bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein kinase D1 variant associated with human epilepsy and peripheral nerve hypermyelination
Authors: Omer Salma , Jin Sheng Chih , Koumangoye Rainelli , Robert Stephanie M. , Duran Daniel , Nelson‐Williams Carol , Huttner Anita , DiLuna Michael , Kahle Kristopher T. , Delpire Eric 
Published: April 2021

AbstractWe report the case of a patient with severe progressive epilepsy and peripheral neuropathy and a novel de novo inactivating variant (p.E79X) in Protein Kinase D1 (PKD1). Using CRISPR/Cas9, we engineered the homologous variant in mice and showed that in the homozygote mouse, it recapitulated the patient peripheral nerve hypermyelination pathology. The lethality of the homozygote mouse prevented us from performing an assessment of locomotor behavior. The mutant heterozygote mouse; however, exhibited a significant increase in kainate‐induced seizure activity over wild‐type mice, supporting the hypothesis that the PKD1 variant is a candidate for the cause of the patient epilepsy. Because PKD1 was previously identified in a kinomic screen as an interacting partner of the K‐Cl cotransporter 3 (KCC3), and since KCC3 is involved in peripheral nerve disease and brain hyperexcitability, one possible mechanism of action of PKD1 in disease is through KCC3. We show that catalytically inactive PKD1 stimulates KCC3 activity, consistent with tonic relief of inhibitory phosphorylation. Our findings implicate a novel role for PKD1 in the human nervous system, and uncover a mechanism that could serve as a potential target to promote nervous system myelination.
The need to rethink African “Ideas of Christ” in the search for human flouring in post‐Covid‐19 era
Authors: Kaunda Chammah J. 
Published: April 2021

AbstractThis article argues that if the African church is to make a meaningful contribution to human survival, livelihood, and dignity in post‐Covid‐19, it must reclaim and reconstitute the Christ of the marginalized and excluded who joins them in their suffering, struggles, and hopes for a liberated and emancipated post‐Covid‐19 Africa. This requires a passionate commitment to rethinking the idea of Christ as a critical resource to mobilize the masses for transformation and bettering their social contexts. The article concludes that the apparent contradiction between Christocapitalist Christian faith and the historical struggles of the masses reveals the underlying contradiction within most churches’ conceptions of Christ.
The COVID‐19 pandemic and the internationalization of production: A review of the literature
Authors: Kersan‐Škabić Ines 
Published: April 2021

AbstractMotivationThe COVID‐19 pandemic has substantially altered the context for cross‐border business. This is reflected in trade flows but the conditions for conducting dispersed production functions across countries are also affected. This “new normal” period presents the need to examine the main problems and challenges in international trade and business.PurposeThe article aims to establish the scope, aspects, and implications of the COVID‐19 pandemic on international trade and on international production by reviewing recent articles which deal with international trade and global value chain (GVC) issues, encompassing both changes that were already taking place and the challenges that began in 2020.Methods and approachThe findings of recent articles on trade flows and changes in GVCs (mainly the period 2019–2021) are described in theoretical terms, compared, and systematically reviewed. Special focus is given to the impact of the pandemic on GVCs, renationalization, and GVCs and the impact of the pandemic on GVC governance, and GVCs in the production of vaccines for the COVID‐19 virus.FindingsA drop in trade was recorded in 2020, alongside the introduction of protective trade policy measures. Reduced GVC activities had a negative impact on welfare and the “renationalization” of GVC‐related activities is not a real solution. For the development of GVCs it is important to find a trade‐off between efficiency and resilience, starting with reorganization (re‐engineering) of GVCs, and probably focusing on regional frameworks. Liberal trade policies are essential to ensure the involvement of GVCs in producing the COVID‐19 vaccines, since the various inputs are produced in different countries.Policy implicationsThe possible directions for the future development of GVCs are elaborated: reshoring, resilience in supply chains, adjustments in governance, diversification, and development of risk‐management strategies. The process of internationalization is not in question, but presents challenges which create the need for adjustments in its future development. Current problems with vaccine production arise in part from the erection of trade barriers and rising nationalism. There is a need for greater cross‐country co‐operation to avoid placing national short‐term interests before long‐term and broader objectives.
Dexmedetomidine protects SH‐SY5Y cells against MPP+‐induced declining of mitochondrial membrane potential and cell cycle deficits
Authors: Chen Yaohua , Chen Cheng , Song Dan , Liu Tingting , Cheng Oumei 
Published: April 2021

AbstractDexmedetomidine (Dex), an adrenergic α2 receptor agonist, is commonly used in deep‐brain stimulation surgery for Parkinson's disease (PD). However, there is evidence that the use of anaesthetics may accelerate the progression of neurodegenerative diseases. The effect of Dex on PD remains unclear. Here, we cultured the all‐trans‐retinoicacid (ATRA) differentiated SH‐SY5Y cells in vitro and then treated with MPP+ (1.5mM) with or without Dex (10nM) or Dex combined with Atipamezole (Ati,100nM, adrenergic α2 receptor inhibitor). The ratio of apoptotic cells, mitochondrial membrane potential (Δψm), reactive oxygen species (ROS), cell cycle and apoptotic markers (Cleaved caspase‐3, 9) were analysed by flow cytometry and immunofluorescence. We found that the levels of apoptotic ratio and cleaved caspase‐3, 9 increased, ROS accumulated, and mitochondrial membrane potential decreased after MPP+treatment, while these changes were partially reversed by Dex. Dex also prevented MPP+ induced cell arrest by increasing G1 phase cells, decreasing S phase cells, and decreasing the expression of cyclinD1 and Cdk4. Moreover the effects of Dex were partially reversed by Ati. These findings reveal that Dex attenuated MPP+‐induced apoptosis of SH‐SY5Y cells by preventing the loss of Δψm, reducing ROS, and regulating the cell cycle. Our findings indicated that Dex is more likely to be a potential drug for the treatment of PD.
Effect of high phosphate diet on the formation of dentin in Fam20c‐deficient mice
Authors: Zhang Hua , Xu Qian , Lu Yongbo , Qin Chunlin 
Published: April 2021

AbstractFAM20C (family with sequence similarity 20‐member C), a kinase that phosphorylates secretory proteins, plays essential roles in various biological processes. In humans, mutations in FAM20C gene cause Raine syndrome, an autosomal recessive hereditary disease manifesting a broad spectrum of developmental defects including skeletal and craniofacial deformities. Our previous studies revealed that inactivation of Fam20c in mice led to hypophosphatemic rickets and that high phosphate (hPi) diet significantly improved the development of the skeleton in Fam20c‐deficient mice. In this study, we evaluated the effects of hPi diet on the formation of dentin in Fam20c‐deficient mice, using plain x‐ray radiography, micro–computed tomography (µCT), histology, and immunohistochemistry. Plain x‐ray radiography and µCT analyses showed that the hPi diet improved the dentin volume fraction and dentin mineral density of the Fam20c‐deficient mice. Histology analyses further demonstrated that the hPi diet dramatically improved the integrity of the mandibular first molars and prevented pulp infection and dental abscesses in Fam20c‐deficient mice. Our results support that the hPi diet significantly increased the formation and mineralization of dentin in Fam20c‐deficient mice, implying that hypophosphatemia is a significant contributor to the dentin defects in Fam20c‐deficient subjects.
Contribution of ethology to evolutionary medicine
Authors: Bender Nicole 
Published: April 2021

AbstractEvolutionary medicine is a concept that arose mainly in the 1990s, and which applies evolutionary biological principles to human medical fields. For instance, evolutionary medicine proposed that there is an evolutionary mismatch between the human anatomy and physiology and novel, man‐made environments, leading to the so‐called diseases of civilization. Constraints exist on the process of natural selection, and evolutionary trade‐offs can prevent traits from being optimal, leaving humans with traits that at first sight seem maladaptive, such as the very narrow birth canal of humans. More generally, certain traits can increase reproduction at the cost of health and longevity. Other traits, such as pain and fever, are related to protective physiological defences, and not diseases. Some medical topics have biological roots in the field of ethology, particularly human ethology, such as the behavioural aspects of psychiatry and addiction. Compulsive overeating and binge eating show similarities to substance‐linked addictions and behavioural addictions. Interactions between behaviour, stress and diseases have ancient evolutionary roots, which may lead to a mismatch to the modern human environment. A subject of high, topical interest is the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, as the behavioural aspects of population compliance are crucial for the success in fighting the pandemic. Ethology, and evolutionary biology in general, can substantially contribute to improving the biological understanding of medical phenomena, and therefore of medical and public health interventions. This applies not only to research but also to education.
Kappa‐opioid receptor‐mediated thermal analgesia evoked by the intrathecal administration of the chemokine CCL1 in mice
Authors: García‐Domínguez Mario , González‐Rodríguez Sara , Hidalgo Agustín , Baamonde Ana , Menéndez Luis 
Published: April 2021

AbstractBackgroundThe chemokine CC motif ligand 1 (CCL1) participates in immune cell recruitment and, as other chemokines, is also involved in nociceptive processing. In contrast with previous reports indicating its participation in allodynia and cold hypernociception when spinally administered, its ability to evoke heat thermal analgesia, mediated by circulating leukocytes and endocannabinoids, after systemic administration has recently been reported.ObjectivesAiming to explore the role played by CCL1 on spinal nociception, we study here the effect of its intrathecal administration on thermal nociception in mice.MethodsBehavioral nociceptive assays, immunohistochemical experiments, white cell blood depletion procedures and qRT‐PCR experiments were performed.ResultsThe intrathecal administration of CCL1 (0.3–30 ng) produced analgesia as measured by the unilateral hot plate test. This effect peaked 1 h after injection, was prevented by the CCR8 antagonist R243 and was accompanied by a reduction of c‐Fos expression in spinal neurons. Whereas blood leukocyte depletion did not modify it, analgesia was abolished by the microglial inhibitor minocycline, but not the astroglial inhibitor aminoadipate. Furthermore, antinociception remained unmodified by the coadministration of cannabinoid type 1 or 2 receptors antagonists. However, it was reversed by naloxone but not by selective blockade of mu‐ or delta‐opioid receptors. The inhibitory effect induced by the selective kappa‐opioid receptor antagonist, nor‐binaltorphimine, and by an anti‐dynorphin A 1‐17 antibody indicates that analgesia evoked by spinal CCL1 is mediated by endogenous dynorphins acting on kappa‐opioid receptors.ConclusionsEndogenous dynorphin and microglia behave as key players in heat thermal analgesia evoked by spinal CCL1 in mice.
Distinct interspecific and intraspecific vulnerability of coastal species to global change
Authors: Nielsen Erica S. , Henriques Romina , Beger Maria , von der Heyden Sophie 
Published: April 2021

AbstractCharacterising and predicting species responses to anthropogenic global change is one of the key challenges in contemporary ecology and conservation. The sensitivity of marine species to climate change is increasingly being described with forecasted species distributions, yet these rarely account for population level processes such as genomic variation and local adaptation. This study compares inter‐ and intraspecific patterns of biological composition to determine how vulnerability to climate change, and its environmental drivers, vary across species and populations. We compare species trajectories for three ecologically important southern African marine invertebrates at two time points in the future, both at the species level, with correlative species distribution models, and at the population level, with gradient forest models. Reported range shifts are species‐specific and include both predicted range gains and losses. Forecasted species responses to climate change are strongly influenced by changes in a suite of environmental variables, from sea surface salinity and sea surface temperature, to minimum air temperature. Our results further suggest a mismatch between future habitat suitability (where species can remain in their ecological niche) and genomic vulnerability (where populations retain their genomic composition), highlighting the inter‐ and intraspecific variability in species’ sensitivity to global change. Overall, this study demonstrates the importance of considering species and population level climatic vulnerability when proactively managing coastal marine ecosystems in the Anthropocene.
Factors associated with the accomplishment of home death among patients receiving physician‐led home healthcare
Authors: Tomita Shiori , Kuga Takao , Osugi Yasuhiro , Kobayashi Daiki 
Published: April 2021

AimTo evaluate unique factors associated with home death in older Asian individuals who received physician‐led home healthcare.MethodsWe carried out a case–control study at a single hospital in Japan from February 2018 to December 2019. We included patients who had started receiving physician‐led home healthcare and died at home as cases, and those receiving the same type of care but died in the hospital as controls. Multivariable logistic regression was used to evaluate factors associated with home death.ResultsA total of 152 patients (mean age 70.3 years [SD 11.2 years]; 86 [56.6%] men) were included, of whom 89 (58.6%) died at home and 63 (41.4%) died in the hospital. Comparing the two groups, the presence of family psychological problems related to care was significantly more common in the hospital death group (home death 49.4%; hospital death 32.3%, P = 0.036). Home death was related to patients aged >85 years compared with patients aged <75 years (adjusted odds ratio 6.47, 95% CI 1.52–27.48) and patients who were in the highest quartile of the number of symptoms (adjusted odds ratio 5.45, 95% CI 1.15–25.95) compared with the lowest. Family members' willingness for the patient to die at home was associated with home death (adjusted odds ratio 7.47, 95% CI 2.13–26.19).ConclusionsOlder age and multiple symptoms were related to accomplishing home death. Patient preference was not associated with the place of death, but family member preference was. These results might reflect family concepts particular to Asia. Geriatr Gerontol Int 2021; 21: 525–531.
Influencing factors for delayed discharge following day surgery: A retrospective case–control study
Authors: Zhu Wei , Huang Mingjun , Dai Yan , Li Jiping 
Published: April 2021

AbstractAimWe aimed to identify the risk factors for delayed discharge in a day surgery centre in west China.BackgroundDelayed discharge affected by various factors is a key indicator for healthcare quality of day surgery. However, few studies have focused on this issue in developing countries where the day surgery started much later.DesignA retrospective case–control design.MethodA random sample of 169 delayed discharge cases and 514 normal discharge cases was randomly selected from 38,021 day surgery cases from May 2011 to May 2019 in a tertiary teaching hospital in west China. Socio‐demographic and clinical characteristics of patients were collected through the hospital electronic database and a chart review. A multivariate logistic regression was conducted to identify the risk factors for delayed discharge.ResultsThe urban employee basic medical insurance, comorbidity, general anaesthesia, pain, fever, bleeding and metabolic disorder were identified as the risk factors for delayed discharge. Living in the city where the hospital located was a protective factor for delayed discharge.ConclusionPost‐operative complications including fever, pain, bleeding and metabolic disorder were the most important risk factors for delayed discharge. The pre‐operative prevention, careful monitoring and rapid reactions to post‐operative complications may reduce delayed discharge.
Structure and viscosity of CaO–Al2O3–B2O3–BaO slags with varying mass ratio of BaO to CaO
Authors: Singh Harishchandra , Shu Qifeng , King Graham , Liang Ziqing , Wang Zhifeng , Cao Wei , Huttula Marko , Fabritius Timo 
Published: April 2021

AbstractThe structure of CaO–Al2O3–B2O3–BaO glassy slags with varying mass ratio of BaO to CaO has been investigated by Raman spectroscopy, 11B and 27Al magic angle spinning nuclear magnetic resonance (MAS‐NMR) spectroscopy and atomic pair distribution function (PDF). 11B MAS‐NMR spectra reveal the dominant coordination of boron as trigonal. Both simulations on 11B MAS‐NMR spectra and Raman spectroscopy indicate the presence of orthoborate as the primary borate group with a few borate groups with one bridging oxygen and minor four‐coordinated boron sites. 27Al MAS‐NMR and PDF show the Al coordination as tetrahedral. Raman spectral study shows that the transverse vibration of AlIV–O–AlIV and AlIV–O–BIII, stretching vibration of aluminate structural units and vibration of orthoborate and pyroborate structural groups. A broader distribution of Al–O bond lengths in PDF also supports the enhanced network connectivity. Viscosity measurements show the increase in viscosity of molten slags with increasing mass ratio of BaO to CaO, which further attributes to the enhanced degree of polymerization of the aluminate network.
Half‐year follow‐up of patients recovering from severe COVID‐19: Analysis of symptoms and their risk factors
Authors: Shang Y. F. , Liu T. , Yu J. N. , Xu X. R. , Zahid K. R. , Wei Y. C. , Wang X. H. , Zhou F. L. 
Published: April 2021

AbstractObjectivesTo understand the sequelae of COVID‐19.MethodsWe followed up 1174 patients with severe coronavirus disease 2019 (COVID‐19)who were recovered and discharged for 6 months.ResultsThere were 175 cases with clear IgG results 6 months after discharge, of which 82 (46.9%) were IgG (+) and 16 (9.1%) were IgG (dim+). Four hundred and forty‐one participants (55.4%) had some kind of sequelae. The most common symptoms were fatigue (25.3%), sleep disorder (23.2%) and shortness of breath (20.4%). In those who had sequelae, 262 (59.4%) had more than one symptom. Critical cases were more likely to have cough (20.5% vs 11.6%, p = 0.023) and hypomnesis (15.1% vs 8.0%, p = 0.041) than severe cases. Furthermore, univariate and multivariate logistic regression analyses revealed that women are more likely to have multiple symptoms (p = 0.002), fatigue (p = 0.009) and sleep disorder (p = 0.008), whereas critical illness was found as independent risk factor for hypomnesis (p = 0.045).ConclusionOur study demonstrated the duration of antibody and sequelae of COVID‐19 and compared the differences amongst different populations.
Connecting the epigenome, metabolome and proteome for a deeper understanding of disease
Authors: Suhre K. , Zaghlool S. 
Published: April 2021

AbstractEpigenome‐wide association studies (EWAS) identify genes that are dysregulated by the studied clinical endpoints, thereby indicating potential new diagnostic biomarkers, drug targets and therapy options. Combining EWAS with deep molecular phenotyping, such as approaches enabled by metabolomics and proteomics, allows further probing of the underlying disease‐associated pathways. For instance, methylation of the TXNIP gene is associated robustly with prevalent type 2 diabetes and further with metabolites that are short‐term markers of glycaemic control. These associations reflect TXNIP’s function as a glucose uptake regulator by interaction with the major glucose transporter GLUT1 and suggest that TXNIP methylation can be used as a read‐out for the organism’s exposure to glucose stress. Another case is the association between DNA methylation of the AHRR and F2RL3 genes with smoking and a protein that is involved in the reprogramming of the bronchial epithelium. These examples show that associations between DNA methylation and intermediate molecular traits can open new windows into how the body copes with physiological challenges. This knowledge, if carefully interpreted, may indicate novel therapy options and, together with monitoring of the methylation state of specific methylation sites, may in the future allow the early diagnosis of impending disease. It is essential for medical practitioners to recognize the potential that this field holds in translating basic research findings to clinical practice. In this review, we present recent advances in the field of EWAS with metabolomics and proteomics and discuss both the potential and the challenges of translating epigenetic associations, with deep molecular phenotypes, to biomedical applications.
Nocturnal cerebral tissue oxygenation in lowlanders with chronic obstructive pulmonary disease travelling to an altitude of 2,590 m: Data from a randomised trial
Authors: Furian Michael , Flueck Deborah , Scheiwiller Philipp M. , Mueller‐Mottet Séverine , Urner Lorenz M. , Latshang Tsogyal D. , Ulrich Silvia , Bloch Konrad E. 
Published: April 2021

SummaryAltitude exposure induces hypoxaemia in patients with chronic obstructive pulmonary disease (COPD), particularly during sleep. The present study tested the hypothesis in patients with COPD staying overnight at high altitude that nocturnal arterial hypoxaemia is associated with impaired cerebral tissue oxygenation (CTO). A total of 35 patients with moderate‐to‐severe COPD, living at <800 m (mean [SD] age 62.4 [12.3] years, forced expiratory volume in 1 s [FEV1] 61 [16]% predicted, awake pulse oximetry ≥92%) underwent continuous overnight monitoring of pulse oximetry (oxygen saturation [SpO2]) and near‐infrared spectroscopy of prefrontal CTO, respectively, at 490 m and 2,590 m. Regression analysis was used to evaluate whether nocturnal arterial desaturation (COPDDesat, SpO2 <90% for >30% of night‐time) at 490 m predicted CTO at 2,590 m when controlling for baseline variables. At 2,590 m, mean nocturnal SpO2 and CTO were decreased versus 490 m, mean change −8.8% (95% confidence interval [CI] −10.0 to −7.6) and −3.6% (95% CI −5.7 to −1.6), difference in change ΔCTO‐ΔSpO2 5.2% (95% CI 3.0 to 7.3; p < .001). Moreover, frequent cyclic desaturations (≥4% dips/hr) occurred in SpO2 and CTO, mean change from 490 m 35.3/hr (95% CI 24.9 to 45.7) and 3.4/hr (95% CI 1.4 to 5.3), difference in change ΔCTO‐ΔSpO2 −32.8/hr (95% CI −43.8 to −21.8; p < .001). Regression analysis confirmed an association of COPDDesat with lower CTO at 2,590 m (coefficient −7.6%, 95% CI −13.2 to −2.0; p = .007) when controlling for several confounders. We conclude that lowlanders with COPD staying overnight at 2,590 m experience altitude‐induced hypoxaemia and periodic breathing in association with sustained and intermittent cerebral deoxygenation. Although less pronounced than the arterial deoxygenation, the altitude‐induced cerebral tissue deoxygenation may represent a risk of brain dysfunction, especially in patients with COPD with nocturnal hypoxaemia at low altitude.