bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping of Re-Assessing Gentrification Process Post-Pandemic COVID-19 in The Old Town Semarang, Indonesia
Authors: Dewi S. P. , Susanti R. , Wungo G. L.
Published: November 2021

The revitalization of The Semarang Old Town revived this area as a tourist destination and generated regional economic growth. Several new restaurants, coffee shops, galleries, and other economic activities emerge along with tourism development. Job vacancies were offered and attracted newcomers to work as well as to invest. Consequently, properties that previously had no economic value became a potential asset, increasing land prices and building rental prices significantly. Hence, gentrification becomes an inevitable phenomenon. Local communities previously inhabited vacant buildings for years were displaced because the buildings would be restored and then rented out. However, these situations changed after the COVID-19 pandemic occurred, that many restrictions on community activities, including tourism. Visitors’ numbers decrease drastically, making many businesses in the Old Town suffer losses. It pointed by several coffee shops and restaurants closed, or they did not extend the rents. In contrast, the number of informal sectors which restricted surged in line with many work terminations. Hence, this study aims to re-assess the gentrification process along with the socio-economic changes after the COVID-19 pandemic. This study used a quantitative method by applying the spatial analysis method, which compares aspects such as physical transformation, space use, land prices, rent prices, land ownership, and population growth before and after the COVID-19 pandemic.
Mapping of Rural Health Services during Covid-19 Pandemic in Central Java, Indonesia: Rethinking Remoteness
Authors: Andini I. , Djunaedi A.
Published: November 2021

Covidl9 pandemic, since 2019 in global world and 2020 in Indonesia, changed human daily life and affected the provision of public services, especially health services. As Covid19 spread through close interactions among humans, rural areas have the advantage of remoteness compared to higher-density urban areas. In the villages with relatively isolated access, the spread of Covid-19 is very low compared to the national average. This paper discusses how remoteness has become two sides of the coin during pandemic by examining at the data of health services in three rural areas in Provinsi Jawa Tengah, Indonesia. Data collected by in-depth interviews showed that although remoteness became a key factor in delaying the spread of Covid19, it also became a key factor in the deterioration of advanced health services in non-covid diseases throughout the pandemic. These findings confirmed the vulnerability of basic services in rural areas, even on Java Island as a center of growth in Indonesia. Using causal network analysis, the discussion revealed that the vulnerability stem from the territorial approach in health service provision making rural areas less resilient during pandemic. This paper concludes that while remoteness provides a barrier in retaining the spread of pandemic disease, it also worsens the medical treatment capacity in non-pandemic diseases in rural areas. Covid19 pandemic raises the need of specific arrangement public health services in remote rural areas.
The Use of Data and Information in Irrigation Water Management (Case Study: Colo Irrigation Area, Bengawan Solo River Basin)
Authors: Werdiningtyas R. , Suminar L. , Kusumastuti K.
Published: November 2021

In term of geography, water is a resource which is not favouring administrative boundaries. Water has its behaviour in flowing. However, we cannot confidently say that water flows following the laws of gravity. There is no guarantee that locations which are close to reservoir or water resource are not prone. Water scarcity when comparing the resource to demand for it is more relative than absolute. Irrigation water management is aimed to guarantee to make every agricultural land has access to water. In other hand, map is an important tool especially for portraying conditions of an area such as river basin. Map have played important roles in water management. This study aims to explore the use of data in decision making in irrigation water management practices. Colo irrigation area in Bengawan Solo river basin was chosen not only its vast coverage area but also because of its complexity in water management. It across two provinces and six municipalities. Content analysis was undertook to analyse two data sets: laws and regulation related to water management practice and the interview of policy actors. Elaborating the implementation of laws and regulations regarding to the use of data and information in irrigation water management, the comparison of the results also disclosed deviations among what it is regulated and what it is implemented. Quantitative and qualitative data that mostly used in practices cannot fully support to inform water conditions, physical and environmental conditions, social economic conditions in wider context. Spatial data is essential tools to represent comprehensive interconnected data and information in wider context. A profound understanding of stakeholder perspectives on the role of each data and information is essential for policy actors in the implementation of integration water resource management. Shared, comprehensive and interconnected data can promote common ground and collaboration potential.
First passage dynamics of stochastic motion in heterogeneous media driven by correlated white Gaussian and coloured non-Gaussian noises
Authors: Mutothya Nicholas Mwilu , Xu Yong , Li Yongge , Metzler Ralf , Mutua Nicholas Muthama
Published: November 2021

We study the first passage dynamics for a diffusing particle experiencing a spatially varying diffusion coefficient while driven by correlated additive Gaussian white noise and multiplicative coloured non-Gaussian noise. We consider three functional forms for position dependence of the diffusion coefficient: power-law, exponential, and logarithmic. The coloured non-Gaussian noise is distributed according to Tsallis’ q-distribution. Tracks of the non-Markovian systems are numerically simulated by using the fourth-order Runge–Kutta algorithm and the first passage times (FPTs) are recorded. The FPT density is determined along with the mean FPT (MFPT). Effects of the noise intensity and self-correlation of the multiplicative noise, the intensity of the additive noise, the cross-correlation strength, and the non-extensivity parameter on the MFPT are discussed.
Quantifying the drivers behind collective attention in information ecosystems
Authors: Calleja-Solanas Violeta , Pigani Emanuele , Palazzi María J , Solé-Ribalta Albert , Suweis Samir , Borge-Holthoefer Javier , Meloni Sandro
Published: November 2021

Understanding human interactions in online communications is of paramount importance for our society. Alarming phenomena such as the spreading of fake news or the formation of echo-chambers can emerge in unhealthy communication environments and, ultimately, undermine the democratic discourse. In this context, unveiling the individual drivers that give rise to collective attention can help to conserve the health of our information ecosystems. Here, following a recently proposed analogy between natural and information ecosystems, we explore how competition for attention in online social networks and the strategies adopted by the users to maximize their visibility shape our communication dynamics. Specifically, by analyzing large-scale datasets from the micro-blogging platform Twitter and performing numerical modeling of the system dynamics, we are able to measure the amount of competition for attention experienced by users and how it changes when exogenous events captivate collective attention. The work relies on topic modeling to extract users’ interests and memes context from the data and a framework based on ecological niche theory to quantify the strength of negative (competitive) and positive (mutualistic) interactions for both users and memes. Interestingly, our findings show two different behaviors. While memes undergo a sharp increase in competition during exceptional events that can lead to their extinction, users perceive a decrease in effective competition due to a stronger effect of mutualistic interaction, explaining the focus of collective attention around specific topics. Finally, to confirm our results we reproduce the observed shifts with a data-driven model of species dynamics.
Efficient red perovskite quantum dot light-emitting diode fabricated by inkjet printing
Authors: Li Danyang , Wang Junjie , Li Miaozi , Guo Biao , Mu Lan , Luo Yu , Xiao Yi , Mai Chaohuang , Wang Jian , Peng Junbiao
Published: November 2021

Perovskite quantum dots (PeQDs) are considered potential display materials due to their high color purity, high photoluminescence quantum yield (PLQY), low cost and easy film casting. In this work, a novel electroluminescence (EL) device consisting of the interface layer of long alkyl-based oleylammonium bromide (OAmBr), which passivates the surface defects of PeQDs and adjusts the carrier transport properties, was designed. The PLQY of the OAmBr/PeQD bilayer was significantly improved. A high-performance EL device with the structure of indium tin oxide/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate/poly(bis(4-phenyl)(2,4,6-trimethylphenyl)amine)/OAmBr/PeQDs/2,2′,2″-(1,3,5-benzinetriyl)-tris(1-phenyl-1H benzimidazole)/LiF/Al was constructed using a spin-coating method. A peak external quantum efficiency (EQE) of 16.5% at the emission wavelength of 646 nm was obtained. Furthermore, an efficient matrix EL device was fabricated using an inkjet printing method. A high-quality PeQD matrix film was obtained by introducing small amounts of polybutene into the PeQDs to improve the printing process. The EQE reached 9.6% for the matrix device with 120 pixels per inch and the same device structure as that of the spin-coating one.
Seven autophagy-related lncRNAs are associated with the tumor immune microenvironment in predicting survival risk of nonsmall cell lung cancer
Authors: Jiang Huihui , Xu Aiqun , Li Min , Han Rui , Wang Enze , Wu Dong , Fei Guanghe , Zhou Sijing , Wang Ran
Published: November 2021

Background

Nonsmall cell lung cancer (NSCLC) ranks first among global cancer-related deaths. Despite the emergence of various immunological and targeted therapies, immune tolerance remains a barrier to treatment.

Methods

It has been found that this obstacle can be overcome by targeting autophagy-related genes (ATGs). ATGs were screened by coexpression analysis and the genes related to the prognosis of lung cancer were screened using Kaplan–Meier (K–M) survival analysis, univariate Cox regression and multivariate Cox regression. The prognostic risk model of ATGs was constructed and verified using K–M survival analysis and receiver operating characteristic (ROC) curve analysis.

Results

The prognostic risk model of ATGs was constructed. Gene set enrichment analysis (GSEA) showed that the function and pathway of ATG enrichment were closely related to immune cell function. CIBERSORT, LM22 matrix and Pearson correlation analysis showed that risk signals were significantly correlated with immune cell infiltration and immune checkpoint genes.

Conclusions

We identified and independently verified the ATG (AL691432.2, MMP2-AS1, AC124067.2, CRNDE, ABALON, AL161431.1, NKILA) in NSCLC patients and found that immune regulation in the tumor microenvironment is closely related to this gene.
A low-carbohydrate diet containing soy protein and fish oil reduces breast but not prostate cancer in C3(1)/Tag mice
Authors: Elisia Ingrid , Yeung Michelle , Wong Jennifer , Kowalski Sara , Larsen Meegan , Shyp Taras , Sorensen Poul H , Krystal Gerald
Published: November 2021

We recently showed that a low-carbohydrate (CHO) diet containing soy protein and fish oil dramatically reduces lung nodules in a mouse model of lung cancer when compared to a Western diet. To explore the universality of this finding, we herein compared this low-CHO diet to a Western diet on in preventing breast and prostate cancer using a mouse model that expresses the SV40 large T-antigen specifically in breast epithelia in females and prostate epithelia in males. We found that breast cancer was significantly reduced with this low-CHO diet and this correlated with a reduction in plasma levels of glucose, insulin, IL-6, TNFα and prostaglandin E2 (PGE2). This also corresponded with a reduction in the Ki67 proliferation index within breast tumors. On the other hand, this low-CHO diet did not reduce the incidence of prostate cancer in the male mice. Although it reduced both blood glucose and insulin to the same extent as in the female mice, there was no reduction in plasma IL-6, TNFα or PGE2 levels, or in the Ki67 proliferation index in prostate lesions. Based on immunohistochemistry studies with antibodies to 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), carnitine palmitoyltransferase Ia (CPT1a) and fatty acid synthase (FAS), it is likely that this difference in response of the two cancer types to this low-CHO diet reflects differences in the glucose dependence of breast and prostate cancer, with the former being highly dependent on glucose for energy and the latter being more dependent on fatty acids.
Versatile TLC-Densitometric Methods for the Synchronous Estimation of Cinnarizine and Acefylline Heptaminol in The Presence of Potential Impurity and Their Reported Degradation Products
Authors: El-Houssini Ola M , Mohammad Mohammad A
Published: November 2021

From evolution, thin-layer chromatography (TLC) attracts attention as a versatile technique for efficient separation and identification of many drug substances and chemicals. Owing to its simplicity and other outstanding advantages, TLC is extensively used by chromatographers in quantification and purity profiling objectives. In the present study two TLC-Densitometric methods are established and validated for the synchronous estimation of Cinnarizine (Cinn) and Acefyline Heptaminol (Acef) in the presence of Cinn/Acef reported degradation products and Thoephylline (Theo) as Acef potential impurity. The proposed methods are based on densitometric measurements of the spots of Cinn and Acef after separation from their degradation products. Separation is attained on silica gel sheet with dichloromethane: methanol: formic acid as a developing system in ratio: (15, 1, 0.5, by volume) and (15, 0.75, 0.4, by volume) for Cinn (method 1) and Acef (method 2) degradation, consecutively. Quantification is done at 254 nm over concentration ranges of 0.2–1.8 and 2–18 μg/spot for Cinn and Acef; respectively, with mean percentage recoveries of 99.18 ± 0.60/99.84 ± 0.53 and 99.19 ± 0.93/99.66 ± 0.58 for method 1 and method 2; consecutively. The two methods are fully validated and proven to be selective, robust and retained their accuracy in up to 50% of Cinn/Acef reported degradation products and Theo. Moreover, the two methods are applied to a coformulated drug product comprising Cinn and Acef showing satisfactory results. Comparison of the obtained results by the proposed methods with that of the reference ones statistically shows no significant differences.
Depression and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study
Authors: Luo Jiao , Xu Zhongwei , Noordam Raymond , van Heemst Diana , Li-Gao Ruifang
Published: November 2021

Background and Aims

Observational studies have suggested a bidirectional association between depression and inflammatory bowel disease [IBD], including Crohn’s disease [CD] and ulcerative colitis [UC]. However, it remains unclear whether the observed associations are causal due to the difficulties of determining sequential temporality. We investigated the association between depression and IBD by using bidirectional two-sample Mendelian randomization [MR].

Methods

Independent genetic variants for depression and IBD were selected as instruments from published genome-wide association studies [GWAS] among individuals of predominantly European ancestry. Summary statistics for instrument–outcome associations were retrieved from three separate databases for both depression [Psychiatric Genomics Consortium, FinnGen and UK Biobank] and IBD [the largest GWAS meta-analysis, FinnGen and UK Biobank], respectively. MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger regression, and sensitivity analyses of Steiger filtering and MR PRESSO. From either direction, analyses were performed per outcome database and were subsequently meta-analysed using a fixed-effect model.

Results

Genetically predicted depression [per log-odds ratio increase] was associated with a higher risk of IBD; odds ratios [95% confidence interval] for IBD, CD and UC were 1.20 [1.05, 1.36], 1.29 [1.07, 1.56] and 1.22 [1.01, 1.47] in a combined sample size of 693 183 [36 507 IBD cases], 212 172 [13 714 CD cases] and 219 686 [15 691 UC cases] individuals, respectively. In contrast, no association was observed between genetically influenced IBD and depression in 534 635 individuals [71 466 depression cases].

Conclusions

Our findings corroborated a causal association of depression on IBD, which may impact the clinical decision on the management of depression in patients with IBD. Though our results did not support a causal effect of IBD on depression, further investigations are needed to clarify the effect of IBD activity on depression [with different symptomology].
Comparison of chest- and wrist-based actigraphy in pulmonary arterial hypertension
Authors: Lachant Daniel , Light Allison , Hannon Kevin , Abbas Farrukh , Lachant Michael , White R James
Published: November 2021

Aims

Activity trackers for clinical trials and remote monitoring are appealing as they provide objective data outside of the clinic setting. Algorithms determine physical activity intensity and count steps. Multiple studies show physical inactivity in pulmonary arterial hypertension (PAH). There are no studies comparing different activity trackers worn on different parts of the body in PAH. We had patients with PAH simultaneously wear two different accelerometers, compared measures between the two devices, and correlated the measures with standard clinical metrics in PAH.

Methods and results

This was a single-centre, prospective observational study. Daily physical activity and daily total steps were measured using Actigraph GT9X Link and MC10 Biostamp nPoint for 5–10 days. Actigraph was worn on the non-dominant hand and the MC10 Biostamp nPoint was worn on the chest and leg with disposable adhesives. Twenty-two participants wore both accelerometers >12 h/day for an average 7.8 days. The average activity time measured by Actigraph was significantly higher than that measured by MC10 (251 ± 25 min vs. 113 ± 18 min, P = 0.0001). Actigraph’s algorithm reported more time in light activity than moderate (190 ± 62 min vs. 60 ± 56 min, P = 0.0001). REVEAL 2.0 scores correlated highly with activity time measured using either device. Invasively measured haemodynamics within 7 days did not correlate with activity time or daily steps.

Conclusion

Different activity trackers yield discordant results in PAH patients. Further studies are needed in determining the best device, optimal wear time, and different thresholds for activities in chronic diseases.
Fasting Concentrations and Postprandial Response of 1,2-Dicarbonyl Compounds 3-Deoxyglucosone, Glyoxal, and Methylglyoxal Are Not Increased in Healthy Older Adults
Authors: Herpich Catrin , Kochlik Bastian , Weber Daniela , Ott Christiane , Grune Tilman , Norman Kristina , Raupbach Jana
Published: November 2021

Dicarbonyl stress describes the increased formation of 1,2-dicarbonyl compounds and is associated with age-related pathologies. The role of dicarbonyl stress in healthy aging is poorly understood. In a preliminary study, we analyzed 1,2-dicarbonyl compounds, namely 3-deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) in plasma of older (25 months, n = 11) and younger (5 months, n = 14) male C57BL/6J (B6) mice via ultra performance liquid chromatography tandem mass spectrometry. Postprandial 3-DG was higher in younger compared to older mice, whereas no differences were found for GO and MGO. Subsequently, in the main study, we analyzed fasting serum of older women (OW, 72.4 ± 6.14 years, n = 19) and younger women (YW, 27.0 ± 4.42 years, n = 19) as well as older men (OM, 74.3 ± 5.20 years, n = 15) and younger men (YM, 27.0 ± 3.34, n = 15). Serum glucose, insulin, 1,2-dicarbonyl concentrations, and markers of oxidative stress were quantified. In a subgroup of this cohort, an oral dextrose challenge was performed, and postprandial response of 1,2-dicarbonyl compounds, glucose, and insulin were measured. In women, there were no age differences regarding fasting 1,2-dicarbonyl concentrations nor the response after the oral dextrose challenge. In men, fasting MGO was significantly higher in OM compared to YM (median: 231 vs 158 nM, p = .006), whereas no age differences in fasting 3-DG and GO concentrations were found. Glucose (310 ± 71.8 vs 70.8 ± 11.9 min·mmol/L) and insulin (7 149 ± 1 249 vs 2 827 ± 493 min·µIU/mL) response were higher in OM compared to YM, which did not translate into a higher 1,2-dicarbonyl response in older individuals. Overall, aging does not necessarily result in dicarbonyl stress, indicating that strategies to cope with 1,2-dicarbonyl formation can remain intact.
“Who Wants to Know all this Stuff?!”: Understanding Older Adults’ Privacy Concerns in Aged Care Monitoring Devices
Authors: Alkhatib Sami , Kelly Ryan , Waycott Jenny , Buchanan George , Grobler Marthie , Wang Shuo
Published: November 2021

Aged care monitoring devices (ACMDs) enable older adults to live independently at home. But to do so, ACMDs collect and share older adults’ personal information with others, potentially raising privacy concerns. This paper presents a detailed account of the different privacy problems in ACMDs that concern older adults. We report findings from interviews and a focus group conducted with older adults who are ageing in place. Using Daniel Solove’s privacy taxonomy to categorize privacy concerns, our analysis suggests that older adults are concerned about the potential for ACMDs to give rise to six problems: surveillance, secondary use of data, breach of confidentiality, disclosure, decisional interference and disturbing others. Other findings indicate that participants are worried about their ability to impose control over collection and management of their personal details and are willing to only accept privacy trade-offs during emergencies. We provide recommendations for ACMD developers and future directions to address findings from this research.
Long-term survival benefit from dual kidney transplantation using kidneys from donors with very extended criteria—a French cohort between 2002 and 2014
Authors: Savoye Emilie , Legendre Christophe , Neuzillet Yann , Peraldi Marie-Noëlle , Grimbert Philippe , Ouali Nacera , Durand Matthieu , Badet Lionel , Kerbaul François , Pastural Myriam , Legeai Camille , Macher Marie-Alice , Snanoudj Renaud
Published: November 2021

Background

This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT).

Methods

Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded.

Results

The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival.

Conclusions

In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.
Change in psoriatic arthritis outcome measures impacts SF-36 physical and mental component scores differently: an observational cohort study
Authors: Skougaard Marie , Jørgensen Tanja S , Jensen Mia J , Ballegaard Christine , Guldberg-Møller Jørgen , Egeberg Alexander , Christensen Robin , Benzin Peter , Stisen Zara R , Merola Joseph F , Coates Laura C , Strand Vibeke , Mease Phillip , Kristensen Lars Erik
Published: November 2021

Objective

The objective was to investigate interplay and physical and mental component scores between change (Δ) in health-related quality of life (HRQoL) quantified by the physical component score (PCS) and mental component score (MCS) retrieved from short-form health survey (SF-36), change in disease activity (ΔDAS28CRP) and manifestations of PsA.

Methods

PsA patients initiating new medical therapy were enrolled. Independent disease measures evaluating disease activity, enthesitis, psoriasis, pain and fatigue were collected at treatment initiation and after 4 months. Interplay between independent disease measures and dependent outcome measures, ΔPCS and ΔMCS, was described with univariate regression analyses. Multivariate regression analyses were applied to assess the impact of independent variables, such as individual disease outcome measures vs ΔDAS28CRP on ΔPCS and ΔMCS.

Results

One hundred and eight PsA patients were included. In the univariate regression analyses, improvement in fatigue, pain and disability were associated with improvement in ΔPCS (β; −2.08, −0.18 and −13.00, respectively; all P < 0.001) and ΔMCS (β; −1.59, −0.12 and −6.07, respectively; P < 0.001, P < 0.001 and P = 0.003, respectively). When patient-reported outcomes were included in the final multivariate models, improvements in ΔPCS and ΔMCS were associated with improvements in pain, fatigue and disability (P < 0.001). Improvement in enthesitis impacted ΔPCS positively (β −0.31, P < 0.001). No association was found between change in skin psoriasis, ΔPCS and ΔMCS (β 0.15, P = 0.056 and β 0.05, P = 0.561, respectively).

Conclusion

In this PsA patient cohort, diminishing pain, disability and fatigue improved PCS and MCS significantly. Changes in enthesitis and psoriasis did not grossly impact HRQoL compared with DAS28CRP. Individual PsA manifestations influence HRQoL differently, which is important clinically when targeting treatment.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT02572700.
Epidemiology of Bleeding in Critically Ill Children With an Underlying Oncologic Diagnosis
Authors: Romano Juliana , Martinez Mario , Levasseur Julie , Killinger James S. , Karam Oliver , Nellis Marianne E.
Published: November 2021

OBJECTIVES:

Critically ill children with malignancy have significant risk of bleeding but the exact epidemiology is unknown. We sought to describe severe bleeding events and associated risk factors in critically ill pediatric patients with an underlying oncologic diagnosis using the newly developed Bleeding Assessment Scale in Critically Ill Children definition.

DESIGN:

Retrospective cohort study.

SETTING:

PICU in comprehensive cancer center,

PATIENTS:

Children ages 28 days to 18 years with an underlying oncologic diagnosis admitted to the PICU during 2018.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Two-hundred sixty-seven admissions met inclusion criteria. Sixty-four percent (171/267) were male, with a median (interquartile range) age of 6.3 years (3.1–12.1 yr). Nine percent (23/267) had at least one severe bleeding event during their PICU admission. There were no significant differences between those with severe bleeding and those without, with respect to gender (p = 0.07), age (p = 0.66), weight (p = 0.76), or transplant status (p = 0.18). There was a difference in the frequency of severe bleeding based on underlying oncologic diagnosis (p = 0.009). For patients with severe bleeding, the median (interquartile range) platelet count and international normalized ratio on the day of bleeding were 102 × 109/L (40–181 × 109/L) and 1.36 (1.26–1.51), respectively. Eighty-seven percent patients (20/23) with severe bleeding received at least one blood component in response to bleeding. Two patients received antifibrinolytics. Patients with severe bleeding had significantly fewer PICU-free days (p = 0.001), fewer ventilator-free days (p < 0.001), and higher 28-day mortality (p = 0.003).

CONCLUSIONS:

Severe bleeding occurred in nearly one-tenth of critically ill children with an underlying oncologic diagnosis without severe thrombocytopenia or coagulopathy. The vast majority received blood component therapy, but few received hemostatic medication. Studies are needed to guide the treatment of severe bleeding in this vulnerable patient population.
Platelet-Rich Plasma in Melasma—A Systematic Review
Authors: Sarkar Rashmi , Gupta Meghna
Published: November 2021

BACKGROUND

Melasma is a common relapsing hyperpigmentation disorder, which is often difficult to treat. Platelet-rich plasma (PRP) is a novel modality often used to treat acne scars, androgenic alopecia, chronic wounds, and skin rejuvenation. Recently, it has had a promising role in the treatment of melasma.

OBJECTIVE

To review the published evidence on the efficacy and safety of PRP in the treatment of melasma.

MATERIALS AND METHODS

A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity.

RESULTS

Seven studies were fulfilled and analyzed. Most studies used intradermal injections of PRP and have shown significant improvement in melasma. Microneedling mediated delivery of PRP has been tried in melasma with good results. A single study showed no additional benefit of PRP in patients treated with topical tranexamic acid. Another study showed no benefit of intense pulsed light in patients treated with intradermal PRP.

CONCLUSION

Platelet-rich plasma inhibits the melanin synthesis through its various components acting through several mechanisms. It demonstrates a moderate grade of recommendation according to the Oxford Center for Evidence-Based Medicine 2011 standards.
Metacarpal bone diameter increases constantly in adult females, but escalated resorption of the inner surface at menopause explains the observed decreased bone mineral density at digital X-ray radiogrammetry
Authors: Samuelsson Carl , Wilczek Michael , Kälvesten Johan , Qureshi Abdul Rashid , Brismar Torkel B.
Published: November 2021

Objective:

To assess how bone morphology and mineralization changes with age, in women by digital X-ray radiogrammetry (DXR). DXR has potential as a screening tool for osteoporosis, as it can evaluate bone mineralization similarly to dual-energy X-ray absorptiometry.

Methods:

The nondominant hand was analyzed with DXR in 13,285 women ages 40-74 years undergoing mammography. 1,556 women attended two consecutive examinations with 18 to 24 months interval. Changes in bone parameters were calculated and compared in 5-year age groups. Regression analysis and ANOVA tests were performed.

Results:

Univariate linear regression showed no significant difference in age or bone size between the groups with single or consecutive measurements. In the group with consecutive measurements, the average inner diameter (DXR-ID) of the metacarpals significantly increased with age from 0.38 cm in the 40-45 years age span to 0.47 cm in the 65+ age group (P < 0.001), whereas DXR bone mineral density (DXR-BMD) decreased from 0.59 g/cm2 to 0.50 g/cm2 in the same age groups (P < 0.001). Intraindividual measurements showed a fourfold increase in yearly DXR-ID increase and concurrent DXR-BMD loss between 50 and 59 years of age (P < 0.001). The outer diameter only increased significantly between the youngest and oldest age group (P < 0.001).

Conclusions:

The faster decrease in DXR-BMD observed during and after menopause is caused by resorption of the inner cortical surface, not matched by outer diameter increase. We speculate that most bones in the human body grow in the same pattern as observed in the metacarpals, partly explaining decreasing BMD at DXR and dual-energy X-ray absorptiometry.

Video Summary:

http://links.lww.com/MENO/A832.
Association between eating alone and cardiovascular diseases in elderly women: a cross-sectional study of KNHANES 2016 data
Authors: Choi Han-Gyo , Kim Hye-Jin , Kang Seok-Jung
Published: November 2021

Objective:

To investigate differences in health behaviors, nutritional status, and the likelihood of having cardiovascular diseases and its risk factors according to the presence of an eating companion in older women.

Methods:

Using 2016 Korean National Health and Nutrition Examination Survey VII-1 data, 590 menopausal women aged ≥65 years were analyzed in this cross-sectional study. Participants who ate more than two meals a day alone were assigned to an eating-alone (EA) group and those who ate more than two meals a day with others were assigned to an eating-with-others (EO) group. Complex-samples general linear analysis, t tests, and logistic regression were used for the analysis of the data.

Results:

Awareness of nutrition labels (P = 0.012), using of nutrition labels (P = 0.014), and impact of nutrition labels (P = 0.016) were lower in the EA group than in the EO group. The intake of energy, carbohydrates, dietary fiber, sodium, and potassium was lower in the EA group than in the EO group (P < 0.05). The likelihood of having angina was 2.58 times higher in the EA group than in the EO group (95% CI, 1.20-5.55).

Conclusions:

Older women who ate alone had poorer nutritional knowledge and intake. In addition, eating alone in older women was strongly associated with the prevalence of angina. Thus, it is necessary to consider nutrition education and cardiovascular disease screening for older women who mainly eat alone.
Induction of innate immune responses by KPC-producing Klebsiella pneumoniae of the pandemic sequence type 258-clade I
Authors: Balaska Asimina , Polonyfi Katerina , Rigatou Anastasia , Miliotis Georgios , Margaroni Maritsa , Daikos George L. , Drogari-Apiranthitou Maria
Published: November 2021

Klebsiella pneumoniae

-carbapenemase-producing

K. pneumoniae

(KPC) sequence-type 258 (ST258) has emerged as an important human pathogen throughout the world. Although lacking known virulence factors, it is associated with significant morbidity and high mortality rates. The pathogenicity of KPC

K. pneumoniae

ST258 strains has not been fully elucidated yet. We sought to investigate the interactions of the KPC

K. pneumoniae

ST258-clade I with different components of innate immunity. Human serum was used to evaluate the serum bactericidal activity and the J774A.1 murine (BALB/c mice) macrophage cell-line was used to examine phagocytosis, mRNA expression and production of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. L-78, a KPC-producing

K. pneumoniae

ST258-clade I strain was used as representative of the strains circulating in Greek hospitals.

K. pneumoniae

ATCC 43816, a virulent K2 strain, was used for comparison. Strain L-78 was susceptible to human serum and rapidly phagocytosed by J774A.1 cells, in contrast to the virulent K2 strain, which was serum-resistant and slowly phagocytosed. Stimulation of the J774A.1 cells with the L-78 strain induced production of IL-1β at concentration levels significantly higher compared to K2, whereas production of TNF-α and IL-6 levels were comparable by the two strains. L-78 was able to induce IL-1β mRNA and NLRP3 mRNA expression. Our findings indicate that

K. pneumoniae

ST258-clade I is serum sensitive, rapidly phagocytosed and is capable of eliciting adequate innate immune response in terms of production of pro-inflammatory cytokines.
Targeting Versus Tailoring Educational Videos for Encouraging Deceased Organ Donor Registration in Black-Owned Barbershops
Authors: Wall Stephen P. , Castillo Patricio , Shuchat-Shaw Francine , Norman Elizabeth , Brown David , Martinez-López Natalia , López-Ríos Mairyn , Seixas Azizi A. , Plass Jan L. , Ravenell Joseph E.
Published: November 2021

In the U.S., Black men have highest risk for requiring kidney transplants but are among those least likely to register for organ donation. Prior outreach used videos culturally targeted for Black communities, yet registration rates remain insufficient to meet demand. Therefore, we assessed whether generic versus videos culturally targeted or personally tailored based on prior organ donation beliefs differentially increase organ donor registration. In a randomized controlled trial, 1,353 participants in Black-owned barbershops viewed generic, targeted, or tailored videos about organ donation. Logistic regression models assessed relative impact of videos on: 1) immediate organ donor registration, 2) taking brochures, and 3) change in organ donation willingness stage of change from baseline. Randomization yielded approximately equal groups related to demographics and baseline willingness and beliefs. Neither targeted nor tailored videos differentially affected registration compared with the generic video, but participants in targeted and tailored groups were more likely to take brochures. Targeted (OR=1.74) and tailored (OR=1.57) videos were associated with incremental increases in organ donation willingness stage of change compared to the generic video. Distributing culturally targeted and individually tailored videos increased organ donor willingness stage of change among Black men in black-owned barbershops but was insufficient for encouraging registration.
Interpretable Visualization of Scientific Hypotheses in Literature-based Discovery
Authors: Tyagin Ilya , Safro Ilya
Published: November 2021

In this paper we present an approach for interpretable visualization of scientific hypotheses that is based on the idea of semantic concept interconnectivity, network-based and topic modeling methods. Our visualization approach has numerous adjustable parameters which provides the domain experts with additional flexibility in their decision making process. We also make use of the Unified Medical Language System metadata by integrating it directly into the resulting topics, and adding the variability into hypotheses resolution. To demonstrate the proposed approach in action, we deployed end-to-end hypothesis generation pipeline AGATHA, which was evaluated by BioCreative VII experts with COVID-19-related queries.
Consequences of endogenous and virally-induced hyperphosphorylated tau on behavior and cognition in a rat model of Alzheimer’s disease
Authors: Kelberman Michael A. , Anderson Claire R. , Chlan Eli , Rorabaugh Jacki M. , McCann Katharine E. , Weinshenker David
Published: November 2021

Background

The locus coeruleus (LC) is one of the earliest brain regions to accumulate hyperphosphorylated tau, but a lack of animal models that recapitulate this pathology has hampered our ability to understand its contributions to the pathophysiology of Alzheimer’s disease (AD).

Objective

We previously reported that TgF344-AD rats, which overexpress mutant human amyloid precursor protein and presenilin-1, accumulate early endogenous hyperphosphorylated tau in the LC. Here, we used TgF344-AD rats and a wild-type (WT) human tau virus to interrogate the effects of endogenous hyperphosphorylated rat tau and human tau in the LC on AD-related neuropathology and behavior.

Methods

Two-month old TgF344-AD and WT rats received bilateral LC infusions of WT human tau or mCherry control virus driven by the noradrenergic-specific PRSx8 promoter. Rats were subsequently assessed at 6 and 12 months for arousal (sleep latency), anxiety-like behavior (open field, elevated plus maze, novelty-suppressed feeding), passive coping (forced swim task), and learning and memory (Morris water maze and fear conditioning). Hippocampal microglia, astrocyte, and AD pathology were evaluated using immunohistochemistry.

Results

In general, the effects of age were more pronounced than genotype or treatment; older rats displayed greater hippocampal pathology, took longer to fall asleep, had reduced locomotor activity, floated more, and had impaired cognition compared to younger animals. TgF344-AD rats showed increased anxiety-like behavior and impaired learning and memory. The tau virus had negligible influence on most measures.

Conclusion

Effects of hyperphosphorylated tau on AD-like neuropathology and behavioral symptoms were subtle. Further investigation of different forms of tau is warranted.
Intratumoral delivery of engineered recombinant modified vaccinia virus Ankara expressing Flt3L and OX40L generates potent antitumor immunity through activating the cGAS/STING pathway and depleting tumor-infiltrating regulatory T cells
Authors: Yang Ning , Wang Yi , Liu Shuaitong , Luna Joseph M. , Mazo Gregory , Tan Adrian Y. , Zhang Tuo , Wang Jiahu , Yan Wei , Choi John , Rossi Anthony , Xiang Jenny Zhaoying , Rice Charles M. , Merghoub Taha , Wolchok Jedd D. , Deng Liang
Published: November 2021

Intratumoral (IT) delivery of immune-activating viruses can serve as an important strategy to turn “cold” tumors into “hot” tumors, resulting in overcoming resistance to immune checkpoint blockade (ICB). Modified vaccinia virus Ankara (MVA) is a highly attenuated, non-replicative vaccinia virus that has a long history of human use. Here we report that IT recombinant MVA (rMVA), lacking E5R encoding an inhibitor of the DNA sensor cyclic GMP-AMP synthase (cGAS), expressing a dendritic cell growth factor, Fms-like tyrosine kinase 3 ligand (Flt3L), and a T cell co-stimulator, OX40L, generates strong antitumor immunity, which is dependent on CD8+ T cells, the cGAS/STING-mediated cytosolic DNA-sensing pathway, and STAT1/STAT2-mediated type I IFN signaling. Remarkably, IT rMVA depletes OX40hi regulatory T cells via OX40L/OX40 interaction and IFNAR signaling. Taken together, our study provides a proof-of-concept for improving MVA-based cancer immunotherapy, through modulation of both innate and adaptive immunity.

One Sentence Summary

Intratumoral delivery of recombinant MVA for cancer immunotherapy
Highly-Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe Polymerase Chain Reaction
Authors: Ratcliff Jeremy , Al-Beidh Farah , Bibi Sagida , Bonsall David , Costa Clemens Sue Ann , Estcourt Lise , Evans Amy , Fish Matthew , Folegatti Pedro M. , Gordon Anthony C. , Jay Cecilia , Jennings Aislinn , Laing Emma , Lambe Teresa , MacIntyre-Cockett George , Menon David , Mouncey Paul R. , Nguyen Dung , Pollard Andrew J. , Ramasamy Maheshi N. , Roberts David J. , Rowan Kathryn M. , Rynne Jennifer , Shankar-Hari Manu , Williams Sarah , Harvala Heli , Golubchik Tanya , Simmonds Peter ,   the AMPHEUS Project, REMAP-CAP Immunoglobulin Domain UK Investigators, and Oxford COVID-19 Vaccine Trial Group
Published: November 2021

Introduction

Tools to detect SARS-Coronavirus-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality.

Methods

An allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil. Probit regression models were developed to compare ASP-PCR performance against 1,771 NGS results for the same cohorts.

Results

Individual SNPs were shown to readily identify specific variants of concern. ASP-PCR was shown to discriminate SARS-CoV-2 lineages with a higher likelihood than NGS over a wide range of viral loads. Comparative advantage for ASP-PCR over NGS was most pronounced in samples with Ct values between 26-30 and in samples that showed evidence of degradation. Results for samples screened by ASP-PCR and NGS showed 99% concordant results.

Discussion

ASP-PCR is well-suited to augment but not replace NGS. The method can differentiate SARS-COV-2 lineages with high accuracy and would be best deployed to screen samples with lower viral loads or that may suffer from degradation. Future work should investigate further destabilization from primer:target base mismatch through altered oligonucleotide chemistry or chemical additives.
PrP concentration in the central nervous system: regional variability, genotypic effects, and pharmacodynamic impact
Authors: Mortberg Meredith A , Zhao Hien T , Reidenbach Andrew G , Gentile Juliana E , Kuhn Eric , O’Moore Jill , Dooley Patrick M , Connors Theresa R , Mazur Curt , Allen Shona W , Trombetta Bianca A , McManus Alison , Moore Matthew R , Liu Jiewu , Cabin Deborah E , Kordasiewicz Holly B , Mathews Joel , Arnold Steven E , Vallabh Sonia M , Minikel Eric Vallabh
Published: November 2021

Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically and pharmacologically validated therapeutic target for prion disease. In order to evaluate PrP concentration as a pharmacodynamic biomarker and assess its contribution to known prion disease risk factors, we developed and validated a plate-based immunoassay reactive for PrP across six species of interest and applicable to brain and cerebrospinal fluid (CSF). PrP concentration varies dramatically between different brain regions in mice, cynomolgus macaques, and humans. PrP expression does not appear to contribute to the known risk factors of age, sex, or common PRNP genetic variants. CSF PrP is lowered in the presence of rare pathogenic PRNP variants, with heterozygous carriers of P102L displaying 55% and of D178N just 31% the CSF PrP concentration of mutation-negative controls. In rodents, pharmacologic reduction of brain Prnp RNA is reflected in brain parenchyma PrP, and in turn in CSF PrP, validating CSF as a sampling compartment for the effect of PrP-lowering therapy. Our findings support the use of CSF PrP as a pharmacodynamic biomarker for PrP-lowering drugs, and suggest that relative reduction from individual baseline CSF PrP concentration may be an appropriate marker for target engagement.