bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical considerations in epilepsy neurostimulation
Authors: Simpson Hugh D. , Schulze‐Bonhage Andreas , Cascino Gregory D. , Fisher Robert S. , Jobst Barbara C. , Sperling Michael R. , Lundstrom Brian N.
Published: June 2022

Neuromodulation is a key therapeutic tool for clinicians managing patients with drug‐resistant epilepsy. Multiple devices are available with long‐term follow‐up and real‐world experience. The aim of this review is to give a practical summary of available neuromodulation techniques to guide the selection of modalities, focusing on patient selection for devices, common approaches and techniques for initiation of programming, and outpatient management issues. Vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (DBS‐ANT), and responsive neurostimulation (RNS) are all supported by randomized controlled trials that show safety and a significant impact on seizure reduction, as well as a suggestion of reduction in the risk of sudden unexplained death in epilepsy (SUDEP). Significant seizure reductions are observed after 3 months for DBS, RNS, and VNS in randomized controlled trials, and efficacy appears to improve with time out to 7 to 10 years of follow‐up for all modalities, albeit in uncontrolled follow‐up or retrospective studies. A significant number of patients experience seizure‐free intervals of 6 months or more with all three modalities. Number and location of epileptogenic foci are important factors affecting efficacy, and together with comorbidities such as severe mood or sleep disorders, may influence the choice of modality. Programming has evolved—DBS is typically initiated at lower current/voltage than used in the pivotal trial, whereas target charge density is lower with RNS, however generalizable optimal parameters are yet to be defined. Noninvasive brain stimulation is an emerging stimulation modality, although it is currently not used widely. In summary, clinical practice has evolved from those established in pivotal trials. Guidance is now available for clinicians who wish to expand their approach, and choice of neuromodulation technique may be tailored to individual patients based on their epilepsy characteristics, risk tolerance, and preferences.
First report of Toumeyella parvicornis (Hemiptera: Coccidae) in Puglia (South‐Eastern Italy)
Authors: Tagarelli Nicola , Avosani Sabina , Tucci Michele , Verrastro Vincenzo
Published: June 2022

This is the first report of the presence of the pine tortoise scale Toumeyella parvicornis Cockerell (Hemiptera: Coccidae) in the Italian region of Puglia (South‐Eastern Italy). The pine tortoise scale was observed in July 2021 on Pinus pinea in the city of Bari. Pinus halepensis trees growing near infested P. pinea were not found to be infested. None of the monitored plants in the other surveyed municipalities within the region had apparent signs of T. parvicornis infestation. Overall, the rapid expansion of T. parvicornis in the Italian Peninsula represents a serious threat to the Pinus species of the entire Mediterranean basin, thus the development of sustainable integrated management strategies is urgently needed.
What does ‘occupancy’ mean in passive acoustic surveys?
Authors: Wood Connor M. , Peery M. Zachariah
Published: June 2022

Occupancy modelling is an increasingly common framework for analysing acoustic data to study the variation in populations through space and time, but different survey designs endow survey locations with varying degrees of biological meaning. Recording units may be preferentially deployed in areas known to be important to a species, which implies an ‘area of occupancy’ conception of a species range, or recording units may be randomly deployed without knowledge of focal species space‐use (e.g. a survey grid), which implies an ‘extent of occurrence’ conception of a species range. Preferential sampling requires substantial pre‐survey information (e.g. the location of focal species territories) but leads to intuitive parameter interpretation and greater precision; vastly greater survey coverage is attainable with random sampling, but the resulting data merit careful post‐processing to achieve precise, ecologically meaningful results. Importantly, occupancy, detection, extinction and colonization estimates are incomparable between study designs. However, an understanding of focal species movement and vocal behaviour can inform the development of creative definitions of acoustic detections – and thus site occupancy – which may help bring the ecological realism of preferential sampling to the data yielded by the more scalable random sampling approach. Understanding the implications of study design choices on parameter interpretation is a fundamental aspect of basic ecological inference and endangered species monitoring.
The Challenge and the Promise of Clinical Suicidology
Authors: Jobes David A.
Published: June 2022

The existing research in clinical assessment and treatment of suicidal patients is reviewed. Data concerning the “life course” of suicidally among outpatient samples of suicidal university students are then presented. These data suggest different subtypes of suicidally, which are further considered using a conceptual model that differentiates intrapsychic versus interpsychic suicidality. The implications of these data and this model are discussed in relation to current changes in mental health care with an emphasis on differential assessment and prescriptive treatments. Future developments in clinical suicidology and ideas for additional research are discussed.
Arterial stiffness and contralateral differences in blood pressure: The Atherosclerosis Risk in Communities (ARIC) study
Authors: Charry Daniela , Gouskova Natalia , Meyer Michelle L. , Ring Kimberley , Nambi Vijay , Heiss Gerardo , Tanaka Hirofumi
Published: June 2022

A large interarm difference in brachial systolic blood pressure (SBP) (≥10 or ≥15 mmHg) is strongly associated with elevated cardiovascular events and mortality. Evidence demonstrating whether such contralateral differences in SBP occur in ankle blood pressure and its association with arterial stiffness is scarce. The aims of this study were to characterize arm and ankle contralateral SBP differences in a sample of community‐dwelling older adults (5077), and to determine whether this difference is associated with arterial stiffness assessed by pulse wave velocity (PWV) between the heart and ankle (haPWV), femoral artery and ankle (faPWV), and brachial artery and ankle (baPWV) in the right and left sides. Prevalence of interarm SBP differences ≥10 and ≥15 mmHg was 5.1% and .7%, respectively; the corresponding prevalence for interankle SBP was 24.9% and 12.0%. Higher BMI and lower ankle‐brachial index (ABI) were significantly correlated with greater interarm SBP differences. Increased age, higher BMI, lower ABI, and greater contralateral differences in haPWV, faPWV, and baPWV were significantly correlated to greater interankle SBP differences. Interankle SBP difference ≥15 mmHg was significantly associated with contralateral differences of >80 cm/s in haPWV (OR = 1.94 [95% CI = 1.52–2.49]), >165 cm/s in faPWV (OR = 1.64 [95% CI = 1.27–2.12]), and >240 cm/s in baPWV (OR = 2.43 [95% CI = 1.94–3.05]). The associations remained significant after adjustment for age, sex, race, BMI, smoking status, and ABI. Compared with interarm differences, interankle differences in SBP are common in older adults. The magnitude of interankle, but not interarm, differences in SBP is associated with various measures of arterial stiffness.
A comprehensive, tri‐national, cross‐sectional analysis of characteristics and impact of pruritus in psoriasis
Authors: Hawro M. , Sahin E. , Steć M. , Różewicka‐Czabańska M. , Raducha E. , Garanyan L. , Philipp S. , Kokolakis G. , Christou D. , Kolkhir P. , Pogorelov D. , Weller K. , Metz M. , Sabat R. , Maleszka R. , Olisova O. , Maurer M. , Hawro T.
Published: June 2022

Background

Pruritus is prevalent in psoriasis but still many features of pruritus, its response to therapy and its burden in psoriasis remain to be better characterized.

Objective

To investigate characteristics and burden of pruritus in an international cohort of patients with psoriasis.

Methods

This cross‐sectional study included a total of 634 patients and 246 controls from Germany, Poland and Russia. Physicians examined and interviewed participants, recording clinical characteristics, such as severity, therapy and localization of psoriatic lesions. Participants filled out self‐reported questionnaires including questions on pruritus severity and impact, characteristics, and response to therapy, and quality of life (QoL). Localization patterns of pruritus and skin lesions were visualized using body heat maps.

Results

Most patients (82%) experienced pruritus throughout their disease, and 75% had current pruritus. The majority of patients (64%) perceived pure pruritus, and those who reported additional painful and/or burning sensations (36%) reported overall stronger pruritus. The scalp was the most frequently reported localization of pruritus, even in the absence of skin lesions. Body surface area (BSA) of pruritus was not linked to pruritus intensity, but to BSA of psoriatic lesions (rho = 0.278; P < 0.001). One third of patients (31%) reported impaired sex‐life, and 4% had suicidal ideations due to pruritus. In up to one third of patients, psoriasis therapies had little or no effect on pruritus. The only therapeutic option offered to some of these patients were antihistamines, which appeared to be effective in most cases.

Conclusion

Pruritus is highly prevalent in psoriasis and is linked to a significant burden. Current psoriasis therapies are frequently insufficient to control pruritus. Managing psoriasis should include the assessment and control of itch. Efficient antipruritic therapies should be developed and be made available for patients with psoriasis.
Mathematical modeling of infrared drying of red pitaya pulp (Stenocereus queretaroensis) for potential use of its betalains
Authors: Ríos‐Moreno Gustavo , Cruz‐Reyes Ivan , Vargas‐Rodríguez Paulina , Félix‐Flores Ma. Guadalupe , Quiñones‐Reyes Guillermo , Lozada‐Rodríguez Leticia
Published: June 2022

Red pitaya fruit has an important concentration of betalains (68.7 mg/100 g fresh sample) that potentially can be used as natural colorants for food, textiles, dye‐sensitized solar cells, etc. Nevertheless, this fruit has a short shelf life. To overcome this problem and to take advantage of their varied and attractive colors, pitayas can be infrared dried. In this work, we evaluated the kinetics of infrared drying of red pitaya pulp in the temperature range of 40–70°C. The drying rate was found to increase with temperature. The time required to diminish moisture content of red pitaya pulp from 80.5% to around 0.1%–0.3% (dry basis) decreased from 625 min at 40 to 240 min at 70°C. The experimental drying data were fitted to nine empirical drying models reported in literature and to one new model herein proposed. Based on statistical criteria, the proposed model was found the best for characterizing drying behavior of red pitaya pulp for the whole range of temperature. Effective moisture diffusivity was moisture content‐dependent, the average values for diffusivity coefficients at each drying temperature were derived from Fick's law and varied from 0.98–4.43 × 10−9 m2/s over the temperature range. Activation energy for moisture diffusion in red pitaya pulp was determined as 42.89 kJ/mol. Best drying temperature was found to be at 70°C, where a higher betalain content and a faster drying process conditions were achieved.

Practical applications

Betalains can be used as healthy natural colorants for food, among others. A limitation for which pitayas have not been exploited as a source of colorants is because of their short shelf life. Due to the important concentration of betalains present in this fruit, it is highly desirable to have methodologies that allow access to their use. To overcome this problem and to take advantage of their varied and attractive colors, red pitaya pulp was infrared dried for its study. Herein the proposed model exhibited an excellent fit to the red pitaya pulp drying process. The commercial exploitation of pitayas as an alternative source of natural colorant betalains may not only provide a wider color spectrum than red beetroot, but also contribute to the sustainable development of the usually underdeveloped semiarid regions.
Multi‐step‐ahead flood forecasting using an improved BiLSTM‐S2S model
Authors: Cao Qing , Zhang Hanchen , Zhu Feilin , Hao Zhenchun , Yuan Feifei
Published: June 2022

Rainfall–runoff modeling is a complex hydrological issue that still has room for improvement. This study developed a coupled bidirectional long short‐term memory (LSTM) with sequence‐to‐sequence (Seq2Seq) learning (BiLSTM‐Seq2seq) model to simulate multi‐step‐ahead runoff for flood events. The bidirectional LSTM with Seq2Seq learning (LSTM‐Seq2Seq) and multilayer perceptron (MLP) was set as benchmarks. The results show that: (1) root mean absolute error is reduced by approximately 19% up to 27%, and the Nash–Sutcliffe coefficient of efficiency is improved by 14% up to 34% for 6‐h‐ahead runoff prediction for BiLSTM‐Seq2Seq compared LSTM‐Seq2Seq and MLP; (2) The BiLSTM‐Seq2Seq model has good performance not only for one‐peak flood events but also for multi‐peak flood events; and (3) BiLSTM‐Seq2Seq can mitigate the time‐delay problem and time lag is shortened by 39% up to 69% in comparison to LSTM‐Seq2Seq and MLP. These results suggest that the time‐delay problem can be mitigated by BiLSTM‐Seq2Seq, which has excellent potential in time series predictions in the hydrological field.
Automatic identification of buildings vulnerable to debris flows in Sichuan Province, China, by GIS analysis and Deep Encoding Network methods
Authors: Wei Li , Hu Kaiheng , Liu Jin
Published: June 2022

Debris flows commonly cause tremendous damage to buildings in mountainous areas. The identification of buildings susceptible to debris flows is vital for settlement risk management. The efficient identification method is a major issue limiting the targeted regional policy setting. By combining geographic information system (GIS) and Deep Encoding Network (DE‐Net) methods, we proposed an automatic identification method for buildings highly susceptible to debris flows with large‐scale digital elevation data and high‐resolution remote sensing imagery. The judgment criteria were based on a vulnerability matrix containing different threshold values of the horizontal distance (HD) and vertical distance (VD) between buildings and channels obtained from the statistics of 362 buildings destroyed by 23 debris flows and the maximum debris flow depths of 26 events, respectively. Five steps, which are debris flow channel extraction, building extraction, building cluster segmentation, distance calculation, and building classification, were implemented in the method. A case study in Puge County, Sichuan Province, demonstrated the high identification potential of the method for buildings susceptible to debris flows in large areas with only scarce information available. The identification results provide valuable information regarding high‐risk residential areas to governments and facilitate targeted measure design in these areas in the initial planning stage.
A systematic review of relationships and sex education outcomes for students with intellectual disability reported in the international literature
Authors: Paulauskaite L. , Rivas C. , Paris A. , Totsika V.
Published: June 2022

Background

Little is known about how to evaluate relationships and sex education (RSE) delivered to students with intellectual disability and what stakeholders perceive are important outcomes. The present study aimed to systematically review existing studies on outcomes of RSE, as the first step in the development of a core outcome set (COS) for students with intellectual disability.

Method

A systematic literature process included two stages: (1) searching for studies reporting on RSE outcomes for students with intellectual disability and (2) studies reporting on measurement properties (e.g. validity, reliability and responsiveness) of standardised instruments identified in stage 1.

Results

A total of 135 RSE outcomes were extracted from 42 studies: 43 outcomes for students in secondary education and 92 outcomes for students in further education. No RSE outcomes were reported for primary education. Outcomes referred to the human body, hygiene, relationships, sexuality, sex and its consequences, inappropriate and appropriate social and sexual behaviour, keeping safe, emotional vocabulary and positive self‐esteem. Outcomes were predominantly knowledge‐based, rather than relating to skills and attitudes development. Students with intellectual disability, parents and teachers perceive different RSE outcomes meaningful. Five instruments were used to measure the outcomes, but none have established psychometric properties with this population.

Conclusions

The comprehensive list of RSE outcomes for students with intellectual disability will be used to inform the next steps of a Core Outcome Set needed for RSE evaluations in research and education settings. There is an urgent need to develop standardised instruments validated for students with intellectual disability.
ERp57 chaperon protein protects neuronal cells from Aβ‐induced toxicity
Authors: Di Risola Daniel , Ricci Daniela , Marrocco Ilaria , Giamogante Flavia , Grieco Maddalena , Francioso Antonio , Vasco‐Vidal Aldrin , Mancini Patrizia , Colotti Gianni , Mosca Luciana , Altieri Fabio
Published: June 2022

Alzheimer's disease (AD) is a neurodegenerative disorder whose main pathological hallmark is the accumulation of Amyloid‐β peptide (Aβ) in the form of senile plaques. Aβ can cause neurodegeneration and disrupt cognitive functions by several mechanisms, including oxidative stress. ERp57 is a protein disulfide isomerase involved in the cellular stress response and known to be present in the cerebrospinal fluid of normal individuals as a complex with Aβ peptides, suggesting that it may be a carrier protein which prevents aggregation of Aβ. Although several studies show ERp57 involvement in neurodegenerative diseases, no clear mechanism of action has been identified thus far. In this work, we gain insights into the interaction of Aβ with ERp57, with a special focus on the contribution of ERp57 to the defense system of the cell. Here, we show that recombinant ERp57 directly interacts with the Aβ25−35 fragment in vitro with high affinity via two in silico‐predicted main sites of interaction. Furthermore, we used human neuroblastoma cells to show that short‐term Aβ25−35 treatment induces ERp57 decrease in intracellular protein levels, different intracellular localization, and ERp57 secretion in the cultured medium. Finally, we demonstrate that recombinant ERp57 counteracts the toxic effects of Aβ25−35 and restores cellular viability, by preventing Aβ25−35 aggregation. Overall, the present study shows that extracellular ERp57 can exert a protective effect from Aβ toxicity and highlights it as a possible therapeutic tool in the treatment of AD.

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Vulvodynia: What is available online? A systematic review of information on the internet
Authors: Loganathan Jemina , Ghai Vishalli , Ilaalagan Ragave , Doumouchtsis Stergios K. ,   CHORUS
Published: June 2022

Aim

This review aimed to evaluate the quality of medicalinformation online for patients relating to vulvodynia. To our knowledge no evaluation of online patient information exists regarding vulvodynia and, at present, there is no standardized or validated method of evaluating medical information on the internet.

Methods

A clearly defined protocol was developed to generate keywords relating to vulvodynia. The three most popular search engines worldwide; google.com, yahoo.com, and bing.com, were searched in September 2020. Three assessors evaluated eligible webpages for accuracy, credibility, readability, and reliability.

Results

Forty‐five webpages were eligible with 38% given HON certification or Information Standard approval. Only one webpage achieved a DISCERN score of ≥63 indicating excellent reliability. No webpages scored a maximum 10 points for credibility. Eleven percent of webpages were rated “accurate” with score 17 or above. The modal Flesch Kincaid Grade Level was 9 with only 15.6% having a readability grade level of 8 or less.

Conclusions

It has been shown in previous studies that patient information available online pertaining to gynecological conditions is frequently inaccurate, with limited regulation and low reliability, and our findings are in agreement with this. As patients increasingly look to the internet for medical information and education, we as clinicians, need to ensure the resources available are of a high standard and regulated. Without ensuring safe and effective healthcare resources, we risk misinformation which can negatively impact clinical care.
Meta‐analysis of the association between periodontal disease, periodontal treatment and carotid intima–media thickness
Authors: Ding Lifang , You Qiqi , Jiang Qingqing , Cao Shiyi , Jiang Shengjun
Published: June 2022

Periodontal disease is a major threat to oral health and would further contribute to systemic diseases without timely control. We aimed to evaluate the relation between periodontal disease, periodontal treatment and carotid intima–media thickness (CIMT) based on available epidemiological and clinical evidence. PubMed and Scopus were searched for relevant studies through May 2021. Observational studies reporting risk estimates with 95% confidence intervals (95% CIs) for the association between periodontal disease (including periodontitis and gingivitis) and risk of increased CIMT (defined as CIMT value that exceeded the cut‐off value of clinical and prognostic significance), as well as interventional studies providing mean values with standard deviations of CIMT before and after periodontal intervention, were included. Random‐effect models for meta‐analysis were used to calculate the summary effect estimates with 95% CIs. A total of 406 citations were retrieved from electronic databases and 45 full‐text articles were screened, leaving 11 articles using ultrasound to measure CIMT with 8744 participants included. Pooled results of seven cross‐sectional studies involving 8558 participants indicated that compared to those without periodontitis, patients with periodontitis and those with severe periodontitis had an odds ratio of 1.42 (95% CI: 1.16, 1.75) and 1.70 (95% CI: 1.24, 2.33) for increased CIMT, respectively. Although publication bias was detected in these results, odds ratios corrected by the trim‐and‐fill method were still statistically significant. Results of four non‐randomized controlled trials with 186 patients suggested that periodontal intervention may help reduce CIMT in patients with periodontal disease in the short term. Periodontitis, especially severe periodontitis, was significantly associated with the risk of increased CIMT. Periodontal intervention might help slow the progression of carotid intima–media thickening in patients with periodontal disease in the short term.
Advanced practice role delineation within Hong Kong: A cross‐sectional study
Authors: Jokiniemi Krista , Chair Sek Ying , Wong Frances Kam Yuet , Bryant‐Lukosius Denise
Published: June 2022

A career ladder for nurses, including several levels of nursing practice and specific roles for advanced practice nurses, was introduced in Hong Kong around the start of the 21st century. To date no studies have distinguished the practices of advanced practice nurses in Hong Kong. This cross‐sectional study, conducted between November 2020 and March 2021, aims to identify and differentiate the practice patterns of advanced practice nurses by utilizing the Advanced Practice Role Delineation tool. A total of 191 responses were obtained. Three roles were identified: nurse consultant, advanced practice nurse, and advanced practice nurse in management. Among the five advanced practice nursing domains, nurses were most frequently involved in Education and in Direct Comprehensive Care activities, while least active in Research and in Publication and Professional Leadership. Identifying activities in various nursing roles helps to differentiate their responsibilities and provides new insights for role utilization and support. Although the role characteristics are shaped by country contexts, research evidence on practice patterns may be used to support international discussion and efforts to promote role clarity and effective role introduction and optimization.
Potential applications of medicinal herbs and phytochemicals in oral and dental health: Status quo and future perspectives
Authors: Dalir Abdolahinia Elaheh , Hajisadeghi Samira , Moayedi Banan Zahra , Dadgar Esmaeel , Delaramifar Amin , Izadian Sepideh , Sharifi Simin , Maleki Dizaj Solmaz
Published: June 2022

Objective

Herbal therapies are utilized to treat a broad diversity of diseases all over the globe. Although no clinical studies have been conducted to demonstrate the antibacterial, antimicrobial, and antiplaque characteristics of these plants, this does not imply that they are ineffectual as periodontal treatments or anti‐cariogenic drugs. However, there is a scarcity of research confirming their efficacy and worth.

Subject

Herbs are utilized in dentistry as antimicrobial, antineoplastic, antiseptic, antioxidant, and analgesics agents as well as for the elimination of bad breath. In addition, the application of herbal agents in tissue engineering improved the regeneration of oral and dental tissues. This study reviews the application of medicinal herbs for the treatment of dental and oral diseases in different aspects.

Methods

This article focuses on current developments in the use of medicinal herbs and phytochemicals in oral and dental health. An extensive literature review was conducted via an Internet database, mostly PubMed. The articles included full‐text publications written in English without any restrictions on a date.

Conclusion

Plants have been suggested, as an alternate remedy for oral–dental problems, and this vocation needs long‐term dependability. More research on herbal medicine potential as pharmaceutical sources and/or therapies is needed.
Epigenetic/genetic variations in CG‐rich elements of immune‐related genes contribute to food allergy development during childhood
Authors: Kostara Maria , Chondrou Vasiliki , Fotopoulos Vassilis , Sgourou Argyro , Tsabouri Sophia
Published: June 2022

Background

Genetic areas of FOXP3 TSDR, human leukocyte antigen‐G (HLA‐G) upstream of CpG island 96, CpG41 and CpG73 islands of the HLA‐DRB1 and HLA‐DQB1 genes respectively, previously documented to display immune‐modulatory properties, were subjected to epigenetic/genetic analysis to assess their influence in IgE‐mediated food allergy (FA) development in children.

Methods

Sixty‐four orally challenged and IgE‐tested food allergic subjects together with 44 controls were recruited. Targeted pyrosequencing analysis to detect DNA methylation status and genetic variations was utilized and experimental results obtained were analyzed by a statistical software platform and correlated to clinical data. Also, transcription factor (TF) binding sites in study areas were unmasked by the JASPAR prediction database.

Results

Parents’ smoking was significantly correlated with aberrant methylation patterns, regardless of food allergic or control status. HLA‐G promoter region showed a trend for hypomethylation in food allergic subjects, with one of the CG sites displaying significantly decreased methylation values. Rs1233333, residing within the HLA‐G promoter region preserved a protective role toward DNA methylation. Variable methylation patterns were recorded for CpG41 of the HLA‐DRB1 gene and hypermethylation of the region was significantly correlated with the presence of single nucleotide polymorphisms (SNPs). TFs’ recognition sites, located in studied genetic areas and exerting pivotal regulatory biological roles, are potentially affected by divergent DNA methylation status.

Conclusions

We propose that HLA‐G expression is triggered by food‐derived allergens, providing a TregFoxP3‐/HLA‐G+ subpopulation generation to promote direct immune tolerance. Furthermore, clear evidence is provided for the underlying co‐operation of genetic polymorphisms with epigenetic events, mainly at the CpG41 island of the HLA‐DRB1 gene, which needs an extended investigation and elucidation.
Photodynamic Stromal Depletion Enhances Therapeutic Nanoparticle Delivery in 3D Pancreatic Ductal Adenocarcinoma Tumor Models
Authors: Karimnia Vida , Stanley M. Elizabeth , Fitzgerald Christian T. , Rizvi Imran , Slack Frank J. , Celli Jonathan P.
Published: June 2022

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human malignancies. PDAC is characterized by dense fibrous stroma which obstructs drug delivery and plays complex tumor‐promoting roles. Photodynamic therapy (PDT) is a light‐based modality which has been demonstrated to be clinically feasible and effective for tumors of the pancreas. Here, we use in vitro heterocellular 3D co‐culture models in conjunction with imaging, bulk rheology and microrheology to investigate photodegradation of non‐cellular components of PDAC stroma (photodynamic stromal depletion, PSD). By measuring the rheology of extracellular matrix (ECM) before and after PDT we find that softening of ECM is concomitant with increased transport of nanoparticles (NPs). At the same time, as shown by us previously, photodestruction of stromal fibroblasts leads to enhanced tumor response to PDT. Here we specifically evaluate the capability of PSD to enhance RNA nanomedicine delivery, using a NP carrying an inhibitor of miR‐21‐5P, a PDAC oncomiR. We confirm improved delivery of this therapeutic NP after PSD by observation of increased expression of PDCD4, a protein target of miR‐21‐5P. Collectively, these results in 3D tumor models suggest that PSD could be developed to enhance delivery of other cancer therapeutics and improve tumor response to treatment.
Top Income Adjustments and Inequality: An Investigation of the EU‐SILC†
Authors: Carranza Rafael , Morgan Marc , Nolan Brian
Published: June 2022

This paper provides a novel assessment of how the World Inequality Database (WID) top income adjustment applied by Blanchet, Chancel, and Gethin (2021) to European Union Statistics on Income and Living Conditions (EU‐SILC) data for 26 countries over 2003–2017 for Distributional National Accounts purposes affects inequality in equivalized gross and disposable household income. On average, the Gini is increased by around 2.4 points for both gross and disposable income, with notable differences across countries but limited impact on trends. EU‐SILC countries that rely on administrative register data see relatively small effects on inequality. Comparing with two other recent studies, differences in impacts on measured inequality depend less on the adjustment method and more on whether external data sources are used.
Constantly changing Nordic welfare states: A Bermuda triangle?
Authors: Greve Bent
Published: June 2022

This introduction discusses recent developments in the Nordic welfare states as well as an overview of the contributions to this regional issue on Nordic welfare states. The issue focuses on topics of demography, financing, solidarity, and migration. The overview points to a potential conflict between resource availability, user expectations, and norms of professionalism. Navigating this ‘Bermuda triangle’ will likely require constant negotiation over the developing path of the Nordic welfare states. Specific challenges include how to maintain the historical tradition of high equality of income, economic opportunity, and access to services for men and women, native and foreign‐born. Welfare states will be constantly recalibrating, to accommodate residents' demands for what they are willing to accept in terms of benefits and what they are willing to pay in terms of social contributions.
On Causee in Sason Arabic
Authors: Akkuş Faruk
Published: June 2022

This article aims to understand the syntax of three causative constructions in Sason Arabic. It demonstrates that in geminate causatives and ‘give’ causatives, the causee is introduced in CauseeP, unlike the embedded agent in ‘make’ causatives, which embed a thematic VoiceP. Despite differing from Voice in several respects, Causee, like Voice, exhibits an active–passive‐like alternation, which provides independent evidence for an analysis of the passive that treats it as a subtype of the Voice head. The article further distinguishes between geminates and ‘give’ causatives on the basis of the (in)compatibility of the causee with an applied argument. In geminates, Causee and Appl are bundled, and the same argument bears two ‐roles, whereas in other causative constructions, Causee and Appl remain separate, with each argument bearing a distinct ‐role.
Simple steps to enable reproducibility: culture conditions affecting Chlamydomonas growth and elemental composition
Authors: Hui Colleen , Schmollinger Stefan , Strenkert Daniela , Holbrook Kristen , Montgomery Hayden R. , Chen Si , Nelson Hosea M. , Weber Peter K. , Merchant Sabeeha S.
Published: June 2022

Even subtle modifications in growth conditions elicit acclimation responses affecting the molecular and elemental makeup of organisms, both in the laboratory and in natural habitats. We systematically explored the effect of temperature, pH, nutrient availability, culture density, and access to CO2 and O2 in laboratory‐grown algal cultures on growth rate, the ionome, and the ability to accumulate Fe. We found algal cells accumulate Fe in alkaline conditions, even more so when excess Fe is present, coinciding with a reduced growth rate. Using a combination of Fe‐specific dyes, X‐ray fluorescence microscopy, and NanoSIMS, we show that the alkaline‐accumulated Fe was intracellularly sequestered into acidocalcisomes, which are localized towards the periphery of the cells. At high photon flux densities, Zn and Ca specifically over‐accumulate, while Zn alone accumulates at low temperatures. The impact of aeration was probed by reducing shaking speeds and changing vessel fill levels; the former increased the Cu quota of cultures, the latter resulted in a reduction in P, Ca, and Mn at low fill levels. Trace element quotas were also affected in the stationary phase, where specifically Fe, Cu, and Zn accumulate. Cu accumulation here depends inversely on the Fe concentration of the medium. Individual laboratory strains accumulate Ca, P, and Cu to different levels. All together, we identified a set of specific changes to growth rate, elemental composition, and the capacity to store Fe in response to subtle differences in culturing conditions of Chlamydomonas, affecting experimental reproducibility. Accordingly, we recommend that these variables be recorded and reported as associated metadata.
H3K4me3 plays a key role in establishing permissive chromatin states during bud dormancy and bud break in apple
Authors: Chen Wenxing , Tamada Yosuke , Yamane Hisayo , Matsushita Miwako , Osako Yutaro , Gao‐Takai Mei , Luo Zhengrong , Tao Ryutaro
Published: June 2022

Bud dormancy helps woody perennials survive winter and activate robust plant development in the spring. For apple (Malus × domestica), short‐term chilling induces bud dormancy in autumn, then prolonged chilling leads to dormancy release and a shift to a quiescent state in winter, with subsequent warm periods promoting bud break in spring. Epigenetic regulation contributes to seasonal responses such as vernalization. However, how histone modifications integrate seasonal cues and internal signals during bud dormancy in woody perennials remains largely unknown. Here, we show that H3K4me3 plays a key role in establishing permissive chromatin states during bud dormancy and bud break in apple. The global changes in gene expression strongly correlated with changes in H3K4me3, but not H3K27me3. High expression of DORMANCY‐ASSOCIATED MADS‐box (DAM) genes, key regulators of dormancy, in autumn was associated with high H3K4me3 levels. In addition, known DAM/SHORT VEGETATIVE PHASE (SVP) target genes significantly overlapped with H3K4me3‐modified genes as bud dormancy progressed. These data suggest that H3K4me3 contributes to the central dormancy circuit, consisting of DAM/SVP and abscisic acid (ABA), in autumn. In winter, the lower expression and H3K4me3 levels at DAMs and gibberellin metabolism genes control chilling‐induced release of dormancy. Warming conditions in spring facilitate the expression of genes related to phytohormones, the cell cycle, and cell wall modification by increasing H3K4me3 toward bud break. Our study also revealed that activation of auxin and repression of ABA sensitivity in spring are conditioned at least partly through temperature‐mediated epigenetic regulation in winter.
The toxic weed Heliotropium europaeum L.: Germination ecology, soil seed bank, and emergence dynamics in diversified cropping systems
Authors: Benvenuti Stefano
Published: June 2022

Heliotropium europaeum is a toxic annual weed that has been found with increasing frequency in the Mediterranean agro‐environment. We investigated, both in laboratory and in field, the ecological aspects of this species in order to verify a possible connection between cropping systems and population increase. Its germination, characterized by a high thermal optimum (about 35°C) is markedly reduced by burial. Strong depth‐mediated germination inhibition was observed with over 2 cm of burial. Nongerminated seeds undergo a secondary dormancy highlighting their ability to form a persistent seed bank. Indeed the seed bank analysis carried out in an agroecosystem based on minimum tillage cropping systems showed a seed accumulation in the shallowest soil layers. The hypothesis that poor seed burial plays a crucial role in the population dynamics of this species was confirmed by the drastic reduction in seedling emergence after only 1 year of plowing. A strongly reduced emergence percentage was shown which causes not only a lower seedling density but also a lower inflorescence density and respective seed ripening. In conclusion, there is a clear relationship between an increase in this species and cultivation systems based on minimum tillage.
An Alternative Approach to Compute Chip Thickness in Milling
Authors: Chen Kaidong , Zhang He , de Wouw Nathan van , Detournay Emmanuel
Published: June 2022

The accurate evaluation of the instantaneous undeformed chip thickness (IUCT) plays a crucial role in the modeling of milling processes. However, the vibrations of the tool–workpiece system can make conventional IUCT models either inaccurate or not applicable. This paper introduces the concept of surface function to describe the milled surface, through which the IUCT can be readily computed. The evolution of this surface function is governed by a partial differential equation (PDE) in the form of a balance law, and the material removal process is characterized by discontinuous conditions at the cutters. A finite volume algorithm is adopted to solve the proposed PDE with discontinuous conditions at the cutters. Through a case study of the asymmetric cutting process, the surface function method demonstrates two main advantages over conventional methods: (i) a detailed description of IUCT evolution considering the influence of the initial shape of the workpiece and (ii) a general framework to accurately compute the IUCT. This method shows a promising potential for computing the IUCT in numerical simulations of chattering phenomenon in the milling process.
Study on the Performance of the Low-Cost Cooling System for Transmit/Receive Module and Broadening the Exploitative Capabilities of the System Using Gravity Heat Pipes
Authors: Nikolaenko Yu. E. , Pekur D. V. , Kravets V. Yu. , Sorokin V. M. , Kozak D. V. , Melnyk R. S. , Lipnitskyi L. V. , Solomakha A. S.
Published: June 2022

The authors use computer simulation and experiment to study thermal characteristics of a less expensive design of the air cooling system for transmit/receive modules based on the heat sink with the dimensions of 25 × 324 × 500 mm made of mass-produced heat sink profile. The total power of the 8 transistors in the transmit/receive module is 224 W. It is shown that the increase in air velocity in the heat sink channels from 1 to 30 m/s causes an approximately twofold drop in the maximum temperature of the mounting surface (from 78.45 to 38.70 °C) and a decrease in thermal resistance of the cooling system by 3.16 (from 0.262 to 0.083 °C/W). The air velocity range from 5 to 10 m/s proves to be the most rational option. For the inlet air temperature of 20 °C, the temperature in the spots where the transistors are mounted remains below 56.3 °C for the air velocity of 5.5 m/s in the heat sink channels and below 51.8 °C for 10.5 m/s. A new original technical solution based on low-cost flat gravity heat pipes with a threaded evaporator will provide the efficiency of the cooling system at higher inlet air temperatures.
Conductive n-type gallium nitride thin films prepared by sputter deposition
Authors: Loretz Patrick , Tschirky Thomas , Isa Fabio , Patscheider Jörg , Trottmann Matthias , Wichser Adrian , Pedrini Jacopo , Bonera Emiliano , Pezzoli Fabio , Jaeger Dominik
Published: June 2022

Given the recent increase in the demand for gallium nitride (GaN) in different markets like optoelectronics and power devices, the request for epitaxially grown GaN will further increase. To meet this high demand, higher throughput and more economical manufacturing technologies must be advanced. In this work, GaN thin films are deposited by reactive sputter deposition from a liquid gallium target at a substrate temperature of 900 °C. The layers are grown epitaxially on c-plane oriented sapphire in an industrial-scale sputter tool from Evatec AG. Due to the growth rate of >1 nm/s and the fast substrate heat-up time, the throughput in a production setup can be increased compared to other GaN growth techniques. The resistivity of the intrinsic insulating GaN can be lowered by intentional Si doping during the sputter deposition process by three orders of magnitude. Thereby, conductive n-type GaN can be grown with different dopant amounts. The carrier mobility of the sputter deposited film is 45 cm2 V−1 s−1 at a carrier concentration of 1.1 × 1020 cm−3 based on room temperature Hall measurements using a van der Pauw geometry. The lowest resistivity reaches 1300 μΩ cm, which is confirmed by sheet resistance measurements. Undoped films exhibit an x-ray diffraction rocking curve full width at half maximum of 0.2°, which increases up to 0.5° for highly Si-doped layers. The presented results show that GaN prepared by reactive sputter deposition from a liquid gallium source is a viable alternative to conventional deposition techniques for GaN.
The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis
Authors: Moubarak Rana S. , de Pablos-Aragoneses Ana , Ortiz-Barahona Vanessa , Gong Yixiao , Gowen Michael , Dolgalev Igor , Shadaloey Sorin A. A. , Argibay Diana , Karz Alcida , Von Itter Richard , Vega-Sáenz de Miera Eleazar Carmelo , Sokolova Elena , Darvishian Farbod , Tsirigos Aristotelis , Osman Iman , Hernando Eva
Published: June 2022

The contribution of epigenetic dysregulation to metastasis remains understudied. Through a meta-analysis of gene expression datasets followed by a mini-screen, we identified Plant Homeodomain Finger protein 8 (PHF8), a histone demethylase of the Jumonji C protein family, as a previously unidentified prometastatic gene in melanoma. Loss- and gain-of-function approaches demonstrate that PHF8 promotes cell invasion without affecting proliferation in vitro and increases dissemination but not subcutaneous tumor growth in vivo, thus supporting its specific contribution to the acquisition of metastatic potential. PHF8 requires its histone demethylase activity to enhance melanoma cell invasion. Transcriptomic and epigenomic analyses revealed that PHF8 orchestrates a molecular program that directly controls the TGFβ signaling pathway and, as a consequence, melanoma invasion and metastasis. Our findings bring a mechanistic understanding of epigenetic regulation of metastatic fitness in cancer, which may pave the way for improved therapeutic interventions.
The role of the atypical chemokine receptor CCRL2 in myelodysplastic syndrome and secondary acute myeloid leukemia
Authors: Karantanos Theodoros , Teodorescu Patric , Perkins Brandy , Christodoulou Ilias , Esteb Christopher , Varadhan Ravi , Helmenstine Eric , Rajkhowa Trivikram , Paun Bogdan C. , Bonifant Challice , Dalton W. Brian , Gondek Lukasz P. , Moliterno Alison R. , Levis Mark J. , Ghiaur Gabriel , Jones Richard J.
Published: June 2022

The identification of new pathways supporting the myelodysplastic syndrome (MDS) primitive cells growth is required to develop targeted therapies. Within myeloid malignancies, men have worse outcomes than women, suggesting male sex hormone–driven effects in malignant hematopoiesis. Androgen receptor promotes the expression of five granulocyte colony-stimulating factor receptor–regulated genes. Among them,
CCRL2
encodes an atypical chemokine receptor regulating cytokine signaling in granulocytes, but its role in myeloid malignancies is unknown. Our study revealed that CCRL2 is up-regulated in primitive cells from patients with MDS and secondary acute myeloid leukemia (sAML). CCRL2 knockdown suppressed MDS92 and MDS-L cell growth and clonogenicity in vitro and in vivo and decreased JAK2/STAT3/STAT5 phosphorylation. CCRL2 coprecipitated with JAK2 and potentiated JAK2-STAT interaction. Erythroleukemia cells expressing JAK2V617F showed less effect of CCRL2 knockdown, whereas fedratinib potentiated the CCRL2 knockdown effect. Conclusively, our results implicate CCRL2 as an MDS/sAML cell growth mediator, partially through JAK2/STAT signaling.
Superconductivity in infinite-layer nickelate La
1−x
Ca
x
NiO
2
thin films
Authors: Zeng Shengwei , Li Changjian , Chow Lin Er , Cao Yu , Zhang Zhaoting , Tang Chi Sin , Yin Xinmao , Lim Zhi Shiuh , Hu Junxiong , Yang Ping , Ariando Ariando
Published: June 2022

We report the observation of superconductivity in infinite-layer Ca-doped LaNiO
2
(La

1−
x

Ca

x

NiO
2
) thin films and construct their phase diagram. Unlike the metal-insulator transition in Nd- and Pr-based nickelates, the undoped and underdoped La

1−
x

Ca

x

NiO
2
thin films are entirely insulating from 300 K down to 2 K. A superconducting dome is observed at 0.15 <
x
< 0.3 with weakly insulating behavior at the overdoped regime. Moreover, the sign of the Hall coefficient
R
H
changes at low temperature for samples with a higher doping level. However, distinct from the Nd- and Pr-based nickelates, the
R
H
-sign-change temperature remains at around 35 K as the doping increases, which begs further theoretical and experimental investigation to reveal the role of the 4f orbital to the (multi)band nature of the superconducting nickelates. Our results also emphasize a notable role of lattice correlation on the multiband structures of the infinite-layer nickelates.
HIV-1 Drug Resistance Assay Using Ion Torrent Next Generation Sequencing and On-Instrument End-to-End Analysis Software
Authors: Pyne Michael T. , Simmon Keith E. , Mallory Melanie A. , Hymas Weston C. , Stevenson Jeffery , Barker Adam P. , Hillyard David R.
Published: June 2022

HIV-1 antiretroviral therapy management requires sequencing the protease, reverse transcriptase, and integrase portions of the HIV-1
pol
gene. Most resistance testing is performed with Sanger sequencing, which has limited ability to detect minor variants.
HDA-2-Containing Complex Is Required for Activation of
Catalase-3
Expression in Neurospora crassa
Authors: He Lingaonan , Duan Zeyu , Yu Muqun , Qi Shaohua , Wang Ying , Lou Huiqiang , He Qun
Published: June 2022

Clearance of reactive oxygen species (ROS) is critical to the survival of aerobic organisms. In the model filamentous fungus
Neurospora crassa
,
catalase-3
(
cat-3
) expression is activated in response to H
2
O
2
-induced ROS stress.