bluuebunny/crossref_metadata_2025 huggingface dataset:
Limited phylogeographic and genetic connectivity in Acacia species of low stature in an arid landscape
Authors: Millar Melissa A. , Binks Rachel M. , Tapper Sarah‐Louise , Macdonald Bronwyn M. , McArthur Shelley L. , Hankinson Margaret , Coates David J. , van Leeuwen Stephen , Byrne Margaret
Published: July 2022

Widespread plant species are expected to maintain genetic diversity and gene flow via pollen and seed dispersal. Stature is a key life history trait that affects seed and potentially pollen dispersal, with limited stature associated with limited dispersal and greater genetic differentiation. We sampled Hill’s tabletop wattle (Acacia hilliana) and curry wattle (Acacia spondylophylla), two co‐distributed, widespread, Acacia shrubs of low stature, across the arid Pilbara region of north‐western Australia. Using chloroplast sequence and nuclear microsatellite data we evaluated patterns of population genetic and phylogeographic diversity and structure, demographic signals, ratios of pollen to seed dispersal, evidence for historical refugia, and association between elevation and diversity. Results showed strong phylogeographic (chloroplast, GST = 0.831 and 0.898 for A. hilliana and A. spondylophylla, respectively) and contemporary (nuclear, FST = 0.260 and 0.349 for A. hilliana and A. spondylophylla, respectively) genetic structure in both species. This indicates limited genetic connectivity via seed and pollen dispersal associated with Acacia species of small stature compared to taller tree and shrub acacias across the Pilbara bioregion. This effect of stature on genetic structure is superimposed on moderate levels of genetic diversity that were expected based on widespread ranges (haplotype diversity h = 25 and 12; nuclear diversity He = 0.60 and 0.47 for A. hilliana and A. spondylophylla, respectively). Contemporary genetic structure was congruent at the greater landscape scale, especially in terms of strong genetic differentiation among geographically disjunct populations in less elevated areas. Measures of diversity and connectivity were associated with traits of greater geographic population proximity, population density, population size, and greater individual longevity, and some evidence for range expansion in A. hilliana. Results illustrate that low stature is associated with limited dispersal and greater patterns of genetic differentiation for congenerics in a common landscape and highlight the complex influence of taxon‐specific life history and ecological traits to seed and pollen dispersal.
Diet and prey selection of clouded leopards and tigers in Laos
Authors: Rasphone Akchousanh , Bousa Anita , Vongkhamheng Chantavy , Kamler Jan F. , Johnson Arlyne , Macdonald David W.
Published: July 2022

In Southeast Asia, conservation of ‘Vulnerable’ clouded leopards (Neofelis nebulosa) and ‘Endangered’ tigers (Panthera tigris) might depend on the management of their preferred prey because large felid populations are limited by the availability of suitable prey. However, the diet of clouded leopards has never been determined, so the preferred prey of this felid remains unknown. The diet of tigers in the region has been studied only from one protected‐area complex in western Thailand, but prey preferences were not determined. To better understand the primary and preferred prey of threatened felids, we used DNA‐confirmed scats and prey surveys to determine the diet and prey selection of clouded leopards and tigers in a hilly evergreen forest in northern Laos. For clouded leopards, the primary prey was wild pig (Sus scrofa; 33% biomass consumed), followed by greater hog badger (Arctonyx collaris; 28%), small rodents (15%), and mainland serow (Capricornis sumatraensis; 13%; hereafter, serow). For tigers, the primary prey was wild pig (44%), followed by serow (18%), sambar (Rusa unicolor; 12%), and Asiatic black bear (Ursus thibetanus; 10%). Compared to availability, serow was positively selected by both clouded leopards (D = 0.69) and tigers (0.61), whereas all other ungulate species were consumed in proportion to the availability or avoided. Our results indicate that clouded leopards are generalist predators with a wide prey spectrum. Nonetheless, mid‐sized ungulates (50–150 kg) comprised nearly half of their diet, and were the preferred prey, supporting a previous hypothesis that the enlarged gape and elongated canines of clouded leopards are adaptations for killing large prey. Because serow was the only ungulate preferred by both felids, we recommend that serow populations be monitored and managed to help conservation efforts for clouded leopards and tigers, at least in hilly evergreen forests of Southeast Asia.
Experimental and observational evidence of negative conspecific density dependence in temperate ectomycorrhizal trees
Authors: Jevon Fiona V. , De La Cruz Dayna , LaManna Joseph A. , Lang Ashley K. , Orwig David A. , Record Sydne , Kouba Paige V. , Ayres Matthew P. , Matthes Jaclyn Hatala
Published: July 2022

Conspecific negative density dependence (CNDD) promotes tree species diversity by reducing recruitment near conspecific adults due to biotic feedbacks from herbivores, pathogens, or competitors. While this process is well‐described in tropical forests, tests of temperate tree species range from strong positive to strong negative density dependence. To explain this, several studies have suggested that tree species traits may help predict the strength and direction of density dependence: for example, ectomycorrhizal‐associated tree species typically exhibit either positive or weaker negative conspecific density dependence. More generally, the strength of density dependence may be predictably related to other species‐specific ecological attributes such as shade tolerance, or the relative local abundance of a species. To test the strength of density dependence and whether it affects seedling community diversity in a temperate forest, we tracked the survival of seedlings of three ectomycorrhizal‐associated species experimentally planted beneath conspecific and heterospecific adults on the Prospect Hill tract of the Harvard Forest, in Massachusetts, USA. Experimental seedling survival was always lower under conspecific adults, which increased seedling community diversity in one of six treatments. We compared these results to evidence of CNDD from observed sapling survival patterns of 28 species over approximately 8 years in an adjacent 35‐ha forest plot. We tested whether species‐specific estimates of CNDD were associated with mycorrhizal association, shade tolerance, and local abundance. We found evidence of significant, negative conspecific density dependence (CNDD) in 23 of 28 species, and positive conspecific density dependence in two species. Contrary to our expectations, ectomycorrhizal‐associated species generally exhibited stronger (e.g., more negative) CNDD than arbuscular mycorrhizal‐associated species. CNDD was also stronger in more shade‐tolerant species but was not associated with local abundance. Conspecific adult trees often have a negative influence on seedling survival in temperate forests, particularly for tree species with certain traits. Here we found strong experimental and observational evidence that ectomycorrhizal‐associating species consistently exhibit CNDD. Moreover, similarities in the relative strength of density dependence from experiments and observations of sapling mortality suggest a mechanistic link between negative effects of conspecific adults on seedling and sapling survival and local tree species distributions.
Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST‐CRT Upgrade trial
Authors: Merkely Béla , Gellér László , Zima Endre , Osztheimer István , Molnár Levente , Földesi Csaba , Duray Gábor , Wranicz Jerzy K. , Németh Marianna , Goscinska‐Bis Kinga , Hatala Robert , Sághy László , Veres Boglárka , Schwertner Walter Richard , Fábián Alexandra , Fodor Eszter , Goldenberg Ilan , Kutyifa Valentina , Kovács Attila , Kosztin Annamária
Published: July 2022

Aims

The BUDAPEST‐CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies.

Methods and results

This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II–IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) levels (2231 pg/ml [25th–75th percentile 1254–4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%).

Conclusion

When compared with prior CRT trial cohorts, the BUDAPEST‐CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT‐proBNP, and frequent previous HF events.

Clinical Trial Registration: ClinicalTrials.gov NCT02270840.
Guideline‐directed medical therapy in patients undergoing transcatheter edge‐to‐edge repair for secondary mitral regurgitation
Authors: Higuchi Satoshi , Orban Mathias , Adamo Marianna , Giannini Cristina , Melica Bruno , Karam Nicole , Praz Fabien , Kalbacher Daniel , Koell Benedikt , Stolz Lukas , Braun Daniel , Näbauer Michael , Wild Mirjam , Doldi Philipp , Neuss Michael , Butter Christian , Kassar Mohammad , Ruf Tobias , Petrescu Aniela , Ludwig Sebastian , Pfister Roman , Iliadis Christos , Unterhuber Matthias , Sampaio Francisco , Ferreira Diogo , Thiele Holger , Baldus Stephan , von Bardeleben Ralph Stephan , Massberg Steffen , Windecker Stephan , Lurz Philipp , Petronio Anna Sonia , Lindenfeld JoAnn , Abraham William T. , Metra Marco , Hausleiter Jörg ,   EuroSMR Investigators
Published: July 2022

Aims

Guideline‐directed medical therapy (GDMT), based on the combination of beta‐blockers (BB), renin–angiotensin system inhibitors (RASI), and mineralocorticoid receptor antagonists (MRA), is known to have a major impact on the outcome of patients with heart failure with reduced ejection fraction (HFrEF). Although GDMT is recommended prior to mitral valve transcatheter edge‐to‐edge repair (M‐TEER), not all patients tolerate it. We studied the association of GDMT prescription with survival in HFrEF patients undergoing M‐TEER for secondary mitral regurgitation (SMR).

Methods and results

EuroSMR, a European multicentre registry, included SMR patients with left ventricular ejection fraction <50%. The outcome was 2‐year all‐cause mortality. Of 1344 patients, BB, RASI, and MRA were prescribed in 1169 (87%), 1012 (75%), and 765 (57%) patients at the time of M‐TEER, respectively. Triple GDMT prescription was associated with a lower 2‐year all‐cause mortality compared to non‐triple GDMT (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60–0.91). The association persisted in patients with glomerular filtration rate <30 ml/min, ischaemic aetiology, or right ventricular dysfunction. Further, a positive impact of triple GDMT prescription on survival was observed in patients with residual mitral regurgitation of ≥2+ (HR 0.62; 95% CI 0.44–0.86), but not in patients with residual mitral regurgitation of ≤1+ (HR 0.83; 95% CI 0.64–1.08).

Conclusion

Triple GDMT prescription is associated with higher 2‐year survival after M‐TEER in HFrEF patients with SMR. This association was consistent also in patients with major comorbidities or non‐optimal results after M‐TEER.
Delineating structural features of North Cameroon using the EIGEN6C4 high‐resolution global gravitational model
Authors: Ghomsi Franck Eitel Kemgang , Pham Luan Thanh , Steffen Rebekka , Ribeiro‐Filho Nelson , Tenzer Robert
Published: July 2022

The Cretaceous basins of the West and Central African Rift System (WCARS) are characterized by sinistral strike–slip movements observed between the Benue and Arabian–Nubian microplates. These basins share a similar basin‐filling structure, history, and tectonic processes. They have attracted a significant interest in the study of their geodynamics and subsurface structure through geophysical exploration methods. Nevertheless, North Cameroon located in this microplate confluence has not yet been investigated in terms of identifying geological structures, such as lineaments and faults. To contribute to a better understanding of the northern Cameroon structural framework and its tectonic context, we investigate the lineaments in northern Cameroon by using the EIGEN‐6C4 gravitational model and a variety of recent processing techniques (Tilt derivative [TDR], Theta Map [TM], Horizontal tilt angle [TDX], and Edge Detector [ED]). Our results show that the lineaments are trending in ENE–WSW, NW–SE, NE–SW, and WNW–ESE directions. These directions are consistent with the Cretaceous Garoua Rift and granitoids of the Cameroon‐Chad line. The presented result clearly delineates continuous architectonic features of the structural edges of the Saharan Metacraton, the Cretaceous Garoua Rift, the Bibemi‐Léré granitoids, and the Adamawa faults.
Violence against health care workers in the workplace in Mozambique – An unrecognised managerial priority
Authors: Patrício Sérgio Roques , Ferrinho Paulo , Sidat Mohsin
Published: July 2022

Introduction

Recognition of the relevance of violence against health workers in their work place has been growing around the world. In Mozambique, workplace violence in the health sector needs better documentation. Therefore, this article is part of a study that describes the typology and the perceived impact of violence against health care workers in their workplace at the Lichinga Provincial Hospital and at the Health Centre of the City of Lichinga in 2019.

Method

This was an observational, descriptive, cross‐sectional study. The study was carried out in a simple random sample of health workers victims of violence at the Provincial Hospital and the Health Centre of the City of Lichinga, in the Province of Niassa in northern Mozambique. The questionnaire applied was adapted from the original developed by the International Labour Organization, the International Council of Nurse, the World Health Organization and Public Services International and applied in Maputo, Mozambique during 2002. Statistical analysis was carried out with Statistical Package for the Social Sciences 20.0 and WinPepi 11.65.

Results

Two hundred and 60 healthcare workers (HCW) were selected to participate, 180 agreed, 145 had inclusion criteria and five gave up participating in the study during the consent procedure. Thus, a total of 140 HCW answered the questionnaire. Predominant types of violence were: verbal threat/aggression 34% (n = 62/180); moral pressure/bullying/mobbing 30% (n = 54/180); ethnic discrimination 9% (n = 16/180); against personal property 6% (n = 10/180); physical 4% (n = 8/180); sexual harassment 4% (n = 8/180). One hundred and 37 victims reported 154 episodes of violence, where 7% (n = 13/180) reported more than one type of violence. Most victims reported no reaction (55%, n = 76/137) and few said that they confronted the offender (16%, n = 22/137, particularly victims of sexual harassment, 38%, n = 3/8). Most HCW reported non‐existence (39%, n = 54/137) or unawareness (32%, n = 44/137) of procedures to report violence within the Institution. Most (80%, n = 33/41) of those knowing about the procedures, knew how to use them. More than half (55%; n = 76/137) of HCW said that they were discouraged to report acts of violence.

Conclusions

Like for previous studies in Mozambique and elsewhere in Africa, the study confirms: a relatively high prevalence, a reluctance to talk about the issue and unawareness about procedures on how to report incidents. The findings reconfirm the necessity for the development and implementation of procedures to address violence incidents towards HCW, to develop support services for victims of health workplace violence. Like elsewhere in Africa, successive health workforce plans in Mozambique have failed to address this issue.
Serial multiple mediation of treatment adherence and disease activity in the relationship between continuity of care and health outcomes among rheumatoid arthritis patients
Authors: İlgün Gülnur , Şahin Bayram
Published: July 2022

Objective

To evaluate the effect of continuity of care on health outcomes (quality of life and functionality) in patients with rheumatoid arthritis and to reveal whether treatment adherence and disease activity have a serial multiple mediator role on this relationship.

Methods

The study was cross‐sectional on 440 rheumatoid arthritis patients who applied to a university hospital rheumatology outpatient clinic. Research data were obtained from both the questionnaire method, which is the primary data source, and the patient files, which are the secondary data source. Process analysis was used in the analysis of the data.

Results

It was found that the continuity of care has a direct effect on the quality of life and the functionality. In addition, it is seen that treatment adherence has a single partial mediator role on the relationship between continuity of care and quality of life; It has been determined that treatment adherence and disease activity have both partial single mediation and serial multiple mediation roles on the relationship between continuity of care and functionality.

Conclusion

It is thought that these findings will provide clinicians with important data and information in the management of rheumatoid arthritis.
Casson nanofluid performance on MHD convective flow past a semi‐infinite inclined permeable moving plate in presence of heat and mass transfer
Authors: Ravindranath Reddy G. , Ramakrishna Reddy K.
Published: July 2022

This article investigates the radiation and chemical reaction effects on the free convection heat and mass transfer flow of Casson nanofluids (Cu and TiO2) over an inclined porous vertical plate embedded in a porous medium in the presence of radiation absorption and constant heat source under fluctuating boundary conditions. The plate is moved with a constant velocity of U0, and temperature and the concentration are assumed to be fluctuating with time harmonically from a constant mean at the plate. The perturbation technique is applied to solve the governing equations of the flow and pointed out the variations in velocity, temperature, and concentration with the use of graphical presentations. The impact of several parameters on local skin friction, Nusselt number, and Sherwood number is also noticed and discussed. It is concluded that the resultant velocity reduces with increasing Casson parameter and suction parameter, velocity, and temperature enhanced with increasing radiation absorption and diffusion thermo parameters. Also, it is noticed that the solutal boundary layer thickness decreases with an increase in chemical reaction parameters. It is because chemical molecular diffusivity reduces for higher values of Kr.
Predicting the severity of peer victimization and bullying perpetration among youth with interpersonal problems: A 6‐month prospective study
Authors: Arango Alejandra , Clark Michael , King Cheryl A.
Published: July 2022

Introduction

Peer victimization is prevalent and associated with adverse outcomes. In this prospective study of youth who self‐reported interpersonal problems, we examined school connectedness, school behavioral difficulties, academic difficulties, and internalizing problems (social anxiety, self‐esteem, depression) as predictors of peer victimization and bullying perpetration severity. We also examined the moderating effects of gender.

Methods

Participants were 218 youth (66.5% female), ages 12–15 years (M = 13.5, SD = 1.1), who screened positive for peer victimization, bullying perpetration, and/or low social connectedness using self‐report measures. Youth were recruited from an emergency department in the United States as part of an intervention trial. Youth identified primarily as African American (53.7%) and Caucasian (31.7%). Youth completed a 6‐month follow‐up assessment (75% retention). Separate Bayesian regression models were used to examine the effects of baseline school connectedness, school behavioral difficulties, academic difficulties, and internalizing problems on the severity of 6‐month peer victimization and bullying perpetration.

Results

Baseline depression was positively related to both peer victimization and bullying perpetration severity. Baseline behavioral problems were positively related to bullying perpetration severity. Interactions indicated that gender moderated the relationship between school connectedness and peer victimization.

Conclusions

Given the adverse outcomes linked with peer victimization and bullying perpetration, an improved understanding of factors that predict victimization and perpetration severity may be helpful in defining intervention targets.
The role of treatment with plasma exchange therapy in two pediatric toxic epidermal necrolysis cases related to COVID‐19
Authors: Varol Fatih , Can Yasar Yusuf , Sahin Ebru , Durak Cansu , Kilic Aziz , Sahin Ceyhan , Gursoy Fatima , Akin Tugba
Published: July 2022

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening mucocutaneous reactions characterized by necrosis and detachment of the epidermis. Drugs and bacterial or viral infections are the most common causes of SJS/TEN. Although cases of SJS/TEN have been reported after hydroxychloroquine, vaccine (mRNA [Biontech], and inactivated vaccine [Sinovac]) administration and during the clinical course of active Coronavirus disease 2019 (COVID‐19), limited data is indicating the COVID‐19 disease as a triggering factor. Also, there are no pediatric cases of SJS/TEN associated with COVID‐19 in the literature. Herein we reported two pediatric cases with a diagnosis of TEN related to COVID‐19. Therapeutic plasma exchange therapy was applied to both of our patients. Although there are a few adult cases in the literature, our article is the first pediatric case report about patients diagnosed with TEN related to COVID‐19 and successfully treated with plasma exchange.
Blue‐green emission of pepsin‐stabilized copper nanoclusters ultrafast detection of hemoglobin in human urine
Authors: Tseng Wei‐Bin , Wang Ing‐Ting , Aiyu Lin , Hsieh Ming‐Mu , Tseng Wei‐Lung
Published: July 2022

This work proposed a straightforward synthesis of copper nanoclusters (CuNCs) with an emission wavelength of 496 nm and a quantum yield of 2.2% by directly using pepsin as a template with low toxicity NaBH4 and ascorbic acid as reducing agents. The chemical composition and optical properties of the pepsin‐stabilized CuNCs (pepsin‐CuNCs) were well‐characterized by spectroscopy‐related techniques. The pepsin‐CuNCs retained the fluorescence intensity at neutral pH, at 37°C, and in high salinity, proving their suitability in biological systems. Although the pepsin‐CuNCs remained only half of the initial fluorescence intensity after 24 days due to air oxidation, their storage stability was comparable to that of CuNCs reported in the literature. Given that the absorption peaks of hemoglobin overlap the excitation and emission wavelengths of pepsin‐CuNCs, this feature allowed pepsin‐CuNCs to serve as a luminescence turn‐off sensor for sensing hemoglobin through the inner‐filter effect process. The pepsin‐CuNC probe provided a fast (within 1 min) platform for hemoglobin detection with a dynamic quantitative range of 0.1–10 μM and a detection limit of 70 nM. Importantly, the proposed probe was well‐suited to detect hemoglobin in nearly undiluted human urine, demonstrating its great potential for the clinical diagnosis of trace hemoglobin in urine.
Prognostic significance of hsa_circ_0048122 to predict liver metastasis in early‐stage colorectal cancer
Authors: Fang Qian , Ni Chuandou , Cai Zhun , Li Wangyong , Xie Jianjin
Published: July 2022

Background

Liver metastasis is the primary cause of lethal colorectal cancer (CRC). The predominant risk of poor patient prognosis in early‐stage CRC emerges as metachronous liver metastasis. This necessitates the search for potential biomarkers for this metastasis to assess treatment outcomes and provide targeted therapy.

Methods

The role of hsa_circ_0048122 in predicting liver metastasis in CRC was probed in this work. This retrospective and multi‐center investigation entailed exploration and identification stages with 158 and 176 patients. While RT‐qPCR was employed to scrutinize hsa_circ_0048122 expression, Kaplan–Meier survival, and multivariate analyses were used to probe its prognostic impact in early‐stage CRC and stage IV CRC cases, respectively.

Results

A strong correlation between liver metastases and hsa_circ_0048122 expression in stage IV CRC patients with a high hsa_circ_0048122 profile indicated a poor overall survival. Likewise, a high expression level of hsa_circ_0048122 appears as a potential predictor of liver metastases in patients' initial stages.

Conclusions

Predicting liver metastasis can be plausibly facilitated using Hsa_circ_0048122 as a biomarker in early‐stage CRC cases.
Serum HDAC4 level in rheumatoid arthritis: Longitudinal change during treatment and correlation with clinical outcomes
Authors: Mou Xiaoyue , Jin Yi , Jin Du , Guan Jintao , Zhang Qian
Published: July 2022

Objective

Histone deacetylase 4 (HDAC4) modulates immunity, inflammation, and osteoblast differentiation to engage in rheumatoid arthritis (RA) etiology. This study aimed to evaluate the HDAC4 longitudinal change and its relationship with clinical features and outcomes in RA patients.

Methods

Eighty‐three RA patients were enrolled. Their serum HDAC4 level was detected by ELISA at baseline (W0), week (W) 4, W12, and W24 after treatment. RA patients were divided into response or non‐response, low disease activity (LDA) or non‐LDA, remission or non‐remission patients according to their treatment outcomes at W24. Meanwhile, serum HDAC4 was detected by ELISA in 20 osteoarthritis patients and 20 healthy controls (HCs).

Results

HDAC4 level was reduced in RA patients compared with HCs (p < 0.001) and osteoarthritis patients (p = 0.009). HDAC4 was negatively related to some of the disease activity indexes such as C‐reactive protein (p = 0.003), tender joint count (p = 0.025), and disease activity score based on 28 joints (p = 0.013) in RA patients; it was also negatively correlated with TNF‐α (p = 0.003), IL‐6 (p = 0.022), and IL‐17A (p = 0.015). However, the HDAC4 level was not related to different treatment histories or current initiating treatment regimens (all p < 0.05). After treatment, HDAC4 was gradually elevated along with the time (p < 0.001). Interestingly, HDAC4 level at W12 (p = 0.041) and W24 (p = 0.012) was higher in response patients versus non‐response patients, and its level at W24 was higher in LDA patients versus non‐LDA patients (p = 0.019), and in remission patients versus non‐remission patients (p = 0.039).

Conclusion

HDAC4 gradually increases during treatment and its elevation estimates good treatment outcomes in RA patients.
Impact of Expanding Eligibility Criteria for Cochlear Implantation – Dynamic Modeling Study
Authors: Nijmeijer Hugo G. B. , Groenewoud Hans M. M. , Mylanus Emmanuel A. M. , Goedegebure André , Huinck Wendy J. , van der Wilt Gert Jan
Published: July 2022

Objectives

Eligibility criteria for cochlear implantation (CI) are shifting due to technological and surgical improvements. The aim of this study was to explore the impact of further expanding unilateral CI criteria in those with severe hearing loss (HL) (61–80 dBHL) in terms of number of CI recipients, costs, quality of life, and cost‐effectiveness.

Methods

A dynamic population‐based Markov model was constructed mimicking the Dutch population in three age categories over a period of 20 years. Health states included severe HL (61–80 dBHL), profound HL (>81 dBHL), CI recipients, and no‐CI recipients. Model parameters were based on published literature, (national) databases, expert opinion, and model calibration.

Results

If persons with severe HL would qualify and opt for CI similar to those with profound HL now, this would lead to a 6–7 times increase of new CI recipients and an associated increase in costs (€550 million) and QALYs (54.000) over a 20‐year period (incremental cost utility ratio: 10.771 euros/QALY [2.5–97.5 percentiles: 1.252–23.171]). One‐way‐sensitivity analysis indicated that model outcomes were most sensitive to regaining employment, utility associated with having a CI, and costs of surgery and testing.

Conclusion

Our findings suggest that expanding eligibility for CI to persons with severe HL could be a cost‐effective use of resources. Clearly, however, it would require a significant increase in diagnostic, operative, and rehabilitative capacity. Our quantitative estimates can serve as a basis for a wider societal deliberation on the question whether such an increase can and should be pursued.

Level of Evidence

NA Laryngoscope, 133:924–932, 2023
The Role of PARP‐1 and NF‐κB in Bile‐Induced DNA Damage and Oncogenic Profile in Hypopharyngeal Cells
Authors: Doukas Panagiotis G. , Vageli Dimitra P. , Judson Benjamin L.
Published: July 2022

Objectives/Hypothesis

We recently documented that acidic bile, a gastroesophageal reflux content, can cause invasive hypopharyngeal squamous cell carcinoma, by inducing widespread DNA damage and promoting nuclear factor kappa B (NF‐κB)‐related oncogenic molecular events. Poly or adenosine diphosphate (ADP)‐ribose polymerase‐1 (PARP‐1), a sensitive sensor of DNA damage, may interact with NF‐κB. We hypothesized that PARP‐1 is activated in hypopharyngeal cells (HCs) with marked DNA damage caused by acidic bile, hence there is an association between PARP‐1 and NF‐κB activation or its related oncogenic profile, in this process.

Study Design

In vitro study.

Methods

We targeted PARP‐1 and NF‐κB(p65), using pharmacologic inhibitors, 1.0 μM Rucaparib (AG014699) and 10 μM BAY 11–7082 {3‐[4=methylphenyl)sulfonyl]‐(2E)‐propenenitrile}, respectively, or silencing their gene expression (siRNAs) and used immunofluorescence, luciferase, cell viability, direct enzyme‐linked immunosorbent assays, and qPCR analysis to detect the effect of targeting PARP‐1 or NF‐κB in acidic bile‐induced DNA damage, PARP‐1, p‐NF‐κB, and B‐cell lymphoma 2 (Bcl‐2) expression, as well as NF‐κB transcriptional activity, cell survival, and mRNA oncogenic phenotype in HCs.

Results

We showed that (i) PARP‐1 is overexpressed by acidic bile, (ii) targeting NF‐κB adequately prevents the acidic bile‐induced DNA double‐strand breaks (DSBs) by gamma H2A histone family member X (γH2AX), oxidative DNA/RNA damage, PARP‐1 overexpression, anti‐apoptotic mRNA phenotype, and cell survival, whereas (iii) targeting PARP‐1 preserves elevated DNA damage, NF‐κB activation, and anti‐apoptotic phenotype.

Conclusion

We document for the first time that the activation of PARP‐1 is an early event during bile reflux‐related head and neck carcinogenesis and that NF‐κB can mediate DNA damage and PARP‐1 activation. Our data encourage further investigation into how acidic bile‐induced activated NF‐κB mediates DNA damage in hypopharyngeal carcinogenesis.

Level of Evidence

NA Laryngoscope, 133:1146–1155, 2023
Clinical characteristics of paraneoplastic syndromes in patients with head and neck cancer
Authors: Diao Wenwen , Liang Ya , Gao Liming , Zhu Yingying , Zhu Xiaoli , Yu Shuting , Xia Xin , Chen Xingming
Published: July 2022

Background

To summarize the clinical manifestations, diagnosis, and prognosis of head and neck cancer (HNC) patients with paraneoplastic syndromes (PNS).

Methods

The clinical data of 1958 patients with HNC admitted to our hospital from January 1996 to December 2020 were retrospectively analyzed. Demographic and cancer‐related characteristics were extracted. Kaplan–Meier survival curves were compared by log‐rank test. Cox regression was performed to evaluate prognostic factors and hazard ratio.

Results

Totally 40 HNC patients with PNS were included in the final analysis, including 36 men and four women with a mean age of 60.4 years (range 40–82). PNS was dermatologic or cutaneous in 23 (57.50%) patients, endocrine in 10 (25.00%), neurologic in five (12.50%), and osteoarticular or rheumatologic in two (5.00%). Twenty‐five (62.50%) patients had Stage III/IV cancer. PNS regressed after antitumor therapy in 28 (70.00%) patients. Recurrence of PNS was observed in nine of 12 (75.00%) patients with cancer recurrence or metastasis. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates of patients with PNS were 51.52% and 44.44%, respectively. The DFS (p = .001) and OS (p = .003) of patients presented with PNS prior to HNC diagnosis were significantly longer than those of patients with synchronous or metachronous PNS. PNS diagnosed before HNC (adjusted hazard ratio [aHR]: 0.31, 95% confidence interval [CI]: 0.11–0.85, p = .02), Stage IV disease (aHR: 3.27, 95% CI: 1.18–9.05, p = .02), and smoking history (aHR: 3.69, 95% CI: 1.04–13.05, p = .04) were significantly associated with OS and DFS.

Conclusions

Early recognition of PNS could provide clues about underlying tumor condition and result in early diagnosis. Prompt detection of cancer‐associated syndromes could lead to a more favorable prognosis for these patients.
Possible clinical implications of the structural variations between the tympanic membrane quadrants
Authors: Kassem Firas , Dagan Or , Biadsee Ameen , Masalha Muhamed , Nachmani Ariela , Nageris Ben , Lee Daniel J. , Ungar Omer J. , Handzel Ophir
Published: July 2022

Introduction

Retraction pockets and marginal perforations of the pars tensa of the tympanic membrane (TM) are most commonly found at superior posterior quadrant (SPQ). The patulous Eustachian tube tends to manifest in the same quadrant. Variation in the structure of the TM may explain these observations.

Material and Methods

A line defined by the manubrium was used to divide the pars tensa into anterior and posterior portions. A transverse line centered on the umbo divides the pars tensa into superior and inferior parts, resulting in four quadrants. Surface areas of each of the TM quadrants were measured in a sample of 23 human adult formalin‐fixed temporal bones. The TMs were completely excised, faced medially, and placed against graph paper to maintain scale measurements, photoed, and measured.

TM thickness was measured on a different set of 20 human temporal bones (TB) preparations with normal external and middle ears. Four random loci were chosen from each pars tensa's TM quadrant. The thickness was measured using high‐magnification power microscopy.

Results

The SPQ was the largest and thinnest of the four quadrants. It occupies 31% of the pars tensa area. It is 69 μm as compared to approximately 85 μm in the other quadrants. The radial lines between the umbo and the annulus are in descending order from superior posterior toward the anterior‐superior radials.

Conclusion

The SPQ has the largest vibratory area and is the thinnest of the four TM quadrants. Variation in the thickness of the middle, fibrous layer accounts for the variation in the thickness of the TM. These findings may explain the tendency of pathologies related to Eustachian tube dysfunction to preferentially manifest in or originate from the SPQ.

Level of evidence: 5
High biomass turnover rates of endosymbiotic nitrogen‐fixing cyanobacteria in the western Bering Sea
Authors: Cheung Shunyan , Liu Kailin , Turk‐Kubo Kendra A. , Nishioka Jun , Suzuki Koji , Landry Michael R. , Zehr Jonathan P. , Leung Szeki , Deng Lixia , Liu Hongbin
Published: July 2022

Recent studies have described active nitrogen fixation in high‐latitude waters, but the ecological controls on the occurrence or activity of nitrogen‐fixing organisms (diazotrophs) in such systems remain unknown. Turnover rates and top‐down controls are also general knowledge gaps for marine diazotrophs. We detected abundant UCYN‐A (endosymbiotic nitrogen‐fixing cyanobacteria) in the Gulf of Anadyr, western Bering Sea, which correlated with high dissolved iron to dissolved inorganic nitrogen ratios (Fe : DIN) due to riverine input. Growth and grazing mortality of UCYN‐A sublineages were almost balanced with higher biomass‐turnover rates compared to the whole phytoplankton community, indicating selective grazing of UCYN‐A in nitrogen‐depleted waters. Grazing rates on UCYN‐A1 (small cells) were higher than for UCYN‐A2/3/4 (large cells), consistent with the general size dependence of phytoplankton growth and grazing mortality. We found that Fe : DIN is a major determinant of UCYN‐A abundances in high‐latitude waters, where UCYN‐A could make substantial contributions to plankton food‐web cycling.
Reversible Complexation Mediated Living Radical Polymerization Using Tetraalkylammonium Chloride Catalysts
Authors: Han Shuaiyuan , Zheng Yichao , Sarkar Jit , Niino Hiroshi , Chatani Shunsuke , Goto Atsushi
Published: July 2022

This work reports the first use of organic chloride salts as catalysts for reversible complexation mediated living radical polymerization. Owing to the strong halogen‐bond forming ability of Cl−, the studied four tetraalkylammonium chloride catalysts (R4N+Cl−) successfully control the polymerizations of methyl methacrylate, yielding polymers with low dispersities up to high monomer conversion (>90%). Benzyldodecyldimethylammonium chloride is further exploited to other methacrylates and yields low‐dispersity block copolymers. The advantages of the chloride salt catalysts are wide monomer scope, good livingness, accessibility to block copolymers, and good solubility in organic media. Because of the good solubility, the use of the chloride salt catalysts can prevent agglomeration of catalysts on reactor walls in organic media, which is an industrially attractive feature. Among halide anions, chloride anion is the most abundant and least expensive halide anion, and therefore, the use of the chloride salt catalysts may lower the cost of the polymerization.
Towards an Enrichment Optimization Algorithm (EOA)‐based Target Specific Docking Functions for Virtual Screening
Authors: Spiegel Jacob , Senderowitz Hanoch
Published: July 2022

Docking‐based virtual screening (VS) is a common starting point in many drug discovery projects. While ligand‐based approaches may sometimes provide better results, the advantage of docking lies in its ability to provide reliable ligand binding modes and approximated binding free energies, two factors that are important for hit selection and optimization. Most docking programs were developed to be as general as possible and consequently their performances on specific targets may be sub‐optimal. With this in mind, in this work we present a method for the development of target‐specific scoring functions using our recently reported Enrichment Optimization Algorithm (EOA). EOA derives QSAR models in the form of multiple linear regression (MLR) equations by optimizing an enrichment‐like metric. Since EOA requires target‐specific active and inactive (or decoy) compounds, we retrieved such data for six targets from the DUD‐E database, and used them to re‐derive the weights associated with the components that make up GOLD's ChemPLP scoring function yielding target‐specific, modified functions. We then used the original ChemPLP function in small‐scale VS experiments on the six targets and subsequently rescored the resulting poses with the modified functions. In addition, we used the modified functions for compounds re‐docking. We found that in many although not all cases, either rescoring the original ChemPLP poses or repeating the entire docking process with the modified functions, yielded better results in terms of AUC and EF1%, two metrics, common for the evaluation of VS performances. While work on additional datasets and docking tools is clearly required, we propose that the results obtained thus far hint to the potential benefits in using EOA‐based optimization for the derivation of target‐specific functions in the context of virtual screening. To this end, we discuss the downsides of the methods and how it could be improved.
Development and experimental analysis of polymer based composite bipolar plate usingAquila Taguchioptimization: Design of experiments
Authors: Raja S. , Verma Akarsh , Rangappa Sanjay Mavinkere , Siengchin Suchart
Published: July 2022

In the proton exchange membrane fuel cells, the bipolar plates (BPs) are being widely used in multifunctional mode. They have many unique properties, including prevention of coolant and gas leakages, dissipation of heat from active portions, distribution of air, gas, and fuel uniformly, electric current conduction between cell to cell as a chain, etc. This experimental work was intense to fabricate polymer‐based composite bipolar plates using hybrid combinations. Composites are prepared by using carbon black (CB), glass fiber (GF), and graphite (G) with epoxy and silicone resins. The mixing of composite materials with resins is controlled by the Aquila Taguchi optimization (ATO) method through the L16 Orthogonal Array (OA). Mixing parameters are chosen as rotational speed (20, 30, 40, and 50 rpm), mixing time (10, 15, 20, and 25 min), and mixing temperature (25, 30, 35, and 40°C). Influencing these parameters increases the electrical conductivity (S/cm) and flexural strength (MPa) of the newly prepared bipolar plate composites. From this analysis, highest electrical conductivity is obtained, such as 268.361 S/cm. Similarly, extreme flexural strength occurred at 134.90 MPa.
3‐Octanoylthio‐1‐propyltriethoxysilane functionalized silica/rubber composites for application in tire: Structure, performance and synergism
Authors: Das Saikat , Pal Kaushik , Chattopadhyay Santanu , Bhowmick Anil K.
Published: July 2022

Increasing the polymer‐filler interaction is a challenge to develop high performance rubber composites. In this study, a new blocked mercaptosilane (3‐Octanoylthio‐1‐propyltriethoxysilane) was used to increase the rubber‐silica interaction by modifying highly dispersible silica and fumed silica surface with this silane. A two‐step process was used for the modification. Successful hydrolysis and condensation reaction was proved by Fourier‐transform infrared spectroscopy. Grafting density and grafting percentage were determined using thermogravimetric analysis. The modified silica/rubber composites were compared with the compositions where silane was separately added during mixing. Dynamic modulus versus strain signatures demonstrated strong polymer‐filler interaction after functionalization of the silica surface. The composites containing modified silica demonstrated improved mechanical properties and abrasion resistance over the unmodified one, which were correlated with the dispersion index. Dynamic mechanical analysis showed 28% improvement of rolling resistance and 67% improvement of ice traction after modification. Amount of silane modified silica also varied in total filler loading for precipitated silica/rubber composites. Silica‐rubber composites, where hybrid silica structure (75/25 modified and pristine silica ratio) was used, displayed interesting property to fulfill the requirement of green tire composites. Such a finding can be extended to developing tires for energy efficient vehicles.
Fabrication and characterization of novel polyurethane Encapsulant with excellent underwater acoustic transparency and hydrophobicity
Authors: Li Zhihua , Zhang Yidan , Yan Shuxuan , Zhang Yibo , Liu Mengmei , Gong Liangjun
Published: July 2022

The preparation of underwater acoustically transparent polyurethane with excellent acoustic transparency, hydrophobicity, and electrical insulation is the current bottleneck prior in the underwater acoustic system. In this work, we synthesized a series of acoustically transparent polybutadiene‐based polyurethane (FPU) modified with a,ω‐dihydroxypoly[(3,3,3‐trifluoropropyl)methylsiloxane] (PTFPMS) by prepolymerization method. The influence of the PTFPMS content on the hydrophobicity, acoustic transparency, electrical insulation, and mechanical properties of FPU were investigated. When the amount of PTFPMS was 10 wt%, the water absorption of FPU reached the minimum of 0.261%, which was 42.9% lower than that of neat polyurethane. Moreover, the acoustic impedance of FPU decreased to 1.584 × 105 g/cm2∙s, which was very close to that of seawater and indicated a favorable acoustic transparency. In addition, the volume resistivity and surface resistivity of FPU were 5.20 × 1014 Ω cm and 2.42 × 1014 Ω cm, respectively, suggesting an excellent electrical insulation. These results revealed that the as‐prepared FPU has promising applications in the fields of underwater acoustically transparent encapsulant.
Factors promoting breast, cervical and colorectal cancer screenings participation: A systematic review
Authors: Vallone Federica , Lemmo Daniela , Martino Maria Luisa , Donizzetti Anna Rosa , Freda Maria Francesca , Palumbo Francesco , Lorenzo Elvira , D’Argenzio Angelo , Caso Daniela
Published: July 2022

Objective

The present study aims at systematically reviewing research conducted on factors promoting breast, cervical and colorectal cancer screenings participation.

Methods

A literature search in MEDLINE/PubMed and PsycInfo from January 2017 to October 2021 was performed. Data extraction, researchers' full agreement and the inclusion criteria produced 102 eligible studies. Data were narratively synthesized and critically interpreted.

Results

Multiple factors favoring or hindering breast, cervical and colorectal cancer screenings were identified and summarized as factors operating at the individual level (background information, individual characteristics, emotions related to screening procedure and to cancer, knowledge and awareness), at the relational level (relationships with healthcare staff, significant others, community members), and at the healthcare system level (systems barriers/policy, lack of staff). A critical appraisal of studies revealed a fragmentation in the literature, with a compartmentalization of studies by type of cancer screening, country and specific populations of destination.

Conclusions

Overall findings indicated that greater integration of research results obtained independently for each cancer diagnosis and within the different countries/populations could foster a more comprehensive understanding of factors potentially enhancing the participation in breast, cervical and colorectal cancer screenings worldwide. This review, which is grounded in the current context of globalization and superdiversification in population, can help to enhance a better integration between research and practices, by supporting the development of more effective and inclusive evidence‐based interventions and health‐promotion campaigns worldwide. Research and practical implications are highlighted and discussed.