bluuebunny/crossref_metadata_2025_split huggingface dataset:
From glucose lowering agents to disease/diabetes modifying drugs: a “SIMPLE” approach for the treatment of type 2 diabetes
Authors: Mosenzon Ofri , Del Prato Stefano , Schechter Meir , Leiter Lawrence A. , Ceriello Antonio , DeFronzo Ralph A. , Raz Itamar 
Published: April 2021

AbstractDuring the last decade we experienced a surge in the number of glucose lowering agents that can be used to treat patients with type 2 diabetes. Especially important are the discoveries that sodium glucose co-transporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve patients’ cardiovascular and renal outcomes. Accordingly, various medical associations have updated their guidelines for the treatment of diabetes in this new era. Though not agreeing on every issue, these position-statements generally share a detailed and often complex workflow that may be too complicated for the busy and overworked primary care setting, where the majority of patients with type 2 diabetes are managed in many countries. Other guidelines, generally those from the cardiology associations focus primarily on the population of patients with high risk for or pre-existing cardiovascular disease, which represent only the minority of patients with type 2 diabetes. We believe that we should re-define SGLT2i and GLP-1 RA as diabetes/disease modifying drugs (DMDs) given the recent evidence of their cardiovascular and renal benefits. Based on this definition we have designed a SIMPLE approach in order to assist primary care teams in selecting the most appropriate therapy for their patients. We believe that most subjects newly diagnosed with type 2 diabetes should initiate early combination therapy with metformin and a prognosis changing DMD. The decision whether to use GLP-1 RA or SGLT2i should be made based on specific patient’s risk factors and preferences. Importantly, DMDs are known to have a generally safe side-effect profile, with lower risk for hypoglycemia and weight gain, further promoting their wider usage. Early combination therapy with DMDs may improve the multiple pathophysiological abnormalities responsible for type 2 diabetes and its complications, thus resulting in the greatest long term benefits.
Impact of the N501Y substitution of SARS-CoV-2 Spike on neutralizing monoclonal antibodies targeting diverse epitopes
Authors: Cheng Lin , Song Shuo , Zhou Bing , Ge Xiangyang , Yu Jiazhen , Zhang Mingxia , Ju Bin , Zhang Zheng 
Published: April 2021

AbstractThe emergence and rapid spread of the B.1.1.7 lineage (VOC-202012/01) SARS-CoV-2 variant has aroused global concern. The N501Y substitution is the only mutation in the interface between the RBD of B.1.1.7 and ACE2, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we assessed the neutralizing activity and binding affinity of a panel of 12 monoclonal antibodies against the wild type and N501Y mutant SARS-CoV-2 pseudovirus and RBD protein, respectively. We found that the neutralization activity and binding affinity of most detected antibodies (10 out of 12) were unaffected, although the N501Y substitution decreased the neutralizing and binding activities of CB6 and increased that of BD-23. These findings could be of value in the development of therapeutic antibodies.
Computer vision-based wood identification and its expansion and contribution potentials in wood science: A review
Authors: Hwang Sung-Wook , Sugiyama Junji 
Published: April 2021

AbstractThe remarkable developments in computer vision and machine learning have changed the methodologies of many scientific disciplines. They have also created a new research field in wood science called computer vision-based wood identification, which is making steady progress towards the goal of building automated wood identification systems to meet the needs of the wood industry and market. Nevertheless, computer vision-based wood identification is still only a small area in wood science and is still unfamiliar to many wood anatomists. To familiarize wood scientists with the artificial intelligence-assisted wood anatomy and engineering methods, we have reviewed the published mainstream studies that used or developed machine learning procedures. This review could help researchers understand computer vision and machine learning techniques for wood identification and choose appropriate techniques or strategies for their study objectives in wood science.
Pressure Relieving Support Surfaces: a Randomised Evaluation 2 (PRESSURE 2): using photography for blinded central endpoint review
Authors:   on behalf of the PRESSURE 2 Trial Group, McGinnis Elizabeth , Smith Isabelle L , Collier Howard , Wilson Lyn , Coleman Susanne , Stubbs Nikki , Brown Sarah , Gilberts Rachael , Henderson Valerie , Walker Kay , Nelson E. Andrea , Nixon Jane 
Published: April 2021

Abstract
Background
PRESSURE 2 is a randomised evaluation of the clinical and cost-effectiveness of two types of mattress for the prevention of pressure ulcers (PUs). The primary clinical endpoint was time to development of a category ≥2 PU. The current ‘gold standard’ for PU identification is expert clinical assessment. Due to the mattress appearance, a blinded assessment of the endpoint is not possible. This poses a risk to the internal validity of the study. A possible approach is to use photographs of skin sites, with central blinded review. However, there are practical and scientific concerns including patients’ consent to photographs, burden of data collection, photograph quality, data completeness and comparison of photographs to the current ‘gold standard’. This paper reports the findings of the PRESSURE 2 photographic validation sub-study.

Method
Where consent was obtained, photographs were taken of all category ≥2 PUs on the first presentation to assess over-reporting, and for the assessment of under-reporting, a random sample of 10% patients had an assessment by an independent clinical assessor who also photographed two skin sites. The staff were trained in taking and transferring photographs using standardised procedures and equipment. A card included in the photograph recorded participant details and a ‘greyscale’ for correction of white balance during processing. Three blinded reviewers assessed the photographs and rated how confident they were in their assessment.

Results
The trial recruited 2029 patients; 85% consented to photography, and 532 photographs were received and used in the blinded central review. The level of confidence varied by skin classification with more confidence observed when the skin was assessed as being less severe than a category ≥2 PU. Overall, there was a very good reliability compared to the gold standard expert clinical assessment (87.8%, kappa 0.82).

Conclusion
Study findings have usefully informed the scientific and practical issues of blinded assessment of PU status to reducing the risk of bias in medical device trials. The reliability of central blinded expert photography was found to be ‘very good’ (PABAK). Photographs have been found to be an acceptable method of data validation for participants. Methods to improve the quality of photographs would increase the confidence in the assessments.

Trial registration
ISRCTN Registry ISRCTN01151335. Registered on 19 April 2013
Effect of solid loading on the behaviour of pectin-degrading enzymes
Authors: Li Fan , Foucat Loïc , Bonnin Estelle 
Published: April 2021

Abstract
Background
Pectin plays a role in the recalcitrance of plant biomass by affecting the accessibility of other cell wall components to enzymatic degradation. Elimination of pectin consequently has a positive impact on the saccharification of pectin-rich biomass. This work thus focused on the behaviour of different pectin-degrading enzymes in the presence of low (5%) to high (35%) solid loading of lemon peel.

Results
High solid loading of lemon peel affected pectin solubilisation differently depending on the pectinase used. Pectin lyase was less sensitive to a reduction of water content than was a mixture of endopolygalacturonase and pectin methylesterase, regardless of whether or not the latter's mode of action is processive or not. Marked changes in water mobility were observed along with enzymatic degradation depending on the enzyme used. However, the pectin lyase resulted in less pronounced shifts in water distribution than polygalacturonase–pectin methylesterase mixtures. At similar pectin concentration, pectin solutions hindered the diffusion of hydrolases more than the solid substrate. This can be attributed to the high viscosity of the highly concentrated pectin solutions while the solid substrate may provide continuous diffusion paths through pores.

Conclusions
The increase in solid substrate loading reduced the efficiency of pectin-degrading enzymes catalysing hydrolysis more significantly than those catalysing β-elimination. LF-NMR experiments highlighted the impact of solid loading on water mobility. Compared to other enzymes and whatever the solid loading, pectin lyase led to longer relaxation times linked with the most destructuration of the solid substrate. This new information could benefit the biorefinery processing of pectin-rich plant material when enzymes are used in the treatment.
Strategies for increasing gait speed in patients with hip osteoarthritis: their clinical significance and effects on hip loading
Authors: Tateuchi Hiroshige , Akiyama Haruhiko , Goto Koji , So Kazutaka , Kuroda Yutaka , Ichihashi Noriaki 
Published: April 2021

Abstract
Background
Changes in gait speed are required in various situations and can be achieved by changing stride length, cadence, or both. Differences in strategies for increasing gait speed may have different effects on hip joint and physical function. The purpose of this study was to determine the effects of strategies for increasing gait speed on hip pain, physical function, and changes in hip loading during gait in patients with hip osteoarthritis (OA). We hypothesized that patients who increase gait speed mainly by increasing cadence would have lesser hip pain, a higher physical function, and a lower rate of increase in hip moments with increasing gait speed.

Methods
Forty-seven patients with secondary hip OA (age, 48.3 ± 11.0 years) were included. Gait speed, stride length, cadence, and peak and impulse of the hip moments were measured during gait at self-selected normal and fast gait speeds. The patients were classified as types S (with mainly increasing stride length, n = 11 [23.4%]), C (with mainly increasing cadence, n = 23 [48.9%]), and SC (with increasing stride length and cadence, n = 13 [27.7%]) according to whether they used changes in stride length and/or cadence to transition from normal to fast gait. Hip pain, physical function, and hip moment changes during gait were compared between types.

Results
The physical function was higher in types C (38.0 ± 8.8, P = 0.018) and SC (40.6 ± 8.5, P = 0.015) than in type S (28.2 ± 7.8), even after adjustment for age and minimum joint space width. Hip pain was not significantly different between types. The robustness of these results was confirmed with sensitivity analysis. The rates of increases in peak external hip adduction (P = 0.003) and internal rotation moments (P = 0.009) were lower in type C than in type SC.

Conclusions
Type C tended to suppress the increase in hip moments during fast gait. Types C and SC, which included increased cadence, maintained higher physical function levels than type S. Encouraging the use of cadence-increasing strategy may be useful for reducing hip loading and maintaining physical function in patients with hip OA.
Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials
Authors: Solipuram Vinod , Mohan Akhila , Patel Roshniben , Ni Ruoning 
Published: April 2021

Abstract
Background
Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk.

Objective
To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone.

Methods
PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel–Haenszel random-effect method.

Results
659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found.

Conclusion
The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.
Carriage of two carbapenem-resistance genes in Pseudomonas aeruginosa isolated from hospital-acquired infections in children from Costa Rica: the importance of local epidemiology
Authors: Pérez-Corrales Cristian , Peralta-Barquero Valeria , Mairena-Acuña Christopher 
Published: April 2021

Abstract
Background
The assessment of Hospital-acquired infections due to multidrug-resistant bacteria involves the use of a variety of commercial and laboratory-developed tests to detect antimicrobial resistance genes in bacterial pathogens; however, few are evaluated for use in low- and middle-income countries.

Methods
We used whole-genome sequencing, rapid commercial molecular tests, laboratory-developed tests and routine culture testing.

Results
We identified the carriage of the metallo-β-lactamase blaVIM-2 and blaIMP-18 alleles in Carbapenem-Resistant Pseudomonas aeruginosa infections among children in Costa Rica.

Conclusions
The blaIMP-18 allele is not present in the most frequently used commercial tests; thus, it is possible that the circulation of this resistance gene may be underdiagnosed in Costa Rica.
Emodin and rhein in Cassia tora ameliorates activity of mitochondrial enzymes involved in oxidative phosphorylation in the retina of diabetic mice
Authors: Ko Eun , Um Min Young , Han Taewon , Shin Sooim , Choi Moonsung 
Published: April 2021

AbstractCassia tora is an annual herb, which has pharmacological effects such as antioxidant, hypolipidemic, and antidiabetic effects. Accordingly, its effect on diabetes has been well-studied. However, it is unclear whether it has an effect on mitochondrial dysfunction associated with diabetes. In this study, the effects of emodin and rhein in C. tora seed ethanolic extract (ER/CSEE) on retinal mitochondrial function were examined in high-fat diet (HFD)-fed mice. HFD-fed mice exhibited decreased mitochondrial function followed by compensatory increase in the expression levels of mitochondrial enzymes. However, ER/CSEE treatment for 12 weeks ameliorated the activity of retinal mitochondrial complexes and reduced the expression level of enzymes involved in oxidative phosphorylation, except that of complex II and citrate synthase in citric acid cycle. This suggests that repairing capacity of enzymes in electron transport chain and citric acid cycle of mitochondria are different in response to the metabolic state. Therefore, it concluded that emodin and rhein play a pharmacological role in fat metabolism by influencing activities of enzymes in citric acid cycle linked with beta-oxidation in retina.
Acrolein scavenger dimercaprol offers neuroprotection in an animal model of Parkinson’s disease: implication of acrolein and TRPA1
Authors: Shi Liangqin , Lin Yazhou , Jiao Yucheng , Herr Seth A. , Tang Jonathan , Rogers Edmond , Chen Zhengli , Shi Riyi 
Published: April 2021

Abstract
Background
The mechanisms underlying lesions of dopaminergic (DA) neurons, an essential pathology of Parkinson’s disease (PD), are largely unknown, although oxidative stress is recognized as a key factor. We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in PD pathology, and that acrolein scavenger hydralazine can reduce the elevated acrolein, mitigate DA neuron death, and alleviate motor deficits in a 6-hydroxydopamine (6-OHDA) rat model. As such, we hypothesize that a structurally distinct acrolein scavenger, dimercaprol (DP), can also offer neuroprotection and behavioral benefits.

Methods
DP was used to lower the elevated levels of acrolein in the basal ganglia of 6-OHDA rats. The acrolein levels and related pathologies were measured by immunohistochemistry. Locomotor and behavioral effects of 6-OHDA injections and DP treatment were examined using the open field test and rotarod test. Pain was assessed using mechanical allodynia, cold hypersensitivity, and plantar tests. Finally, the effects of DP were assessed in vitro on SK-N-SH dopaminergic cells exposed to acrolein.

Results
DP reduced acrolein and reversed the upregulation of pain-sensing transient receptor potential ankyrin 1 (TRPA1) channels in the substantia nigra, striatum, and cortex. DP also mitigated both motor and sensory deficits typical of PD. In addition, DP lowered acrolein and protected DA-like cells in vitro. Acrolein’s ability to upregulate TRPA1 was also verified in vitro using cell lines.

Conclusions
These results further elucidated the acrolein-mediated pathogenesis and reinforced the critical role of acrolein in PD while providing strong arguments for anti-acrolein treatments as a novel and feasible strategy to combat neurodegeneration in PD. Considering the extensive involvement of acrolein in various nervous system illnesses and beyond, anti-acrolein strategies may have wide applications and broad impacts on human health.
Gendered determinants of food insecurity in ongoing regional conflicts, North and South Kivu, the Democratic Republic of Congo
Authors: Bapolisi Wyvine Ansima , Ferrari Giovanfrancesco , Bisimwa Ghislain , Merten Sonja 
Published: April 2021

Abstract
Background
Food insecurity remains a major concern worldwide. In North and South Kivu provinces, the Democratic Republic of the Congo, repeated wars and gender-based violence exacerbate the situation. However, little is known about the determinants of food insecurity in the region.

Objective
This study analyzed the gendered determinants of food insecurity in North and South Kivu in the Democratic Republic of Congo, a region of ongoing civil conflict.

Methods
1754 women were included in a cross-sectional study. Multilevel ordinal logistic regression was used to identify household-level determinants of food insecurity.

Results
The poorest households were five times more likely to be food insecure (OR = 5.66, 95% CI 3.74–8.55). Women’s participation in decision-making about resource allocation decreased the risk for household food insecurity (OR = 0.68, 95% CI 0.57–0.87), while higher tolerance to gender-based violence increased the risk of food insecurity (OR = 1.29, 95% CI 1.05–1.54).

Conclusion
Involving empowered women in decision-making about resource allocation and actions to reduce gender-based violence could help mitigate food insecurity.
Impacts of phased–out land restoration programs on vegetation cover change in Eastern Tigray, Ethiopia
Authors: Gebregergs Tirhas , Teka Kassa , Taye Gebeyehu , Gidey Eskinder , Dikinya Oagile 
Published: April 2021

Abstract
Background
Land restoration programs in Tigray, also called integrated watershed management (IWM) practices, were implemented by the government and non–governmental organizations since 1980s. These practices aimed at reversing land degradation processes, environmental rehabilitation, and ensure food security at both community and household levels. Most of the implemented IWM projects are now phased–out. The aim of this study is therefore; therefore, to investigate the impacts of phased–out land restoration programs on vegetation cover changes in Eastern Tigray, Ethiopia. Both Thematic Mapper (TM) and Enhanced Thematic Mapper plus (ETM+) Landsat imageries at 30 meter by 30 meter spatial resolution were used to examine the land use and land cover conditions taking successful and unsuccessful IWM interventions as case studies. Three time periods were used in the change analysis: before IWM implementation (2007), at the time of IWM projects phase-out (2010), and after IWM phase-out (2017).

Results
The results indicated that for all successful integrated watershed management projects, both the bush/shrub land (19.6 ha) and grassland (8.95 ha) increased during the intervention time for Negash (S-1), Deberewahabit (S-2) and Gemad (S-3) watersheds. However, the bush/shrub land decreased after the integrated watershed management projects phased–out by 9.8 and 11.3 ha for S-1 and S-3 watersheds. At the unsuccessful IWM projects, bush/shrub land increased by 18.21, 11.3 and 9.5 ha during the intervention period, and decreased after project phased–out by 3.92 and 7.2 ha at Debretsion (S-4) and Laelay wukro (S-5) watersheds. Furthermore, cultivated land increased after phased–out in most of the watersheds.

Conclusions
This study concluded that vegetation cover has been declined in all watersheds after the phased–out period. This may affect significantly the environment in general and livelihood of the community in particular. Therefore, there is a need to provide an emphasis after the implementation of watershed projects and evaluate its impacts regularly.