bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation to Climate Change under Climate Change Treaties
Authors: Bator Agata , Borek Agnieszka
Published: July 2021

On the ground that climate change poses a great threat to societies and economies, it became evident for policy makers that attention should be given to the problem of adaptation, i.e. adaptation measures should be undertaken to minimize the adverse impacts of climate change. As the debate on the adverse impacts of climate change advanced at international level, states are taking actions at national, regional and local levels. Along with the increase awareness regarding importance of adaptation, regulations designed to prepare states to strengthen their resilience to climate change, has been developed in climate change treaties. Paris Agreement seems to be the first global agreement which addresses adaptation as one of its key goals and links it with mitigation efforts. The purpose of this article is to discuss the most important regulations and programmes within the regime established by the Framework Convention and the Paris Agreement concerning adaptation to climate change.
Legal Aspects of Adaptation Finance under the UNFCCC Regime with Special Reference to the Adaptation Fund
Authors: Mordasewicz Karolina , Kowalczyk Marcin
Published: July 2021

This article addresses the legal aspects of the financing of adaptation to climate change, with special consideration given to one of the climate funds – the Adaptation Fund (AF). In the complex structure of climate finance, the AF attracts attention as it differs from other funds in several aspects. As an exception from other United Nations (UNs) climate funds, AF has not been recognised as an operating entity of the Financial Mechanism of the Convention. AF is also an unprecedented example under the Convention of a fund serving in parallel two decision-making bodies (CMP and CMA) under two agreements (Kyoto Protocol and Paris Agreement) ratified by non-overlapping sets of parties; with a Fund Board elected by both bodies collectively. AFs funding source is specific, it was designed to be financed from shares of the proceeds of sales of certified emission reduction units (CERs) generated by Clean Development Mechanism (CDM) projects but since 2012 there is a limited possibility of offsetting the emissions with CERs under the EU emissions trading system (ETS). For several years Parties were unable to agree the operating principles and procedures of a new mechanism established in article 6(4) of the Paris Agreement, which will resemble CDM, and would constitute a source of funding for the AF. Once this source of funding is available, the AF would cease to serve the Kyoto Protocol. Despite the above problems, AF was seen as a good example of how future climate funding can be designed. We examine the evolution of the above legal problems, including the most recent decisions and conclusions adopted during Conference of Parties (COP)25 in Madrid.
External Aspects of the EU ETS in Aviation in Light of CORSIA
Authors: Jaśkowski Marek
Published: July 2021

According to International Civil Aviation Organization (ICAO) Assembly Resolution A40-19, the Carbon Offsetting and Reduction Scheme for International Aviation mechanism (CORSIA) is to be the only global market-based measure (MBM) applied to CO2 emissions from international aviation. This solution has been dictated by the intention to avoid a patchwork of duplicative State or regional MBMs and to ensure that international aviation CO2 emissions should be accounted for only once. The present contribution assesses the margin of autonomy left for Emissions Trading System of the EU (EU ETS) mechanism in the light of this clause, considering its legal status and divergent interpretations. Moreover, the recent 2020 roadmap for revision of the EU ETS Directive concerning aviation, published by the European Commission, is briefly discussed.
An Iranian Shāh-nāma Writer at the Court of Bāyezid II: Malekzāda Āhi
Authors: Genç Vural
Published: July 2021

Malekzāda Āhi was an Iranian-born Shāh-nāma writer (shāh-nāmaji, Ott. şehnameci) who served at the court of the Ottoman sultan Bāyezid II (r. 1481–1512) and composed the first Ottoman dynastic history to bear the title of “Shāh-nāma.” Accompanying the sultan since his years as a prince, Malekzāda wrote his Shāh-nāma after the tradition of Ferdowsi (d. 1019–20) and Nezāmi (d. 1209), in addition to many odes (qasidas) in praise of his patron. Despite his contemporary reputation as the “master of the verse (malek al-kalam)” in the sultan’s palace, a series of unfortunate accidents led to his relative obscurity in modern historiography. Malekzāda Āhi’s experience as a Shāh-nāma writer is representative of the position held by Iranian artists and scholars in the early sixteenth-century Ottoman palace. His Shāh-nāma also should be regarded as one of the earliest transmissions of the Shāh-nāma style of history-writing to the Ottoman realm. In this article, I attempt to uncover Malekzāda Āhi’s real identity and shed light on his activities in the palace circle, based on archival documents that are studied here for the first time.
The Revival of Adat and the Articulation of the ‘Kingdom Slot’ in Loloda, North Halmahera, Indonesia
Authors: Song Seung-Won , Mansur Mustafa
Published: July 2021

This article examines the historical background behind the recent reinstallation of Loloda’s kingship in North Halmahera, Indonesia. This marginalized group of people reignited their mythic narratives to renegotiate their centrality and power as a region, strengthening both their ethnic and cultural identities in the process. Through the narrative of the Kie Romtoha (Five Mountains), the activists placed Loloda alongside the four other mythic centres of Maluku called the Kie Raha (Four Mountains) and promoted the myth of Jou Tolo, a royal ancestor, to conform with the royal origin stories of the Kie Raha states. This article illustrates how the Loloda people were not only able to rise above their societal position by rearticulating these myths, but were also able to utilize these stories to facilitate religious reconciliation in modern times, despite there being a painful history of division between Muslims and Christians within this community.
Critical review of the nomenclature and taxonomy of Sorghastrum canescens (Poaceae: Panicoideae: Andropogoneae), an endemic Brazilian species
Authors: MACIEL JEFFERSON RODRIGUES , PROENÇA CAROLYN ELINORE BARNES , VALLS JOSÉ FRANCISCO MONTENEGRO , OLIVEIRA REGINA CÉLIA DE
Published: July 2021

Some taxonomic groups impose the need to use continuous morphological characteristics in taxon delimitation, and the grass genus Sorghastrum is a clear case of this necessity. Sorghastrum canescens was described based on the length of its awns. However, insufficient and scattered sampling has obscured the identity of this species for at least 137 years, while it was considered synonym of S. incompletum var. incompletum. In this study we evaluate statistical differences in the original and current morphological concepts of S. canescens using analysis of variance and posterior pairwise comparison of means and medians. We also retrieved the nomenclatural history of the binomial S. canescens to clarify possible errors in the synonymization of this species. All the statistical evidence refutes the hypothesis that S. canescens is a synonym of S. incompletum var. incompletum. Historical data revealed an error in the identification of the correct basionym of S. canescens and this error has been repeated in several taxonomic revisions. We were also able to establish an approximate date for the type-collection of S. canescens. We therefore propose the reestablishment of the name Sorghastrum canescens and provide morphological descriptions and illustration of this species.
The Dendrothripinae (Thysanoptera, Thripidae) of Saudi Arabia, with new records, one new species, and revised status of Pseudodendrothrips stuardoi (Moulton)
Authors: RASOOL IFTEKHAR , MOUND LAURENCE A. , SOLIMAN AHMED M. , ALDHAFER HATHAL M.
Published: July 2021

Two genera Dendrothrips Uzel and Pseudodendrothrips Schmutz are recorded from Saudi Arabia. A key is provided to eight members of Dendrothrips that have antennae with 9-segments and D. saudicus sp. n. is described in this group. P. aegyptiacus (Priesner) and P. stuardoi are newly reported from Saudi Arabia, with P. stuardoi rev. stat. from the leaves of Ficus carica being newly distinguished from P. mori (Niwa) that lives on the leaves of Morus alba. Some published records of P. mori from Mediterranean countries are possibly misidentifications of P. stuardoi.
Research on the Mechanism of Asiaticoside Inhibiting Osteoclast Differentiation and Promoting the Recovery of Steroid-Induced Osteonecrosis of the Femoral Head (SIONFH)
Authors: Miao Meijing , Guo Liping , Su Pengfei , Ji Jinshan , Li Baoli
Published: July 2021

Our study aims to assess whether asiaticoside promotes the recovery of SINOFH by inhibiting bone marrow stem cells (BMSCs) differentiation into osteoclasts (OC). BMMs were induced to form OC system by dexamethasone in vitro and ELISA detected the expression of OC-related genes
formation by asiaticoside. BMSCs were cultured followed by analysis of BMSCs morphology under microscope, gene expression by qRT-PCR. TRACP and c-Src level by western blot, RANKL, OPG and TRACP5b level by ELISA. Asiaticoside inhibited the expression of OC formation in SIONFH. The expression
of OC-related genes increased with the induction days. With the increasing of induction days, asiaticoside level in culture fluid was decreased. While after asiaticoside interference, OCrelated genes and proteins levels were significantly down-regulated. Aasiaticoside can significantly increase
the RANKL signaling protein expression. In conclusion, asiaticoside promotes the recovery of SINOFH by inhibiting BMSCs differentiation into OC.
Downregulation of General Control Nonderepressible 2/Eukaryotic Initiation Factor 2α Attenuates Inflammation, Oxidative Stress and Cell Apoptosis in Retinal Cells Induced by High Glucose
Authors: Zhao Shuyu , Yin Yuqian , Qin Hong
Published: July 2021

Background: Diabetic retinopathy (DR), the frequent complication of diabetes mellitus, has been the main factor of clinical blindness. It is of great clinical significance to seek a novel therapeutic target of DR. The present study aims to investigate the important role of GCN2/eIF2α
in DR and the underlying mechanism. Materials and Methods: The expression levels of GCN2 and p-eIF2α were measured by western blot assay and q-PCR. The inflammation levels were assessed by ELISA assay and oxidative stress was measured by colorimetric method. Then, the key
proteins related to the function of endothelial cell were measured by western blot assay. Cell apoptotic rate was detected by flow cytometry and proteins related to cell apoptosis were detected by western blot assay. Results: High glucose activated GCN2/eIF2α signaling
pathway in HRCECs. Downregulation of GCN2 attenuated HG-induced cell apoptosis, inflammatory and oxidative stress in HRCECs. Meanwhile, downregulation of GCN2 ameliorated HG-induced endothelial cell dysfunction. Inhibition of GCN2 inhibited p-eIF2α, ATF4, CHOP and activated UCP2.
Conclusion: The results in this study proved that knockdown of GCN2 could significantly mitigate HG-induced injury, suggesting GCN2/eIF2α as a potential target for DR therapy.
DL-3-n-Butylphthalide Alleviates Inflammation and Aging in Advanced Glycation End Products-Induced Mesangial Cells
Authors: Song Gang , Lei Li , Zhang Sheng , Dong Pei , Hu Dajun
Published: July 2021

Age-induced decline in renal function could markedly increase the risk of chronic kidney disease. DL-3-n-butylphthalide (DI-NBP) has notable anti-inflammasome and anti-oxidant effects. However, it’s still unclear whether DI-NBP exerts functions in renal senescence. Thus,
the study aims to investigate the effects of DI-NBP on AGE-induced mesangial cells aging and illuminate related pathological process. The cell proliferation levels were detected by CCK8 assay and EDU/DAPI staining, along with the identification of aging-related proteins (β-Gal,
p53, p21, p16) by β-Gal staining or Western blot. Intracellular reactive oxygen species (ROS) detection was also performed by ROS kit. In addition, inflammation was evaluated by NLRP3 inflammasome and inflammation-related markers. The results presented increased cell proliferation.
Moreover, AGEs-induced cell aging was significantly decreased by DI-NBP, accompanied by decreased ROS levels. Furthermore, DI-NBP reduced NLRP3/caspase1 axis activation and inhibited inflammation in AGEs-induced mesangial cell aging. Thus, DI-NBP might produce significant protective effects
on renal aging via decreasing pro-aging-related proteins, oxidative stress and inflammation. DI-NBP could be a potential drug for delaying renal aging.
Glucagon-Like Skin-1’s Effect on Islet β Cells in High Glucose via AMPK/mTOR Pathway
Authors: Luo Minhong , Liu Hao , Mo Caiju , Wu Qiang , Chen Zhenwei , Yang Tiecheng
Published: July 2021

This study investigated whether GLP-1 affects islet β cells in high glucose and the possible mechanism. INS-1 cells are separated into group A (treated with 5.6 mmol/L glucose), group B (group A+100 nmo1/L liraglutide), group C (cells were cultured in 16.7 mmol/L glucose)
and group D (group C+100 nmo1/L liraglutide) followed by analysis of cell activity by CCK-8, apoptosis by Hoechst staining, INS level by ELISA, AMPK/mTOR signaling protein level by immunoblotting and RT-PCR. Compared with group A, cell proliferation was significantly increased in group B (P
<0.05) and decreased in group C which had lower cell proliferation than group D (P <0.05). However, opposite results were obtained regarding cell apoptosis in four groups (P <0.05); group B showed higher INS level (145.36±8.55 pg/ml) and group C had lower level
(80.14±5.36 pg/ml) than group A (105.23±7.78 pg/ml) (P <0.05). Meanwhile, AMPK and p-AMPK levels were significantly lower in group B and higher in group C than group A (P <0.05) with lower level in group D than group C (P <0.05). Whereas, opposite
expression profile of p-mTOR and mTOR was found in these groups (P <0.05). High glucose inhibits INS-1 cell proliferation and promotes apoptosis. GLP-1 analogue inhibits INS-1 cell apoptosis in high glucose and accelerate proliferation possibly via regulation of AMPK/mTOR signaling
pathway.
MicroRNA-487a-3p Regulates the Senescence of Mesenchymal Stem Cells by Targeting Silencing Information Regulator-Associated Enzyme 1 (SIRT1)
Authors: Shen Yiwei , Li Xue , Wu Xiaoke , Li Yi , Shen Yiwei , Fan Zhenliang
Published: July 2021

SIRT1 is known to be closely associated with cellular senescence, while the relationship between miR-487a-3p and SIRT1 and their role in mesenchymal stem cells (MSCs) remains unclear. MiRDB analysis showed SIRT1 is a target of miR-487a-3p. Here we investigated whether miR-487a-3p modulates
senescence of mesenchymal stem cells by targeting SIRT1. The human MSCs (hMSCs) were divided into control group (NC group), miR-487a-3p Mimics group, pCMV-SIRT+miR-487a-3p Mimics group followed by analysis of miR-487a-3p expression by qPCR and protein level of SIRT1, P21 and P53 by western
blot. Dual luciferin report assay verified the binding of miR-487a-3p to SIRT1 mRNA and β-galactosidase activity staining detected hMSCs senescence. miR-487a-3p level was significantly elevated after miR-487a-3p Mimics treatment (P <0.01) without difference between miR-487a-3p
Mimics group and pCMV-SIRT1 group+miR-487a-3pMimics (P >0.05). miR-487a-3p mimics significantly decreased SIRT1 level (P < 0.01), which was reversed by pCMVSIRT1 plasmid transfection (P <0.05). Moreover, miR-487a-3p could bind SIRT1 mRNA 3′-UTR region. Further
more, miR-487a-3p Mimics induced cellular senescence as displayed by increased β-galactosidase activity (P <0.01) and increased level of senescence-related proteins P21 and P53 (P < 0.01), which were all reversed by overexpression of SIRT1 (P < 0.05).
In conclusion, miR-487a-3p reduced SIRT1 expression, thus promoting hMSCs senescence, while overexpression of SIRT1 could counteract the senescence of hMSCs induced by miR-487a-3p.
The Effect of MicroRNA-92a (miR-92a) on Non-Small Cell Lung Cancer (NSCLC) Cell Biological Behaviors and Janus Protein-Tyrosine Kinase 1 (JAK1)/Signal Transducer and Activator of Transcription (STAT3) Signaling
Authors: Yi Jianghong , Zhao Jie , Xiao Pengfei , Gao Minghui
Published: July 2021

Our study investigates miR-92a’s effect on the biological behaviors of non-small cell lung cancer (NSCLC) cells and Janus protein-tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) signal transduction. A549 cells were divided into KB group (no transfection),
NC group (negative control transfection), and SY group (transfection with miR-92a inhibitor) followed by analysis of the expression of miR-92a, JAK1, and STAT3 by qRT-PCR, cell proliferation, invasion and apoptosis as well as JAK1/STAT3 protein expression. The miR-92a, JAK1, and STAT3 expression
in SY group were significantly lower than NC group and KB group (P <0.05), indicating the successful transfection. The A549 cell proliferation in SY group was significantly decreased compared with NC and KB group (P <0.05). Cell apoptosis rate in SY group was 25.23±2.31%,
which was significantly higher than that in NC (8.15±0.82%) and KB group (8.08±0.79%). The number of cell invasion in SY group was significantly reduced (88.6±7.32) compared with NC group (189.71±15.37) and KB group (181.32±14.62) (F = 937.8, P
<0.001). SY group showed significantly lower JAK1/STAT3 protein expression than NC and KB group. In conclusion, silencing miR-92a can inhibit proliferation, migration, and invasion of A549 cells, which may be related to JAK1/STAT3 signaling pathway.
Alendronate Regulates Knee Arthritis by Extracellular-Signal-Regulated Kinase (ERK) Pathway in Rat Model
Authors: Jin Xin , Zi Lu , Hu Xiaojun
Published: July 2021

The incidence of knee arthritis is high and treatment effect is not satisfactory. Alendronate (ALN) can treat metabolic bone diseases. But its role and mechanism in knee arthritis remains unclear. SD rats were randomly assigned into control group; model group; and alendronate group
followed by analysis of the pathological changes by HE staining and Masson staining, bone mineral density by dual energy bone densitometry, expression of glycosaminoglycan and MMP-3 by immunohistochemistry, BMP-2 and BMP-4 expression by Real time PCR, IL-1β, IL-6 secretion by ELISA
as well as ERK signaling protein level by Western blot. In model group, the pathological changes of joint inflammation were obvious with fibrosis on the cartilage surface, significantly increased synovial hyperplasia score, inflammatory infiltration score and Mankin score, decreased bone density,
expression of glycosaminoglycan, MMP-3, BMP-2 and BMP-4 as well as increased IL-1β, IL-6 secretion and ERK1/2 expression (P <0.05). Alendronate treatment can significantly improve joint inflammation, reduce inflammatory infiltration score and Mankin score, increase bone
density, expression of glycosaminoglycan, MMP-3, BMP-2 and BMP-4, decrease the secretion of IL-1β, IL-6 and expression of ERK1/2 in a rat model of knee arthritis (P <0.05). Alendronate can promote glycosaminoglycans and MMP-3 expression, and synthesis of BMP-2 and BMP-4
by inhibiting ERK pathway, inhibiting the secretion of inflammatory factors, thus ameliorating knee arthritis.
A Constrained Data Assimilation Algorithm Based on GSI Hybrid 3D-EnVar and Its Application
Authors: Wang Jia , Zhang Minghua
Published: July 2021

Data assimilation (DA) at mesoscales is important for severe weather forecasts, yet the techniques of data assimilation at this scale remain a challenge. This study introduces dynamical constraints in the Gridpoint Statistical Interpolation (GSI) three-dimensional ensemble variational (3D-EnVar) data assimilation algorithm to enable the use of high-resolution surface observations of precipitation to improve atmospheric analysis at mesoscales. The constraints use the conservations of mass and moisture. Mass constraint suppresses the unphysical high-frequency oscillation, while moisture conservation constrains the atmospheric states to conform with the observed high-resolution precipitation. We show that the constrained data assimilation (CDA) algorithm significantly reduced the spurious residuals of the mass and moisture budgets compared to the original data assimilation (ODA). A case study is presented for a squall line over the Southern Great Plains on 20 May 2011 during Midlatitude Continental Convective Clouds Experiment (MC3E) of the Atmospheric Radiation Measurement (ARM) program by using ODA or CDA analysis as initial condition of forecasts. The state variables, and the location and intensity of the squall line are better simulated in the CDA experiment. Results show how surface observation of precipitation can be used to improve atmospheric analysis through data assimilation by using the dynamical constraints of mass and moisture conservations.
Measuring the effects of tourists’ relative willingness to spend and third-degree price discrimination on inbound tourism expenditure differentials
Authors: Alfarhan Usamah F , Nusair Khaldoon , Al-Azri Hamed , Al-Muharrami Saeed , Hua Nan
Published: July 2021

Tourism expenditures are determined by a set of antecedents that reflect tourists’ willingness and ability to spend, and de facto incremental monetary outlays at which willingness and ability is transformed into total expenditures. Based on the neoclassical theoretical argument of utility-constrained expenditure minimization, we extend the current literature by applying a sustainability-based segmentation criterion, namely, the Legatum Prosperity IndexTM to the decomposition of a total expenditure differential into tourists’ relative willingness to spend and an upper bound of third-degree price discrimination, using mean-level and conditional quantile estimates. Our results indicate that understanding the price–quantity composition of international inbound tourism expenditure differentials assists agents in the tourism industry in their quest for profit maximization.
Population differentiated copy number variation of Bos taurus, Bos indicus and their African hybrids
Authors: Jang Jisung , Terefe Endashaw , Kim Kwondo , Lee Young Ho , Belay Gurja , Tijjani Abdulfatai , Han Jian‑Lin , Hanotte Olivier , Kim Heebal
Published: July 2021

Background

CNV comprises a large proportion in cattle genome and is associated with various traits. However, there were few population-scale comparison studies on cattle CNV.

Results

Here, autosome-wide CNVs were called by read depth of NGS alignment result and copy number variation regions (CNVRs) defined from 102 Eurasian taurine (EAT) of 14 breeds, 28 Asian indicine (ASI) of 6 breeds, 22 African taurine (AFT) of 2 breeds, and 184 African humped cattle (AFH) of 17 breeds. The copy number of every CNVRs were compared between populations and CNVRs with population differentiated copy numbers were sorted out using the pairwise statistics VST and Kruskal-Wallis test. Three hundred sixty-two of CNVRs were significantly differentiated in both statistics and 313 genes were located on the population differentiated CNVRs.

Conclusion

For some of these genes, the averages of copy numbers were also different between populations and these may be candidate genes under selection. These include olfactory receptors, pathogen-resistance, parasite-resistance, heat tolerance and productivity related genes. Furthermore, breed- and individual-level comparison was performed using the presence or copy number of the autosomal CNVRs. Our findings were based on identification of CNVs from short Illumina reads of 336 individuals and 39 breeds, which to our knowledge is the largest dataset for this type of analysis and revealed important CNVs that may play a role in cattle adaption to various environments.
Prevalence, aetiologies and prognosis of the symptom cough in primary care: a systematic review and meta-analysis
Authors: Bergmann Milena , Haasenritter Jörg , Beidatsch Dominik , Schwarm Sonja , Hörner Kaja , Bösner Stefan , Grevenrath Paula , Schmidt Laura , Viniol Annika , Donner-Banzhoff Norbert , Becker Annette
Published: July 2021

Background

Cough is a relevant reason for encounter in primary care. For evidence-based decision making, general practitioners need setting-specific knowledge about prevalences, pre-test probabilities, and prognosis. Accordingly, we performed a systematic review of symptom-evaluating studies evaluating cough as reason for encounter in primary care.

Methods

We conducted a search in MEDLINE and EMBASE. Eligibility criteria and methodological quality were assessed independently by two reviewers. We extracted data on prevalence, aetiologies and prognosis, and estimated the variation across studies. If justifiable in terms of heterogeneity, we performed a meta-analysis.

Results

We identified 21 eligible studies on prevalence, 12 on aetiology, and four on prognosis. Prevalence/incidence estimates were 3.8–4.2%/12.5% (Western primary care) and 10.3–13.8%/6.3–6.5% in Africa, Asia and South America. In Western countries the underlying diagnoses for acute cough or cough of all durations were respiratory tract infections (73–91.9%), influenza (6–15.2%), asthma (3.2–15%), laryngitis/tracheitis (3.6–9%), pneumonia (4.0–4.2%), COPD (0.5–3.3%), heart failure (0.3%), and suspected malignancy (0.2–1.8%). Median time for recovery was 9 to 11 days. Complete recovery was reported by 40.2- 67% of patients after two weeks, and by 79% after four weeks. About 21.1–35% of patients re-consulted; 0–1.3% of acute cough patients were hospitalized, none died. Evidence is missing concerning subacute and chronic cough.

Conclusion

Prevalences and incidences of cough are high and show regional variation. Acute cough, mainly caused by respiratory tract infections, is usually self-limiting (supporting a “wait-and-see” strategy). We have no setting-specific evidence to support current guideline recommendations concerning subacute or chronic cough in Western primary care. Our study presents epidemiological data under non non-pandemic conditions. It will be interesting to compare these data to future research results of the post-pandemic era.
Disability trajectories prior to death for ten leading causes of death among middle-aged and older adults in Taiwan
Authors: Chiu Ching-Ju , Li Meng-Ling , Chang Chia-Ming , Wu Chih-Hsing , Tan Maw Pin
Published: July 2021

Background

Prolonged life expectancy is associated with increased prevalence of chronic diseases. The aim of this study was to determine the different disability trajectories for the top ten leading causes of death in Taiwan .

Methods

A total of 2,431 participants aged 50–96 in 1996 from the Taiwan longitudinal study on aging (TLSA) who died from 1996 to 2016 were analyzed. Integration of Cause of Death Data and TLSA helped sort out participants who had died from the ten leading causes of death. The level of physical disability was evaluated with the Activities of Daily Living Scale (ADLs), ranging from 0 to 6 points, in 1996, 1999, 2003, 2007, and 2011. A multilevel model was used to investigate the levels and rates of change in disability development before death.

Results

The outcome of the research showed that the earliest group to experience physical limitation was individuals living with diabetes. The groups with the highest ADL scores were participants with diabetes, cerebrovascular disease, and hypertension-related diseases. Most groups reach ADL scores ≥ 1 (mild-level) during 4–6 years before death except chronic hepatitis and cirrhosis and injury.

Conclusions

People who had died from the ten leading causes of death experienced different disability trajectories before death. The trajectory of the participants who had died from diabetes showed a unique pattern with the earliest occurrence and more severe deterioration in terms of development of disabilities. Disability trajectories provide a prediction of survival status for middle-aged and older adults associated with the ten leading causes of death.
Treatment of spasticity in children and adolescents with cerebral palsy in Northern Europe: a CP-North registry study
Authors: Hägglund Gunnar , Hollung Sandra Julsen , Ahonen Matti , Andersen Guro L. , Eggertsdóttir Guðbjörg , Gaston Mark S. , Jahnsen Reidun , Jeglinsky-Kankainen Ira , Nordbye-Nielsen Kirsten , Tresoldi Ilaria , Alriksson-Schmidt Ann I.
Published: July 2021

Background

Spasticity is present in more than 80% of the population with cerebral palsy (CP). The aim of this study was to describe and compare the use of three spasticity reducing methods; Botulinum toxin-A therapy (BTX-A), Selective dorsal rhizotomy (SDR) and Intrathecal baclofen therapy (ITB) among children and adolescents with CP in six northern European countries.

Methods

This registry-based study included population-based data in children and adolescents with CP born 2002 to 2017 and recorded in the follow-up programs for CP in Sweden, Norway, Denmark, Iceland and Scotland, and a defined cohort in Finland.

Results

A total of 8,817 individuals were included. The proportion of individuals treated with SDR and ITB was significantly different between the countries. SDR treatment ranged from 0% ( Finland and Iceland) to 3.4% (Scotland) and ITB treatment from 2.2% (Sweden) to 3.7% (Denmark and Scotland). BTX-A treatment in the lower extremities reported 2017–2018 ranged from 8.6% in Denmark to 20% in Norway (p < 0.01). Mean age for undergoing SDR ranged from 4.5 years in Norway to 7.3 years in Denmark (p < 0.01). Mean age at ITB surgery ranged from 6.3 years in Norway to 10.1 years in Finland (p < 0.01). Mean age for BTX-A treatment ranged from 7.1 years in Denmark to 10.3 years in Iceland (p < 0.01). Treatment with SDR was most common in Gross Motor Function Classification System (GMFCS) level III, ITB in level V, and BTX-A in level I. The most common muscle treated with BTX-A was the calf muscle, with the highest proportion in GMFCS level I. BTX-A treatment of hamstring and hip muscles was most common in GMFCS levels IV-V in all countries.

Conclusion

There were statistically significant differences between countries regarding the proportion of children and adolescents with CP treated with the three spasticity reducing methods, mean age for treatment and treatment related to GMFCS level. This is likely due to differences in the availability of these treatment methods and/or differences in preferences of treatment methods among professionals and possibly patients across countries.
Clinical relevance of SARS-CoV-2 infection in late pregnancy
Authors: Ruggiero Marta , Somigliana Edgardo , Tassis Beatrice , Li Piani Letizia , Uceda Renteria Sara , Barbara Giussy , Lunghi Giovanna , Pietrasanta Carlo , Ferrazzi Enrico
Published: July 2021

Background

Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive.

Methods

To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive.

Results

Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79–9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ.

Conclusions

SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.
Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin
Authors: Jang Se-Kyeong , Hong Sung-Eun , Lee Da-Hee , Kim Ji-Young , Kim Ji Yea , Ye Sang-Kyu , Hong Jungil , Park In-Chul , Jin Hyeon-Ok
Published: July 2021

Background

Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood.

Methods

To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed.

Results

Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib.

Conclusions

ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.
Beta-hydroxy beta-methylbutyrate/arginine/glutamine (HMB/Arg/Gln) supplementation to improve the management of cachexia in patients with advanced lung cancer: an open-label, multicentre, randomised, controlled phase II trial (NOURISH)
Authors: Pascoe Jennifer , Jackson Aimee , Gaskell Charlotte , Gaunt Claire , Thompson Joyce , Billingham Lucinda , Steven Neil
Published: July 2021

Background

Cancer cachexia causes significant morbidity and mortality in advanced lung cancer patients. Clinical benefit of β-hydroxy-β-methylbutyrate, arginine, and glutamine (HMB/Arg/Gln) was assessed in newly diagnosed patients.

Methods

NOURISH, a prospective, two-arm, open-label, multi-centre, randomised controlled phase II trial compared cachexia in patients who received HMB/Arg/Gln with those who did not. All patients received structured nutritional, exercise and symptom control via a Macmillan Durham Cachexia Pack. Conducted in five UK centres, patients aged > 18 years, with newly diagnosed advanced small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), who were able to take oral nutrition, with a performance status of 0-to-2 and a life expectancy > 4 months were eligible for trial entry. Patients suitable for treatment with curative intent were ineligible. The trial was designed as a signal-seeking pilot study with target recruitment of 96 patients. One-to-one randomisation was stratified by diagnosis (SCLC or NSCLC), stage of disease (locally advanced or metastatic) and performance status. The primary outcome measure was treatment success defined as a patient being alive without significant loss of lean body mass (not > 5%) by 12 weeks. Secondary outcome measures included quality of life.

Results

Between February-2012 and February-2013, 38 patients were recruited, 19 to each arm. Baseline characteristics were balanced. The trial was halted due to slow accrual and partial adherence. Trial data demonstrated no evidence of treatment benefit. No serious adverse events were reported during the trial.

Conclusions

Further evaluation of HMB/Arg/Gln in this setting could not be recommended on the basis of this trial.

Clinical trial registration

ISRCTN registry: 39911673; 14-Apr-2011 10.1186/ISRCTN39911673.
A methylation-based nomogram for predicting survival in patients with lung adenocarcinoma
Authors: Wang Xuelong , Zhou Bin , Xia Yuxin , Zuo Jianxin , Liu Yanchao , Bi Xin , Luo Xiong , Zhang Chengwei
Published: July 2021

Background

DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients.

Method

The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves.

Result

We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47–3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19–3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively.

Conclusions

The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients.
Associations between symptom severity and well-being among Thai patients with schizophrenia: a cross-sectional analytical study
Authors: Teetharatkul Teerapat , Vitayanont Arnont , Liabsuetrakul Tippawan , Aunjitsakul Warut
Published: July 2021

Background

Severity of symptoms in patients with schizophrenia is a determinant of patient’s well-being, but evidence in low- and middle-income countries is limited. We aimed to measure the symptom severity using objective measurements, the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity scale (CGI-S), and their associations with well-being in patients with schizophrenia.

Methods

Patients with schizophrenia aged ≥18 years, without active psychosis including no history of hospitalization within the last 6 months, were included. Symptom severity was measured by the clinicians using BPRS and CGI-S. The patients’ well-being was assessed by self-report using the Subjective Well-being under Neuroleptic treatment scale (SWN) as continuous and binary outcomes (categorized into adequate or poor well-being). Correlations between symptom severity (BPRS and CGI-S scores) and well-being (SWN score) were analyzed using Pearson’s correlation. Association between well-being status and BPRS was analyzed using multivariate logistic regression.

Results

Of 150 patients, BPRS and CGI-S were inversely correlated with SWN score (r = − 0.47; p < 0.001 and − 0.21; p < 0.01, respectively). BPRS Affect domain had the highest correlation with SWN (r = − 0.51, p < 0.001). In multivariate logistic regression, BPRS score and being unemployed were associated with poor well-being status (adjusted OR 1.08; 95%CI 1.02–1.14; p = 0.006, and 4.01; 95%CI 1.38–11.7; p = 0.011, respectively).

Conclusion

Inverse relationships between symptom severity and well-being score were found. Higher BPRS Affect domain was significantly associated with lower patients’ well-being. The use of BPRS tool into routine clinical practice could serve as an adjunct to physician’s clinical evaluation of patients’ symptoms and may help improve patient’s well-being. Further research on negative symptoms associated with well-being is required.
Epidemiological characteristics and initial spatiotemporal visualisation of COVID-19 in a major city in the Middle East
Authors: MohammadEbrahimi Shahab , Mohammadi Alireza , Bergquist Robert , Dolatkhah Fatemeh , Olia Mahsa , Tavakolian Ayoub , Pishgar Elahe , Kiani Behzad
Published: July 2021

Background

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged initially in China in December 2019 causing the COVID-19 disease, which quickly spread worldwide. Iran was one of the first countries outside China to be affected in a major way and is now under the spell of a fourth wave. This study aims to investigate the epidemiological characteristics of COVID-19 cases in north-eastern Iran through mapping the spatiotemporal trend of the disease.

Methods

The study comprises data of 4000 patients diagnosed by laboratory assays or clinical investigation from the beginning of the disease on Feb 14, 2020, until May 11, 2020. Epidemiological features and spatiotemporal trends of the disease in the study area were explored by classical statistical approaches and Geographic Information Systems.

Results

Most common symptoms were dyspnoea (69.4%), cough (59.4%), fever (54.4%) and weakness (19.5%). Approximately 82% of those who did not survive suffered from dyspnoea. The highest Case Fatality Rate (CFR) was related to those with cardiovascular disease (27.9%) and/or diabetes (18.1%). Old age (≥60 years) was associated with an almost five-fold increased CFR. Odds Ratio (OR) showed malignancy (3.8), nervous diseases (2.2), and respiratory diseases (2.2) to be significantly associated with increased CFR with developments, such as hospitalization at the ICU (2.9) and LOS (1.1) also having high correlations. Furthermore, spatial analyses revealed a geographical pattern in terms of both incidence and mortality rates, with COVID-19 first being observed in suburban areas from where the disease swiftly spread into downtown reaching a peak between 25 February to 06 March (4 incidences per km2). Mortality peaked 3 weeks later after which the infection gradually decreased. Out of patients investigated by the spatiotemporal approach (n = 727), 205 (28.2%) did not survive and 66.8% of them were men.

Conclusions

Older adults and people with severe co-morbidities were at higher risk for developing serious complications due to COVID-19. Applying spatiotemporal methods to identify the transmission trends and high-risk areas can rapidly be documented, thereby assisting policymakers in designing and implementing tailored interventions to control and prevent not only COVID-19 but also other rapidly spreading epidemics/pandemics.
Effectiveness of a community-level social mobilization intervention in achieving the outcomes of polio vaccination campaigns during the post-polio-endemic period: Evidence from CORE Group polio project in Uttar Pradesh, India
Authors: Choudhary Manojkumar , Solomon Roma , Awale Jitendra , Dey Rina , Singh Jagajeet Prasad , Weiss William
Published: July 2021

Background

A social mobilization (SM) initiative contributed to India’s success in polio elimination. This was the CORE Group Polio Project (CGPP) India, a partner of the Uttar Pradesh (UP) SM Network and which continued its SM activities, even during the polio-free period through a network of multi-level social mobilizers. This paper assesses the effects of this community-level SM (CLSM) intervention on the extent of community engagement and performance of polio Supplementary Immunization Activity campaigns (SIAs) during the post-polio-endemic period (i.e., from March 2012 to September 2017).

Methods

This study followed a quasi-experimental design. We used secondary, cluster-level data from CGPP India’s Management Information System, including 52 SIAs held from January 2008 to September 2017, covering 56 blocks from 12 districts of UP. We computed various indicators and performed Generalized Estimating Equations based analysis to assess the statistical significance of differences between the outcomes of intervention and non-intervention areas. We then estimated the effects of the SM intervention using Interrupted time-series, Difference-in-Differences and Synthetic Control Methods. Finally, we estimated the population influenced by the intervention.

Results

The performance of polio SIAs changed over time, with the intervention areas having better outcomes than non-intervention areas. The absence of CLSM intervention during the post-polio-endemic period would have negatively impacted the outcomes of polio SIAs. The percentage of children vaccinated at polio SIA booths, percentage of ‘X’ houses (i.e., households with unvaccinated children or households with out-of-home/out-of-village children or locked households) converted to ‘P’ (i.e., households with all vaccinated children or households without children eligible for vaccination), and percentage of resistant houses converted to polio acceptors would have gone down by 14.1 (Range: 12.7 to 15.5), 6.3 (Range: 5.2 to 7.3) and 7.4 percentage points, respectively. Community engagement would have reduced by 7.2 (Range: 6.6 to 7.7) percentage points.

Conclusions

The absence of CLSM intervention would have significantly decreased the level of community engagement and negatively impacted the performance of polio SIAs of the post-polio-endemic period. The study provides evidence of an added value of deploying additional human resource dedicated to social mobilization to achieve desired vaccination outcomes in hard-to-reach or programmatically challenging areas.