bluuebunny/crossref_metadata_2025 huggingface dataset:
LINE-1 repression in Epstein–Barr virus-associated gastric cancer through viral–host genome interaction
Authors: Zhang Mengyu , Sun Weikang , You Xiaoxin , Xu Dongge , Wang Lingling , Yang Jingping , Li Erguang , He Susu
Published: March 2023

Long INterspersed Element 1 (LINE-1 or L1) acts as a major remodeling force in genome regulation and evolution. Accumulating evidence shows that virus infection impacts L1 expression, potentially impacting host antiviral response and diseases. The underlying regulation mechanism is unclear. Epstein–Barr virus (EBV), a double-stranded DNA virus linked to B-cell and epithelial malignancies, is known to have viral–host genome interaction, resulting in transcriptional rewiring in EBV-associated gastric cancer (EBVaGC). By analyzing publicly available datasets from the Gene Expression Omnibus (GEO), we found that EBVaGC has L1 transcriptional repression compared with EBV-negative gastric cancer (EBVnGC). More specifically, retrotransposition-associated young and full-length L1s (FL-L1s) were among the most repressed L1s. Epigenetic alterations, especially increased H3K9me3, were observed on FL-L1s. H3K9me3 deposition was potentially attributed to increased TASOR expression, a key component of the human silencing hub (HUSH) complex for H3K9 trimethylation. The 4C- and HiC-seq data indicated that the viral DNA interacted in the proximity of the TASOR enhancer, strengthening the loop formation between the TASOR enhancer and its promoter. These results indicated that EBV infection is associated with increased H3K9me3 deposition, leading to L1 repression. This study uncovers a regulation mechanism of L1 expression by chromatin topology remodeling associated with viral–host genome interaction in EBVaGC.
Nutrition and food security in Nepal: a narrative review of policies
Authors: Adhikari Nabin , Adhikari Mukesh , Shrestha Namuna , Pradhananga Priza , Poudel Bikram , Dhungel Saurya , Joshi Prakash Chandra , Ide Nicole , Sharma Guna Nidhi , Shrestha Archana
Published: March 2023

In the past few decades, the Nepali government has endorsed several nutritional policies, strategies, and guidelines. Given the lack of a comprehensive review of such policy documents, this review aims to describe the nutrition and food security policies and understand the existing policy gaps in Nepal. Findings from this study can be used to develop policies and programs to address Nepal's current and future nutritional needs. Policies relevant to nutrition and food security were identified by searching government websites and directly approaching relevant government ministries. Thematic analysis was conducted using framework methods under 8 predetermined themes: nutrition intervention, food security, food system, capacity building of human resources, nutrition education, nutrition governance, research, and monitoring and evaluation. The contents of each document reviewed were manually extracted in a spreadsheet stratified by the themes, and the findings were summarized for the respective themes. A total of 30 policy documents were reviewed. Most policies have focused on undernutrition; only a few have addressed overnutrition and diet-related noncommunicable diseases. Food security through a sustainable food system has been considered a key policy area in Nepal. Other areas in the food and nutrition policy landscape are capacity building for human resources, behavior change practices, nutrition governance, monitoring, and evaluation. Policy gaps have been identified in the quality and sustainability of nutrition programs; access to health care services; competent human resources for nutrition; intersectoral coordination and commitment; and support for monitoring, evaluation, and research activities. Most policies have tried to address a wide range of components of food and nutrition security; however, strategies focused on overnutrition and diet-related noncommunicable diseases are lacking. Several gaps are identified in this policy review; the findings can guide the policymakers to address these gaps via further policy development.
Buddhism and Kingship
Authors: Doney Lewis
Published: March 2023

Kingship has been an important and contested element of realpolitik and rhetoric since the beginnings of Buddhism. Siddhārtha Gautama (fl. c. fifth century bce) is said to have been born a prince augured to either conquer or renounce the world, who chose the latter path. Those who follow the Buddha’s example in “going forth” (Skt. niṣkrāmati) from the world, join the monastic sangha and are then (theoretically) subject only to monastic law (Skt. vinaya) rather than state jurisdiction or its tax obligation. Yet, this “going forth” takes place within a society on which the sangha is largely dependent for donations, in return for which householders gain religious merit (Skt. puṇya). This means that social support, from householders up to kings or emperors, is often negotiated within Buddhism, whether symbolically or in practice. This situation created a rich diversity of approaches to kings (whether seen as positive protectors of the dharma, negative causes of Buddhist decline, or a mixture of the two) that often expanded into ideal types, reached cosmic proportions, and affected real sangha-ruler relations (even to such extremes as Buddhist literature sanctioning either royal deification or regicide). Rulers down the millennia donated land to the sangha, and the important role of building stupas, temples, and monasteries (less often, nunneries) in the countries where Buddhism spread often announced Buddhism as a (if not the) state religion and a (re)new(ed) part of the landscape. Royal patronage was behind many countries’ voluminous Buddhist canons, containing foundational conceptions of kingship, and the scriptoria and repositories necessary for their survival. The status of state religion cuts both ways though, and monarchs were often legitimized by Buddhism or controlled it, at times even persecuted it. Some rulers were ordained as monks or nuns, either after abdicating or during their reigns, while certain monastics ruled regions or countries—further blurring the boundaries between the world and “going forth” from it. Buddhist kingship ideals also influenced modern states and either merged or conflicted with other societal or international values. This often led to a bureaucratic or ideological distancing of the state from Buddhist kingship metaphors, unless embracing them served national identity. This entry is divided into sub-entries on Early Buddhism, then “Southern” (toward the Theravāda), “Eastern” (mostly Mahayana) and “Northern” (predominantly tantric) Buddhist countries. Yet, traditions can persist (unacknowledged) within later, more popular movements, and geographic typologies collapse at various meeting points and times in Buddhist Asia.
Yoga in Southeast Asia
Authors: Acri Andrea
Published: March 2023

From at least the first half of the first millennium of the current era up to c. 1500 ce and beyond, Indic cosmologies, religions, and ritual systems based on Sanskrit texts reached Southeast Asia, influencing many of the societies and cultures of the region. The traditions of yoga that originated in the Indian subcontinent—understood here both in the narrow sense of specific philosophical and soteriological traditions described in Sanskrit sources (for example, Pātañjala yoga or tantric ṣaḍaṅgayoga) and in the wider sense of inner and outer psycho-physical techniques of self-cultivation, meditation, visualization, ascesis (tapas), etc., were an integral part of the phenomenon of “Indicization.” Yoga traditions were transmitted to the region by the seventh century at the latest and developed there well beyond the end of the Hindu–Buddhist period into the modern period in Islamic contexts, such as in the Javanese tradition of mysticism (kejawen), or in Hindu contexts, for instance in Bali. Southeast Asian cultures document a resilient interest in psycho-physical practices geared toward the attainment of physical and spiritual power, supernatural faculties, control of and influence over other people’s will, etc. Thus, Indic yoga traditions in Indonesia should not be studied as mere cultural transplants, but as phenomena involving an active Southeast Asian agency on the one hand, and reflecting local concerns on the other. Besides being a worthy object of study in their own right, yoga traditions in Southeast Asia also enlighten us about dynamics of cultural transfer within the wider transcultural context of the “Indic world,” i.e., a wide cultural-geographical area that included both South and Southeast Asia. Last but not least, they provide an independent, yet parallel, source of data to better understand yoga traditions in South Asia itself. Our knowledge about yoga traditions in Southeast Asia mainly derives from textual documents in Sanskrit and premodern and modern vernacular languages of Java (Old Javanese, Modern Javanese), Bali (Old Javanese, Balinese), and Sumatra (Classical Malay), as well as from sparse art historical evidence and modern and contemporary practices. This bibliographical article surveys this multifaceted evidence, focusing mainly on the premodern period and Sanskrit–Old Javanese sources, but also including Indic traditions that evolved into modern contexts. It does not include the contemporary forms of transnational yoga, which are attracting a significant number of followers in Southeast Asia, but which constitute modern imports with hardly any links with pre-existing traditions of yoga.
Cities and Crime
Authors: Woldoff Rachael , Washington Heather
Published: March 2023

The subject of urban crime has long fascinated researchers, policymakers, social workers, journalists, and the public. Historically, the subject of crime has been so linked to urban places that the very mention of cities has evoked images of violent slums and fear of victimization. It is common for government officials to publicly politicize and racialize urban crime as they pander to certain blocks of voters. For instance, among his many derogatory comments about cities and urban populations, former US President Donald Trump—a New Yorker—tweeted about needing help with “crime-infested inner-cities.” Why the emphasis on crime in cities? A main reason is that crime is not randomly distributed. Rather, environmental opportunities for crime vary by time and place, and cities tend to have characteristics that increase vulnerability to crime. Though cities vary along many dimensions, including culture, climate, history, politics, and demographic characteristics (e.g., population size, density, racial and ethnic heterogeneity, age structure, and migration patterns), crime rates historically have been higher in urban communities than in rural, suburban, and smaller-sized places, on average. For this reason, many consider cities to be the ideal social laboratory for studying crime. Urban sociology has been essential to the theory and research on crime as a place-based social problem. Research on the spatial distribution of crime has compared different levels and scales of analysis, including samples of cities, Metropolitan Statistical Areas, and neighborhoods (as defined by residents, researchers, or administrative census boundaries). Many studies focus on a single city, or even a single neighborhood. In addition, the urban crime literature covers topics that are quite varied, including different place-based theoretical approaches, concepts, explanations of causes and consequences, and policies. For example, researchers have explored topics related to the impact of neighborhood residential mobility on crime, the consequences of residents’ experiences with crime on their sense of neighborhood attachment, and the ways in which crime control policies affect the distribution of crime and residents’ lives. The books and articles outlined below are not exhaustive, but instead we view them as a curated sampling of the vast range of research on these topics—simply one of many ways to organize the vast amount of work that has accumulated on the important but broad subject of cities and crime. We respectfully acknowledge that this summary is focused on the United States and that many subtopics relevant to urban crime necessarily have been omitted because of space constraints but deserve their own bibliographies to be drafted by experts in those subfields.
Examining the Early Distribution of the Artemisinin-Resistant Plasmodium falciparum kelch13 R561H Mutation in Areas of Higher Transmission in Rwanda
Authors: Kirby Rebecca , Giesbrecht David , Karema Corine , Watson Oliver , Lewis Savannah , Munyaneza Tharcisse , Butera Jean De Dieu , Juliano Jonathan J , Bailey Jeffrey A , Mazarati Jean-Baptiste
Published: March 2023

Background

Artemisinin resistance mutations in Plasmodium falciparum kelch13 (Pfk13) have begun to emerge in Africa, with Pfk13-R561H being the first reported in Rwanda in 2014, but limited sampling left questions about its early distribution and origin.

Methods

We genotyped P. falciparum positive dried blood spot (DBS) samples from a nationally representative 2014–2015 Rwanda Demographic Health Surveys (DHS) HIV study. DBS were subsampled from DHS sampling clusters with >15% P. falciparum prevalence, as determined by rapid testing or microscopy done during the DHS study (n clusters = 67, n samples = 1873).

Results

We detected 476 parasitemias among 1873 residual blood spots from a 2014–2015 Rwanda Demographic Health Survey. We sequenced 351 samples: 341/351 were wild-type (97.03% weighted), and 4 samples (1.34% weighted) harbored R561H that were significantly spatially clustered. Other nonsynonymous mutations found were V555A (3), C532W (1), and G533A (1).

Conclusions

Our study better defines the early distribution of R561H in Rwanda. Previous studies only observed the mutation in Masaka as of 2014, but our study indicates its presence in higher-transmission regions in the southeast of the country at that time.
Predicting Hyperglycemia Among Patients Receiving Alpelisib Plus Fulvestrant for Metastatic Breast Cancer
Authors: Ge Xuan , Behrendt Carolyn E , Yost Susan E , Patel Niki , Samoa Raynald , Stewart Daphne , Sedrak Mina , Lavasani Sayeh , Waisman James , Yuan Yuan , Mortimer Joanne
Published: March 2023

Background

Hyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors.

Patients and Methods

We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method.

Results

The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects’ risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28).

Conclusion

While receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib.
Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study
Authors: Lemij Annelieke A , Liefers Gerrit Jan , Derks Marloes G M , Bastiaannet Esther , Fiocco Marta , Lans Titia E , van der Pol Carmen C , Vulink Annelie J E , van Gerven Leander , Guicherit Onno R , Linthorst-Niers Eugenie M H , Merkus Jos W S , van Dalen Thijs , Portielje Johanneke E A , de Glas Nienke A
Published: March 2023

Background

A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline.

Methods

Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed.

Results

A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline −11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes.

Discussion

Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.
Target Landscape of Conserved Plant MicroRNAs and the Complexities of Their Ancient MicroRNA-Binding Sites
Authors: Wong Gigi Y , Millar Anthony A
Published: March 2023

In plants, microRNA (miRNA)—target interactions (MTIs) require high complementarity, a feature from which bioinformatic programs have predicted numerous and diverse targets for any given miRNA, promoting the idea of complex miRNA networks. Opposing this is a hypothesis of constrained miRNA specificity, in which functional MTIs are restricted to the few targets whose required expression output is compatible with the expression of the miRNA. To explore these opposing views, the bioinformatic pipeline Targets Ranked Using Experimental Evidence was applied to strongly conserved miRNAs to identity their high-evidence (HE) targets across species. For each miRNA family, HE targets predominantly consisted of homologs from one conserved target gene family (primary family). These primary families corresponded to the known canonical miRNA–target families, validating the approach. Very few additional HE target families were identified (secondary family), and if so, they were likely functionally related to the primary family. Many primary target families contained highly conserved nucleotide sequences flanking their miRNA-binding sites that were enriched in HE homologs across species. A number of these flanking sequences are predicted to form conserved RNA secondary structures that preferentially base pair with the miRNA-binding site, implying that these sites are highly structured. Our findings support a target landscape view that is dominated by the conserved primary target families, with a minority of either secondary target families or non-conserved targets. This is consistent with the constrained hypothesis of functional miRNA specificity, which potentially in part is being facilitated by features beyond complementarity.
Diversity of woodland strawberry inflorescences arises from heterochrony regulated by TERMINAL FLOWER 1 and FLOWERING LOCUS T
Authors: Lembinen Sergei , Cieslak Mikolaj , Zhang Teng , Mackenzie Kathryn , Elomaa Paula , Prusinkiewicz Przemyslaw , Hytönen Timo
Published: March 2023

A vast variety of inflorescence architectures have evolved in angiosperms. Here, we analyze the diversity and development of the woodland strawberry (Fragaria vesca) inflorescence. Contrary to historical classifications, we show that it is a closed thyrse: a compound inflorescence with determinate primary monopodial axis and lateral sympodial branches, thus combining features of racemes and cymes. We demonstrate that this architecture is generated by 2 types of inflorescence meristems differing in their geometry. We further show that woodland strawberry homologs of TERMINAL FLOWER 1 (FvTFL1) and FLOWERING LOCUS T (FvFT1) regulate the development of both the racemose and cymose components of the thyrse. Loss of functional FvTFL1 reduces the number of lateral branches of the main axis and iterations in the lateral branches but does not affect their cymose pattern. These changes can be enhanced or compensated by altering FvFT1 expression. We complement our experimental findings with a computational model that captures inflorescence development using a small set of rules. The model highlights the distinct regulation of the fate of the primary and higher-order meristems, and explains the phenotypic diversity among inflorescences in terms of heterochrony resulting from the opposite action of FvTFL1 and FvFT1 within the thyrse framework. Our results represent a detailed analysis of thyrse architecture development at the meristematic and molecular levels.
INDETERMINATE1 autonomously regulates phosphate homeostasis upstream of the miR399-ZmPHO2signaling module in maize
Authors: Wang Xufeng , Yuan Dan , Liu Yanchun , Liang Yameng , He Juan , Yang Xiaoyu , Hang Runlai , Jia Hong , Mo Beixin , Tian Feng , Chen Xuemei , Liu Lin
Published: March 2023

The macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of phosphate (Pi) acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 (miR399) in maize (Zea mays) is associated with premature senescence after pollination. Knockout of ZmPHO2 (Phosphate 2), a miR399 target, resulted in a similar premature senescence phenotype. Strikingly, we discovered that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression was independent of the external inorganic orthophosphate status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we show that ZmPHO2 was under selection during maize domestication and cultivation, resulting in a more sensitive response to Pi starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.
Plasma membrane-associated calcium signaling regulates arsenate tolerance in Arabidopsis
Authors: Liu Yisong , Zhang Yanting , Wang Zhangqing , Guo Shiyuan , Fang Yanjun , Zhang Zhenqian , Gao Huiling , Ren Huimin , Wang Cun
Published: March 2023

Arsenate [As(V)] is a metalloid with heavy metal properties and is widespread in many environments. Dietary intake of food derived from arsenate-contaminated plants constitutes a major fraction of the potentially health-threatening human exposure to arsenic. However, the mechanisms underlying how plants respond to arsenate stress and regulate the function of relevant transporters are poorly understood. Here, we observed that As(V) stress induces a significant Ca2+ signal in Arabidopsis (Arabidopsis thaliana) roots. We then identified a calcium-dependent protein kinase, CALCIUM-DEPENDENT PROTEIN KINASE 23 (CPK23), that interacts with the plasma membrane As(V)/Pi transporter PHOSPHATE TRANSPORTER 1;1 (PHT1;1) in vitro and in vivo. cpk23 mutants displayed a sensitive phenotype under As(V) stress, while transgenic Arabidopsis plants with constitutively active CPK23 showed a tolerant phenotype. Furthermore, CPK23 phosphorylated the C-terminal domain of PHT1;1, primarily at Ser514 and Ser520. Multiple experiments on PHT1;1 variants demonstrated that PHT1;1S514 phosphorylation is essential for PHT1;1 function and localization under As(V) stress. In summary, we revealed that plasma-membrane-associated calcium signaling regulates As(V) tolerance. These results provide insight for crop bioengineering to specifically address arsenate pollution in soils.
Calcium-binding protein OsANN1 regulates rice blast disease resistance by inactivating jasmonic acid signaling
Authors: Zhao Qiqi , Liu Rui , Zhou Qinzheng , Ye Jie , Meng Fanwei , Liu Jun , Yang Chao
Published: March 2023

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases in rice (Oryza sativa L.). Plant annexins are calcium- and lipid-binding proteins that have multiple functions; however, the biological roles of annexins in plant disease resistance remain unknown. Here, we report a rice annexin gene, OsANN1 (Rice annexin 1), that was induced by M. oryzae infection and negatively regulated blast disease resistance in rice. By yeast 2-hybrid screening, we found that OsANN1 interacted with a cytochrome P450 monooxygenase, HAN1 (“HAN” termed “chilling” in Chinese), which has been reported to catalyze the conversion of biologically active jasmonoyl-L-isoleucine (JA-Ile) to the inactive form 12-hydroxy-JA-Ile. Pathogen inoculation assays revealed that HAN1 was also a negative regulator in rice blast resistance. Genetic evidence showed that OsANN1 acts upstream of HAN1. OsANN1 stabilizes HAN1 in planta, resulting in the inactivation of the endogenous biologically active JA-Ile. Taken together, our study unravels a mechanism where an OsANN1–HAN1 module impairs blast disease resistance via inactivating biologically active JA-Ile and JA signaling in rice.
Deplatforming did not decrease Parler users’ activity on fringe social media
Authors: Horta Ribeiro Manoel , Hosseinmardi Homa , West Robert , Watts Duncan J
Published: March 2023

Online platforms have banned (“deplatformed”) influencers, communities, and even entire websites to reduce content deemed harmful. Deplatformed users often migrate to alternative platforms, which raises concerns about the effectiveness of deplatforming. Here, we study the deplatforming of Parler, a fringe social media platform, between 2021 January 11 and 2021 February 25, in the aftermath of the US Capitol riot. Using two large panels that capture longitudinal user-level activity across mainstream and fringe social media content (N = 112, 705, adjusted to be representative of US desktop and mobile users), we find that other fringe social media, such as Gab and Rumble, prospered after Parler’s deplatforming. Further, the overall activity on fringe social media increased while Parler was offline. Using a difference-in-differences analysis (N = 996), we then identify the causal effect of deplatforming on active Parler users, finding that deplatforming increased the probability of daily activity across other fringe social media in early 2021 by 10.9 percentage points (pp) (95% CI [5.9 pp, 15.9 pp]) on desktop devices, and by 15.9 pp (95% CI [10.2 pp, 21.7 pp]) on mobile devices, without decreasing activity on fringe social media in general (including Parler). Our results indicate that the isolated deplatforming of a major fringe platform was ineffective at reducing overall user activity on fringe social media.
E-learning and practical performance in musculoskeletal ultrasound: a multicentre randomized study
Authors: Carstensen Stine Maya Dreier , Just Søren Andreas , Velander Marie , Konge Lars , Hubel Martin Slusarczyk , Rajeeth Savarimuthu Thiusius , Pfeiffer Jensen Mogens , Østergaard Mikkel , Terslev Lene
Published: March 2023

Objectives

To examine the effect of pre-course e-learning on residents’ practical performance in musculoskeletal ultrasound (MSUS).

Methods

This was a multicentre, randomized controlled study following the Consolidated Standards of Reporting Trials (CONSORT) statement. Residents with no or little MSUS experience were randomized to either an e-learning group or a traditional group. One week before a 2-day face-to-face MSUS course, the e-learning group received access to an interactive platform consisting of online lectures, assignments, and practical instruction videos aligned with the content of the course. The traditional group only received standard pre-course information (program, venue, and time). All participants performed a pre- and post-course practical MSUS examination and were assessed by two individual raters, blinded to the group allocation, using the validated Objective Structured Assessment of Ultrasound Skills (OSAUS) tool.

Results

Twenty-eight participants completed the study. There were no statistically significant differences in the pre- or post-course practical MSUS performance between the e-learning group and the traditional group; the mean pre-course OSAUS score (s.d.) in the -learning group was 5.4 (3.7) compared with 5.2 (2.4) in the traditional group (P = 0.8), whereas the post-course OSAUS score in the e-learning group was 11.1 (2.8) compared with 10.9 (2.4) in the traditional group (P = 0.8). There was a significant difference between the mean pre- and post-course scores (5.74 points, P < 0.001). The OSAUS assessment tool demonstrated good inter-rater reliability (intra-class correlation = 0.84).

Conclusion

We found no significant impact of pre-course e-learning on novices’ acquisition of practical MSUS skills. Hands-on training is of the utmost importance and improves MSUS performance significantly. The OSAUS assessment tool is an applicable tool with high interrater reliability.

Trial registration

https://clinicaltrials.gov/ NCT04959162.
Sensitivity analysis of EQ-5D-3L index scores in terms of discriminative and known-groups validity in SLE: introducing Adequate Health State
Authors: Hua Nicole , Gomez Alvaro , Lindblom Julius , Emamikia Sharzad , Enman Yvonne , Grannas David , Heintz Emelie , Regardt Malin , Parodis Ioannis
Published: March 2023

Objectives

To investigate the ability of different EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) index scores to discriminate between verum drug and placebo (discriminant validity) as well as between responders and non-responders (known-groups validity) in the SLE patient population of two phase III clinical trials of belimumab.

Methods

Data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N = 1684), which both showed superiority of belimumab to placebo, were utilized. Responders were defined as SLE Responder Index 4 (SRI-4) achievers at week 52. The Pearson’s χ2 and Mann–Whitney U tests were used for comparisons, and logistic regression analysis was used for adjustments for confounders and assessment of independence.

Results

While full health state (FHS; EQ-5D index score 1) showed the best ability to discriminate between belimumab and placebo [adjusted odds ratio (OR) 1.47; 95% CI 1.11, 1.96; P = 0.008] and between SRI-4 responders and non-responders (adjusted OR 3.47; 95% CI 1.29, 10.98; P = 0.020), the discriminative ability of EQ-5D index scores 0.800 or more reached statistical significance for both discriminant validity (adjusted OR 1.29; 95% CI 1.02, 1.63; P = 0.036) and known-groups validity (adjusted OR 3.08; 95% CI 1.16, 9.69; P = 0.034).

Conclusion

Overall, higher EQ-5D index scores were associated with increasing ability to discriminate between belimumab and placebo, and between responders and non-responders. EQ-5D index scores less stringent than FHS may be clinically relevant health-related quality of life goals of treatment in patients with SLE, introducing the concept of EQ-5D adequate health state when FHS is not achievable.
The chances in the redox priming of nondormant recalcitrant seeds by spermidine
Authors: Fuchs Hanna , Plitta-Michalak Beata P , Małecka Arleta , Ciszewska Liliana , Sikorski Łukasz , Staszak Aleksandra M , Michalak Marcin , Ratajczak Ewelina
Published: March 2023

The problems posed by seed sensitivity to desiccation and aging have motivated the development of various techniques for mitigating their detrimental effects. The redox priming of seeds in antioxidant solution to improve their postharvest performance is one of the approaches. Spermidine (Spd) was tested as an invigorating solution on nondormant recalcitrant (desiccation-sensitive) seeds of the silver maple (Acer saccharinum L.). The treatment resulted in an 8–10% increase in germination capacity in seeds subjected to mild and severe desiccation, while in aged seeds stored for 6 months, no significant change was observed. The cellular redox milieu, genetic stability, mitochondrial structure and function were investigated to provide information about the cellular targets of Spd activity. Spermidine improved the antioxidative capacity, especially the activity of catalase, and cellular membrane stability, protected genome integrity from oxidative damage and increased the efficiency of mitochondria. However, it also elicited a hydrogen peroxide burst. Therefore, it seems that redox priming in nondormant seeds that are highly sensitive to desiccation, although it positively affected desiccated seed performance, may not be a simple solution to reinvigorate stored seeds with a low-efficiency antioxidant system.
The Older, the Less Digitally Fluent? The Role of Age Stereotypes and Supervisor Support
Authors: Hampel Kilian , Kunze Florian
Published: March 2023

Over the last decades, digital technologies have progressively made their way into the workplace. Therefore, it becomes increasingly important for employees to have digital competencies, which can be measured through digital fluency, including its two sub dimensions, namely digital knowledge and digital self-efficacy. This is particularly the case for older workers, who might be affected by a digital divide that proposes younger and older employees have different prerequisites for digital fluency. Drawing from the stereotype embodiment theory, we argue that age is generally negatively related to self-perceptions of digital fluency and particularly impactful when older employees hold negative age stereotypes against older workers and therefore self-stereotype themselves. Furthermore, we argue that developmental support from the direct supervisor has the potential to either amplify or alleviate this negative relation: While a lack of supervisor support may lead to the activation of internalized negative age stereotypes, strong support by the supervisor could strengthen the employees’ self-perceptions in several ways. Performing multiple regression analyses on survey data collected from 1,007 employees, we find support for our three hypotheses. Negative age stereotypes exacerbate the negative relationship between age and digital fluency, whereas the interplay of high individual stereotypes and low supervisor support is the most negative condition for the relation of age on digital fluency. On the other hand, strong supervisor support with low negative stereotypes counteract existing age differences in digital fluency. Therefore, our findings have important theoretical and practical implications.
P4HA2‐mediated HIF‐1α stabilization promotes erdafitinib‐resistance in FGFR3‐alteration bladder cancer
Authors: Li Xuexiang , Li Yunxue , Liu Bing , Chen Liang , Lyu Fang , Zhang Pu , He Qingliu , Cheng Lulin , Liu Chunyu , Song Yarong , Xing Yifei
Published: March 2023

Erdafitinib is a novel fibroblast growth factor receptor (FGFR) inhibitor that has shown great therapeutic promise for solid tumor patients with FGFR3 alterations, especially in urothelial carcinoma. However, the mechanisms of resistance to FGFR inhibitors remain poorly understood. In this study, we found Erdafitinib could kill cells by inducing incomplete autophagy and increasing intracellular reactive oxygen species levels. We have established an Erdafitinib‐resistant cell line, RT‐112‐RS. whole transcriptome RNA sequencing (RNA‐Seq) and Cytospace analysis performed on Erdafitinib‐resistant RT‐112‐RS cells and parental RT‐112 cells introduced P4HA2 as a linchpin to Erdafitinib resistance. The gain and loss of function study provided evidence for P4HA2 conferring such resistance in RT‐112 cells. Furthermore, P4HA2 could stabilize the HIF‐1α protein which then activated downstream target genes to reduce reactive oxygen species levels in bladder cancer. In turn, HIF‐1α could directly bind to P4HA2 promoter, indicating a positive loop between P4HA2 and HIF‐1α in bladder cancer. These results suggest a substantial role of P4HA2 in mediating acquired resistance to Erdafitinib and provide a potential target for bladder cancer treatment.
Physical activity‐induced alterations of the gut microbiota are BMI dependent
Authors: Shah Shrushti , Mu Chunlong , Moossavi Shirin , Shen‐Tu Grace , Schlicht Kristina , Rohmann Nathalie , Geisler Corinna , Laudes Matthias , Franke Andre , Züllig Thomas , Köfeler Harald , Shearer Jane
Published: March 2023

Physical inactivity is one of the leading causes of chronic metabolic disease including obesity. Increasing physical activity (PA) has been shown to improve cardiometabolic and musculoskeletal health and to be associated with a distinct gut microbiota composition in trained athletes. However, the impact of PA on the gut microbiota is inconclusive for individuals performing PA in their day‐to‐day life. This study examined the role of PA and hand‐grip strength on gut microbiome composition in middle‐aged adults (40–65 years, n = 350) with normal (18.5–24.9 kg/m2) and overweight (25–29.9 kg/m2) body mass index (BMI). PA was recorded using the International Physical Activity Questionnaire, and hand‐grip strength was measured using a dynamometer. Serum samples were assessed for lipidomics while DNA was extracted from fecal samples for microbiome analysis. Overweight participants showed a higher concentration of triacylglycerols, and lower concentrations of cholesteryl esters, sphingomyelin, and lyso‐phosphotidylcholine lipids (p < .05) compared with those with normal BMI. Additionally, overweight participants had a lower abundance of the Oscillibacter genus (p < .05). The impact of PA duration on the gut microbiome was BMI dependent. In normal but not overweight participants, high PA duration showed greater relative abundance of commensal taxa such as Actinobacteria and Proteobacteria phyla, as well as Collinsella and Prevotella genera (p < .05). Furthermore, in males with normal BMI, a stronger grip strength was associated with a higher relative abundance of Faecalibacterium and F. prausnitzii (p < .05) compared with lower grip strength. Taken together, data suggest that BMI plays a significant role in modeling PA‐induced changes in gut microbiota.
Does Offloading with Felt Foot Plates Heal Diabetic Foot Ulcers?
Authors: Christensen Deborah , Botchway Albert
Published: March 2023

OBJECTIVE

To determine (1) if offloading with a felt foot plate heals a diabetic foot ulcer, (2) the rate of healing with the felt foot plate, and (3) the impact on rate of healing from the confounding factors of patient weight and growth factors on healing times.

METHODS

The researchers conducted a retrospective chart cohort review over 3 years.

RESULTS

Using a multivariable linear and logistic regression model, the data showed a statistically significant reduction in the diabetic foot ulcer area over time. Confounding factors of patient weight and growth factors did not impact healing times.

CONCLUSIONS

Offloading a diabetic foot ulcer with a felt foot plate is adequate for healing.
Cultural Adaptation, Content Validation, and Reliability of the SACS 2.0 Instrument for Colombian Spanish
Authors: Torres Yesly Johana Rincón , Gamboa Sandra Guerrero , Moreno-Ramos Mily Constanza
Published: March 2023

OBJECTIVE

To realize the cultural adaptation and content validation and evaluate the reliability of the SACS 2.0 instrument in Colombian Spanish.

METHODS

The researchers conducted a methodological study with a quantitative approach. The adaptation process was carried out in five stages: translation, synthesis, reverse translation, evaluation by a committee of experts, and testing of the adapted version. In addition, the interobserver reliability was evaluated by four nurses who examined 210 stomas.

RESULTS

All of the proposed stages were carried out successfully, and an adapted version of the instrument in Colombian Spanish was obtained. During the content validation stage, the instrument obtained a content validity index of 1. The adapted version of the test showed substantial agreement for the aspect of clarity, adequacy, and understandability. In the interobserver reliability, there was agreement in 95.7% of the evaluations for the classification of the lesions according to the quadrants (κ = 0.97–0.99).

CONCLUSIONS

Authors achieved a culturally adapted, valid, and reliable instrument for the evaluation and classification of peristomal skin alterations in Colombian Spanish.
Effect of Adding Perineural Methylprednisolone to Peripheral Nerve Blocks Combined With Intravenous Dexamethasone for Prolonged Postdischarge Analgesia After Fast-track Total Knee Arthroplasty
Authors: Akaravinek Piraya , Kampitak Wirinaree , Tanavalee Aree , Ngarmukos Srihatach , Tanavalee Chotetawan , Limsakul Kamonwan
Published: March 2023

Objectives:

Patients undergoing total knee arthroplasty (TKA) may experience moderate-to-severe subacute pain after hospital discharge that may be undermanaged. We aimed to evaluate the effect of methylprednisolone added to ultrasound-guided peripheral nerve blocks (PNBs) combined with multimodal analgesia including intravenous dexamethasone for prolonged analgesia after early discharge.

Materials and Methods:

We randomized 80 patients who underwent fast-track TKA into 2 groups. All patients received a periarticular injection, PNBs, and multiple doses of intravenous dexamethasone. The methylprednisolone group received 140 mg methylprednisolone in PNBs, while the nonmethylprednisolone group did not. The primary outcome was the incidence of moderate-to-severe pain (Numerical Rating Scale ≥4) during the first 12 postdischarge days. The secondary outcomes included pain scores until 3 postoperative months, incidence of rebound pain, functional performances, patient satisfaction, and adverse events.

Results:

No significant between-group differences were noted in the incidence of moderate-to-severe pain during the first 12 postdischarge days (nonmethylprednisolone vs. methylprednisolone groups: 70% vs. 69.2%, P=0.941). However, this incidence was significantly higher in the methylprednisolone group between 2 weeks and 1 month (P=0.015) and between 1 and 3 months (P=0.004) postoperatively. No between-group differences in the Numerical Rating Scale scores at the postdischarge time points, incidence of rebound pain, and functional performance results were noted.

Discussion:

Adding perineural methylprednisolone to ultrasound-guided PNBs for multimodal analgesia with intravenous dexamethasone did not prolong analgesia and improved the functional ability after fast-track TKA within 12 postdischarge days. However, the incidence moderate-to-severe pain may increase between the 2-week and 3-month follow-up.
Glucocorticoid-induced osteoporosis in premenopausal women: management for the rheumatologist
Authors: Chakrabarti Katherine , McCune W. Joseph
Published: March 2023

Purpose of review

This review seeks to summarize the literature relevant to the treatment of glucocorticoid-induced osteoporosis in premenopausal women; an issue commonly encountered by rheumatologists and yet lacking good clinical practice guidelines.

Recent findings

Although most of the relevant literature on osteoporosis includes postmenopausal women only, data from both randomized controlled trials and case reports suggest bisphosphonates can be an effective and well tolerated treatment for premenopausal patients. Data for other medications to treat premenopausal osteoporosis is less robust.

The use of bisphosphonates in young women may be safer than initially thought and should likely be used for the treatment of glucocorticoid-induced osteoporosis in rheumatology clinics. Further research is needed to continue to understand long-term risk.
Is External Beam Radiation Therapy Really Associated With Low Rates of Heterotopic Ossification After Acetabular Surgery?
Authors: Boissonneault Adam , Harkin Elizabeth , Slobogean Gerard , Gupta Jayesh , Benzel Caroline , O'Hara Nathan , O'Toole Robert V
Published: March 2023

Objectives:

Describe rate of postoperative heterotopic ossification (HO) after acetabular surgery in patients who received external beam radiation (XRT) as HO prophylaxis.

Design:

Retrospective.

Setting:

Level I trauma center.

Patients/Participants:

Consecutive series of patients who presented to a single, level I, academic trauma center over a 10-year period (2008–2018) for surgical fixation of an acetabular fracture. Patients eligible for inclusion were those who underwent surgical fixation of an acetabular fracture through a posterior (Kocher–Langenbeck), combined anterior and posterior, or extensile exposure. Patients were excluded if an isolated anterior approach was performed or if an acute total hip arthroplasty was performed at the time of index surgery.

Intervention:

XRT.

Main Outcome:

Severe HO (Brooker class III or IV).

Results:

The severe HO (Brooker class III or IV) rate for entire cohort was 12% (44 of 361 patients). Of these 44 patients, 30 patients were classified as Brooker III and 14 patients were classified as Brooker IV. The Brooker IV rate for the entire cohort was 4% (14 of 361 patients). Severe HO rates showed a declining trend over the period examined, with a risk reduction of −1.0% per year (95% confidence interval −2.1% to 0.2%; P = 0.10).

Conclusion:

To our knowledge, this is the largest single consecutive series on acetabular fracture patients who received XRT as HO prophylaxis. The overall severe HO rate was 12%, which is similar to other comparably large series data on patients who did not receive XRT after surgical fixation acetabular fractures. Although these data suggest that XRT may not be beneficial when used universally for all patients, comparative studies are required to rule out the benefits of XRT for preventing HO in this population.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.