bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread geographic distribution of Aedes aegypti (Diptera: Culicidae) kdr variants in Panama
Authors: García Joel , Chong Mabelle , Rojas Ambar L , McMillan W Owen , Bennett Kelly L , Lenhart Audrey E , Chaves Luis F , Loaiza Jose R 
Published: September 2024

Abstract
We searched for evidence of knockdown resistance (kdr) mutations in the voltage-gated sodium channel gene of Aedes aegypti (Linnaeus) (Diptera: Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) mosquitoes from Panama. Conventional PCR was performed on 469 Ae. aegypti and 349 Ae. albopictus. We did not discover kdr mutations in Ae. albopictus, but 2 nonsynonymous kdr mutations, V1016I (found in 101 mosquitoes) and F1534C (found in 29 of the mosquitoes with the V1016I), were detected in Ae. aegypti. These kdr mutations were present in all specimens that were successfully sequenced for both IIS5-S6 and IIIS6 regions, which included samples collected from 8 of the 10 provinces of Panama. No other kdr mutations were found in Ae. aegypti, including V1016G, which has already been reported in Panama. Findings suggest that the V1016I-F1534C variant is prevalent in Panama, which might be related to the introduction and passive movement of mosquitoes as part of the used-tire trade. However, we cannot rule out the possibility that selection on de novo replacement of kdr mutations also partially explains the widespread distribution pattern of these mutations. These 2 ecological and evolutionary processes are not mutually exclusive, though, as they can occur in tandem. Research in Panama needs to calculate the genotypic and allelic frequencies of kdr alleles in local Ae. aegypti populations and to test whether some combinations confer phenotypic resistance or not. Finally, future studies will have to track the introduction and spreading of new kdr mutations in both Aedes species.
Forest encroachment in Eastern European forest-steppes at a decadal time scale
Authors: Erdős László , Ónodi Gábor , Tölgyesi Csaba , Kröel-Dulay György , Bátori Zoltán , Aradi Eszter , Török Péter , Ho Khanh Vu , Puspitasari Indri , Körmöczi László 
Published: September 2024

Abstract
In the Eurasian forest-steppe, with increasing aridity, the balance between naturally co-existing forest and grassland patches is expected to shift towards grassland dominance in the long run, although feedback mechanisms and changes in land-use may alter this process. In this study, we compared old and recent aerial photographs of Hungarian forest-steppes to find out whether and how the forest proportion and the number of forest patches change at the decadal time scale. The percentage area covered by forest significantly increased in all study sites. The observed forest encroachment may be a legacy from earlier land-use: due to ceased or reduced grazing pressure, forests are invading grasslands until the potential forest cover allowed by climate and soil is reached. The number of forest patches significantly increased at one site (Fülöpháza), while it decreased at two sites (Bugac and Orgovány) and showed no significant change at the fourth site (Tázlár). This indicates that forest encroachment can happen at least in two different ways: through the emergence of new forest patches in the grassland, and through the extension and coalescence of already existing forest patches. Though the present work revealed increasing tree cover at a decadal time scale, the dynamic process should be monitored in the future to see how the vegetation reacts to further aridification. This could help devise a conservation strategy, as the woody/non-woody balance has a profound influence on basic ecosystem properties.
Homoharringtonine promotes non-small-cell lung cancer cell death via modulating HIF-1α/ERβ/E2F1 feedforward loop
Authors: Su Qi , Ren Jiayan , Chen Kun , Leong Sze Wei , Han Xu , Li Na , Wu Jianlin , Zhang Yanmin 
Published: September 2024

Abstract

Objectives
Hypoxia conditions promote the adaptation and progression of non-small-cell lung cancer (NSCLC) via hypoxia-inducible factors (HIF). HIF-1α may regulate estrogen receptor β (ERβ) and promote the progression of NSCLC. The phytochemical homoharringtonine (HHT) exerts strong inhibitory potency on NSCLC, with molecular mechanism under hypoxia being elusive.

Methods
The effects of HHT on NSCLC growth were determined by cell viability assay, colony formation, flow cytometry, and H460 xenograft models. Western blotting, molecular docking program, site-directed mutagenesis assay, immunohistochemical assay, and immunofluorescence assay were performed to explore the underlying mechanisms of HHT-induced growth inhibition in NSCLC.

Key findings
HIF-1α/ERβ signaling-related E2F1 is highly expressed and contributes to unfavorable survival and tumor growth. The findings in hypoxic cells, HIF-1α overexpressing cells, as well as ERβ- or E2F1-overexpressed and knockdown cells suggest that the HIF-1α/ERβ/E2F1 feedforward loop promotes NSCLC cell growth. HHT suppresses HIF-1α/ERβ/E2F1 signaling via the ubiquitin-proteasome pathway, which is dependent on the inhibition of the protein expression of HIF-1α and ERβ. Molecular docking and site-directed mutagenesis revealed that HHT binds to the GLU305 site of ERβ. HHT inhibits cell proliferation and colony formation and promotes apoptosis in both NSCLC cells and xenograft models.

Conclusion
The formation of the HIF-1α/ERβ/E2F1 feedforward loop promotes NSCLC growth and reveals a novel molecular mechanism by which HHT induces cell death in NSCLC.
Administrative border effects in COVID-19 related mortality
Authors: Berta Paolo , Bratti Massimiliano , Fiorio Carlo V , Pisoni Enrico , Verzillo Stefano 
Published: September 2024

Abstract
Lombardy, the first region in Italy to be hit by COVID-19 and one of the first in Western countries, was in the spotlight during the first wave of the pandemic in 2020 due to its high mortality rates. Simple regional comparisons are, however, hampered by potentially unobservable variables affecting mortality, such as the virus spread. To address this ‘unobserved heterogeneity’ concern, we adopt a Difference in Geographic Regression Discontinuity Design (DiD-GRDD), which compares 2020 vs. 2017–2019 excess mortality in Lombardy’s municipalities close to the administrative borders with neighbouring municipalities in other regions. Our study documents a one to two percentage point higher excess mortality in Lombardy limited to the oldest age group (81+). An exploratory mediation analysis points to the management of nursing homes during the pandemic as a possible critical factor explaining higher mortality in Lombardy.
Nonparametric estimation via partial derivatives
Authors: Dai Xiaowu 
Published: September 2024

Abstract
Traditional nonparametric estimation methods often lead to a slow convergence rate in large dimensions and require unrealistically large dataset sizes for reliable conclusions. We develop an approach based on partial derivatives, either observed or estimated, to effectively estimate the function at near-parametric convergence rates. This novel approach and computational algorithm could lead to methods useful to practitioners in many areas of science and engineering. Our theoretical results reveal behaviour universal to this class of nonparametric estimation problems. We explore a general setting involving tensor product spaces and build upon the smoothing spline analysis of variance framework. For d-dimensional models under full interaction, the optimal rates with gradient information on p covariates are identical to those for the (d−p)-interaction models without gradients and, therefore, the models are immune to the curse of interaction. For additive models, the optimal rates using gradient information are n, thus achieving the parametric rate. We demonstrate aspects of the theoretical results through synthetic and real data applications.
Analyzing Potential Non-Ignorable Selection Bias in an Off-Wave Mail Survey Implemented in a Long-Standing Panel Study
Authors: Schroeder Heather M , West Brady T 
Published: September 2024

Abstract
Typical design-based methods for weighting probability samples rely on several assumptions, including the random selection of sampled units according to known probabilities of selection and ignorable unit nonresponse. If any of these assumptions are not met, weighting methods that account for the probabilities of selection, nonresponse, and calibration may not fully account for the potential selection bias in a given sample, which could produce misleading population estimates. This analysis investigates possible selection bias in the 2019 Health Survey Mailer (HSM), a sub-study of the longitudinal Health and Retirement Study (HRS). The primary HRS data collection has occurred in “even” years since 1992, but additional survey data collections take place in the “off-wave” odd years via mailed invitations sent to selected participants. While the HSM achieved a high response rate (83 percent), the assumption of ignorable probability-based selection of HRS panel members may not hold due to the eligibility criteria that were imposed. To investigate this possible non-ignorable selection bias, our analysis utilizes a novel analysis method for estimating measures of unadjusted bias for proportions (MUBP), introduced by Andridge et al. in 2019. This method incorporates aggregate information from the larger HRS target population, including means, variances, and covariances for key covariates related to the HSM variables, to inform estimates of proportions. We explore potential non-ignorable selection bias by comparing proportions calculated from the HSM under three conditions: ignoring HRS weights, weighting based on the usual design-based approach for HRS “off-wave” mail surveys, and using the MUBP adjustment. We find examples of differences between the weighted and MUBP-adjusted estimates in four out of ten outcomes we analyzed. However, these differences are modest, and while this result gives some evidence of non-ignorable selection bias, typical design-based weighting methods are sufficient for correcting for it and their use is appropriate in this case.
HIV-1 usurps mixed-charge domain-dependent CPSF6 phase separation for higher-order capsid binding, nuclear entry and viral DNA integration
Authors: Jang Sooin , Bedwell Gregory J , Singh Satya P , Yu Hyun Jae , Arnarson Bjarki , Singh Parmit K , Radhakrishnan Rajalingam , Douglas AidanDarian W , Ingram Zachary M , Freniere Christian , Akkermans Onno , Sarafianos Stefan G , Ambrose Zandrea , Xiong Yong , Anekal Praju V , Montero Llopis Paula , KewalRamani Vineet N , Francis Ashwanth C , Engelman Alan N 
Published: September 2024

Abstract
HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with nuclear speckles (NSs). Although CPSF6 displays liquid-liquid phase separation (LLPS) activity in vitro, the contributions of its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) with capsid binding FG motif and C-terminal mixed-charge domain (MCD), to LLPS activity and to HIV-1 infection remain unclear. Herein, we determined that the PrLD and MCD both contribute to CPSF6 LLPS activity in vitro. Akin to FG mutant CPSF6, infection of cells expressing MCD-deleted CPSF6 uncharacteristically arrested at the nuclear rim. While heterologous MCDs effectively substituted for CPSF6 MCD function during HIV-1 infection, Arg-Ser domains from related SR proteins were largely ineffective. While MCD-deleted and wildtype CPSF6 proteins displayed similar capsid binding affinities, the MCD imparted LLPS-dependent higher-order binding and co-aggregation with capsids in vitro and in cellulo. NS depletion reduced CPSF6 puncta formation without significantly affecting integration into NS-proximal chromatin, and appending the MCD onto a heterologous capsid binding protein partially restored virus nuclear penetration and integration targeting in CPSF6 knockout cells. We conclude that MCD-dependent CPSF6 condensation with capsids underlies post-nuclear incursion for viral DNA integration and HIV-1 pathogenesis.
A single rare σ70 variant establishes a unique gene expression pattern in the E. coli pathobiont LF82
Authors: Arroyo-Mendoza Melissa , Proctor Alexandra , Correa-Medina Abraham , DeWolf Sarah , Brand Meghan Wymore , Rosas Virginia , Lorenzi Hernan , Wannemuehler Michael J , Phillips Gregory J , Hinton Deborah M 
Published: September 2024

Abstract
LF82, an adherent-invasive Escherichia coli (AIEC) pathobiont, is associated with Crohn's disease, an inflammatory bowel disease of unknown etiology. Although AIEC phenotypes differ from those of ‘commensal’ or pathogenic E. coli, work has failed to identify genetic features accounting for these differences. We have investigated a natural, but rare, single nucleotide polymorphism (SNP) in LF82 present within the highly conserved rpoD gene, encoding σ70 [primary sigma factor, RNA polymerase (RNAP)]. We demonstrate that σ70 D445V results in transcriptomic and phenotypic changes consistent with LF82 phenotypes, including increased antibiotic resistance and biofilm formation and increased capacity for methionine biosynthesis. RNA-seq analyses comparing σ70 V445 versus σ70 D445 identified 24 genes upregulated by σ70 V445 in both LF82 and the laboratory E. coli K-12 strain MG1655. Using in vitro transcription, we demonstrate that σ70 D445V directly increases transcription from promoters for several of the up-regulated genes and that the presence of a 16 bp spacer and -14 G:C is associated with this increase. The position of D445V within RNAP suggests that it could affect RNAP/spacer interaction. Our work represents the first identification of a distinguishing SNP for this pathobiont and suggests an underrecognized mechanism by which pathobionts and strain variants can emerge.
Biology of calcium homeostasis regulation in intestine and kidney
Authors: Deluque Amanda Lima , Dimke Henrik , Alexander R Todd 
Published: September 2024

ABSTRACT
Calcium (Ca2+) is an essential divalent cation involved in many bodily functions including bone composition, cell growth and division, blood clotting, and muscle contraction. The bone, intestine and kidneys are important for the maintenance of Ca2+ homeostasis. Ninety-nine percent of body Ca2+ is stored in the skeleton as hydroxyapatite. The small, and to a lesser extent the large intestine absorbs Ca2+ from the diet. Once in the circulation, Ca2+ is filtered by the glomerulus and the majority, &gt;95%, is reabsorbed along the nephron. The remainder is excreted in the urine. Two general (re)absorptive pathways contribute to the vectorial transport of Ca2+ across renal and intestinal epithelia: (i) a paracellular pathway, which is reliant on claudins in the tight junction of epithelium and the electrochemical gradient, and (ii) a transcellular pathway, which requires different influx, intracellular buffering/shuttling and basolateral efflux mechanisms, to actively transport Ca2+ across the epithelial cell. Blood Ca2+ levels are maintained by hormones including parathyroid hormone, 1,25-dihydroxyvitamin D3 and fibroblast growth factor 23, and through effects of Ca2+-sensing receptor (CaSR) signaling. Disruption of Ca2+ homeostasis can result in altered blood Ca2+ levels and/or hypercalciuria, the latter is a phenomenon closely linked to the formation of kidney stones. Genetic alterations affecting renal Ca2+ handling can cause hypercalciuria, an area of expanding investigation. This review explores the molecular mechanisms governing Ca2+ homeostasis by the intestine and kidneys and discusses clinical aspects of genetic disorders associated with Ca2+-based kidney stone disease.
Approach Bias and Tobacco Craving as Mechanisms of the Effect of Approach Bias Retraining on Smoking Cessation
Authors: Garey Lorra , Rinck Mike , Rosenfield David , Nizio Pamella , Beevers Christopher G , Brown Richard A , Conroy Busch Haley E , Dutcher Christina D , McSpadden Bryan , Zvolensky Michael J , Smits Jasper A J 
Published: September 2024

Abstract

Introduction
Approach bias, the automatic tendency to advance toward, rather than move away from appetitive cues, has been associated with greater tobacco cravings, dependence, and likelihood of smoking relapse. Approach bias retraining (ABR) has emerged as one way to reduce approach bias and promote avoidance of smoking cues. Yet, additional research is needed to identify the mechanisms that may help explain the effect of ABR on smoking cessation.

Aims and Methods
The current study uses data collected as part of a randomized controlled trial to test two unique mechanisms of action ([1] approach bias and [2] tobacco craving) for the efficacy of standard smoking cessation treatment (ST) augmented by ABR on smoking abstinence. Participants were 96 adult daily smokers (Mage = 43.1, SD = 10.7) motivated to quit smoking.

Results
Results showed that lower approach bias and lower cravings at a treatment session were significantly related to the next session smoking abstinence (p’s &lt; .018). Furthermore, deviations in approach bias partially mediated the effect of ABR on smoking abstinence (ab = −12.17, 95% CI: [−29.67, −0.53]). However, deviations in tobacco craving did not mediate this relation (ab = .40, 95% CI: [−0.27, 1.34]).

Conclusions
The current findings add to the extant literature by identifying approach bias as a mechanism of action of the effect of ABR on smoking abstinence during smoking cessation treatment.

Implications
The current study adds to the best of our knowledge on the effectiveness of ABR as a part of smoking cessation treatment. Results indicate that reductions in approach bias partially mediate the effect of ABR on smoking abstinence. These findings are consistent with previous research on alcohol-dependent adults and underline the potential of ABR to reduce approach bias and promote smoking cessation among smokers. Such findings could inform the development of future research exploring more targeted and effective smoking cessation interventions, ultimately improving outcomes for individuals attempting to quit smoking.
Bauxite mine and alumina refinery workers: mortality and cancer risk
Authors: Kinsman N , Del Monaco A , Dimitriadis C , Xie S , Benke G , Sim M R , Walker-Bone K 
Published: September 2024

Abstract

Background
Aluminium industry workers are at risk of long-term health consequences.

Aims
To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers.

Methods
A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment.

Results
Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11–4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60–3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06–1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66–6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36–3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02–3.65]. Overall cancer incidence was otherwise similar to the general Australian population.

Conclusions
Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation.
Protective Effects of 23-Valent Pneumococcal Polysaccharide Vaccination Against Mortality: The VENUS Study
Authors: Murata Fumiko , Maeda Megumi , Fukuda Haruhisa 
Published: September 2024

Abstract
This retrospective matched cohort study investigated the protective effects of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against pneumonia mortality and all-cause mortality in Japanese adults aged ≥65 years. We analyzed claims data, vaccination records, and death certificate records between October 2016 and December 2019 from 55 509 PPSV23-vaccinated individuals and 55 509 unvaccinated individuals. Cox proportional hazards analyses were performed to calculate the adjusted hazard ratios (HRs) of PPSV23 vaccination for mortality. The results showed that PPSV23 vaccination was significantly associated with a reduction in all-cause mortality (adjusted HR, 0.52; P &lt; .001) but not pneumonia mortality (adjusted HR, 0.70; P = .374).
Therapeutic and restorative landscapes: including preferences for bluespaces in planning urban infrastructure
Authors: Eager Kate , McManus Phil 
Published: September 2024

Abstract
The impact of urbanization on our mental health and well-being calls for urban design and infrastructure development to include accessibility to restorative spaces and therapeutic landscapes, like green and blue spaces, that can potentially improve our wellbeing. Research in the suburb of Glebe in Sydney (Australia) aimed to identify the preferences for, and use of, different types of green and blue spaces. Semi-structured interviews involving photo elicitation (12 participants) and an online survey (53 respondents) showed that bluespaces and the combination of blue and green spaces, are preferred over built and green spaces. Bluespace preferences are explained by four key themes: (i) ineffable emotions and the ‘affect’ of space; (ii) childhood memories; (iii) the separation of human and nature through language and (iv) environmental and social sustainability. The design of bluespace to improve the quality and access to urban bluespaces, such as lakes, rivers, creeks and canals, involves the provision of adequate and appropriate infrastructure. Restorative spaces and therapeutic landscapes thereby become more accessible and potentially can improve health and wellbeing for more city residents.
Unintended consequences of a night float system in Paediatric Residency
Authors: Al Maawali Ali , Puran Allan , Talarico Susanna , Bismilla Zia 
Published: September 2024

ABSTRACT

Objectives
Many residency programs implement ‘night float’ (NF) systems as alternatives to a traditional 24-h call model in an attempt to comply with duty-hour regulations. Research evaluating NF systems has focused primarily on the perspective of the resident with respect to fatigue and quality of life. Understanding the broader consequences of NF models from both trainee and faculty points of view is essential to creating effective and sustainable systems to comply with duty-hour regulations while maximizing patient care, education, and quality of life (QoL).

Methods
This study used qualitative thematic analysis situated in a constructivist paradigm to explore the experience of an NF system by residents and faculty. Semi-structured interviews were conducted with 15 trainees and 3 faculty members at a large academic pediatric hospital to understand their perceptions of an NF call structure compared to the traditional 24-h call schedule.

Results
Three themes were identified: (i) Implications for resident; (ii) Implications for patient and family; and (iii) Implications for curriculum. Eight sub-themes were identified, highlighting both intended and unintended consequences of the NF system.

Conclusions
The NF system resulted in the intended outcomes of decreased fatigue and improved continuity of patient care. Unintended outcomes also occurred, however, including negative effects on assessment and feedback, lack of integration of competencies, and mixed results on resident quality of life. These areas require special attention when designing and implementing NF systems.