bluuebunny/crossref_metadata_2025 huggingface dataset:
The Polymorphism Analyses of Short Tandem Repeats as a Basis for Understanding the Genetic Characteristics of the Guanzhong Han Population
Authors: Mei Shuyan , Liu Yanfang , Zhao Congying , Xu Hui , Li Shuanglin , Zhu Bofeng
Published: February 2021

The short tandem repeat (STR) loci are polymorphic markers in the combined DNA index system (CODIS) and non‐CODIS STR loci. Due to the highly polymorphic characteristic of STR loci, they are popular and widely used in forensic DNA typing laboratories. In this study, 22 STR loci (1 CODIS, 21 non‐CODIS STR loci) and an Amelogenin locus were genotyped and analyzed in 590 unrelated individuals of the Guanzhong Han population. None of the 22 STR loci deviated from the Hardy–Weinberg equilibrium, and all the loci were in the linkage equilibrium state. We observed 247 alleles, and the corresponding allelic frequencies ranged from 0.0008 to 0.3695 in the Guanzhong Han population. The combined power of discrimination and the cumulative exclusion probability was 0.999 999 999 999 999 999 999 999 999 346 36 and 0.999 999 999 709 74, respectively. The results including Nei’s DA genetic distance, multidimensional scaling analysis, and principal component analysis showed that the Guanzhong Han population has closer genetic affinities with Northern Han, Chengdu Han, and Xinjiang Hui groups from China based on allelic frequencies of 15 overlapped STR loci from Guanzhong Han and 13 reference groups. The present results indicated that Microreader™ 23sp ID kit included highly polymorphic loci, and it could be well used for individual identification, paternity testing, and population genetics in the Guanzhong Han population.
Abstract IA014: Regulation of disseminated tumor cell dormancy in brain by the perivascular niche
Authors: Ghajar Cyrus M.
Published: March 2021

The brain provides compelling evidence that tumour dormancy is not simply an intriguing biological phenomenon. Given effective therapy, it may emerge as a culprit of lethality. To date, the mechanism by which the brain microenvironment drives disseminated tumor cells (DTCs) into a dormant state remain elusive. Here, I describe our studies leveraging serial intravital imaging to demonstrate that a large fraction of disseminated breast tumor cells within brain persist as single cells, and that every one of these cells is physically associated with microvasculature. Despite occupying a vascular niche, however, the burden for enforcing dormancy does not lie with endothelium. Instead, perivascular astrocytes are the dominant effector. Specifically, we show that astrocytic laminin-211 signals through DTC dystroglycan to suppress proliferation. Transcriptomic data suggest quiescence may ultimately be driven by sequestration of the Hippo effector yes-associated protein. We view these findings as a first step towards therapies that maintain DTC dormancy to prevent brain metastasis.

Citation Format: Cyrus M. Ghajar. Regulation of disseminated tumor cell dormancy in brain by the perivascular niche [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA014.
Abstract IA019: Collagen mineralization and its role in breast cancer bone metastasis
Authors: Fischbach Claudia
Published: March 2021

Skeletal metastasis of breast cancer is associated with changes in bone mineral density, therapy resistance, and poor clinical prognosis. Most emphasis to date has been placed on studying the role of bone and marrow cells in this process, but the functional contribution of skeletal extracellular matrix (ECM) remains largely unclear. Better understanding these connections is critical as mineralized collagen, the basic building block of bone, is a key component of the osteogenic niche that tumor cells target during dissemination and that changes as a function of diet, age, and exercise. Using correlative materials science and tissue engineering approaches, we have characterized metastasis-relevant bone matrix characteristics across multiple length scales and recapitulated these properties in vitro to investigate the functional relationship between collagen mineralization and tumor cell phenotype. Breast cancer cells cultured on mineralized substrates exhibited reduced adhesion forces and accordingly reduced collagen fiber alignment relative to cells cultured on control collagen. These changes were attributed to mineral-mediated differences in collagen stress relaxation and altered mechanosignaling with consequences on tumor cell migration and expression of cancer stem cell markers. RNAseq analysis in combination with functional studies confirmed that tumor cells interacting with control vs. mineralized collagen exhibited altered proliferative and therapy-resistant capability. In vivo studies confirmed the relevance of bone matrix mineralization to secondary tumor growth and therapy resistance. These results suggest that changes in collagen mineralization directly impact hallmark features of skeletal metastasis including tumor cell dissemination, growth, and therapy resistance and underline the critical importance of bone mineral in the pathogenesis of breast cancer bone metastasis.

Citation Format: Claudia Fischbach. Collagen mineralization and its role in breast cancer bone metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA019.
Abstract PO026: Loss of STAT5 in macrophages potentiates tissue remodeling and tumor-promoting phenotype in breast cancer
Authors: Jesser Emily A. , Schwertfeger Kathryn L.
Published: March 2021

Despite advances in treating breast cancer, limited targeted therapeutics exist for the triple negative breast cancer (TNBC) subtype, therefore it remains the most fatal relative to other breast cancer subtypes. Since TNBC tumor cells utilize the Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway for growth and proliferation signals, new therapeutics are being developed to target components of this pathway like STAT5. However, this pathway is also important for infiltrating inflammatory cells such as, macrophages, and their function in the tumor microenvironment. My data indicates that STAT5 is critical for tissue remodeling phenotypes and cell survival in macrophages, which can have a significant impact on tumor progression. I have observed increases in macrophage production of extracellular matrix components when STAT5 signaling is impaired, as well as a localization of STAT5-active macrophages at the tumor border suggesting a role in metastatic restraint. I have also shown that loss of STAT5 in tumor-associated macrophages correlates to an increase in tumor metastases in vivo. The goal of my research is to define the specific functional contributions of STAT5 to macrophage polarization and macrophage-mediated resistance of tumors to JAK/STAT inhibition. To address these questions, my research employs the use of mouse mammary tumor models, clinically-relevant JAK/STAT inhibition and conditional knockout strategies to understand how macrophages can shift from tumor-hostile to tumor-friendly, as well as, provide rationale for potential therapeutic interventions to maintain an anti-tumor response against TNBC.

Citation Format: Emily A. Jesser, Kathryn L. Schwertfeger. Loss of STAT5 in macrophages potentiates tissue remodeling and tumor-promoting phenotype in breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO026.
Abstract PO034: Hypoxia-derived extracellular vesicles promote triple-negative breast cancer invasion in vitro
Authors: Pachane Bianca Cruz , Altei Wanessa Fernanda , Sobreiro Selistre-de-Araujo Heloisa
Published: March 2021

The increase of tumor mass and complexity triggers cell invasion, a key step of the metastatic cascade, through hypoxia-derived signalization. The decrease in oxygen levels on the inner tumor mass stimulates the secretion of extracellular vesicles (EV) to the microenvironment, whose cargo may induce an invasive behavior of breast cancer cells. In an attempt to identify key players in hypoxic EV-mediated cell invasion in breast cancer, we are investigating the molecular, cellular and biochemical changes triggered by hypoxic-EVs to triple-negative breast cancer cells (MDA-MB-231). EVs have been isolated from conditioned culture media by differential ultracentrifugation and characterized by particle analysis (NTA), transmission electron microscopy (TEM), protein quantification and western blot of EV markers according to the MISEV2018. EV-treated cells were submitted to invasion assays in i) invasion chamber with extracellular matrix-based hydrogel and ii) a fluorescent gelatin-coated surface. Cell lysate and EV samples were probed for matrix metalloproteases by western blot and zymography. Morphological analysis of cells after EV treatment have been conducted after cytoskeleton staining using fluorescent probes. EVs derived from hypoxia and normoxia-cultured MDA-MB-231 are similarly sized and enriched with CD63, FLOT-1 and ALIX, although hypoxic-EVs have displayed higher protein concentration and particle concentration. Hypoxic EVs promoted cell invasion in an extracellular matrix-based hydrogel after 6h and 16h under normal oxygen conditions. Gelatin degradation has also been observed after EV treatment in normoxia, with results akin to degradation found in cells under hypoxia. While protease activity has been detected in EVs via zymography, we have yet to confirm the role of matrix metalloproteases in EV-related cell invasion. While little morphological changes have been observed upon EV treatment in gelatin-adhered cells, they acquire an epithelial morphology in uncoated circumstances, thus indicating a key role of adhesion molecules to hypoxia-derived invasive behavior. In conclusion, hypoxia-derived EVs from breast cancer cells generate morphological and physiological changes to tumor cells in regular oxygen levels, leading to an invasive behavior in collagen-based matrixes.

Citation Format: Bianca Cruz Pachane, Wanessa Fernanda Altei, Heloisa Sobreiro Selistre-de-Araujo. Hypoxia-derived extracellular vesicles promote triple-negative breast cancer invasion in vitro [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO034.
Abstract PO039: Novel in vivo imaging method to evaluate "Don't eat me" signal of tumor against microglia
Authors: Tsuji Takahiro , Wake Hiroaki , Shindo Mariko , Kato Daisuke , Ozasa Hiroaki , Hirai Toyohiro
Published: March 2021

Tumor formation is promoted by increased expression of “Don’t eat me” signals such as CD47 in cancer cells that inhibit phagocytic action of macrophages. However, the signals can regulate generation of brain metastasis is still unclear. In the brain, microglia and perivascular macrophages are the only resident immune cells of the brain parenchyma. Here, we have developed an in-vivo imaging method that can allow us to evaluate microglial phagocytosis of tumor and to detemine the fates of cancer cells in the brain. The skull of the CX3CR1-EGFP mice, in which microglia is specifically labeled with EGFP, was replaced with a glass coverslip, and the fluorescently labeled lung cancer cells (CMT167-mCherry) were injected via the internal carotid artery of the mice. The fate of arrested cancer cells in the brain vascular was monitored for 12-16 days. Of the 324 cancer cells (4 mice), 49.8% (N=138) of cells displaced from their original site, 40.4% (N=112) of cells developed micro-metastasis, and 6.9% (N=27) of cells were processed by microglia resulting in cell death. To evaluate the “Don’t eat me” signal against microglia, a CD47 gene knockout cell line was monitored as well, and these cells developed significantly less micro-metastasizes compared with CD47 positive cells. This in vivo imaging of the brain metastasis potentially provide a method for monitoring of tumor fate and validation of crucial target.

Citation Format: Takahiro Tsuji, Hiroaki Wake, Mariko Shindo, Daisuke Kato, Hiroaki Ozasa, Toyohiro Hirai. Novel in vivo imaging method to evaluate "Don't eat me" signal of tumor against microglia [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO039.
Abstract PR005: The dynamic tumor microenvironment: Oncostreams are self-organizing structures that modulate glioma progression and treatment
Authors: Comba Andrea , Motsch Sebastien , Dunn Patrick , Hollon Todd , Zamler Daniel , Argento Anna , Kahana Alon , Kish Phillip , Castro Maria , Lowenstein Pedro
Published: March 2021

Intratumoral heterogeneity is a hallmark of high grade gliomas. However, whether heterogeneity is static or dynamic remains unknown. Here we demonstrate that gliomas’ core and border regions display areas of self-organized collective motion, which we have termed oncostreams. Histologically oncostreams appear as multicellular fascicles of elongated and aligned glioma cells with mesenchymal-like morphology, and their density correlates positively with tumor malignant behavior. Using time lapse confocal imaging of organotypic brain slices of experimental glioma we discovered oncostream dynamics, namely, as two self-organizing patterns of collective motion: streams (bidirectional motion) and flocks (unidirectional motion). Oncostreams were also present in human glioblastoma multiforme, and could also be detected using objective artificial indigent approaches. They were present in 47% of TCGA-GBM grade IV tumor tissues, in 8.6 % of TCGA-LGG grade III, and were absent in TCGA-LGG grade II. Oncostreams are heterogeneous, contain GFAP+ cells, Iba1+ microglia/macrophages cells, and ACTA2+ mesenchymal cells aligned along Sox2+ tumor cells. We propose that oncostreams function as highways possibly stimulating the spread of slower-moving glioma cells and/or non-tumor cells throughout the tumor mass, reinforcing a potential role of oncostreams in determining spatial heterogeneity and remodeling of the tumor microenvironment. To analyze the molecular landscape of oncostreams we used laser capture microdissection coupled to RNA-Seq and bioinformatics analysis: we detected the existence of genetic networks specific to oncostreams. Oncostreams were aligned along highly expressed extracellular matrix proteins, among them Col1a1 was the most differentially expressed. Genetic inhibition of Col1a1 dissembled oncostreams, decreased glioma heterogeneity and improved animal survival. We propose that oncostreams dynamics will be a promising avenue to understand glioma behavior, and treat these malignant tumors.

Citation Format: Andrea Comba, Sebastien Motsch, Patrick Dunn, Todd Hollon, Daniel Zamler, Anna Argento, Alon Kahana, Phillip Kish, Maria Castro, Pedro Lowenstein. The dynamic tumor microenvironment: Oncostreams are self-organizing structures that modulate glioma progression and treatment [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PR005.
The evolution of warfare in Africa
Authors: Reno William
Published: February 2021

It is widely noted that armed conflict in Africa has evolved away from the prominence of insurgencies that are able to mobilize supporters around political programs in favor of more fragmented organizations in the service of their leaders' quests for power and wealth. The causes of this shift are found in changes in the domestic politics of African states that have taken place in recent decades. Regime strategies to disorganize and co-opt opponents and to suppress mass political mobilization have restricted the social spaces in which ideologues formerly organized and recruited cadres. Emigration among educated groups that previously supplied the bulk of insurgent leaders and cadres further reduces the influence of these groups. Alongside these changes, the development of parallel political structures that are rooted in the control of commerce channels resources to new leaders who lead insurgencies to establish their own dominance in this system of politics. This competition crowds out remaining ideologues who would pursue a vision of more radical change.
Rumours of Mau Mau in Northern Rhodesia, 1950-1960
Authors: Gewald Jan-Bart
Published: February 2021

In 1950s Northern Rhodesia, present day Zambia, rumours abounded amongst the African population intimating that the white settlers and administration were extensively involved in witchcraft, cannibalism and blood-sucking. In turn, members of the white settler community believed very much the same with regard to the African population of the territory. The development of nationalist politics and the increasing unionization of African workers in colonial Zambia led to agitation that was matched with increasing disquiet and fears on the part of white settlers. The emergence of ‘Mau Mau’ in Kenya and rumours of ‘Mau Mau’ in Northern Rhodesia served to underscore European settler fears in Northern Rhodesia. Based on research in the National Archives of Zambia and Great Britain, this paper explores the manner in which public rumour played out in Northern Rhodesia and gave emphasis to settler fears and fantasies in the territory.
Caractérisation phéno-morphologique de quelques lignées de fève (Vicia faba L.) sélectionnées et adaptées aux conditions de culture dans les régions arides en Tunisie
Authors: Dridi Bouthaina Al Mohandes , Loumerem Mohamed , Houimli Samira lbn Maaouia , Jabbes Naouel , Tlahig Samir
Published: February 2021

Cette étude avait pour objectif la caractérisation phéno-morphologique de 13 lignées de fève sélectionnées à l’Institut des Régions Arides de Medenine (Tunisie) à partir de 42 populations traditionnelles. La variabilité phéno-morphologique de ces lignées a été documentée et suivie du semis jusqu’ à la maturité des graines par des mesures biométriques et des évaluations qualitatives sur différentes parties des plantes. Les caractères morphologiques ont été décrits en se basant sur le descripteur de l’UPOY (2000) pour l’espèce Vicia faba L. L’analyse des résultats permet de distinguer 2 groupes en se basant sur le critère précocité et le poids de cent graines. Le premier groupe est constitué par la lignée 8 et se disringue par le fair qu’elle est la plus précoce et présente le poids de cent graines le plus éléve. Le deuxième groupe se subdivise en 3 sous-groupes qui different entre eux par la vigueur et la productivité de la plante. Le premier sous-groupe renferme les lignées 5, 10, 11, 12 et 13 se caractérise par un nombre de fleurs par racème plus faible, avec un poids moyen de cent graines variant de 162, 96 à 165, 24 get des nombres de graines par gousse les plus éléves. Le deuxième sous-groupe englobe les lignées 6, 7, et 9 qui sont les plus homogènes du point de vue de la date de 50 % floraison, hauteur finale de la plante et longueur de la foliole. Le dernier sous-groupe incl us les lignées 1, 2, 3 et 4 qui sont caractérisées par un nombre de gousses par plante, un nombre de tiges par plante, et un nombre de fleurs par racème les plus éléves. Ces lignées devraient être conservées et valorisées pour les programmes d’amélioration variétale de l’espece Vicia faba par des sélections successives jusqu’à l’obtention d’une variété synthétique plus productive et mieux adaptée aux conditions arides du Sud Tunisien.
European and Cameroonian scholarship on ethnicity and the making of identities in Cameroon: colonial and post-colonial trails
Authors: Vubo Emmanuel Yenshu
Published: February 2021

Relations between colonial and post-colonial studies in and on Cameroon have been both continuous and discontinuous. As reflected in the domains of historiography and social anthropology, this has impacted on ethnic self-representations and popular labeling. This paper examines contrasting drives that have led to a replication of colonial redefinitions of ethnicity and how this informs current discussions on ethnicity in Cameroon. The argument is that certain research works have informed or substantially influenced the identity question when one aknowledges that the colonial period is a bench mark epoch in the establishment of certain categories of ethnic perception. Although substantially deconstructed at the scientific level, these categories have survived and continue to influence social categories of perception that become common sense intrusions (what Bourdieu called doxa) into social science.
Beyond vegetative propagation of indigenous fruit trees: case of Dacryodes edulis (G. Don) H. J. Lam and Allanblackia floribunda Oliv.
Authors: Asaah Ebenezar K. , Tchoundjeu Zac , Van Damme Patrick
Published: February 2021

Indigenous fruits/nuts of Africa’s humid tropics are increasingly being recognized for their contribution to food security, health (nutrition/medicine), income generation, employment and environmental benefits. However, cultivation of the trees yielding these fruits/nuts is constrained by lack of improved planting materials that are true-to-type and have a short enough juvenile phase to fruit production. In addition, information on both above and belowground growth attributes of these species is scarce. This paper presents an overview of the results of a doctoral research focused on two African indigenous fruit tree species, i.e. Dacryodes edulis (G. Don) H.J. Lam (Burseraceae) and Allanblackia floribunda Oliv. (Clusiaceae), which are currently under domestication. For D. edulis, the objective was to assess and compare the structural and fine rooting systems together with the above ground growth attributes of fruiting trees propagated either sexually or vegetatively. The research aim for A. floribunda was to shorten the long juvenile phase before first fruiting through grafting techniques. In summary, the results from the studies on D. edulis suggest that vegetative propagation of the species, reduces the long juvenile phase to fruiting and maintains trueness in the transfer of desirable traits over generations, it also results in trees that are apparently less competitive for below ground resources, have more stable root system, and are bigger in stature and higher in carbon sinks compared to trees of seed origin. In parallel, A. floribunda was shown to be amenable to grafting both under nursery and field (in situ) conditions. Furthermore, a grafted A. floribunda tree transplanted in the field in 2007, flowered and carried a single fruit to maturity after 4 years, thereby reducing the long juvenile period to first fruit production from about 10-12 years reported in literature to less than 5 years. The findings of this doctoral research are therefore pertinent to efforts towards indigenous fruit/nut tree domestication. However, research should be confirmed as it can be considered a pilot study, one that aims to obtain insights into the effect of vegetative propagation methods on above and below ground growth and development of improved planting materials of D. edulis and A. floribunda under domestication.
A Nonparametric Procedure to Assess the Accuracy of the Normality Assumption for Annual Rainfall Totals, Based on the Marginal Statistics of Daily Rainfall: An Application to the NOAA/NCDC Rainfall Database
Authors: Ruggiu Dario , Viola Francesco , Langousis Andreas
Published: March 2021

We develop a nonparametric procedure to assess the accuracy of the normality assumption for annual rainfall totals (ART), based on the marginal statistics of daily rainfall. The procedure is addressed to practitioners and hydrologists that operate in data-poor regions. To do so we use 1) goodness-of-fit metrics to conclude on the approximate convergence of the empirical distribution of annual rainfall totals to a normal shape and classify 3007 daily rainfall time series from the NOAA/NCDC Global Historical Climatology Network database, with at least 30 years of recordings, into Gaussian (G) and non-Gaussian (NG) groups; 2) logistic regression analysis to identify the statistics of daily rainfall that are most descriptive of the G/NG classification; and 3) a random-search algorithm to conclude on a set of constraints that allows classification of ART samples on the basis of the marginal statistics of daily rain rates. The analysis shows that the Anderson–Darling (AD) test statistic is the most conservative one in determining approximate Gaussianity of ART samples (followed by Cramer–Von Mises and Lilliefors’s version of Kolmogorov–Smirnov) and that daily rainfall time series with fraction of wet days fwd < 0.1 and daily skewness coefficient of positive rain rates skwd > 5.92 deviate significantly from the normal shape. In addition, we find that continental climate (type D) exhibits the highest fraction of Gaussian distributed ART samples (i.e., 74.45%; AD test at α = 5% significance level), followed by warm temperate (type C; 72.80%), equatorial (type A; 68.83%), polar (type E; 62.96%), and arid (type B; 60.29%) climates.
Removing tar and nicotine from mainstream cigarette smoke using sepiolite-modified filter tips
Authors: Sarıkaya Yüksel , Kahya Naime Didem , Pekdemir Abdullah Devrim , Önal Müşerref
Published: March 2021

The objective of this work was to use air-dried sepiolite granules as an additive in cigarette filter tips to increase the removal yield of tar and nicotine from mainstream smoke. Granules with a mass of 95 mg per cigarette filter and a mean particle size (D) of 0.05–0.41 mm were used to constrain the effects of the mean particle size and mass of sepiolite in the removal process. The granules were sandwiched in common cellulose acetate filter tips. Maximum removal yields of 90% were obtained when D ≤ 0.10 mm. Filters containing granules with a mean size of 0.10 mm and mass variations from 35 to 95 mg were tested, and increasing amounts of sepiolite added led to progressively greater yields of tar and nicotine from 20% to 90%. The sepiolite granules were examined using scanning electron microscopy with energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy and X-ray diffraction techniques both before and after smoke experimentation. It is suggested that tar and nicotine were condensed both on the fibre clusters of the sepiolite granules and in the voids between them during the flow of the mainstream smoke.
Removal of cement-augmented screws in distal femoral fractures and the effect of retained screws and cement on total knee arthroplasty: a biomechanical investigation
Authors: Wähnert Dirk , Grüneweller Niklas , Gueorguiev Boyko , Vordemvenne Thomas , Gehweiler Dominic
Published: February 2021

Background

Given the increasing number of osteoporotic fractures of the distal femur, screw augmentation with bone cement is an option to enhance implant anchorage. However, in implant removal or revision surgeries, the cement cannot be removed from the distal femur without an extended surgical procedure. Therefore, the aims of this study were to investigate (1) whether cement augmentation has any influence on screw removal and removal torque, and (2) whether the implantation of a femoral component of a knee arthroplasty and its initial interface stability are affected by the remaining screws/cement.

Material and methods

Eight pairs of fresh-frozen human female cadaveric distal femurs (mean age, 86 years) with a simulated AO/OTA 33 A3 fracture were randomized in paired fashion to two groups and fixed with a distal femoral locking plate using cannulated perforated locking screws. Screw augmentation with bone cement was performed in one of the groups, while the other group received no screw augmentation. Following biomechanical testing until failure (results published separately), the screws were removed and the removal torque was measured. A femoral component of a knee arthroplasty was then implanted, and pull-out tests were performed after cement curing. Interference from broken screws/cement was assessed, and the maximum pull-out force was measured.

Results

The mean screw removal torque was not significantly different between the augmented (4.9 Nm, SD 0.9) and nonaugmented (4.6 Nm, SD 1.3, p = 0.65) screw groups. However, there were significantly more broken screws in in the augmented screw group (17 versus 9; p < 0.001). There was no significant difference in the pull-out force of the femoral component between the augmented (2625 N, SD 603) and nonaugmented (2653 N, SD 542, p = 0.94) screw groups.

Conclusion

The screw removal torque during implant removal surgery does not significantly differ between augmented and nonaugmented screws. In the augmented screw group, significantly more screws failed. To overcome this, the use of solid screws in holes B, C, and G can be considered. Additionally, it is possible to implant a femoral component for knee arthroplasty that retains the initial anchorage and does not suffer from interference with broken screws and/or residual cement.

Level of Evidence

5
Physical activity, resilience, emotions, moods, and weight control of older adults during the COVID-19 global crisis
Authors: Zach Sima , Zeev Aviva , Ophir Miki , Eilat-Adar Sigal
Published: March 2021

Background

The main purpose of the research was to examine the differences between adults in the age group 70+ and two other age groups (45–59 and 60–69), concerning their healthy and active lifestyle. The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. However, some studies of crises suggest that older adults tend to perceive events as less stressful than do younger people. Therefore, we examined healthy behavior in populations at risk according to the age cutoff-points used by the Ministry of Health at the time of vaccination, and divided the participants into three age groups (45–59, 60–69, and 70+) following health organizations’ recommendations.

Methods

Participants were 1202 people, 381 males and 821 females, aged 45–90. A survey comprised of six parts was used: Demographic background, the International Physical Activity Questionnaire–short version, Positive and Negative Affect Schedule – PANAS, the Connor and Davidson Resilience Scale, a questionnaire for measuring depressive moods, and questions regarding weight change, based on the Israeli National Health and Nutrition (MABAT) survey. Data were collected in Israel during the first complete lockdown. The questionnaire was distributed via e-mail, WhatsApp, Twitter, and Facebook using a snowball sampling method.

Results

Resilience and negative feelings and depression symptoms were higher in age group 45–59 compared to 70+ year-old participants, and the depression symptoms score was also higher among participants aged 45–59 compared to ages 60–69. Physical activity was associated with higher resilience, fewer depression symptoms, and fewer negative emotions. Regarding gender and psychological variables, no differences were found. During the time of lockdown, weight change was not prevalent and sleeping hours increased.

Conclusion

In adults at 70+, the physical activity level, physical activity before and during the lockdown, emotions, sleeping hours, and weight change were similar to the other adult groups that were examined (45–59 and 60–69). However, in the older adults groups (70+ and 60–69), resilience and depression symptoms were lower than in the youngest age group.
A data visualisation method for assessing exposure misclassification in case-crossover studies: the example of tricyclic antidepressants and the risk of hip fracture in older people
Authors: Leach Michael J. , Roughead Elizabeth E. , Pratt Nicole L.
Published: February 2021

Background

The case-crossover design is suited to medication safety studies but is vulnerable to exposure misclassification. Using the example of tricyclic antidepressants and the risk of hip fracture, we present a data visualisation tool for observing exposure misclassification in case-crossover studies.

Methods

A case-crossover study was conducted using Australian Government Department of Veterans’ Affairs claims data. Beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012 were included. The case window was defined as 1–50 days pre fracture. Control window one and control window two were defined as 101–150 and 151–200 days pre fracture, respectively. Patients were stratified by whether exposure status changed when control window two was specified instead of control window one. To visualise potential misclassification, each subject’s tricyclic antidepressant dispensings were plotted over the 200 days pre fracture.

Results

The study population comprised 8828 patients with a median age of 88 years. Of these subjects, 348 contributed data to the analyses with either control window. The data visualisation suggested that 14% of subjects were potentially misclassified with control window one while 45% were misclassified with control window two. The odds ratio for the association between tricyclic antidepressants and hip fracture was 1.18 (95% confidence interval = 0.91–1.52) using control window one, whereas risk was significantly increased (odds ratio = 1.43, 95% confidence interval = 1.11–1.83) using control window two.

Conclusions

Exposure misclassification was less likely to be present with control window one than with an earlier control window, control window two. When specifying different control windows in a case-crossover study, data visualisation can help to assess the extent to which exposure misclassification may contribute to variable results.
Automated segmentation of the individual branches of the carotid arteries in contrast-enhanced MR angiography using DeepMedic
Authors: Ziegler Magnus , Alfraeus Jesper , Bustamante Mariana , Good Elin , Engvall Jan , de Muinck Ebo , Dyverfeldt Petter
Published: February 2021

Background

Non-invasive imaging is of interest for tracking the progression of atherosclerosis in the carotid bifurcation, and segmenting this region into its constituent branch arteries is necessary for analyses. The purpose of this study was to validate and demonstrate a method for segmenting the carotid bifurcation into the common, internal, and external carotid arteries (CCA, ICA, ECA) in contrast-enhanced MR angiography (CE-MRA) data.

Methods

A segmentation pipeline utilizing a convolutional neural network (DeepMedic) was tailored and trained for multi-class segmentation of the carotid arteries in CE-MRA data from the Swedish CardioPulmonsary bioImage Study (SCAPIS). Segmentation quality was quantitatively assessed using the Dice similarity coefficient (DSC), Matthews Correlation Coefficient (MCC), F2, F0.5, and True Positive Ratio (TPR). Segmentations were also assessed qualitatively, by three observers using visual inspection. Finally, geometric descriptions of the carotid bifurcations were generated for each subject to demonstrate the utility of the proposed segmentation method.

Results

Branch-level segmentations scored DSC = 0.80 ± 0.13, MCC = 0.80 ± 0.12, F2 = 0.82 ± 0.14, F0.5 = 0.78 ± 0.13, and TPR = 0.84 ± 0.16, on average in a testing cohort of 46 carotid bifurcations. Qualitatively, 61% of segmentations were judged to be usable for analyses without adjustments in a cohort of 336 carotid bifurcations without ground-truth. Carotid artery geometry showed wide variation within the whole cohort, with CCA diameter 8.6 ± 1.1 mm, ICA 7.5 ± 1.4 mm, ECA 5.7 ± 1.0 mm and bifurcation angle 41 ± 21°.

Conclusion

The proposed segmentation method automatically generates branch-level segmentations of the carotid arteries that are suitable for use in further analyses and help enable large-cohort investigations.
Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia
Authors: Lan Yang , Liu Fang , Chang Lixian , Liu Lipeng , Zhang Yingchi , Yi Meihui , Cai Yuli , Feng Jing , Han Zhibo , Han Zhongchao , Zhu Xiaofan
Published: February 2021

Background

Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA).

Methods

We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone.

Results

Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153).

Conclusions

Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).
Levothyroxine and the risk of adverse pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis
Authors: Bein Magnus , Yu Oriana Hoi Yun , Grandi Sonia Marzia , Frati Francesca Y. E. , Kandil Ihab , Filion Kristian B.
Published: February 2021

Background

Levothyroxine replacement therapy may decrease the risk of adverse pregnancy outcomes among women with subclinical hypothyroidism (SCH). The aim of this study is to conduct a systematic review and meta-analysis to examine the risk of adverse pregnancy, perinatal, and early childhood outcomes among women with SCH treated with levothyroxine.

Methods

A systematic literature search was conducted using Ovid-Medline, Ovid-EMBASE, Pubmed (non-Medline), Ebsco-CINAHL Plus with full text and Cochrane Library databases. Randomized controlled studies (RCTs) and observational studies examining the association between treatment of SCH during pregnancy and our outcomes of interest were included. Studies that compared levothyroxine treatment versus no treatment were eligible for inclusion. Data from included studies were extracted and quality assessment was performed by two independent reviewers.

Results

Seven RCTs and six observational studies met our inclusion criteria. A total of 7342 individuals were included in these studies. RCTs demonstrated several sources of bias, with lack of blinding of the participants or research personnel; only one study was fully blinded. In the observational studies, there was moderate to serious risk of bias due to lack of adjustment for certain confounding variables, participant selection, and selective reporting of results. Pooled analyses showed decreased risk of pregnancy loss (RR: 0.79; 95% CI: 0.67 to 0.93) and neonatal death (RR: 0.35; 95% CI: 0.17 to 0.72) associated with levothyroxine treatment during pregnancy among women with SCH. There were no associations between levothyroxine treatment and outcomes during labour and delivery, or cognitive status in children at 3 or 5 years of age.

Conclusion

Treatment of SCH with levothyroxine during pregnancy is associated with decreased risks of pregnancy loss and neonatal death. Given the paucity of available data and heterogeneity of included studies, additional studies are needed to address the benefits of levothyroxine use among pregnant women with SCH.
Access to after-hours primary care: a key determinant of children’s medical home status
Authors: Han Bing , Chen Peggy Guey-Chi , Yu Hao
Published: February 2021

Background

The medical home (MH) model has been promoted by both the federal and state governments in the United States in recent years. To ascertain American children’s MH status, many studies have relied on a large set of survey items, posing a considerable burden on their parents. We aimed to identify individual survey items or domains that best predict MH status for children and use them to develop brief markers of MH status. We also examined whether the identified items differed by status of special health care needs and by racial/ethnic group.

Method

Using the 9-year data from Medical Expenditure Panel Survey, we examined associations between children’s MH status and individual survey items or domains. We randomly split the data into two halves with the first half (training sample,n = 8611) used to identify promising items, and the second half (validation sample,n = 8779) used to calculate all statistical measures. After discovering significant predictors of children’s MH status, we incorporated them into several brief markers of MH status. We also conducted stratified analyses by status of special health care needs and by racial/ethnic group.

Results

Less than half (48.7%) of the 8779 study children had a MH. The accessibility domain has stronger association with children’s MH status (specificity = 0.84, sensitivity = 1, Kappa = 0.83) than other domains. The top two items with the strongest association with MH status asked about after-hours primary care access, including doctors’ office hours at night or on the weekend and children’s difficulty accessing care after hours. Both belong to the accessibility domain and are one of several reliable markers for children’s MH status. While each of the two items did not differ significantly by status of special health care needs, there were considerable disparities across racial/ethnic groups with Latino children lagging behind other children.

Conclusion

Accessibility, especially the ability to access health care after regular office hours, appears to be the major predictor of having a MH among children. The ongoing efforts to promote the MH model need to target improving accessibility of health care after regular hours for children overall and especially for Latino children.
Severe volcanic SO2 exposure and respiratory morbidity in the Icelandic population – a register study
Authors: Carlsen Hanne Krage , Valdimarsdóttir Unnur , Briem Haraldur , Dominici Francesca , Finnbjornsdottir Ragnhildur Gudrun , Jóhannsson Thorsteinn , Aspelund Thor , Gislason Thorarinn , Gudnason Thorolfur
Published: February 2021

Background

The Holuhraun volcanic eruption September 2014 to February 2015 emitted large amounts of sulfur dioxide (SO2). The aim of this study was to determine the association between volcanic SO2 gases on general population respiratory health some 250 km from the eruption site, in the Icelandic capital area.

Methods

Respiratory health outcomes were: asthma medication dispensing (AMD) from the Icelandic Medicines Register, medical doctor consultations in primary care (PCMD) and hospital emergency department visits (HED) in Reykjavík (population: 215000) for respiratory disease from 1 January 2010 to 31 December 2014. The associations between daily counts of health events and daily mean SO2 concentration and high SO2 levels (24-h mean SO2 > 125 μg/m3) were analysed using generalized additive models.

Results

After the eruption began, AMD was higher than before (129.4 vs. 158.4 individuals per day, p < 0.05). For PCMD and HED, there were no significant differences between the number of daily events before and after the eruption (142.2 vs 144.8 and 18.3 vs 17.5, respectively). In regression analysis adjusted for other pollutants, SO2 was associated with estimated increases in AMD by 0.99% (95% CI 0.39–1.58%) per 10 μg/m3 at lag 0–2, in PCMD for respiratory causes 1.26% (95% CI 0.72–1.80%) per 10 μg/m3 SO2 at lag 0–2, and in HED by 1.02% (95% CI 0.02–2.03%) per 10 μg/m3 SO2 at lag 0–2. For days over the health limit, the estimated increases were 10.9% (95% CI 2.1–19.6%), 17.2% (95% CI 10.0–24.4%) for AMD and PCMD. Dispensing of short-acting medication increased significantly by 1.09% (95% CI 0.49–1.70%), and PCMD for respiratory infections and asthma and COPD diagnoses and increased significantly by 1.12% (95% CI 0.54–1.71%) and 2.08% (1.13–3.04%).

Conclusion

High levels of volcanic SO2 are associated with increases in dispensing of AMD, and health care utilization in primary and tertiary care. Individuals with prevalent respiratory disease may be particularly susceptible.
The impact of reactive oxygen species in the development of cardiometabolic disorders: a review
Authors: Akhigbe Roland , Ajayi Ayodeji
Published: February 2021

Oxidative stress, an alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity, has been implicated in the pathogenesis of cardiometabolic disorders (CMD). At physiological levels, ROS functions as signalling mediators, regulates various physiological functions such as the growth, proliferation, and migration endothelial cells (EC) and smooth muscle cells (SMC); formation and development of new blood vessels; EC and SMC regulated death; vascular tone; host defence; and genomic stability. However, at excessive levels, it causes a deviation in the redox state, mediates the development of CMD. Multiple mechanisms account for the rise in the production of free radicals in the heart. These include mitochondrial dysfunction and uncoupling, increased fatty acid oxidation, exaggerated activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX), reduced antioxidant capacity, and cardiac metabolic memory. The purpose of this study is to discuss the link between oxidative stress and the aetiopathogenesis of CMD and highlight associated mechanisms. Oxidative stress plays a vital role in the development of obesity and dyslipidaemia, insulin resistance and diabetes, hypertension via various mechanisms associated with ROS-led inflammatory response and endothelial dysfunction.