bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of Stroke and Population‐Attributable Fractions of Risk Factors in Latin America and the Caribbean
Authors: Pacheco‐Barrios Kevin , Giannoni‐Luza Stefano , Navarro‐Flores Alba , Rebello‐Sanchez Ingrid , Parente Joao , Balbuena Ana , de Melo Paulo S. , Otiniano‐Sifuentes Ricardo , Rivera‐Torrejón Oscar , Abanto Carlos , Alva‐Diaz Carlos , Musolino Patricia L. , Fregni Felipe 
Published: October 2022

Background
Stroke burden characterization studies in low‐ and middle‐income countries are scarce. We estimated the burden of stroke and its risk factors in Latin America and the Caribbean (LAC).

Methods and Results
We extracted GBD (Global Burden of Disease) study 2019 data on overall stroke and 3 subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) for 20 LAC countries. We estimated absolute and age‐standardized rates of disability‐adjusted life years, years of life lost, years lived with disability, and deaths. The population‐attributable fractions of 17 risk factors were estimated. All analyses were performed at regional and national levels by stroke subtype, sex, and age subgroups. In 2019, the LAC region had the fourth largest stroke burden worldwide (6.8 million disability‐adjusted life years), predominantly attributable to premature deaths (89.5% of disability‐adjusted life years). Intracerebral hemorrhage was the primary cause of the overall stroke burden (42% of disability‐adjusted life years), but ischemic stroke was the leading cause of disability (69% of total years lived with disability). Haiti and Honduras had the highest age‐standardized rates. Older adults and men had the largest burdens, although women had the highest rate of disability. Socioeconomic development level did not influence the burden. The major risk factor clusters were metabolic (high systolic blood pressure [population‐attributable fraction=53%] and high body mass index [population‐attributable fraction=37%]), which were more influential in hemorrhagic events, women, and older adults. Household air pollution was an important risk factor in low‐income countries in LAC.

Conclusions
The stroke burden and stroke‐related mortality in LAC are higher than the worldwide averages. However, stroke is a highly preventable disease in this region. Up to 90% of the burden could be reduced by targeting 2 modifiable factors: blood pressure and body mass index. Further research and implementation of primary and secondary prevention interventions are needed, as well as integrated national stroke care programs for acute, subacute, and rehabilitation management in LAC.
Finitude in Maurice Blondel
Authors: Emma-Adamah Victor 
Published: October 2022

Abstract
The thought of Maurice Blondel has been read (representatively by Emmanuel Falque) as the theological aspirational movement of human action towards the divine, and therefore as the pre-emptive presence of the infinite to human experience. In this reading, absent has been the appreciation of an original Blondelian account of finitude as the essential experience of a human being-toward-death. Against this approach, this essay explores Blondel’s notion of human finitude as a ‘metaphysical experience’ of the existentially revelatory function of death. To this extent, Blondel’s account of finitude positions the philosopher of Aix, beyond the usual contexts of twentieth-century Catholic apologetic philosophy, squarely within Continental philosophical proposals of finitude as seen in Heidegger, Foucault, and Deleuze. Blondel brings to prominence a French Spiritualist account of the positive value of endurance and resistance against death as the revelatory site of a finitude that is neither determined by an a priori closed boundary nor theologically overdetermined as an aspiration to the infinite.
Naldurg Fort, Deccan, India: Dam, Fortifications, Palace
Authors: Morelle Nicolas 
Published: October 2022

Abstract
The introduction of new water supply techniques in the Deccan region of India helped make water a crucial factor in local warfare. Improved water supply and conservation influenced military networks, especially at sites located on the strategic frontiers between local polities. Water management also served residential complexes within fortified sites and agricultural improvements in the surrounding arid landscape. This survey of the Naldurg Fort, overlooking a lofty gorge on the Bhima River in the modern state of Maharashtra, examines how builders in the sixteenth and seventeenth centuries dammed available water to service a strategic frontier military garrison, thereby creating a refreshing environment for a pleasure palace and garden.
All photographs and the survey are by Nicolas Morelle.
Water and Work in Mughal Gardens and Landscapes
Authors: Wescoat James L. 
Published: October 2022

Abstract
Laborers and draft animals played underexamined roles in building and operating the waterworks of Mughal gardens and landscapes. This article analyzes four sources of evidence about water-related work: Mughal paintings; historical texts on the political economy of Mughal waterworks; historical sources assessed in relation to modern estimates of human and animal energy needed to build and operate the waterworks; and historical sources considered in relation to the work of natural waters shaping land and society in material and cultural terms. Taken together, these four lines of inquiry provide a unified framework for research on Mughal waterworks and livelihoods.
Falaj Communities in Oman: A Case for Local Governance?
Authors: Bandyopadhyay Soumyen , Mershen Birgit 
Published: October 2022

Abstract
This contribution studies the complex arrangement of legal, socio-economic, and technical aspects of the aflāj (s. falaj) water distribution and irrigation system, and how they have shaped communities and built environments in Oman, where the falaj has provided the virtual lifeline of oasis life since the first millennium BCE. Three case studies of falaj communities are presented, Birkat al-Mawz, al-Ḥamrāʾ, and Misfāt al-ʿAbrīyin, which developed during the prosperous early-Yaʿrubi period in the mid-eleventh/seventeenth century. It investigates the extent to which the Ibāḍī-Islamic legal framework allowed flexibility for the local governance, management, and organisation of this ancient system, and its adaptation to diverse demographic, environmental, and emergent socio-political conditions.
A Novel Standardized Drought and Flood Potential Index Based on Reconstructed Daily GRACE Data
Authors: Xiong Jinghua , Guo Shenglian , Abhishek  , Li Jun , Yin Jiabo 
Published: October 2022

Abstract
Multiple indicators derived from the Gravity Recovery and Climate Experiment (GRACE) satellite have been used in monitoring floods and droughts. However, these measures are constrained by the relatively short time span (∼20 years) and coarse temporal resolution (1 month) of the GRACE and GRACE Follow-On missions, and the inherent decay mechanism of the land surface system has not been considered. Here we reconstructed the daily GRACE-like terrestrial water storage anomaly (TWSA) in the Yangtze River basin (YRB) during 1961–2015 based on the Institute of Geodesy at Graz University of Technology (ITSG)-Grace2018 solution using the random forest (RF) model. A novel antecedent metric, namely, standardized drought and flood potential index (SDFPI), was developed using reconstructed TWSA, observed precipitation, and modeled evapotranspiration. The potential of SDFPI was evaluated against in situ discharge, VIC simulations, and several widely used indices such as total storage deficit index (TSDI), self-calibrated Palmer drought severity index (sc-PDSI), and multiscale standardized precipitation evapotranspiration index (SPEI). Daily SDFPI was utilized to monitor and characterize short-term severe floods and droughts. The results illustrate a reasonably good accuracy of ITSG-Grace2018 solution when compared with the hydrological model output and regional water balance estimates. The RF model presents satisfactory performances for the TWSA reconstruction, with a correlation coefficient of 0.88 and Nash–Sutcliffe efficiency of 0.76 during the test period 2011–15. Spatiotemporal propagation of the developed SDFPI corresponds well with multiple indices when examined for two typical short-term events, including the 2003 flood and 2013 drought. A total of 22 submonthly exceptional floods and droughts were successfully detected and featured using SDFPI, highlighting its outperformance and capabilities in providing inferences for decision-makers and stakeholders to monitor and mitigate the short-term floods and droughts.
Transcriptional regulation mechanism of wheat varieties with different nitrogen use efficiencies in response to nitrogen deficiency stress
Authors: Wang Hanxia , Ma Qiaoyun , Shan Fuhua , Tian Liping , Gong Jie , Quan Wei , Yang Weibing , Hou Qiling , Zhang Fengting , Zhang Shengquan 
Published: October 2022

Abstract
Background
As one of the microelements, nitrogen play essential roles in cereal production. Although the use of chemical fertilizers has significantly improved the yield of wheat, it has also caused increasingly adverse environmental pollution. Revealing the molecular mechanism manipulating wheat nitrogen use efficiency (NUE), and cultivating wheat germplasms with high nitrogen use efficiency has become important goals for wheat researchers. In this study, we investigated the physiological and transcriptional differences of three wheat cultivars with different NUE under low nitrogen stress.

Results
The results showed that, under low nitrogen conditions, the activities of nitrogen metabolism-related enzymes (GS, NR, GDH), antioxidant enzymes (SOD, POD, CAT) and soluble protein contents of ZM366 (high NUE cultivar) were higher than those of JD8 (low NUE cultivar). The hybrid cultivar of ZM366 and JD8 showed mid-parent or over-parent heterosis. Transcriptome analysis revealed that ‘alanine, aspartate and glutamate metabolism’, ‘terpenoid backbone biosynthesis’ and ‘vitamin B6 metabolism’ pathways play key roles in nitrogen use efficiency in wheat. The significant enhancement of the ‘Calvin cycle’ and ‘photorespiration’ in ZM366 contributed to its higher level of carbon metabolism under low nitrogen stress, which is an important attribute differs from the other two varieties. In addition, the activation of ABA signal transduction and biosynthesis pathways also helps to maintain NUE under low- nitrogen conditions. Moreover, bHLH transcription factors were also found to play a positive role in wheat NUE.

Conclusions
In conclusion, these results enriched our knowledge of the mechanism of wheat NUE, and provided a theoretical basis for improving wheat NUE and breeding new cultivars.
Physical performance in older age by sex and educational level: the HUNT Study
Authors: Melsæter Kjerstin N. , Tangen Gro G. , Skjellegrind Håvard K. , Vereijken Beatrix , Strand Bjørn H. , Thingstad Pernille 
Published: October 2022

Abstract
Background
Population-based studies on physical performance provide important information on older people’s health but rarely include the oldest and least-healthy segment of the population. The aim of this study was to provide representative estimates of physical performance by age, sex, and educational level based on recent data from a population-based health study in Norway that includes older people with a wide range in age and function.

Methods
In the fourth wave of the Trøndelag Health Study (2017–2019), all participants aged 70 + were invited to an additional examination of physical performance assessed by the Short Physical Performance Battery (SPPB), either by attending a testing station or by visits from ambulatory teams. The distribution and variation in SPPB total and subscores, as well as gait speed, are presented by sex, age, and educational level.

Results
The SPPB was registered in 11,394 individuals; 54.8% were women; the age range was 70–105.4 years, with 1,891 persons aged 85 + . SPPB scores decreased by 0.27 points (men) and 0.33 points (women) for each year of age, and gait speed by 0.02 m/sec (men) and 0.03 m/sec (women). Using a frailty cut-off for gait speed at < 0.8 m/sec, the proportion of participants categorized as frail increased from 13.9% in the 70–74 years cohort to 73.9% in participants aged 85 + . Level of education $$\le$$
≤
10 years corresponded to 6 years (men) and 4 years (women) earlier onset of frailty (SPPB $$\le$$
≤
9) compared to education $$\ge$$
≥
14 years.

Conclusion
We found that the SPPB captured a gradual decline and wide distribution in physical performance in old age. The results provide information about physical performance, health status, and risk profiles at a population level and can serve as reference data for clinicians, researchers, and healthcare planners.
Screening and evaluation of cytotoxicity and antiviral effects of secondary metabolites from water extracts of Bersama abyssinica against SARS-CoV-2 Delta
Authors: Zekeya Never , Mamiro Bertha , Ndossi Humphrey , Mallya Rehema Chande , Kilonzo Mhuji , Kisingo Alex , Mtambo Mkumbukwa , Kideghesho Jafari , Chilongola Jaffu 
Published: October 2022

Abstract
Background
Bersama abyssinica is a common herb in Africa, with diverse medical uses in different areas. The plant is well-known in Tanzania for treating respiratory disorders such as TB, tonsillitis, bronchitis, and asthma, and it has lately been utilized to treat COVID-19 symptoms. Water extract of leaf and stem bark has been registered as an herbal medication known as 'Coviba Dawa' in Tanzania for the relief of bacterial respiratory infections. The extracts, however, have not been scientifically tested for their anti-viral activities. The aim of this work was to test for the cytotoxicity and antiviral effects of bioactive ingredients from B. abyssinica extracts against the Delta variant of the SARS-CoV-2 coronavirus.

Methods
B. abyssinica leaves and stem bark were dried under shade in room temperature and then pulverized to obtain small pieces before soaking into different solvents. One hundred grams of each, leaves and stem bark, were extracted in petroleum ether, dichloromethane, ethyl acetate and methanol. Water extract was obtained by decoction of stem bark and leaves into water. Phenols, flavonoids, tannins, and antioxidants were confirmed as components of the extracts. Analysis of polar extracts of bark stem bark and leaves was done. Antiviral screening and cytotoxicity experiments were conducted in a Biosafety Level 3 (BSL-3) Laboratory facility according to International Standard Operating Procedures (SOPs).

Results
By the use of LC–MS/MS analysis, this study confirmed the existence of four phenolic compounds in B. abyssinica water extract; 2,4-di-tert-butylphenol, 4-formyl-2-methoxyphenyl propionate, 7,8-Dihydroxy-4-methylcoumarin, and 2,3, 6-trimethoxyflavone with antioxidant activity. This study showed that, while the water extracts of B. abyssinica had significant antiviral activity against SARS Cov2 virus, it showed no cytotoxicity effect on Vero E6 cells. In particular, the water extract (Coviba dawa) showed 75% while ethylacetate fraction of B. abyssinica leaves showed a 50% in vitro viral inhibition, indicating that these substances may be useful for the development of future anti-viral agents.

Conclusion
We therefore recommend isolation of compounds for further profiling and development with a broader concentration range. We further recommend studies that determine the antiviral activity of extracts of B.abyssinica on other viral pathogens of clinical concern.
GSK872 and necrostatin-1 protect retinal ganglion cells against necroptosis through inhibition of RIP1/RIP3/MLKL pathway in glutamate-induced retinal excitotoxic model of glaucoma
Authors: Liu Mengyuan , Li Haibo , Yang Rongliang , Ji Dan , Xia Xiaobo 
Published: October 2022

Abstract
Background
Glaucoma, the major cause of irreversible blindness worldwide, is characterized by progressive degeneration of retinal ganglion cells (RGCs). Current treatments for glaucoma only slow or partially prevent the disease progression, failing to prevent RGCs death and visual field defects completely. Glutamate excitotoxicity via N-methyl-d-aspartic acid (NMDA) receptors plays a vital role in RGCs death in glaucoma, which is often accompanied by oxidative stress and NLRP3 inflammasome activation. However, the exact mechanisms remain unclear.

Methods
The glutamate-induced R28 cell excitotoxicity model and NMDA-induced mouse glaucoma model were established in this study. Cell counting kit-8, Hoechst 33342/PI dual staining and lactate dehydrogenase release assay were performed to evaluate cell viability. Annexin V-FITC/PI double staining was used to detect apoptosis and necrosis rate. Reactive oxygen species (ROS) and glutathione (GSH) were used to detect oxidative stress in R28 cells. Levels of proinflammatory cytokines were measured by qRT-PCR. Transmission electron microscopy (TEM) was used to detect necroptotic morphological changes in RGCs. Retinal RGCs numbers were detected by immunofluorescence. Hematoxylin and eosin staining was used to detect retinal morphological changes. The expression levels of RIP1, RIP3, MLKL and NLRP3 inflammasome-related proteins were measured by immunofluorescence and western blotting.

Results
We found that glutamate excitotoxicity induced necroptosis in RGCs through activation of the RIP1/RIP3/MLKL pathway in vivo and in vitro. Administration of the RIP3 inhibitor GSK872 and RIP1 inhibitor necrostatin-1 (Nec-1) prevented glutamate-induced RGCs loss, retinal damage, neuroinflammation, overproduction of ROS and a decrease in GSH. Furthermore, after suppression of the RIP1/RIP3/MLKL pathway by GSK872 and Nec-1, glutamate-induced upregulation of key proteins involved in NLRP3 inflammasome activation, including NLRP3, pro-caspase-1, cleaved-caspase-1, and interleukin-1β (IL-1β), was markedly inhibited.

Conclusions
Our findings suggest that the RIP1/RIP3/MLKL pathway mediates necroptosis of RGCs and regulates NLRP3 inflammasome activation induced by glutamate excitotoxicity. Moreover, GSK872 and Nec-1 can protect RGCs from necroptosis and suppress NLRP3 inflammasome activation through inhibition of RIP1/RIP3/MLKL pathway, conferring a novel neuroprotective treatment for glaucoma.
Inflammation and cell-to-cell communication, two related aspects in frailty
Authors: Pansarasa Orietta , Mimmi Maria Chiara , Davin Annalisa , Giannini Marta , Guaita Antonio , Cereda Cristina 
Published: October 2022

Abstract
Background
Frailty is a complex, multi-dimensional age-related syndrome that increases the susceptibility to adverse health outcomes and poor quality of life. A growing consensus supports the contribution of chronic inflammation and immune system alterations to frailty, however a clear role of such alterations remains to be elucidated. Furthermore, pro- and anti-inflammatory cytokines together with other signaling molecules might spread from activated cells to the adjacent ones through extracellular vesicles (EVs), which have also a role in cellular aging. The aim of the present research was to investigate if EVs play a role in the immune function in frailty.

Results
In 219 older adults aged 76–78 years, selected from the InveCe.Ab study (Abbiategrasso, Italy), we investigated inflammation and EVs-mediated intercellular communication. C-reactive protein (CRP) and pro- (IL-1β, IL-2, IL-6, IL-8, IL-12 p70, TNFα and IFNγ) and anti- (IL-4, IL-10, IL-13) inflammatory cytokines were evaluated on plasma of Frail and non-Frail subjects. We reported a significant increase in CRP, interleukin-1β and -6 (IL-1β, IL-6) and tumor necrosis factor alpha (TNFα) plasma levels in frailty. In female Fr subjects, we also reported an increase in interferon‐gamma (IFN‐γ) and, surprisingly, in IL-13, an anti-inflammatory cytokine, whose increase seems to oppose the inflammaging theory.
An inflammatory panel (toll-like receptors 2 and 4 (TLR2 and TLR4), tumor necrosis factor receptors TNFRec5/CD 40 and TNFRec1B/CD120B) and a panel including receptors involved in cellular senescence (insulin-like growth factor 1 receptor (CD221) and interleukin 6 receptor (IL-6R)) were indeed analysed in plasma isolated large EVs (lEVs) from Frail (n = 20) and non-Frail (n = 20) subjects. In lEVs isolated from plasma of Frail subjects we reported an increase in TLR2 and TLR4, TNFRec5/CD 40 and TNFRec1B/CD120B, suggesting a chronic state of inflammation. In addition, CD221 and IL-6R increases in lEVs of Frail individuals.

Conclusions
To conclude, the pro-inflammatory status, notably the increase in circulating cytokines is pivotal to understand the potential mechanisms underlying the frailty syndrome. Moreover, cytokines release from EVs, mainly the large ones, into the extracellular space suggest their contribution to the formation of a pro-inflammatory and pro-senescent microenvironment that, in turn, can contribute to frailty.
Spinal microglia contribute to sustained inflammatory pain via amplifying neuronal activity
Authors: Gu Nan , Yi Min-Hee , Murugan Madhuvika , Xie Manling , Parusel Sebastian , Peng Jiyun , Eyo Ukpong B. , Hunt Christine L. , Dong Hailong , Wu Long-Jun 
Published: October 2022

AbstractMicroglia are highly dynamic immune cells of the central nervous system (CNS). Microglial processes interact with neuronal elements constantly on the order of minutes. The functional significance of this acute microglia-neuron interaction and its potential role in the context of pain is still largely unknown. Here, we found that spinal microglia increased their process motility and electrophysiological reactivity within an hour after the insult in a mouse model of formalin-induced acute, sustained, inflammatory pain. Using an ablation strategy to specifically deplete resident microglia in the CNS, we demonstrate that microglia participate in formalin-induced acute sustained pain behaviors by amplifying neuronal activity in the spinal dorsal horn. Moreover, we identified that the P2Y12 receptor, which is specifically expressed in microglia in the CNS, was required for microglial function in formalin-induced pain. Taken together, our study provides a novel insight into the contribution of microglia and the P2Y12 receptor in inflammatory pain that could be used for potential therapeutic strategies.