bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular epidemiology and characteristics of respiratory syncytial virus among hospitalized children in Guangzhou, China
Authors: Umar Sajid , Yang Rongyuan , Wang Xinye , Liu Yuntao , Ke Peifeng , Qin Sheng 
Published: November 2023

Abstract
Background
Human respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and hospitalization, especially in children. Highly mutagenic nature and antigenic diversity enable the RSV to successfully survive in human population. We conducted a molecular epidemiological study during 2017–2021 to investigate the prevalence and genetic characteristics of RSV.

Methods
A total of 6499 nasopharyngeal (NP) swabs were collected from hospitalized children at Department of Pediatrics, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China. All NP swab specimens were preliminary screened for common respiratory viruses and then tested for RSV using specific PCR assays. Partial G genes of RSV were amplified for phylogenetic analysis and genetic characterization.

Results
The overall detection rate for common respiratory viruses was 16.12% (1048/6499). Among those, 405 specimens (6.20%, 405/6499) were found positive for RSV. The monthly distribution of RSV and other respiratory viruses was variable, and the highest incidence was recorded in Autumn and Winter. Based on the sequencing of hypervariable region of G gene, 93 RSV sequences were sub-grouped into RSV-A (56, 60.2%) and RSV-B (37, 39.8%). There was no coinfection of RSV-A and RSV-B in the tested samples. Phylogenetic analysis revealed that RSV-A and RSV-B strains belonged to ON1 and BA9 genotypes respectively, indicating predominance of these genotypes in Guangzhou. Several substitutions were observed which may likely change the antigenicity and pathogenicity of RSV. Multiple glycosylation sites were noticed, demonstrating high selection pressure on these genotypes.

Conclusion
This study illustrated useful information about epidemiology, genetic characteristics, and circulating genotypes of RSV in Guangzhou China. Regular monitoring of the circulating strains of RSV in different parts of China could assist in the development of more effective vaccines and preventive measures.
Local perfusion of capillaries reveals disrupted beta-amyloid homeostasis at the blood-brain barrier in Tg2576 murine Alzheimer’s model
Authors: Hanafy Amira Sayed , Lamprecht Alf , Dietrich Dirk 
Published: November 2023

Abstract
Background
Parenchymal accumulation of beta-amyloid (Aβ) characterizes Alzheimer’s disease (AD). Aβ homeostasis is maintained by two ATP-binding cassette (ABC) transporters (ABCC1 and ABCB1) mediating efflux, and the receptor for advanced glycation end products (RAGE) mediating influx across the blood-brain barrier (BBB). Altered transporter levels and disruption of tight junctions (TJ) were linked to AD. However, Aβ transport and the activity of ABCC1, ABCB1 and RAGE as well as the functionality of TJ in AD are unclear.

Methods
ISMICAP, a BBB model involving microperfusion of capillaries, was used to assess BBB properties in acute cortical brain slices from Tg2576 mice compared to wild-type (WT) controls using two-photon microscopy. TJ integrity was tested by vascularly perfusing biocytin-tetramethylrhodamine (TMR) and quantifying its extravascular diffusion as well as the diffusion of FM1-43 from luminal to abluminal membranes of endothelial cells (ECs). To assess ABCC1 and ABCB1 activity, calcein-AM was perfused, which is converted to fluorescent calcein in ECs and gets actively extruded by both transporters. To probe which transporter is involved, probenecid or Elacridar were applied, individually or combined, to block ABCC1 and ABCB1, respectively. To assess RAGE activity, the binding of 5-FAM-tagged Aβ by ECs was quantified with or without applying FPS-ZM1, a RAGE antagonist.

Results
In Tg2576 mouse brain, extravascular TMR was 1.8-fold that in WT mice, indicating increased paracellular leakage. FM1-43 staining of abluminal membranes in Tg2576 capillaries was 1.7-fold that in WT mice, indicating reduced TJ integrity in AD. While calcein was undetectable in WT mice, its accumulation was significant in Tg2576 mice, suggesting lower calcein extrusion in AD. Incubation with probenecid or Elacridar in WT mice resulted in a marked calcein accumulation, yet probenecid alone had no effect in Tg2576 mice, implying the absence of probenecid-sensitive ABC transporters. In WT mice, Aβ accumulated along the luminal membranes, which was undetectable after applying FPS-ZM1. In contrast, marginal Aβ fluorescence was observed in Tg2576 vessels, and FPS-ZM1 was without effect, suggesting reduced RAGE binding activity.

Conclusions
Disrupted TJ integrity, reduced ABCC1 functionality and decreased RAGE binding were identified as BBB alterations in Tg2576 mice, with the latter finding challenging the current concepts. Our results suggest to manage AD by including modulation of TJ proteins and Aβ-RAGE binding.
A rapid and sensitive, multiplex, whole mount RNA fluorescence in situ hybridization and immunohistochemistry protocol
Authors: Huang Tian , Guillotin Bruno , Rahni Ramin , Birnbaum Kenneth D. , Wagner Doris 
Published: November 2023

Abstract
Background
In the past few years, there has been an explosion in single-cell transcriptomics datasets, yet in vivo confirmation of these datasets is hampered in plants due to lack of robust validation methods. Likewise, modeling of plant development is hampered by paucity of spatial gene expression data. RNA fluorescence in situ hybridization (FISH) enables investigation of gene expression in the context of tissue type. Despite development of FISH methods for plants, easy and reliable whole mount FISH protocols have not yet been reported.

Results
We adapt a 3-day whole mount RNA-FISH method for plant species based on a combination of prior protocols that employs hybridization chain reaction (HCR), which amplifies the probe signal in an antibody-free manner. Our whole mount HCR RNA-FISH method shows expected spatial signals with low background for gene transcripts with known spatial expression patterns in Arabidopsis inflorescences and monocot roots. It allows simultaneous detection of three transcripts in 3D. We also show that HCR RNA-FISH can be combined with endogenous fluorescent protein detection and with our improved immunohistochemistry (IHC) protocol.

Conclusions
The whole mount HCR RNA-FISH and IHC methods allow easy investigation of 3D spatial gene expression patterns in entire plant tissues.
Sharp unifying generalizations of Opial’s inequality
Authors: Klaassen Chris A. J. 
Published: November 2023

AbstractOpial’s inequality and its ramifications play an important role in the theory of differential and difference equations. A sharp unifying generalization of Opial’s inequality is presented that contains both its continuous and discrete versions. This generalization, based on distribution functions, is extended to the case of derivatives of arbitrary order. This extension optimizes and improves the constant given in the literature. The special case of derivatives of second order is studied in more detail. Two closely related Opial inequalities with a weight function are presented as well. The associated Wirtinger inequality is studied briefly.
The fate of intracoelomic acoustic transmitters in Atlantic salmon (Salmo salar) post-smolts and wider considerations for causal factors driving tag retention and mortality in fishes
Authors: Lawrence M. J. , Wilson B. M. , Reid G. K. , Hawthorn C. , English G. , Black M. , Leadbeater S. , McKindsey C. W. , Trudel M. 
Published: November 2023

AbstractAcoustic telemetry is a widely used method in assessing behavioural dynamics in fishes. Telemetry transmitters (tags) are often surgically implanted in the coelom of the animal with limited in situ testing and sometimes only assuming that they have minimal rates of post-release tag shedding and mortality. However, fish are capable of expelling tags and mortalities do occur following release, with the mechanism (s) underlying these effects not well-understood. The purpose of this research was to address causal factors underlying tag expulsion and tagging mortality in fishes. We conducted an empirical assessment of tag retention and post-surgical mortality rates in post-smolt Atlantic salmon (Salmo salar) fitted with dummy (non-transmitting) acoustic tags over a 92-day monitoring period. This was complimented with a meta-analysis of factors affecting tag retention and post-surgical mortality rates in the wider literature. Post-smolt salmon had high rates of tag expulsion (54.8%), impaired growth, and a foreign body response evident but exhibited low rates of mortality following tag implantation (≤ 5.1%). The meta-analysis showed that mortality was generally low across all studies (12.4%) and was largely unaffected by model cofactors. Tag retention rates were high among the studies investigated here (86.7%) and had a weak negative relationship with tag:body mass ratios. Our results suggest that while mortality is often low among tagging studies, including this one, caution must be exercised in assessing stationary tag location data as they may represent an expelled tag rather than a mortality event. Our results also indicate that tag dimensions are not nearly as important as the tag:body mass ratio.
The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials
Authors: Yousefi Mohsen , Fateh Sahand Tehrani , Nikbaf-Shandiz Mahlagha , Gholami Fatemeh , Rastgoo Samira , Bagher Reza , Khadem Alireza , Shiraseb Farideh , Asbaghi Omid 
Published: November 2023

AbstractPurposeDyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles.MethodsThe random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI).ResultsOur meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = − 13.43 mg/dl, 95% CI: − 19.20, − 7.67;P < 0.001) and TC (WMD = − 1.93 mg/dl, 95% CI: − 3.71, − 0.15;P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50,P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = − 18.00,P = 0.032), with a decline observed after 50 weeks of treatment.ConclusionThe findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.
From power to architecture: an analysis on the identity transformation of Tagaytay people’s park in the sky through edifice complex and democratization theory
Authors: Rivera-Lutap Jocelyn A. , Castillo John Benedict A. 
Published: November 2023

AbstractThe study of architecture in relation to the principles of political power places a different perspective in understanding how the built environs with heritage value were shaped in time and are being constantly shaped at the present. Its relevance cannot be understated, as in spite of its actuality, it is a side of the field that may still be considered sensitive to some. Architecture is never neutral. It corresponds to the patron’s ideals, intentions, and ideological orientation, communicated by the designer through his technical knowledge in artistic articulation of forms. In a larger scale, architectural identity can therefore be affected by those possessing power and can serve as tactile channel in redirecting society. This study presents the case of People’s Park in the Sky in the Philippines, a colossal brutalist mansion, originally named Palace in the Sky, situated at Mt. Sungay peak in Tagaytay City. Commissioned in 1981 by Imelda Marcos, the wife of authoritarian head Ferdinand Marcos, the palace was not completed and eventually transformed into a public urban park. Supported by the concept of Edifice Complex and Democratization theory, methodical assessment of the political links of the said architecture was executed in two parts: examination of historical accounts and first-hand site investigations. The findings of the analysis revealed that there is a present architectural crisis in the park, emerging from its long-time neglect since the 1986 transition years, and if not taken proper institutional action, its genuine identity and legacy could be forgotten and eventually lost in the near future.
Assessing hydroclimate response to land use/cover change using coupled atmospheric-hydrological models
Authors: Chen Chia-Jeng , Chi Min-Hung , Ye Jing-Ru 
Published: November 2023

AbstractModeling techniques provide a straightforward means to dissect regional hydroclimate in response to changes in land use conditions. This study uses the Weather Research and Forecasting Model (WRF) and WRF-Hydrological modeling system (WRF-Hydro), driven by survey-based land use data in 1995 and 2015, to assess how central Taiwan’s hydroclimate responds to land use/cover change. We first run WRF-Hydro with observed rainfall as meteorological forcing to ensure reasonable runoff simulation, and then select ten cases under weak synoptic forcings in July and August in recent decades for the simulation under two land use conditions. The WRF-only simulation (i.e., uncoupled with WRF-Hydro) can reveal significant changes in heat fluxes and surface variables due to land use/cover change, including sensible and latent heat fluxes, 2-m temperature and specific humidity, and precipitation over the hotspots of urbanization or downwind areas. Coupling WRF with WRF-Hydro discloses varied runoff characteristics subject to land use/cover change: a general increase in average peak flow (~ 4.3%) and total runoff volume (~ 5.0%) accompanied by less definite time-to-peak flow, indicating a synergistic but sometimes competitive relationship between the pure hydrologic/hydraulic perspective and land–atmosphere interactions. By taking the difference between the uncoupled and coupled simulations, we verify that surface pressure, precipitation, and soil moisture are more sensitive to a better depiction of terrestrial hydrological processes; differences in the spatial variances of soil moisture can be as high as two orders of magnitude. Our findings highlight the importance of more comprehensive model physics in regional hydroclimate modeling.
Cognitive–behavioural therapy as a comprehensive treatment for personality disorders
Authors: Carreiras Diogo , Castilho Paula , Rijo Daniel , Salvador Maria do Céu , Carona Carlos 
Published: November 2023

SUMMARYPersonality disorders are a group of psychological disorders characterised by a developmental nature, long-lasting impairment and emotional suffering. Personality disorders have an estimated prevalence rate of approximately 8% in community settings, but in in-patient settings the rate might be as high as 76%. Cognitive–behavioural therapies (CBTs) include psychotherapies that emphasise the identification and modification of maladaptive thought patterns and behaviours that contribute to the maintenance of psychological disorders. CBTs have demonstrated their effectiveness in treating various types of personality disorder. This article focuses on the nature of personality disorders and their categorial and dimensional assessment and neurobiology. We present three influential CBT models used in personality disorders: schema therapy, cognitive interpersonal therapy and dialectical behaviour therapy. For each one, we outline the rationale, intervention strategies and therapeutic techniques, with practical examples and summary tables to illustrate their application.
Trends of Utilization of Systemic Therapies for Metastatic Renal Cell Carcinoma in the Canadian Health Care System
Authors: Cardenas Luisa M. , Ghosh Sunita , Finelli Antonio , Wood Lori , Kollmannsberger Christian , Basappa Naveen , Graham Jeffrey , Heng Daniel , Bjarnason Georg , Soulières Denis , Bossé Dominick , Castonguay Vincent , Saleh Ramy , Tanguay Simon , Bhindi Bimal , Breau Rodney H. , Pouliot Frederic , Lalani Aly-Khan A. 
Published: November 2023

PURPOSE Standard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011. METHODS We included patients with mRCC enrolled in the Canadian Kidney Cancer Information System, a prospective cohort of patients from 14 Canadian academic centers, who received systemic therapy from January 1, 2011, to December 31, 2021. Patients were stratified by treatment era (cohort 1: 2011-2015, cohort 2: 2016-2021). Stacked bar charts were used to present treatment proportions; Sankey diagrams were used to show the evolution of treatment sequencing between the two cohorts. RESULTS Four thousand one hundred seven patients were diagnosed with mRCC, of whom 2,752 (67%) received systemic therapy. Among these patients, mean age was 64 years, 74% were male, 75% had clear cell histology, and International Metastatic RCC Database Consortium risk classification was favorable, intermediate, and poor in 16%, 56%, and 28%, respectively. Utilization of immune checkpoint inhibition (ICI)–based treatments has increased in Canada and reflects global and local patterns of approval and adoption. The use of therapies after doublet ICI has mostly shifted toward vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) that were previously used in first line with subsequent treatments reflecting approved and available agents after previous VEGF-TKI. Clinical trial participation among patients who received systemic therapy was 18% in first, 21% in second, and 24% in third line. CONCLUSION In Canada's publicly funded health care system, availability of standard mRCC therapies broadly reflects access from government-funded clinical trials and compassionate access program sources. In an evolving therapeutic landscape, ongoing advocacy is required to continue to facilitate patient access to efficacious therapies.
DNA Mutational Profiling in Patients With Colorectal Cancer Treated With Standard of Care Reveals Differences in Outcome and Racial Distribution of Mutations
Authors: Innocenti Federico , Mu Wancen , Qu Xueping , Ou Fang-Shu , Kabbarah Omar , Blanke Charles David , Venook Alan P. , Lenz Heinz-Josef , Rashid Naim U. 
Published: November 2023

PURPOSE CALGB (Alliance)/SWOG 80405 was a randomized phase III trial that in first-line patients with metastatic colorectal cancer (mCRC) treated with bevacizumab or cetuximab with chemotherapy. We aimed to discover novel mutated genes associated with prognosis and differential response to therapy with the biologics. METHODS Primary tumor DNA from 548 patients was sequenced using FoundationOne. The effect of mutated genes and mutations on overall survival (OS) was tested adjusting for microsatellite instability status, BRAF V600E, all RAS mutations, arm, sex, and age. RESULTS The median number (lower-upper quartile) of mutated genes was 5 (3-7), 5 (3-6) in microsatellite stable and 12.5 (4.5-32) in microsatellite instability-high tumors. Mutated KRAS and APC were more frequent in Black (53% and 85%) than White (27% and 65%, respectively) patients while BRAF V600E was less frequent in Black (5%) than White (14%) patients. The median OS in patients with BRAF non-V600E (2.2% of patients) was 31.9 months (95% CI, 15.1 to not applicable [NA]) similar to that of BRAF wild-type (WT) patients (31.2 months [95% CI, 29.0 to 33.9]). Mutated LRP1B (10.7% of patients) was associated with improved OS compared with WT LRP1B (hazard ratio, 0.57 [95% CI, 0.40 to 0.80]). RNF43 (5.6% of patients) interacted with treatment arms as, in the cetuximab arm, patients with mutated RNF43 had a median OS of 11.5 (95% CI, 10.8 to NA) months compared with 30.1 (95% CI, 24.9 to 35.3) months in patients with WT RNF43, whereas in the bevacizumab arm, patients with mutated RNF43 had a median OS of 25.0 (95% CI, 14.2 to NA) months compared with 31.3 (95% CI, 29.0 to 34.3) months in patients with WT RNF43. CONCLUSION These results can provide new tools to predict patient outcome and improve therapeutic decisions and trial participation in patient minorities. The molecular alterations identified in this study may direct biomarker-driven studies.
Homologous Recombination Deficiency Landscape of Breast Cancers and Real-World Effectiveness of Poly ADP-Ribose Polymerase Inhibitors in Patients With Somatic BRCA1/2, Germline PALB2, or Homologous Recombination Deficiency Signature
Authors: Batalini Felipe , Madison Russell W. , Sokol Ethan S. , Jin Dexter X. , Chen Kuei-Ting , Decker Brennan , Pavlick Dean C. , Frampton Garrett M. , Wulf Gerburg M. , Garber Judy E. , Oxnard Geoffrey , Schrock Alexa B. , Tung Nadine M. 
Published: November 2023

PURPOSE Poly ADP-ribose polymerase inhibitors (PARPi) are approved for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (mBC) and germline pathogenic/likely pathogenic variant (hereafter mutation) in the BRCA1/ 2 genes (g BRCA); however, clinical benefit has also been demonstrated in mBC with somatic BRCA1/ 2 mutations (s BRCA) or germline PALB2 mutations (g PALB2). This study aims to describe the genomic landscape of homologous recombination repair (HRR) gene alterations in mBC and assess PARPi treatment outcomes for patients with g BRCA compared with other HRR genes and by status of a novel homologous recombination deficiency signature (HRDsig). METHODS A real-world (RW) clinico-genomic database (CGDB) of comprehensive genomic profiling (CGP) linked to deidentified, electronic health record–derived clinical data was used. CGP was analyzed for HRR genes and HRDsig. The CGDB enabled cohort characterization and outcomes analyses of 177 patients exposed to PARPi. RW progression-free survival (rwPFS) and RW overall survival (rwOS) were compared. RESULTS Of 28,920 patients with mBC, g BRCA was detected in 3.4%, whereas the population with any BRCA alteration or g PALB2 increased to 9.5%. HRDsig+ represented 21% of patients with mBC. BRCA and g PALB2 had higher levels of biallelic loss and HRDsig+ than other HRR alterations. Outcomes on PARPi were assessed for 177 patients, and g BRCA and s BRCA/ gPALB2 cohorts were similar: g BRCA versus s BRCA/g PALB2 rwPFS was 6.3 versus 5.4 months (hazard ratio [HR], 1.37 [0.77-2.43]); rwOS was 16.2 versus 21.2 months (HR, 1.45 [0.74-2.86]). Additionally, patients with HRDsig+ versus HRDsig– had longer rwPFS (6.3 v 2.8 months; HR, 0.62 [0.42-0.92]) and numerically longer rwOS (17.8 v 13.0 months; HR, 0.72 [0.46-1.14]). CONCLUSION Patients with s BRCA and g PALB2 derive similar benefit from PARPi as those with g BRCA alterations. In combination, HRDsig+, s BRCA, and g PALB2 represent an additional 19% of mBC that can potentially benefit from PARPi. Randomized trials exploring a more inclusive biomarker such as HRDsig are warranted.