anh , Kagan Jonathan C.
Published: December 2020

Innate immune signaling pathways comprise multiple proteins that promote inflammation. This multistep means of information transfer suggests that complexity is a prerequisite for pathway design. Herein, we examined this possibility by studying caspases that regulate inflammasome-dependent inflammation. Several caspases differ in their ability to recognize bacterial LPS and cleave interleukin-1β (IL-1β). No caspase is known to contain both activities, yet distinct caspases with complementary activities bookend an LPS-induced pathway to IL-1β cleavage. Using unique caspases present in carnivorans as a guide, we identified molecular determinants of IL-1β cleavage specificity within caspase-1. This knowledge enabled the redesign of human caspase-4 to operate as a one-protein signaling pathway, which intrinsically links LPS detection to IL-1β cleavage and release, independent of inflammasomes. Strikingly, cat caspase-4 displays the activities of redesigned human caspase-4. These findings illustrate natural signaling pathway diversity and highlight how multistep innate immune pathways can be condensed into a single protein.
Cortical depth-dependent human fMRI of resting-state networks using EPIK
Authors: Pais-Roldán Patricia , Yun Seong Dae , Palomero-Gallagher Nicola , Shah N. Jon
Published: December 2020

Recent laminar-fMRI studies have substantially improved understanding of theevokedcortical responses in multiple sub-systems; in contrast, the laminar component ofresting-state networksspread over the whole brain has been less studied due to technical limitations. Animal research strongly suggests that the supragranular layers of the cortex play a critical role in maintaining communication within the default mode network (DMN); however, whether this is true in this and other human cortical networks remains unclear. Here, we used EPIK, which offers unprecedented coverage at sub-millimeter resolution, to investigate cortical broad resting-state dynamics with depth specificity in healthy volunteers. Our results suggest that human DMN connectivity is primarily supported by intermediate and superficial layers of the cortex, and furthermore, the preferred cortical depth used for communication can vary from one network to another. This has major implications for the characterization of network-related diseases and should occupy future high-resolution studies. In addition, the laminar connectivity profile of some networks showed a tendency to change upon engagement in a motor task. In line with these connectivity changes, we observed that the amplitude of the low-frequency-fluctuations (ALFF), as well as the regional homogeneity (ReHo), exhibited a different laminar slope when subjects were either performing a task or were in a resting state (less variation among laminae, i.e., lower slope, during task performance compared to rest). The varied laminar profiles concerning network connectivity, ALFF, and ReHo, observed across two brain states (task vs. rest) suggest the potential diagnostic value of laminar fMRI in psychiatric diseases, e.g., to differentiate the cortical dynamics associated with disease stages linked, or not linked, to behavioral changes. The evaluation of laminar-fMRI across the brain encompasses computational challenges; nonetheless, it enables the investigation of a new dimension of the human neocortex, which may be key to understanding neurological disorders from a novel perspective.
Single cell transcriptomics of primate sensory neurons identifies cell types associated with human chronic pain
Authors: Kupari Jussi , Usoskin Dmitry , Lou Daohua , Parisien Marc , Hu Yizhou , Fatt Michael , Lönnerberg Peter , Spångberg Mats , Eriksson Bengt , Barkas Nikolaos , Kharchenko Peter V , Loré Karin , Khoury Samar , Diatchenko Luda , Ernfors Patrik
Published: December 2020

Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of human chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.
Genomic Evidence for the Chinese Mountain Cat as a Wildcat Conspecific (Felis silvestris bieti) and Its Introgression to Domestic Cats
Authors: Yu He , Xing Yue-Ting , Meng Hao , He Bing , Li Wen-Jing , Qi Xin-Zhang , Zhao Jian-You , Zhuang Yan , Xu Xiao , O’Brien Stephen J. , Luo Shu-Jin
Published: December 2020

The enigmatic Chinese mountain cat, endemic to the Qinghai-Tibet Plateau, has a controversial taxonomic status, whether a true species or conspecific with the wildcat(Felis silvestris) and whether it may have contributed to the domestication of cats(F. s. catus) in Asia. Here, we sampled 270 domestic and wild cats across China, sequenced 51 nuclear genomes, 55 mitogenomes, and multi-locus regions from modern and museum specimens. Genome-wide phylogenies supported taxonomic classification of the Chinese mountain cat as wildcat subspecies,F. s. bieti. No involvement ofF. s. bietiin cat domestication in East Asia was detected, confirming that domestic cats shared a single origin from the African wildcat(F. s. lybica). A complex hybridization scenario including ancient introgression from the Asiatic wildcat(F. s. ornata) toF. s. bieti, and contemporary gene flow betweenF. s. bietiand sympatric domestic cats in the Tibetan region, raises the prospect of disrupting the genetic integrity ofF. s. bieti, an issue with profound conservation implications.
A framework for predicting potential host ranges of pathogenic viruses based on receptor ortholog analysis
Authors: Du Guifang , Ding Yang , Li Hao , Wang Xuejun , Wang Junting , Sun Yu , Tao Huan , Huang Xin , Xu Kang , Hong Hao , Jiang Shuai , Wang Shengqi , Chen Hebing , Bo Xiaochen
Published: December 2020

Viral zoonoses are a serious threat to public health and global security, as reflected by the current scenario of the growing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. However, as pathogenic viruses are highly diverse, identification of their host ranges remains a major challenge. Here, we present a combined computational and experimental framework, called REceptor ortholog-based POtential virus hoST prediction (REPOST), for the prediction of potential virus hosts. REPOST first selects orthologs from a diverse species by identity and phylogenetic analyses. Secondly, these orthologs is classified preliminarily as permissive or non-permissive type by infection experiments. Then, key residues are identified by comparing permissive and non-permissive orthologs. Finally, potential virus hosts are predicted by a key residue–specific weighted module. We performed REPOST on SARS-CoV-2 by studying angiotensin-converting enzyme 2 orthologs from 287 vertebrate animals. REPOST efficiently narrowed the range of potential virus host species (with 95.74% accuracy).
The diversification of termites: inferences from a complete species-level phylogeny
Authors: Pie Marcio R. , Carrijo Tiago F. , Caron Fernanda S.
Published: December 2020

Termites play a major role in a variety of ecological processes in tropical and subtropical biomes worldwide, such as decomposition, soil formation and aeration, and nutrient cycling. These important ecosystem services were achieved through their highly complex societies and remarkable adaptations, including the evolution of sterile worker castes, the acquisition of endosymbionts, and the capacity for extensive environmental engineering, yet the causes and consequences of their ecological success are still poorly understood. The goals of our study were (1) to provide the first complete, species-level phylogeny of all currently recognized termite species by integrating the available genetic and taxonomic data, as well as methods of phylogenetic imputation and divergence time estimation; and (2) to explore variation in speciation rates among termite lineages. We provide the inferred relationships as a set of 1,000 pseudo-posterior trees, which can be used in future comparative analyses. We demonstrate that speciation rates have been relatively constant throughout the history of termites, with two positive shifts in speciation rates: one at their origin of Euisoptera and the other concordant with evolution of Termitidae. On the other hand, there was no obvious trend towards deceleration in speciation rates for termites as a whole, nor within the most species-rich families. The provided trees might represent a valuable resource for termite comparative studies by summarizing the available phylogenetic information, while accounting for uncertainty in the inferred topologies.
Testing for the resistance of newly generated hybrid cacao germplasm in the gene pool of Cocoa Research Institute of Nigeria (CRIN) againstPhytophthora megakaryapathogen causing black pod disease of cocoa
Authors: Tijani A. A. , Otuonye A. H. , Otusanya M. O. , Olaiya A. O. , Adenuga O. O. , Afolabi C. G.
Published: December 2020

Black pod disease caused byP. PalmivoraandP. megakaryais an important disease affectingcacaoin West Africa which produces 70% of the world output. Resistance to the pathogen is therefore, an important factor to be considered when breeding for high yielding and earliness in fruiting. Resistance to the pathogen using Leaf Disc Test (LDT) was conducted at the Plant Pathology Laboratory, Ibadan, on detached 15mm diameter discs of two-month-old leaves obtained from nineteen newly generatedcacaohybrids in the gene pool of the Institute. Attached Whole Leaf Test (AWLT) was also conducted on few selected hybrids in the screen house at the same institute. Ten μl zoospores suspension ofP. megakaryapathogen adjusted to inoculum strength of 3×105zoospores/ml using haemocytometer was used for the inoculation of thecacaoLD. Using 0-5 disease rating scale, data was taken on the 5thand 7thday after inoculation for LDT and on the 6thday after inoculation for AWLT. Data obtained were subjected to Analysis of Variance and significant means were separated using Student Newman Kuels Test at p<0.05. The LDT classified the hybrids into five groups namely: Resistant (hybrid 001, 003 and 005); Moderately Resistant (hybrid 006, 007, 008,013,015,018 and 019) Moderately Susceptible (hybrid 004, 014 and 017); Susceptible (hybrid 002, 010, 011 and 016) and Highly Susceptible (hybrid 009 and 012). Scores from LDT significantly correlated (r= 0.92**) with that of AWLT. It was observed from the study thatcacaohybrid 001, 003 and 005 showed traits of resistant and therefore, could be incorporated into the national breeding programs for the development of high-yielding and resistantcacaocultivars. The moderately resistant hybrids could be conserved for future germplasm enhancement program.
Oxidative stress conditions result in trapping of PHF-core tau (297-391) intermediates
Authors: Maina Mahmoud B. , Al-Hilaly Youssra K. , Burra Gunashekar , Rickard Janet , Harrington Charlie , Wischik Claude , Serpell Louise C.
Published: December 2020

The self-assembly of tau into paired helical filaments (PHF) in neurofibrillary tangles (NFTs) is a significant event in Alzheimer’s disease (AD) pathogenesis. Oxidative stress, which accompanies AD, induces multiple post-translational modifications in proteins including the formation of dityrosine (DiY) cross-links, previously observed for Aβ. Here, metal catalysed- and ultra-violet oxidation were used to study the influence of DiY cross-linking on the self-assembly of the PHF-core tau fragment. We report that DiY cross-linking facilitates tau assembly into tau oligomers and prevents their elongation into filaments. The DiY cross-linked tau oligomers were not toxic to cells. Our findings suggest that DiY cross-linking of pre-assembled tau, promotes the formation of soluble tau oligomers that show no acute toxicity.
DOT1L Complex Regulates Transcriptional Initiation in Human Cells
Authors: Wu Aiwei , Zhi Junhong , Tian Tian , Chen Lixue , Liu Ziling , Fu Lei , Roeder Robert G. , Yu Ming
Published: December 2020

DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17 and ENL/AF9, is dysregulated in most of the cases of mixed lineage leukemia (MLL) and is believed to regulate transcriptional elongation without much evidence. Here we show that the depletion of DOT1L reduced the global occupancy without affecting the traveling ratio or the elongation rate of Pol II, suggesting it not a major elongation factor. An examination of general transcription factors (GTFs) binding revealed globally reduced TBP and TFIIA occupancies near promoters after DOT1L loss, pointing to a role in transcriptional initiation. Proteomic studies uncovered that DOT1L regulates transcriptional initiation likely by facilitating the recruitment of TFIID. Moreover, ENL, a DOT1L complex subunit with a known role in DOT1L recruitment, also regulates transcriptional initiation. Furthermore, DOT1L stimulates H2B monoubiquitination by limiting the recruitment of human SAGA complex, and the connection between Dot1/DOT1L and SAGA complex is conserved between yeast and human. These results advanced current understanding of roles of DOT1L complex in transcriptional regulation and MLL.
The Relative Roles of Voice and Gesture in Early Communication Development
Authors: Burkhardt-Reed Megan M. , Long Helen L. , Bowman Dale D. , Bene Edina R. , Oller D. Kimbrough
Published: December 2020

Both vocalization and gesture are universal modes of communication and fundamental features of language development. Many believe that language evolved out of early gestural use; however, evidence reported here suggests vocalization precedes gesture in human communication and forms the predominant foundation for language. To our knowledge no prior research has investigated the rates of emergence of both gesture and vocalization in human infants to evaluate this question. We evaluated the rates of gesture and speech-like vocalizations (protophones) of 10 infants at 4, 7, and 11 months of age using parent-infant laboratory recordings. We found that infant protophones outnumbered gestures substantially at all three ages, ranging from >30 times more protophones than gestures at 3 months, to more than twice as many protophones as gestures at 11 months. The results suggest that vocalization is the predominant mode of communication in human infants from the beginning of life.
Application of mid-infrared free-electron laser for structural analysis of biological materials
Authors: Kawasaki Takayasu , Zen Heishun , Ozaki Kento , Yamada Hironari , Wakamatsu Kazumasa , Ito Shosuke
Published: December 2020

A mid-infrared free-electron laser (MIR-FEL) is a synchrotron-radiation-based femto- to pico-second pulse laser. It has unique characteristics such as variable wavelengths in the infrared region and an intense pulse energy. So far, MIR-FELs have been utilized to perform multi-photon absorption reactions against various gas molecules and protein aggregates in physical chemistry and biomedical fields. However, the applicability of MIR-FELs for the structural analysis of solid materials is not well recognized in the analytical field. In the current study, an MIR-FEL is applied for the first time to analyse the internal structure of biological materials by using fossilized inks from cephalopods as the model sample. Two kinds of fossilized inks that were collected from different strata were irradiated at the dry state by tuning the oscillation wavelengths of the MIR-FEL to the phosphoryl stretching mode of hydroxyapatite (9.6 µm) and to the carbonyl stretching mode of melanin (5.8 µm), and the subsequent structural changes in those materials were observed by using infrared microscopy and far-infrared spectroscopy. The structural variation of these biological fossils is discussed based on the infrared-absorption spectral changes that were enhanced by the MIR-FEL irradiation, and the potential use of MIR-FELs for the structural evaluation of biomaterials is suggested.
High-resolution macromolecular crystallography at the FemtoMAX beamline with time-over-threshold photon detection
Authors: Jensen Maja , Ahlberg Gagnér Viktor , Cabello Sánchez Juan , Bengtsson Åsa U. J. , Ekström J. Carl , Björg Úlfarsdóttir Tinna , Garcia-Bonete Maria-Jose , Jurgilaitis Andrius , Kroon David , Pham Van-Thai , Checcia Stefano , Coudert-Alteirac Hélène , Schewa Siawosch , Rössle Manfred , Rodilla Helena , Stake Jan , Zhaunerchyk Vitali , Larsson Jörgen , Katona Gergely
Published: December 2020

Protein dynamics contribute to protein function on different time scales. Ultrafast X-ray diffraction snapshots can visualize the location and amplitude of atom displacements after perturbation. Since amplitudes of ultrafast motions are small, high-quality X-ray diffraction data is necessary for detection. Diffraction from bovine trypsin crystals using single femtosecond X-ray pulses was recorded at FemtoMAX, which is a versatile beamline of the MAX IV synchrotron. The time-over-threshold detection made it possible that single photons are distinguishable even under short-pulse low-repetition-rate conditions. The diffraction data quality from FemtoMAX beamline enables atomic resolution investigation of protein structures. This evaluation is based on the shape of the Wilson plot, cumulative intensity distribution compared with theoretical distribution, I/σ, R
merge/R
meas and CC1/2 statistics versus resolution. The FemtoMAX beamline provides an interesting alternative to X-ray free-electron lasers when studying reversible processes in protein crystals.
Crystal structure and Hirshfeld surface analysis of 4-(2,6-dichlorobenzyl)-6-[(E)-2-phenylethenyl]pyridazin-3(2H)-one
Authors: Daoui Said , Cinar Emine Berrin , Dege Necmi , Chelfi Tarik , El Kalai Fouad , Abudunia Abdulmalik , Karrouchi Khalid , Benchat Noureddine
Published: December 2020

The title pyridazinone derivative, C19H14Cl2N2O, an important pharmacophore with a wide variety of biological applications is not planar, the chlorophenyl and pyridazinone rings being almost perpendicular, subtending a dihedral angle of 85.73 (11)°. The phenyl ring of the styryl group is coplanar with the pyridazinone ring [1.47 (12)°]. In the crystal, N—H...O hydrogen bonds form inversion dimers with an R
2
2(8) ring motif and C—H...Cl hydrogen bonds also occur. The roles of the intermolecular interactions in the crystal packing were clarified using Hirshfeld surface analysis, and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (37.9%), C...H/H...C (18.7%), Cl...H/ H...Cl (16.4%) and Cl...C/C...Cl (6.7%) contacts.
Crystal structure, Hirshfeld surface analysis and DFT study of 1-ethyl-3-phenyl-1,2-dihydroquinoxalin-2-one
Authors: Al Ati Gamal , Chkirate Karim , Mashrai Ashraf , Mague Joel T. , Ramli Youssef , Achour Redouane , Essassi El Mokhtar
Published: December 2020

In the title molecule, C16H14N2O, the dihydroquinoxaline moiety is not planar as there is a dihedral angle of 4.51 (5)° between the constituent rings. In the crystal, C—H...O hydrogen bonds form helical chains about the crystallographic 21screw axis in theb-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (51.7%), H...C/C...H (26%) and H...O/O...H (8.5%) interactions. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated HOMO–LUMO energy gap is 3.8918 eV.
Integrated mode of transport: a predictive model for route guidance
Authors: Ravish Roopa , Rangaswamy Shanta
Published: December 2020

Purpose

The purpose of this study is to provide real-time route guidance within city to help commuters.

Design/methodology/approach

In urban areas to avoid road congestion and to reach the destination on time, intelligent transport system (ITS) utilizes recent advanced technology. To support this, existing route guidance system (RGS) suggests alternative route to commuters. However, ITS requires a system which suggests the alternative route along with the mode of transport such as public, private, taxi services etc. Integrated mode of transport (IMT) implemented in this paper guides the commuters of urban area with the best mode of transport. Inputs to our IMT predictive model are the commuter's choice of (1) minimum travel time (2) minimum cost (3) flexible route and (4) less traffic intensity along with source and destination locations. Based on these user inputs, IMT predictive model suggests optimal mode of transport. In this paper to implement the IMT model, we have considered the transport facility available in Bangalore, a city in India. The city has metro train, bus and taxi services available to the commuters. Implementation is divided into two parts. In the first part, the model checks for the end-to-end connectivity/availability of metro train facility. If metro train connectivity exists, the model concludes this as the best mode of travel. In the second part, for the routes which are not connected by metro train, the optimal mode of transport through road network will be suggested. In the first part, to check the existence of metro train along the routes between source and destination, location-IQ API is used. In the later part, to suggest transport along the road network, Q-learning algorithm of reinforcement learning technique is used.

Findings

The findings are the predictive model algorithm to find the best mode of transfer and reinforcement model used in real time route guidance system.

Originality/value

This is a new Idea, not proposed in any research work.
Factors influencing customer switching behavior in Islamic banks: evidence from Kuwait
Authors: Ghamry Sherif , Shamma Hamed M.
Published: December 2020

Purpose

With increasing competition, Islamic banks in Kuwait are currently facing difficulties in retaining their customers as customers now have the option to switch from one bank to another. As the banking industry offers almost identical products and services, customers are more likely to change their bank when they get a better offer from another bank, especially if the customer is dissatisfied with the current bank. Thus, this study aims at identifying the most significant factors that make Islamic bank customers switch their bank.

Design/methodology/approach

The data for this study was collected through a survey with a response rate of 25.5%. Logistic regression was used to analyze the collected data and examine the effect of each factor on the customer switching behavior.

Findings

The results of empirical analysis reveal that the service convenience, service reliability, level of technology and Sharia compliance are the most significant factors influencing the customer switching behavior in Kuwaiti Islamic banks. Thus, Islamic bank managers should focus on these factors when building their strategies to increase their customer’s satisfaction and loyalty. Loyal customers are more profitable than new customers as they are more likely to use more services, spread a positive word of mouth and, more importantly, they are more likely to resist competitors’ offers.

Practical implications

Identifying and understanding these factors will enable Islamic bank managers to direct their efforts and resources to the most cost-effective ways that help them to retain their customers, and accordingly, increase bank profits.

Originality/value

To the best of the authors’ knowledge, this is the first study to examine the customer switching behavior in Kuwait, and one of the few to present a model that explains the stages through which customers pass until they reach the switching decision.
The challenge of online privacy preservation in Muslim-majority countries during the COVID-19 pandemic
Authors: El-Bassiouny Dina , El-Bassiouny Noha
Published: December 2020

Purpose

E-learning has become a predominant platform for education as a result of the COVID-19 pandemic. Yet, privacy issues have emerged from online learning that posed challenges on the users of e-learning systems. Privacy preservation in Muslim-majority countries with conservative cultures was a concern based on socio-cultural norms. This paper aims to analyze this situation through the lens of social identity theory.

Design/methodology/approach

This practice paper represents a conceptual viewpoint.

Findings

In this paper, the authors offer recommended solutions as best practices for Muslim-majority countries and similar contexts. Such proposed solutions consider social and cultural influences in e-learning systems to have an effective education process.

Originality/value

This practice paper is unique in its approach, as it documents the privacy concerns in Muslim-majority countries during the COVID-19 pandemic.
Impact of socio‐economic deprivation on endometrial cancer survival in the North West of England: a prospective database analysis
Authors: Njoku K , Barr CE , Hotchkies L , Quille N , Wan YL , Crosbie EJ
Published: December 2020

Objective

To assess the impact of socio‐economic deprivation on endometrial cancer survival.

Design

Single‐centre prospective database study.

Setting

North West England.

Population

Women with endometrial cancer treated between 2010 and 2015.

Methods

Areal‐level socio‐economic status, using the English indices of multiple deprivation from residential postcodes, was analysed in relation to survival using Kaplan–Meier estimation and multivariable Cox regression.

Main outcome measures

Overall survival, cancer‐specific survival and patterns and rates of recurrence.

Results

A total of 539 women, with a median age of 66 years (interquartile range, IQR 56–73 years) and a body mass index (BMI) of 32 kg/m2 (IQR 26–39 kg/m2), were included in the analysis. Women in the most deprived social group were younger (median 64 years, IQR 55–72 years) and more obese (median 34 kg/m2, IQR 28–42 kg/m2) than women in the least deprived group (median age 68 years, IQR 60–74 years; BMI 29 kg/m2, IQR 25–36 kg/m2; P = 0.002 and <0.001, respectively). There were no differences in endometrial cancer type, stage or grade between social groups. There was no difference in recurrence rates, however, women in the middle and most deprived social groups were more likely to present with distant/metastatic recurrence (80.6 and 79.2%, respectively) than women in the least deprived group (43.5%, P < 0.001). Women in the middle and most deprived groups had a two‐fold (adjusted hazard ratio, HR = 2.00, 95% CI 1.07–3.73, P = 0.030) and 53% (adjusted HR = 1.53, 95% CI 0.77–3.04, P = 0.221) increase in cancer‐specific mortality compared with women in the least deprived group. There were no differences in overall survival.

Conclusions

We found that socio‐economically deprived women with endometrial cancer were more likely to develop fatal recurrence. Larger studies are needed to confirm these findings and to identify modifiable contributing factors.

Tweetable abstract

Socio‐economic deprivation is linked to an increased risk of death from endometrial cancer in the North West of England.
Ancient Microorganisms and Carotenoids Preserved in Fluid Inclusions in Halite from Chaka Salt Lake, Western China: Evidence from Micro‐observation and in situ Raman Spectroscopy
Authors: CHEN Yong , WANG Jiuyuan , ZHOU Zhenzhu , CHEN Xiaolan , ZHAO Zhenyu , SHI Peng , HAN Yun
Published: December 2020

Trapped ancient microorganisms in halite fluid inclusions are of special interest to the understanding of biology and ecology in salt lake systems. With the integration of petrologic, microthermometric, and Raman spectroscopic analyses, this study utilizes fluid inclusions from Chaka Salt Lake, eastern Qaidam Basin, NW China, to assess the possibility of microorganism‐trapping by fluid inclusions. Here, we report that the solid phase of some primary fluid inclusions contains carotenoids, which is interpreted as evidence of Dunaliella algae, and that the coexisting liquid phase comprises SO42‐. The homogenization temperatures of single‐phase primary fluid inclusions indicate that the precipitation temperature of the Holocene halite in Chaka Salt Lake ranges from 13.5°C to 36.4°C. This suggests that fluid inclusions in halite are a good medium for trapping and preserving ancient microorganisms and organic matter in salt lakes, and that Raman spectroscopy has good potential to identify halophilic archaea.
Economic Impacts of the COVID−19 Lockdown in a Remittance‐Dependent Region
Authors: Gupta Anubhab , Zhu Heng , Doan Miki Khanh , Michuda Aleksandr , Majumder Binoy
Published: December 2020

The economic impacts of COVID‐19 lockdowns on poor and vulnerable households living in rural areas of developing countries are not well understood due to a lack of detailed micro‐survey data at the household level. Utilizing weekly financial transaction data collected from households residing in a rural region of India, we estimate the impacts of India's COVID‐19 lockdown on household income, food security, welfare, and access to local loan markets. A large portion of households living in our study region is reliant on remittances from migrants to sustain their livelihoods. Our analysis reveals that in the month immediately after India's lockdown announcement, weekly household local income fell by INR 1,022 (US$ 13.5), an 88% drop compared to the long‐term average with another 63% reduction in remittance. In response to the massive loss in earnings, households substantially reduced meal portions and consumed fewer food items. Impacts were heterogeneous; households in lower income quantiles lost a higher percentage of their income and expenditures, but government food aid slightly mitigated the negative impacts. We also find an increase in the effective interest rate of local borrowing in cash and a higher demand for in‐kind loans, which are likely to have an adverse effect on households who rely on such services. The results from this paper have immediate relevance to policymakers considering additional lockdowns as the COVID‐19 pandemic resurges around the globe and to governments thinking about responses to future pandemics that may occur.
Testicular steroid sulfatase overexpression is associated with Leydig cell dysfunction in primary spermatogenic failure
Authors: Lardone Maria C. , Reyes Ian N. , Ortiz Eliana , Piottante Antonio , Palma Cristián , Ebensperger Mauricio , Castro Andrea
Published: December 2020

Background

Decreased testosterone (T) to LH ratio and increased 17β‐estradiol (E2) serum concentrations represent a common finding among patients with severe spermatogenic failure, suggesting a concurrent Leydig cell steroidogenic dysfunction. Aromatase overexpression has been associated with increased serum and intratesticular E2 in these patients. However, it is unknown whether the sulfatase pathway contributes to the increased availability of active estrogens in patients with primary spermatogenic failure.

Objectives

To assess estrogen sulfotransferase (SULT1E1) and steroid sulfatase (STS) mRNA abundance in testicular tissue of patients with Sertoli cell‐only syndrome (SCOS) and normal tissues, its association with serum and intratesticular hormone levels, and to explore the mRNA and protein testicular localization of both enzymes.

Materials and Methods

Testicular tissues of 23 subjects with SCOS (cases) and 22 patients with obstructive azoospermia and normal spermatogenesis (controls) were obtained after biopsy. SULT1E1 and STS transcripts accumulation was quantified by RT‐qPCR. For mRNA and protein localization, we performed RT‐qPCR in Leydig cell clusters and seminiferous tubules isolated by laser‐capture microdissection and immunofluorescence in testicular tissues. Serum and intratesticular hormones were measured by immunoradiometric assays.

Results

SULT1E1 mRNA accumulation was similar in both groups. The amount of STS mRNA was higher in cases (p = 0.007) and inversely correlated with T/LH ratio (r = −0.402; p = 0.02). Also, a near significant correlation was observed with intratesticular E2 (r = 0.329, p = 0.057), in agreement with higher intratesticular E2 in cases (p < 0.001). Strong STS immunoreaction was localized in the wall of small blood vessels but not in Leydig cells. Both SULT1E1 and STS mRNA abundance was similar in Leydig cell clusters and the tubular compartment, except for lower SUTL1E1 mRNA in the seminiferous tubules of SCOS patients (p = 0.001).

Conclusions

Our results suggest that an unbalance of the STS/SULT1E1 pathway contributes to the testicular hyperestrogenic microenvironment in patients with primary spermatogenic failure and Leydig cell dysfunction.
European Standards of Care for Newborn Health—A project protocol
Authors: Lindacher Verena , Altebaeumer Philine , Marlow Neil , Matthaeus Valerie , Straszewski Iris Nikola , Thiele Nicole , Pfeil Johanna M. , Zimmermann Luc J.I. , Mader Silke ,   the European Standards of Care for Newborn Health project members
Published: December 2020

Aim

Among children who receive hospital care, preterm infants are Europe's largest group, whose numbers are continually increasing. Currently, no pan‐European standards of care for preterm or critically ill infants are available, except for a few specific topics, and practices vary widely in different regions.

Methods

The European Foundation for the Care of Newborn Infants (EFCNI) has initiated a transdisciplinary collaboration project to provide agreed standards for high‐quality perinatal and neonatal care, whose implementation will ensure fairer and more equitable care across Europe. This will improve care for these vulnerable infants and their families, ameliorate the long‐term conditions found in preterm and critically ill infants and enhance the quality of family life of affected families. More than 220 experts—healthcare professionals, patient representatives and other relevant stakeholders—have come together for the first time to develop a broad reference guidance in neonatology and associated fields.

Results

Ninety‐six standards on 11 overarching topic areas were developed and endorsed.

Conclusion

This reference framework serves as a basis for the development of binding national standards for high‐quality care. A robust translation and implementation strategy is facilitated, with the goal of improved health outcomes following preterm birth all around Europe.