bluuebunny/crossref_metadata_2025 huggingface dataset:
Thymulin and peroxiredoxin 6 have protective effects against streptozotocin-induced type 1 diabetes in mice
Authors: Novoselova Elena G , Glushkova Olga V , Lunin Sergey M , Khrenov Maxim O , Parfenyuk Svetlana B , Novoselova Tatyana V , Sharapov Mars G , Gordeeva Alina E , Novoselov Vladimir I , Fesenko Evgeny E
Published: March 2021

Protective effects of peroxiredoxin 6 (PRDX6) in RIN-m5F β-cells and of thymulin in mice with alloxan-induced diabetes were recently reported. The present work was aimed at studying the efficiency of thymulin and PRDX6 in a type 1 diabetes mellitus model induced by streptozotocin in mice. Effects of prolonged treatment with PRDX6 or thymic peptide thymulin on diabetes development were evaluated. We assessed the effects of the drugs on the physiological status of diabetic mice by measuring blood glucose, body weight, and cell counts in several organs, as well as effects of thymulin and PRDX6 on the immune status of diabetic mice measuring concentrations of pro-inflammatory cytokines in blood plasma (TNF-α, interleukin-5 and 17, and interferon-γ), activity of NF-κB and JNK pathways, and Hsp90α expression in immune cells. Both thymulin and PRDX6 reduced the physiological impairments in diabetic mice at various levels. Thymulin and PRDX6 provide beneficial effects in the model of diabetes via very different mechanisms. Taken together, the results of our study indicated that the thymic peptide and the antioxidant enzyme have anti-inflammatory functions. As increasing evidences show diabetes mellitus as a distinct comorbidity leading to acute respiratory distress syndrome and increased mortality in patients with COVID-19 having cytokine storm, thymulin, and PRDX6 might serve as a supporting anti-inflammatory treatment in the therapy of COVID 19 in diabetic patients.
Displacement Effect and Ratchet Effect: Testing of Two Alternative Hypotheses
Authors: Jaén-García Manuel
Published: March 2021

This article empirically tests the displacement effect of Peacock and Wiseman (PW) and the ratchet effect of Bird, both of which are alternatives to Wagner’s law on the growth of public expenditure. The displacement effect explains why the (horizontal) trend line moves upward in discrete steps over time, whereas the ratchet effect affirms that public expenditure “ratchets” during drops in the economy and remains at a higher level after the economy stabilizes. The following innovations are introduced in the present study: (a) empirical testing was conducted for Spain and an extensive time period, 1880–2016; (b) the relationship between PR and expenditure was considered, introducing Gross Domestic Product (GDP) as a control variable; and (c) testing was performed using two differentiated methodologies. More specifically, the two methodologies employed were unit roots and cointegration with structural breakpoints and the more recent wavelet methodology. Given that PW refer to situations of social upheaval and its consequences, this study places its focus on analyzing the changes produced in Spain’s public expenditure with respect to the Spanish Civil War of 1936–1939 and to other disruptions both before and after this date. It was concluded that the displacement effect explains the development of Spanish public expenditure for the crises of 1982 and 1998. Meanwhile, wavelet methodology explains growth that took place in 1920 and 1980. In contrast, the ratchet effect does not explain the development of Spanish public expenditure over the study period.
Risk Factors Associated With Complications After Operative Treatment of Multiligament Knee Injury
Authors: Patel Neel K. , Lian Jayson , Nickoli Michael , Vaswani Ravi , Irrgang James J. , Lesniak Bryson P. , Musahl Volker
Published: March 2021

Background:

Many factors can affect clinical outcomes and complications after a complex multiligament knee injury (MLKI). Certain aspects of the treatment algorithm for MLKI, such as the timing of surgery, remain controversial.

Purpose:

To determine the risk factors for common complications after MLKI reconstruction.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

A retrospective review was conducted on 134 patients with MLKI who underwent reconstruction between 2011 and 2018 at a single academic center. Patients included in the review had a planned surgical reconstruction of >1 ligament based on clinical examination and magnetic resonance imaging. Complications were categorized as (1) wound infection requiring irrigation and debridement, (2) arthrofibrosis requiring manipulation under anesthesia and/or lysis of adhesions, (3) deep venous thrombosis, (4) need for removal of hardware, and (5) revision ligament surgery. The potential risk factors for complications included patient characteristics, injury pattern categorized according to Schenck classification (knee dislocation [KD] I–KD IV), and timing of surgery. Significant risk factors for complications were analyzed by t test, chi-square test, and Fisher exact test.

Results:

A total of 108 patients met the inclusion criteria; of these, 29.6% experienced at least 1 complication. Smoking (odds ratio [OR], 3.20 [95% CI, 1.28-8.02]; P = .01) and planned staged surgery (OR, 2.71 [95% CI, 1.04-7.04]; P = .04) significantly increased the overall risk of complication, while increased time from injury to surgery (OR, 0.99 [95% CI, 0.98-0.998]; P < .01) significantly decreased the risk. Increasing time from injury to surgery (OR, 0.99 [95% CI, 0.97-0.998]; P = .02) also led to a slightly but significantly decreased risk for arthrofibrosis.

Conclusion:

The study findings suggest that smoking, decreased time from injury to initial surgery, and planned staged procedures may increase the rate of complications. Further studies are needed to determine which changes in the treatment algorithm are most effective to reduce the complication rate in patients.
Population structure and uropathogenic potential of extended-spectrum cephalosporin-resistant Escherichia coli from retail chicken meat
Authors: Buberg May Linn , Mo Solveig Sølverød , Sekse Camilla , Sunde Marianne , Wasteson Yngvild , Witsø Ingun Lund
Published: March 2021

Background

Food-producing animals and their products are considered a source for human acquisition of antimicrobial resistant (AMR) bacteria, and poultry are suggested to be a reservoir for Escherichia coli resistant to extended-spectrum cephalosporins (ESC), a group of antimicrobials used to treat community-onset urinary tract infections in humans. However, the zoonotic potential of ESC-resistant E. coli from poultry and their role as extraintestinal pathogens, including uropathogens, have been debated. The aim of this study was to characterize ESC-resistant E. coli isolated from domestically produced retail chicken meat regarding their population genetic structure, the presence of virulence-associated geno- and phenotypes as well as their carriage of antimicrobial resistance genes, in order to evaluate their uropathogenic potential.

Results

A collection of 141 ESC-resistant E. coli isolates from retail chicken in the Norwegian monitoring program for antimicrobial resistance in bacteria from food, feed and animals (NORM-VET) in 2012, 2014 and 2016 (n = 141) were whole genome sequenced and analyzed. The 141 isolates, all containing the beta-lactamase encoding gene blaCMY-2, were genetically diverse, grouping into 19 different sequence types (STs), and temporal variations in the distribution of STs were observed. Generally, a limited number of virulence-associated genes were identified in the isolates. Eighteen isolates were selected for further analysis of uropathogen-associated virulence traits including expression of type 1 fimbriae, motility, ability to form biofilm, serum resistance, adhesion- and invasion of eukaryotic cells and colicin production. These isolates demonstrated a high diversity in virulence-associated phenotypes suggesting that the uropathogenicity of ESC-resistant E. coli from chicken meat is correspondingly highly variable. For some isolates, there was a discrepancy between the presence of virulence-associated genes and corresponding expected phenotype, suggesting that mutations or regulatory mechanisms could influence their pathogenic potential.

Conclusion

Our results indicate that the ESC-resistant E. coli from chicken meat have a low uropathogenic potential to humans, which is important knowledge for improvement of future risk assessments of AMR in the food chains.
Low incidence of ABL-class and JAK-STAT signaling pathway alterations in uniformly treated pediatric and adult B-cell acute lymphoblastic leukemia patients using MRD risk-directed approach – a population-based study
Authors: Norvilas Rimvydas , Dirse Vaidas , Semaskeviciene Ruta , Mickeviciute Orinta , Gineikiene Egle , Stoskus Mindaugas , Vaitkeviciene Goda , Rascon Jelena , Griskevicius Laimonas
Published: March 2021

Background

ABL-class and JAK-STAT signaling pathway activating alterations have been associated with both a poor post-induction minimal residual disease (MRD) response and an inferior outcome in B-cell acute lymphoblastic leukemia (B-ALL). However, in most of the studies patients received non-uniform treatment.

Methods

We performed a population-based analysis of 160 (122 pediatric and 38 adult) Lithuanian BCR-ABL1-negative B-ALL patients who had been uniformly treated according to MRD-directed NOPHO ALL-2008 protocol. Targeted RNA sequencing and FISH analysis were performed in cases without canonical B-ALL genomic alterations (high hyperdiploids and low hypodiploids included).

Results

We identified ABL-class fusions in 3/160 (1.9%) B-ALL patients, and exclusively in adults (p = 0.003). JAK-STAT pathway fusions were present in 4/160 (2.5%) cases. Of note, P2RY8-CRLF2 fusion was absent in both pediatric and adult B-ALL cases. Patients with ABL-class or JAK-STAT pathway fusions had a poor MRD response and were assigned to the higher risk groups, and had an inferior event-free survival (EFS) / overall survival (OS) compared to patients without these fusions. In a multivariate analysis, positivity for ABL-class and JAK-STAT fusions was a risk factor for worse EFS (p = 0.046) but not for OS (p = 0.278) in adults.

Conclusions

We report a low overall frequency of ABL-class and JAK-STAT fusions and the absence of P2RY8-CRLF2 gene fusion in the Lithuanian BCR-ABL1 negative B-ALL cohort. Future (larger) studies are warranted to confirm an inferior event-free survival of ABL-class/JAK-STAT fusion-positive adult patients in MRD-directed protocols.
Factors associated with problematic internet use among a large sample of Lebanese adolescents
Authors: Dib Joseph E. , Haddad Chadia , Sacre Hala , Akel Marwan , Salameh Pascale , Obeid Sahar , Hallit Souheil
Published: March 2021

Background

International literature clearly describes factors associated with problematic internet use, including substance dependence, online gambling, social impairment, and functional difficulties. Therefore, it was imperative to assess the extent to which young adolescents in Lebanese schools are affected by problematic internet use (PIU) and the factors associated with it. This large-scale Lebanese survey aims to evaluate the relationship between PIU, depression, and substance use, including alcohol consumption and nicotine use (cigarettes and waterpipe) among adolescents in Lebanese schools.

Methods

This cross-sectional study conducted between January and May 2019 assessed internet use through the Internet Addiction Test (IAT), with ‘severe internet use’ being the threshold for problematic internet use. It enrolled a total of 1810 adolescents aged 14 to 17 from 16 schools from all Lebanese Mohafazat.

Results

The majority of the participants had an average internet use 74.8% (95% Confidence Interval (CI): 0.72–0.76), 20.7% (95% CI: 0.18–0.22) had a frequent internet use, and 4.5% (95% CI: 0.03–0.05) had a severe internet use. Higher alcohol dependence (ß = 0.456, p < 0.001), higher depression (ß = 0.079, p = 0.001), and having separated parents vs. living together (ß = 0.136, p < 0.001) were significantly associated with higher IAT scores. Higher waterpipe dependence (ß = -0.218, p < 0.001) was significantly associated with lower IAT scores.

Conclusion

This study, the first and largest of its kind in the Middle East, showed that some psychiatric disorders, such as depression and substance use (smoking and alcohol), are associated with more problematic internet use among Lebanese adolescents. These results could serve as the first step for policymakers towards implementing early awareness campaigns to look at this problem more in-depth and come up with efficient actions to avoid it.
Scaling up public health interventions: case study of the polio immunization program in Indonesia
Authors: Cintyamena Utsamani , Azizatunnisa’ Luthfi , Ahmad Riris Andono , Mahendradhata Yodi
Published: March 2021

Background

The scaling up of public health interventions has received greater attention in recent years; however, there remains paucity of systematic investigations of the scaling up processes. We aim to investigate the overall process, actors and contexts of polio immunization scaling up in Indonesia from 1988 until 2018.

Methods

A mixed method study with sequential explanatory design was conducted. We carried out a quantitative survey of 323 actors involved in the polio program at national and sub-national levels, followed by Key Informant Interviews (KII)s. Document review was also carried out to construct a timeline of the polio eradication program with milestones. We carried out descriptive statistical analysis of quantitative data and thematic analysis of qualitative data.

Results

The scaling up of polio immunization in Indonesia started as a vertical expansion approach led by the Ministry of Health within a centralized health system. The coverage of immunization increased dramatically from 5% in the earlier 80s to 67.5% in 1987; incremental increases followed until achieving Universal Child Immunization (UCI) in 1990 and subsequently 95% coverage in 1995. Engagement of stakeholders and funding made the scaling up of polio immunization a priority. There was also substantial multisector involvement, including institutions and communities. Local area monitoring (LAM) and integrated health posts (Posyandu) were key to the polio immunization implementation strategy. Challenges for scaling up during this centralized period included cold chain infrastructure and limited experience in carrying out mass campaigns. Scaling up during the decentralized era was slower due to expansion in the number of provinces and districts. Moreover, there were challenges such as the negative perception of immunization side-effects, staff turnover, and the unsmooth transition of centralization towards decentralization.

Conclusion

Vertical scaling up of polio immunization program intervention was successful during the centralized era, with involvement of the president as a role model and the engine of multi sector actors. Posyandu (integrated health posts) played an important role, yet its revitalization after the reform-decentralization era has not been optimum.
Exploring the influence of human mobility factors and spread prediction on early COVID-19 in the USA
Authors: Zheng Zhicheng , Xie Zhixiang , Qin Yaochen , Wang Kun , Yu Yan , Fu Pinde
Published: March 2021

Background

COVID-19 is still spreading rapidly around the world. In this context, how to accurately predict the turning point, duration and final scale of the epidemic in different countries, regions or cities is key to enabling decision makers and public health departments to formulate intervention measures and deploy resources.

Methods

Based on COVID-19 surveillance data and human mobility data, this study predicts the epidemic trends of national and state regional administrative units in the United States from July 27, 2020, to January 22, 2021, by constructing a SIRD model considering the factors of “lockdown” and “riot”.

Results

(1) The spread of the epidemic in the USA has the characteristics of geographical proximity. (2) During the lockdown period, there was a strong correlation between the number of COVID-19 infected cases and residents’ activities in recreational areas such as parks. (3) The turning point (the point of time in which active infected cases peak) of the early epidemic in the USA was predicted to occur in September. (4) Among the 10 states experiencing the most severe epidemic, New York, New Jersey, Massachusetts, Texas, Illinois, Pennsylvania and California are all predicted to meet the turning point in a concentrated period from July to September, while the turning point in Georgia is forecast to occur in December. No turning points in Florida and Arizona were foreseen for the forecast period, with the number of infected cases still set to be growing rapidly.

Conclusions

The model was found accurately to predict the future trend of the epidemic and can be applied to other countries. It is worth noting that in the early stage there is no vaccine or approved pharmaceutical intervention for this disease, making the fight against the pandemic reliant on non-pharmaceutical interventions. Therefore, reducing mobility, focusing on personal protection and increasing social distance remain still the most effective measures to date.
The trochanteric double contour is a valuable landmark for assessing femoral offset underestimation on standard radiographs: a retrospective study
Authors: Blümel Stefan , Stadelmann Vincent A. , Brioschi Marco , Küffer Alexander , Leunig Michael , Rüdiger Hannes A.
Published: March 2021

Background

Inaccurate projection on standard pelvic radiographs leads to the underestimation of femoral offset—a critical determinant of postoperative hip function—during total hip arthroplasty (THA) templating. We noted that the posteromedial facet of the greater trochanter and piriformis fossa form a double contour on radiographs, which may be valuable in determining the risk of underestimating femoral offset. We evaluate whether projection errors can be predicted based on the double contour width.

Methods

Plain anteroposterior (AP) pelvic radiographs and magnetic resonance images (MRIs) of 64 adult hips were evaluated retrospectively. Apparent femoral offset, apparent femoral head diameter and double contour widths were evaluated from the radiographs. X-ray projection errors were estimated by comparison to the true neck length measured on MRIs after calibration to the femoral heads. Multivariate analysis with backward elimination was used to detect associations between the double contour width and radiographic projection errors. Femoral offset underestimation below 10% was considered acceptable for templating.

Results

The narrowest width of the double line between the femoral neck and piriformis fossa is significantly associated with projection error. When double line widths exceed 5 mm, the risk of projection error greater than 10% is significantly increased compared to narrower double lines, and the acceptability rate for templating drops below 80% (p = 0.02).

Conclusion

The double contour width is a potential landmark for excluding pelvic AP radiographs unsuitable for THA templating due to inaccurate femoral rotation.
The effects on pain, physical function, and quality of life of quadriceps strengthening exercises combined with Baduanjin qigong in older adults with knee osteoarthritis: a quasi-experimental study
Authors: Wang Fenglan , Zhang Xiaoli , Tong Xiao , Zhang Min , Xing Fengmei , Yang Kun , Jiao Nana , Duan Zhiguang
Published: March 2021

Background

Exercise is recommended as a principal treatment for individuals with knee osteoarthritis (KOA). However, the best choice for an optimal exercise program able to promote long-term compliance in KOA patients is not clear. This study aims to compare the effect of combined exercise (CE: quadriceps strengthening exercises (QSE) and Baduanjin qigong training (BDJ)) versus QSE alone and BDJ alone on older adults with KOA.

Methods

A three-arm, quasi-experimental trial with repeated measurements was used. As a cluster randomized trial, participants from three community centers were assigned respectively to QSE group, BDJ group and CE group. We assessed pain intensity, physical function, self-efficacy, and health-related quality-of-life (HRQoL) using standardized instruments at baseline, 3 months and 6 months follow-up.

Results

One hundred and twenty-eight participants with KOA aged over 60 completed the study. Over the 6 months, there were significant group interaction effects on pain intensity (F = 28.888, P < 0.001), physical function (F = 26.646, P < 0.001), and self-efficacy (F = 22.359, P < 0.001), and, based on a short form-12 item health survey questionnaire (SF-12), physical component summary (F = 7.470, P < 0.001), and mental component summary (F = 10.207, P < 0.001). Overall, the CE group exhibited significantly greater improvement in all outcomes when compared to the QSE group and the BDJ group.

Conclusions

CE treatment is more effective than QSE and BDJ in pain relief, increasing physical function, improving self-efficacy, and raising quality-of-life in community-dwelling KOA older adults. Moreover, it promotes long-term compliance in KOA community patients.

Trial registration

Chinese Clinical Trails Registry number ChiCTR2000033387 (retrospectively registered). Registered 30 May 2020.
Cannula breakage during 25G+ minimally invasive vitrectomy: a case report
Authors: Shu Zhimin , Jin Siyan , Shan Chenli , Ma Linlin , Liu Jia , Yang Ning , Zhao Jinsong
Published: March 2021

Background

With the continuous improvement of surgical instruments in vitrectomy, the use of a trocar and cannula not only optimizes the incision process but also facilitates insertion and withdrawal of instruments during the procedure. Nevertheless, incision-related complications have also been reported in the literature. However, cannula fractures during 25G+ minimally invasive vitrectomy have rarely been reported.

Case presentation

A 62-year-old man underwent 25G+ pars plana vitrectomy for proliferative diabetic retinopathy. At the beginning of the operation, we used a trocar with a cannula to perform the sclerotomy. After the trocar was pulled out, the cannula was not seen on the surface of the sclera. Thus the inside and outside of the eye were carefully searched. The broken cannula tip was found in the ciliary body corresponding to the superonasal sclerotomy site and was subsequently removed.

Conclusions

Awareness regarding the risk of intraoperative fractures of 25G+ minimally invasive ocular surgical instruments is imperative. Whenever a broken or missing cannula is encountered, the residual part should be immediately extracted to avoid revision surgeries and postoperative complications.
Establishment of a nomogram for predicting the surgical difficulty of anterior cervical spine surgery
Authors: Ji Chengyue , Rong Yuluo , Wang Jiaxing , Yin Guoyong , Fan Jin , Tang Pengyu , Jiang Dongdong , Liu Wei , Ge Xuhui , Yu Shunzhi , Cai Weihua
Published: March 2021

Background

For a long time, surgical difficulty is mainly evaluated based on subjective perception rather than objective indexes. Moreover, the lack of systematic research regarding the evaluation of surgical difficulty potentially has a negative effect in this field. This study was aimed to evaluate the risk factors for the surgical difficulty of anterior cervical spine surgery (ACSS).

Methods

This was a retrospective cohort study totaling 291 consecutive patients underwent ACSS from 2012.3 to 2017.8. The surgical difficulty of ACSS was defined by operation time longer than 120 min or intraoperative blood loss equal to or greater than 200 ml. Evaluation of risk factors was performed by analyzing the patient’s medical records and radiological parameters such as age, sex, BMI, number of operation levels, high signal intensity of spinal cord on T2-weighted images, ossified posterior longitudinal ligament (OPLL), sagittal and coronal cervical circumference, cervical length, spinal canal occupational ratio, coagulation function index and platelet count.

Results

Significant differences were reported between low-difficulty and high-difficulty ACSS groups in terms of age (p = 0.017), sex (p = 0.006), number of operation levels (p < 0.001), high signal intensity (p < 0.001), OPLL (p < 0.001) and spinal canal occupational ratio (p < 0.001). Multivariate logistic regression analysis revealed that number of operation levels (OR = 5.224, 95%CI = 2.125–12.843, p < 0.001), high signal intensity of spinal cord (OR = 4.994, 95%CI = 1.636–15.245, p = 0.005), OPLL (OR = 6.358, 95%CI = 1.932–20.931, p = 0.002) and the spinal canal occupational ratio > 0.45 (OR = 3.988, 95%CI = 1.343–11.840, p = 0.013) were independently associated with surgical difficulty in ACSS. A nomogram was established and ROC curve gave a 0.906 C-index. There was a good calibration curve for difficulty estimation.

Conclusion

This study indicated that the operational level, OPLL, high signal intensity of spinal cord, and spinal canal occupational ratio were independently associated with surgical difficulty and a predictive nomogram can be established using the identified risk factors. Optimal performance was achieved for predicting surgical difficulty of ACSS based on preoperative factors.
Insights into the demographic history of Asia from common ancestry and admixture in the genomic landscape of present-day Austroasiatic speakers
Authors: Tagore Debashree , Aghakhanian Farhang , Naidu Rakesh , Phipps Maude E. , Basu Analabha
Published: March 2021

Background

The demographic history of South and Southeast Asia (S&SEA) is complex and contentious, with multiple waves of human migration. Some of the earliest footfalls were of the ancestors of modern Austroasiatic (AA) language speakers. Understanding the history of the AA language family, comprising of over 150 languages and their speakers distributed across broad geographical region in isolated small populations of various sizes, can help shed light on the peopling of S&SEA. Here we investigated the genetic relatedness of two AA groups, their relationship with other ethno-linguistically distinct populations, and the relationship of these groups with ancient genomes of individuals living in S&SEA at different time periods, to infer about the demographic history of this region.

Results

We analyzed 1451 extant genomes, 189 AAs from India and Malaysia, and 43 ancient genomes from S&SEA. Population structure analysis reveals neither language nor geography appropriately correlates with genetic diversity. The inconsistency between “language and genetics” or “geography and genetics” can largely be attributed to ancient admixture with East Asian populations. We estimated a pre-Neolithic origin of AA language speakers, with shared ancestry between Indian and Malaysian populations until about 470 generations ago, contesting the existing model of Neolithic expansion of the AA culture. We observed a spatio-temporal transition in the genetic ancestry of SEA with genetic contribution from East Asia significantly increasing in the post-Neolithic period.

Conclusion

Our study shows that contrary to assumptions in many previous studies and despite having linguistic commonality, Indian AAs have a distinct genomic structure compared to Malaysian AAs. This linguistic-genetic discordance is reflective of the complex history of population migration and admixture shaping the genomic landscape of S&SEA. We postulate that pre-Neolithic ancestors of today’s AAs were widespread in S&SEA, and the fragmentation and dissipation of the population have largely been a resultant of multiple migrations of East Asian farmers during the Neolithic period. It also highlights the resilience of AAs in continuing to speak their language in spite of checkered population distribution and possible dominance from other linguistic groups.
A universal power law for modelling the growth and form of teeth, claws, horns, thorns, beaks, and shells
Authors: Evans Alistair R. , Pollock Tahlia I. , Cleuren Silke G. C. , Parker William M. G. , Richards Hazel L. , Garland Kathleen L. S. , Fitzgerald Erich M. G. , Wilson Tim E. , Hocking David P. , Adams Justin W.
Published: March 2021

Background

A major goal of evolutionary developmental biology is to discover general models and mechanisms that create the phenotypes of organisms. However, universal models of such fundamental growth and form are rare, presumably due to the limited number of physical laws and biological processes that influence growth. One such model is the logarithmic spiral, which has been purported to explain the growth of biological structures such as teeth, claws, horns, and beaks. However, the logarithmic spiral only describes the path of the structure through space, and cannot generate these shapes.

Results

Here we show a new universal model based on a power law between the radius of the structure and its length, which generates a shape called a ‘power cone’. We describe the underlying ‘power cascade’ model that explains the extreme diversity of tooth shapes in vertebrates, including humans, mammoths, sabre-toothed cats, tyrannosaurs and giant megalodon sharks. This model can be used to predict the age of mammals with ever-growing teeth, including elephants and rodents. We view this as the third general model of tooth development, along with the patterning cascade model for cusp number and spacing, and the inhibitory cascade model that predicts relative tooth size. Beyond the dentition, this new model also describes the growth of claws, horns, antlers and beaks of vertebrates, as well as the fangs and shells of invertebrates, and thorns and prickles of plants.

Conclusions

The power cone is generated when the radial power growth rate is unequal to the length power growth rate. The power cascade model operates independently of the logarithmic spiral and is present throughout diverse biological systems. The power cascade provides a mechanistic basis for the generation of these pointed structures across the tree of life.
Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies
Authors: Chou Yi-Te , Lin Chih-Yu , Wen Jyun-Wei , Hung Ling-Chun , Chang Ying-Feng , Yang Chia-Min , Wu Li-chen , Ho Ja-an Annie
Published: March 2021

Background

Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT.

Results

To achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently.

Conclusions

Taken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC.
BiVO4/Fe3O4@polydopamine superparticles for tumor multimodal imaging and synergistic therapy
Authors: Wang Ze , Wang Guan , Kang Tingting , Liu Shuwei , Wang Lu , Zou Haoyang , Chong Yu , Liu Yi
Published: March 2021

Background

Despite tremendous progress has been achieved in tumor theranostic over the past decade, accurate identification and complete eradication of tumor cells remain a great challenge owing to the limitation of single imaging modality and therapeutic strategy.

Results

Herein, we successfully design and construct BiVO4/Fe3O4@polydopamine (PDA) superparticles (SPs) for computed tomography (CT)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging and radiotherapy (RT)/photothermal therapy (PTT) synergistic therapy toward oral epithelial carcinoma. On the one hand, BiVO4NPs endow BiVO4/Fe3O4@PDA SPs with impressive X-ray absorption capability due to the high X-ray attenuation coefficient of Bi, which is beneficial for their utilization as radiosensitizers for CT imaging and RT. On the other hand, Fe3O4NPs impart BiVO4/Fe3O4@PDA SPs with the superparamagnetic property as a T2-weighted contrast agent for MR imaging. Importantly, the aggregation of Fe3O4NPs in SPs and the presence of PDA shell greatly improve the photothermal conversion capability of SPs, making BiVO4/Fe3O4@PDA SPs as an ideal photothermal transducer for PA imaging and PTT. By integrating advantages of various imaging modalities (CT/PA/MR) and therapeutic strategies (RT/PTT), our BiVO4/Fe3O4@PDA SPs exhibit the sensitive multimodal imaging feature and superior synergistic therapeutic efficacy on tumors.

Conclusions

Since there are many kinds of building blocks with unique properties appropriating for self-assembly, our work may largely enrich the library of nanomateirals for tumor diagnosis and treatment.
A study of the correlation between M2 macrophages and lymph node metastasis of colorectal carcinoma
Authors: Wang Yanping , Wang Jikun , Yang Chunyu , Wang Yue , Liu Jinhao , Shi Zuoxiu , Chen Yanlei , Feng Yang , Ma Xueqian , Qiao Shifeng
Published: March 2021

Background

Lymph node metastasis is a major prognostic sign of colorectal carcinoma and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development by enhancing invasiveness and promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal carcinoma.

Methods

Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes using immunohistochemistry. Furthermore, the relationships between M2 macrophages identified by expression of CD163 and lymph node metastasis were analyzed using the independent sample t-test and Chi-square test.

Results

M2 macrophages were increased in metastatic lymph nodes and non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in patients with micro-metastases.

Conclusions

The presence of M2 macrophages represents an important indicator for lymph node metastasis in colorectal carcinoma and may be a potential marker for its prediction. Thus, M2 macrophage localization might offer a new target for the comprehensive treatment of colorectal carcinoma.
Significance of frailty in prognosis after surgery in patients with pancreatic ductal adenocarcinoma
Authors: Yamada Shinichiro , Shimada Mitsuo , Morine Yuji , Imura Satoru , Ikemoto Tetsuya , Saito Yu , Miyazaki Katsuki , Tokunaga Takuya , Nishi Masaaki
Published: March 2021

Background

Frailty is an important consideration for older patients undergoing surgery. We aimed to investigate whether frailty could be a prognostic factor in patients with pancreatic ductal adenocarcinoma who underwent pancreatic resection.

Methods

One hundred and twenty patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were enrolled. Frailty was defined as a clinical frailty scale score ≥4. Patients were divided into frailty (n = 29) and non-frailty (n=91) groups, and clinicopathological factors were compared between the two groups.

Results

The frailty group showed an older age, lower serum albumin concentration, lower prognostic nutritional index, larger tumor diameter, and higher rate of lymph node metastasis than the non-frailty group (p < 0.05). Neutrophil–lymphocyte ratio and modified Glasgow prognostic score tended to be higher in the frailty group. Cancer-specific and disease-free survival rates were significantly poor in the frailty group (p < 0.05). With a multivariate analysis, frailty was an independent prognostic factor of cancer-specific survival.

Conclusions

Frailty can predict the prognosis of patients with pancreatic ductal adenocarcinoma who undergo pancreatic resection.
Stakeholder attitudes to the regulation of traditional and complementary medicine professions: a systematic review
Authors: Carè Jenny , Steel Amie , Wardle Jon
Published: March 2021

Background

There has been a considerable increase in the number of traditional and complementary medicine (T&CM) practitioners over the past 20 years and in some jurisdictions are estimated to outnumber general practitioners. Despite this globally significant role, it is apparent that worldwide not all T&CM professions operate under adequate accountability and regulatory oversight for maintaining public protection. To date there has been no published systematic examination of stakeholder opinions regarding regulated and unregulated T&CM occupations. In response, this review aims to investigate, describe, and analyse attitudes held by a range of stakeholder groups towards the regulation of T&CM professions.

Methods

A database search of AMED, CINAHL, Embase, Ovid MEDLINE, ProQuest, PsycINFO, PubMed, Scopus, and Google Scholar was conducted for original research published between 2000 and 2020 on stakeholder opinions regarding the regulation of T&CM professions.

Results

Sixty studies across 15 countries reported on the views of six health care stakeholder groups: consumers, T&CM practitioners, conventional medicine practitioners, professional associations, education providers, and policy-makers. Across all stakeholder groups there was between 15% and 95% (median 61%) support for, and 1% to 57% (median 14%) opposition to the regulation of various T&CM professions. The main reasons for supporting regulation included providing greater public protection, raising training and practice standards, establishing title protection, and gaining acceptance from conventional medicine providers. Concerns regarding regulation included potential restrictions to practice, misappropriation of practice, and medical oversight of T&CM practitioners. Few studies canvassed the views of professional associations (n = 6), education providers (n = 2), and policy-makers (n = 2).

Conclusions

There appears to be broad support for the regulation of T&CM professions, although there was wide variation in attitudes as to how this should be applied. Further research, with a particular focus on policy-makers, education providers, and professional associations, is critical to inform appropriate health policy and practice recommendations relating to T&CM professional regulation across jurisdictions. Systematic review registration: the a priori protocol for this systematic review was registered in PROSPERO and is available at: www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42020198767.
The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial
Authors: Doaei Saeid , Gholami Somayeh , Rastgoo Samira , Gholamalizadeh Maryam , Bourbour Fatemeh , Bagheri Seyedeh Elaheh , Samipoor Forough , Akbari Mohammad Esmail , Shadnoush Mahdi , Ghorat Fereshteh , Mosavi Jarrahi Seyed Alireza , Ashouri Mirsadeghi Narjes , Hajipour Azadeh , Joola Parvin , Moslem Alireza , Goodarzi Mark O.
Published: March 2021

Background

Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19.

Methods

A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention.

Results

The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups.

Conclusion

Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted.

Trial registry

Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213
Viscoelastic properties of white and gray matter-derived microglia differentiate upon treatment with lipopolysaccharide but not upon treatment with myelin
Authors: van Wageningen Thecla A. , Antonovaite Nelda , Paardekam Erik , Brevé John J. P. , Iannuzzi Davide , van Dam Anne-Marie
Published: March 2021

Background

The biomechanical properties of the brain have increasingly been shown to relate to brain pathology in neurological diseases, including multiple sclerosis (MS). Inflammation and demyelination in MS induce significant changes in brain stiffness which can be linked to the relative abundance of glial cells in lesions. We hypothesize that the biomechanical, in addition to biochemical, properties of white (WM) and gray matter (GM)-derived microglia may contribute to the differential microglial phenotypes as seen in MS WM and GM lesions.

Methods

Primary glial cultures from WM or GM of rat adult brains were treated with either lipopolysaccharide (LPS), myelin, or myelin+LPS for 24 h or left untreated as a control. After treatment, microglial cells were indented using dynamic indentation to determine the storage and loss moduli reflecting cell elasticity and cell viscosity, respectively, and subsequently fixed for immunocytochemical analysis. In parallel, gene expression of inflammatory-related genes were measured using semi-quantitative RT-PCR. Finally, phagocytosis of myelin was determined as well as F-actin visualized to study the cytoskeletal changes.

Results

WM-derived microglia were significantly more elastic and more viscous than microglia derived from GM. This heterogeneity in microglia biomechanical properties was also apparent when treated with LPS when WM-derived microglia decreased cell elasticity and viscosity, and GM-derived microglia increased elasticity and viscosity. The increase in elasticity and viscosity observed in GM-derived microglia was accompanied by an increase in Tnfα mRNA and reorganization of F-actin which was absent in WM-derived microglia. In contrast, when treated with myelin, both WM- and GM-derived microglia phagocytose myelin decrease their elasticity and viscosity.

Conclusions

In demyelinating conditions, when myelin debris is phagocytized, as in MS lesions, it is likely that the observed differences in WM- versus GM-derived microglia biomechanics are mainly due to a difference in response to inflammation, rather than to the event of demyelination itself. Thus, the differential biomechanical properties of WM and GM microglia may add to their differential biochemical properties which depend on inflammation present in WM and GM lesions of MS patients.
Precision therapeutic targets for COVID-19
Authors: Krumm Zachary A. , Lloyd Grace M. , Francis Connor P. , Nasif Lith H. , Mitchell Duane A. , Golde Todd E. , Giasson Benoit I. , Xia Yuxing
Published: March 2021

Beginning in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel pathogen that causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 has infected more than 111 million people worldwide and caused over 2.47 million deaths. Individuals infected with SARS-CoV-2 show symptoms of fever, cough, dyspnea, and fatigue with severe cases that can develop into pneumonia, myocarditis, acute respiratory distress syndrome, hypercoagulability, and even multi-organ failure. Current clinical management consists largely of supportive care as commonly administered treatments, including convalescent plasma, remdesivir, and high-dose glucocorticoids. These have demonstrated modest benefits in a small subset of hospitalized patients, with only dexamethasone showing demonstrable efficacy in reducing mortality and length of hospitalization. At this time, no SARS-CoV-2-specific antiviral drugs are available, although several vaccines have been approved for use in recent months. In this review, we will evaluate the efficacy of preclinical and clinical drugs that precisely target three different, essential steps of the SARS-CoV-2 replication cycle: the spike protein during entry, main protease (MPro) during proteolytic activation, and RNA-dependent RNA polymerase (RdRp) during transcription. We will assess the advantages and limitations of drugs that precisely target evolutionarily well-conserved domains, which are less likely to mutate, and therefore less likely to escape the effects of these drugs. We propose that a multi-drug cocktail targeting precise proteins, critical to the viral replication cycle, such as spike protein, MPro, and RdRp, will be the most effective strategy of inhibiting SARS-CoV-2 replication and limiting its spread in the general population.