bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of granulocyte colony‐stimulating factor on FOLFIRINOX‐induced neutropenia prevention: A population pharmacokinetic/pharmacodynamic approach
Authors: Macaire Pauline , Paris Justine , Vincent Julie , Ghiringhelli François , Bengrine‐Lefevre Leïla , Schmitt Antonin
Published: May 2020

Aims

Granulocyte colony‐stimulating factor (G‐CSF) is frequently prescribed to prevent chemotherapy‐induced neutropenia, but the administration schedule remains empirical in case of bimonthly chemotherapy such as FOLFIRINOX regimen. This pharmacokinetic/pharmacodynamic (PK/PD) study was performed to determine the effect of different G‐CSF regimens on the incidence and duration of neutropenia following FOLFIRINOX administration in order to propose an optimal G‐CSF dosing schedule.

Methods

A population PK/PD model was developed to describe individual neutrophil time course from absolute neutrophil counts (ANC) obtained in 40 advanced cancer patients receiving FOLFIRINOX regimen. The structural model considered ANC dynamics, neutropenic effect of cytotoxics and the stimulating effect of G‐CSF on neutrophils. Final model estimates were used to simulate different G‐CSF dosing schedules for 1000 virtual subjects. The incidence and duration of neutropenia were then calculated for different G‐CSF dosing schedules.

Results

The final model successfully described the myelosuppressive effect induced by the 3 cytotoxics for all patients. Simulations showed that pegfilgrastim administration reduced the risk of severe neutropenia by 22.9% for subjects with low ANC at the start of chemotherapy. Median duration in this group was also shortened by 3.1 days when compared to absence of G‐CSF. Delayed G‐CSF administration was responsible for higher incidence and longer duration of neutropenia compared to absence of administration.

Conclusion

The PK/PD model well described our population's ANC data. Simulations showed that pegylated‐G‐CSF administration 24 hours after the end of chemotherapy seems to be the optimal schedule to reduce FOLFIRINOX‐induced neutropenia. We also underline the potential negative effect of G‐CSF maladministration.
Diagnostic conversion from unipolar depression to bipolar disorder, schizophrenia, or schizoaffective disorder: A nationwide prospective 15‐year register study on 43 495 inpatients
Authors: Baryshnikov Ilya , Sund Reijo , Marttunen Mauri , Svirskis Tanja , Partonen Timo , Pirkola Sami , Isometsä Erkki T.
Published: May 2020

Objective

To examine temporal patterns and predictors for diagnostic conversion from unipolar depression (UD) to bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD).

Methods

A prospective nationwide register‐based cohort (n = 43 495) of all first psychiatric hospitalizations due to UD during 1996‐2011 was followed up to 15 years. We used cumulative incidence function (CIF) analyses and the Fine‐Gray subdistribution model to define the cumulative incidence of the conversions and subdistribution hazard ratios (SHRs) for predictors.

Results

The overall 15‐year cumulative incidence of conversion was 11.1% (95% CI 10.7‐11.6): 7.4% (95% CI 7.0‐7.8) for BD, 2.5% (95% CI 2.3‐2.7) for schizophrenia, and 1.3% (95% CI 1.1‐1.4) for SAD. The highest crude incidence rate emerged during the first year. Psychotic depression predicted higher conversion risk to BD (SHR = 2.0, 95% CI 1.5‐2.7), schizophrenia (SHR = 5.3, 95% CI 3.3‐8.7), and SAD (SHR = 10.6, 95% CI 4.0‐28.4) than mild depression. Female sex, greater overall disturbance, and comorbid personality disorder predicted conversion to BD, whereas young age and male sex to psychotic disorders.

Conclusions

Among patients with first hospitalization due to UD, approximately one in nine converts to another major psychiatric disorder during 15 years, with the highest risk occurring within the first year. Patients with psychotic depression are particularly vulnerable for conversion to other major psychiatric disorders. Conversion to psychotic disorders occurs earlier than to BD. Males are at higher risk for progression to psychotic disorders, whereas females, patients with recurrent depressive episodes, severe disturbance of overall functioning, and personality disorder are at higher risk for converting to BD.
Genomic analysis of multiple myeloma using targeted capture sequencing in the Japanese cohort
Authors: Kanamori Takashi , Sanada Masashi , Ri Masaki , Ueno Hiroo , Nishijima Dai , Yasuda Takahiko , Tachita Takuto , Narita Tomoko , Kusumoto Shigeru , Inagaki Atsushi , Ishihara Rei , Murakami Yuki , Kobayashi Nobuhiko , Shiozawa Yusuke , Yoshida Kenichi , Nakagawa Masahiro M. , Nannya Yasuhito , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Miyano Satoru , Horibe Keizo , Handa Hiroshi , Ogawa Seishi , Iida Shinsuke
Published: May 2020

Previous genomic studies have revealed the genomic landscape of myeloma cells. Although some of the genomic abnormalities shown are believed to be correlated to the molecular pathogenesis of multiple myeloma and/or clinical outcome, these correlations are not fully understood. The aim of this study is to elucidate the correlation between genomic abnormalities and clinical characteristics by targeted capture sequencing in the Japanese multiple myeloma cohort. We analysed 154 patients with newly diagnosed multiple myeloma. The analysis revealed that the study cohort consisted of a less frequent hyperdiploid subtype (37·0%) with relatively high frequencies of KRAS mutation (36·4%) and IGH‐CCND1 translocation (26·6%) compared with previous reports. Moreover, our targeted capture sequencing strategy was able to detect rare IGH‐associated chromosomal translocations, such as IGH‐CCND2 and IGH‐MAFA. Interestingly, all 10 patients harboured MAX mutations accompanied by 14q23 deletion. The patients with del(17p) exhibited an unfavourable clinical outcome, and the presence of KRAS mutation was associated with shorter survival in patients with multiple myeloma, harbouring IGH‐CCND1. Thus, our study provides a detailed landscape of genomic abnormalities, which may have potential clinical application for patients with multiple myeloma.
Detrital zircon age spectra of middle and upper Eocene outcrop belts, U.S. Gulf Coast region
Authors: Craddock William H. , Coleman James L. , Kylander‐Clark Andrew R. C.
Published: May 2020

Recently reported detrital zircon (DZ) data help to associate the Paleogene strata of the Gulf of Mexico region to various provenance areas. By far, recent work has emphasised upper Paleocene‐lower Eocene and upper Oligocene strata that were deposited during the two episodes of the highest sediment supply in the Paleogene. The data reveal a dynamic drainage history, including (1) initial routing of western Cordilleran drainages towards the Gulf of Mexico in the Paleocene, (2) an eastward shift of the western continental divide, from the Jura‐Cretaceous cordilleran arc to the eastern edge of the Laramide province after the Paleocene and (3) a southward shift, along the eastern Laramide province, of the headwaters of river systems draining to the Mississippi and Houston embayments at some time between the early Eocene and Oligocene. However, DZ characterisation of most (~20 Myr) of the middle Eocene‐lower Oligocene section remains limited. We present 60 DZ age spectra, most of which are from the middle or upper Eocene outcrop belts, with 50–200‐km spacing. We define six to eight distinct groups of DZ age spectra for middle and upper Eocene strata. Data from this and other studies resolve at least six substantial temporal changes in age spectra at various positions along the continental margin. The evolving age spectra constrain the middle and upper Eocene drainage patterns of large parts of interior North America. The most well‐resolved aspects of these drainage patterns include (1) persistent rivers that flowed from erosional landscapes across the Paleozoic Appalachian orogen either into the low‐lying Mississippi embayment or directly into the eastern Gulf; (2) at least during marine regressions, a trunk channel that likely flowed southward along the axial part of Mississippi Embayment and integrated tributaries from the east and west; and (3) rivers that flowed to the Houston embayment in the middle Eocene that likely originated in the Laramide province in central Colorado and southern Wyoming, as Precambrian basement highs in those source areas were being unroofed.
Household food insecurity and dental caries in Korean adults
Authors: Lee Min Hee , Park Jeong‐Won , Kwon Yu‐Jin
Published: May 2020

Objective

Food security is important to health maintenance and disease prevention. The aim of this study was to identify the association between household food insecurity and dental caries in Korean adults.

Method

Data from 14 770 adults included in the 2013‐2015 Korea National Health and Nutritional Survey were analysed. Household food insecurity was evaluated using the 18‐item US Household Food Security/Hunger Survey Module. General characteristics differences based on household food security were compared with weighted one‐way analysis of variance for continuous variables and weighted chi‐squared tests for categorical variables. A modified Poisson approach was used to calculate prevalence ratios and 95% confidence intervals (95% CIs).

Results

The prevalence of untreated dental caries in permanent teeth was 28.9% (CI;27.6, 30.2), 36.7% (33.0, 40.5) and 48.9% (40.0, 57.8) among individuals with household food security, household food insecurity without hunger and household food insecurity with hunger, respectively. Relative to those who were food‐secure, the prevalence ratios (95% CIs) for dental caries were 1.12 (0.97‐1.31) and 1.35 (1.02‐1.80) for those with household food insecurity without and with hunger, respectively, adjusting for age, sex, body mass index, socioeconomic status, life style, dietary and dental factors.

Conclusion

We found that household food insecurity is associated with prevalence of untreated dental caries in Korean adults. Healthcare providers ought to consider the important role that food security can play in the prevention and management of oral health in adults.
A homozygous variant in NDUFA8 is associated with developmental delay, microcephaly, and epilepsy due to mitochondrial complex I deficiency
Authors: Yatsuka Yukiko , Kishita Yoshihito , Formosa Luke E. , Shimura Masaru , Nozaki Fumihito , Fujii Tatsuya , Nitta Kazuhiro R. , Ohtake Akira , Murayama Kei , Ryan Michael T. , Okazaki Yasushi
Published: May 2020

Mitochondrial complex I deficiency is caused by pathogenic variants in mitochondrial and nuclear genes associated with complex I structure and assembly. We report the case of a patient with　NDUFA8‐related mitochondrial disease. The patient presented with developmental delay, microcephaly, and epilepsy. His fibroblasts showed apparent biochemical defects in mitochondrial complex I. Whole‐exome sequencing revealed that the patient carried a homozygous variant in NDUFA8. His fibroblasts showed a reduction in the protein expression level of not only NDUFA8, but also the other complex I subunits, consistent with assembly defects. The enzyme activity of complex I and oxygen consumption rate were restored by reintroducing wild‐typeNDUFA8 cDNA into patient fibroblasts. The functional properties of the variant in NDUFA8 were also investigated using NDUFA8 knockout cells expressing wild‐type or mutated NDUFA8 cDNA. These experiments further supported the pathogenicity of the variant in complex I assembly. This is the first report describing that the loss of NDUFA8, which has not previously been associated with mitochondrial disease, causes severe defect in the assembly of mitochondrial complex I, leading to progressive neurological and developmental abnormalities.
Ten years of experience with the Ponto bone‐anchored hearing system—A systematic literature review
Authors: Lagerkvist Helén , Carvalho Karin , Holmberg Marcus , Petersson Ulrika , Cremers Cor , Hultcrantz Malou
Published: May 2020

Background

Bone‐anchored hearing systems (BAHSs) are widely used for hearing rehabilitation and are indicated in cases of conductive and mixed hearing loss and in single‐sided deafness. The Ponto system, that is one available option, has been on the market since 2009.

Objective of review

The aim of this study is to systematically review the literature reporting on the Ponto system, with regard to audiological and surgical outcomes and patient's quality‐of‐life scores.

Type of review

A systematic literature search was performed in the PubMed database 2009‐July 2019.

Search strategy

Search term: ((osseointegrated hearing aid) OR (bone conduction implant) OR (bone anchored hearing) OR BAHA OR BAHS OR BAHI). Pre‐defined inclusion and exclusion criteria were applied.

Evaluation method

English‐language articles reporting original clinical data (audiological, surgical or quality‐of‐life outcomes) on the Ponto system were included.

Articles reporting on Ponto and another BAHS system where the results on Ponto constituted less than 50% of the patient population or including only results on testband or softband devices were excluded.

Results

Audiological outcomes were discussed in 20 publications. Improvement against the unaided thresholds was demonstrated. The functional improvement was on average 33.9 dB. The effective gain or remaining air‐bone gap was on average 6.7 dB. All evaluated data showed aided speech reception thresholds significantly below normal speech level. Twenty‐seven publications reported surgical and follow‐up data for the Ponto system. Implant survival was 97.7%, adverse skin reactions (Holgers ≥ 2) were 5% across visits and 15% across patients. No complications were life‐threatening, causing permanent disability/damage or requiring a hospitalisation. Five studies reported quality of life using the Glasgow benefit inventory, 98% reported an improvement when analysing the score on an individual level.

Conclusions

The outcomes of this systematic review confirm that percutaneous systems provide consistent audiological benefits and improved quality of life for patients. Further, the review demonstrates that the percutaneous systems are safe, with relatively low complication rates. Skin‐related complications are the most common complication type and are experienced by approximately one patient out of seven, or in less than one of 20 follow‐up visits.
Weight change before and after adenotonsillectomy in children: An analysis based upon pre‐surgery body mass category
Authors: Beauchamp Marshall T. , Regier Betsy , Nzuki Anne , Swinburne Romine Rebecca , Sweeney Brooke , Liu Mei , M. Davis Ann
Published: May 2020

Objectives

To determine the standardised body mass index (BMIz) trajectory before and after adenotonsillectomy/tonsillectomy between children in different weight classifications in a larger sample than has been studied previously, and to identify which patient factors would explain the difference in these outcomes.

Design

We used a retrospective chart review and leveraged data of weight status pre‐ and post‐adenotonsillectomy/tonsillectomy from a cohort of paediatric patients seen between May 2004 and April 2017.

Setting

Data were collected from an electronic medical record at a single Midwest paediatric health system.

Participants

The study population included a convenience sample of 1,751 paediatric patients who underwent adenotonsillectomy or tonsillectomy and had at least two height and weight measurements recorded on the same date both before and after surgery.

Main Outcome Measures

Change in BMIz trajectories before and after surgery.

Results

Of 1751 paediatric patients (ages 3‐11) underwent adenotonsillectomy/tonsillectomy procedures. Age at time of surgery and gender were not significant predictors. Children in different weight classifications demonstrated differences in BMIz trajectory after surgery. Children with overweight/obesity experience a decrease in BMIz, whereas children with underweight or normal weight experience an increase in BMIz.

Conclusions

Improvement in weight status is seen after surgery: increased BMI for those underweight and decreased BMI for those with overweight/obesity. We advocate for behavioural strategies as a first‐line treatment in children with underweight or overweight/obesity, and results suggest that coordinating these efforts alongside adenotonsillectomy/tonsillectomy when indicated for medical reasons may be warranted. However, further research is needed to confirm these findings due to the observational nature of this study.
Use of the COPD Assessment Test (CAT) to screen for COPD in dairy farmers: AIRBAg study
Authors: Jan Simon , Metten Marie‐Astrid , Chapron Anthony , Marette Solenne , Robert Ange‐Marie , Guillot Stéphanie , Mailloux Carole , Jouneau Stéphane , Viel Jean‐François ,   the AIRBAG research group
Published: May 2020

Objectives

People at risk of chronic obstructive pulmonary disease (COPD) can benefit from appropriate medical management before severe symptoms appear. This study assesses the value of the COPD Assessment Test (CAT) questionnaire for screening dairy farmers, who tend to be slow or reluctant to seek health care.

Methods

During the time period 2012‐2017, 2089 randomly selected dairy farmers in Brittany (France) were invited to complete self‐administered questionnaires (including the CAT) and to undergo an occupational health check‐up using an electronic mini‐spirometer and conventional spirometry. Those showing symptoms suggestive of COPD and/or a ratio FEV1/FEV6 < 80% were sent to a pulmonologist for a further check‐up, including spirometry with a reversibility test. Multivariate logistic models based on CAT scores and socio‐demographic or work‐related factors were developed to predict COPD.

Results

The 1231 farmers who underwent the occupational health check‐up included 1203 who met the inclusion/exclusion criteria. Pulmonologist identified 16 (1.3%) cases of COPD. A multivariate logistic regression model (covariates: CAT sum score, on‐farm time, BMI, smoking status, free‐stall mulching) provided an area under the receiver‐operating characteristic curve (AUC) of 0.87 (95% CI: 0.75‐0.98). Using a cut‐off of 0.007 gave a sensitivity of 93.8% and a specificity of 62.4%. Another model that included CAT breathlessness and the same covariates performed marginally better (AUC = 0.88, 95% CI: 0.77‐0.98).

Conclusion

Our predictive models can both benefit dairy farmers by providing early diagnosis and management of their COPD and avoid unnecessary, costly spirometry during the screening process.
Development of novel machine learning model for right ventricular quantification on echocardiography—A multimodality validation study
Authors: Beecy Ashley N. , Bratt Alex , Yum Brian , Sultana Razia , Das Mukund , Sherifi Ines , Devereux Richard B. , Weinsaft Jonathan W. , Kim Jiwon
Published: May 2020

Purpose

Echocardiography (echo) is widely used for right ventricular (RV) assessment. Current techniques for RV evaluation require additional imaging and manual analysis; machine learning (ML) approaches have the potential to provide efficient, fully automated quantification of RV function.

Methods

An automated ML model was developed to track the tricuspid annulus on echo using a convolutional neural network approach. The model was trained using 7791 image frames, and automated linear and circumferential indices quantifying annular displacement were generated. Automated indices were compared to an independent reference of cardiac magnetic resonance (CMR) defined RV dysfunction (RVEF < 50%).

Results

A total of 101 patients prospectively underwent echo and CMR: Fully automated annular tracking was uniformly successful; analyses entailed minimal processing time (<1 second for all) and no user editing. Findings demonstrate all automated annular shortening indices to be lower among patients with CMR‐quantified RV dysfunction (all P < .001). Magnitude of ML annular displacement decreased stepwise in relation to population‐based tertiles of TAPSE, with similar results when ML analyses were localized to the septal or lateral annulus (all P ≤ .001). Automated segmentation techniques provided good diagnostic performance (AUC 0.69–0.73) in relation to CMR reference and compared to conventional RV indices (TAPSE and S′) with high negative predictive value (NPV 84%–87% vs 83%–88%). Reproducibility was higher for ML algorithm as compared to manual segmentation with zero inter‐ and intra‐observer variability and ICC 1.0 (manual ICC: 0.87–0.91).

Conclusions

This study provides an initial validation of a deep learning system for RV assessment using automated tracking of the tricuspid annulus.
Effects of female body size and age and male mating status on male combat in Anastatus disparis (Hymenoptera: Eupelmidae)
Authors: Liu Peng‐Cheng , Wei Jian‐Rong , Han Xuan , Hao De‐Jun , Wang Zi‐Yi , Wang Zi‐Qi , Wang Qiong
Published: May 2020

1. Aggressive behaviour is widely exhibited by animals to acquire important resources and usually shows a dangerous or nondangerous pattern. Dangerous fighting patterns are usually characterized by fights ending with contestants being severely injured or killed. Resource value is an important nonstrategic factor influencing fighting behaviour. Studies of many species addressing nondangerous fighting behaviour have shown that when resource values change, organisms usually adjust their fighting behaviour accordingly. Only a few species show dangerous fighting patterns. Thus, few relevant studies have addressed how variation in resource value affects aggression with a dangerous fighting pattern.

2. Here, an egg parasitoid wasp, Anastatus disparis, which exhibits a dangerous fighting pattern to acquire mating opportunities, was used as an experimental model to study the adjustment of fighting behaviour resulting from a change in resource value.

3. Our results show that the female properties of body size and age affect their objective resource value and that males increased their fighting intensity for relatively large and young females. However, male mating status in A. disparis may not influence the subjective value of mate resources, and fighting intensity did not significantly differ between mated and virgin males. In addition, the number of times a male had previously mated had no significant effect. These results suggest that mating opportunities are important for both virgin and mated males, resulting in neither of them showing any adjustment in fighting for mating opportunities.

4. Generally, A. disparis males with extreme fighting patterns adjust their fighting behaviour according to the variation in resource value, which avoids the meaningless costs of injury and death.
Are Accommodations for English Learners on State Accountability Assessments Evidence‐Based? A Multistudy Systematic Review and Meta‐Analysis
Authors: Rios Joseph A. , Ihlenfeldt Samuel D. , Chavez Carlos
Published: May 2020

The objectives of this two‐part study were to: (a) investigate English learner (EL) accommodation practices on state accountability assessments of reading/English language arts and mathematics in grades 3–8, and (b) conduct a meta‐analysis of EL accommodation effectiveness on improving test performance. Across all distinct testing programs, we found that at least one EL test accommodation was provided for both test content areas. The most popular accommodations provided were supplying students with word‐to‐word dual language dictionaries, reading aloud test directions and items in English, and allowing flexible time/scheduling. However, we found minimal evidence that testing programs provide practitioners with recommendations on how to assign relevant accommodations to EL test takers’ English proficiency level. To evaluate whether accommodations used in practice are supported with evidence of their effectiveness, a meta‐analysis was conducted. On average, across 26 studies and 95 effect sizes (N = 11,069), accommodations improved test performance by .16 standard deviations. Both test content and sampling design were found to moderate accommodation effectiveness; however, none of the accommodations investigated were found to have intervention effects that were statistically different from zero. Overall, these results suggest that currently employed EL test accommodations lack evidence of their effectiveness.
Seizure detection at home: Do devices on the market match the needs of people living with epilepsy and their caregivers?
Authors: Bruno Elisa , Viana Pedro F. , Sperling Michael R. , Richardson Mark P.
Published: May 2020

In patients with epilepsy, the potential to prevent seizure‐related injuries and to improve the unreliability of seizure self‐report have fostered the development and marketing of numerous seizure detection devices for home use. Understanding the requirements of users (patients and caregivers) is essential to improve adherence and mitigate barriers to the long‐term use of such devices. Here we reviewed the evidence on the needs and preferences of users and provided an overview of currently marketed devices for seizure detection (medically approved or with published evidence for their performance). We then compared devices with known needs. Seizure‐detection devices are expected to improve safety and clinical and self‐management, and to provide reassurance to users. Key factors affecting a device’s usability relate to its design (attractive appearance, low visibility, low intrusiveness), comfort of use, confidentiality of recorded data, and timely support from both technical and clinical ends. High detection sensitivity and low false alarm rates are paramount. Currently marketed devices are focused primarily on the recording of non–electroencephalography (EEG) signals associated with tonic‐clonic seizures, whereas the detection of focal seizures without major motor features remains a clear evidence gap. Moreover, there is paucity of evidence coming from real‐life settings. A joint effort of clinical and nonclinical experts, patients, and caregivers is required to ensure an optimal level of acceptability and usability, which are key aspects for a successful continuous monitoring aimed at seizure detection at home.
Increased expression of miR‐338‐3p impairs Treg‐mediated immunosuppression in pemphigus vulgaris by targeting RUNX1
Authors: Xu Meinian , Liu Qingxiu , Li Songshan , Zhang Wenjing , Huang Xiaowen , Han Kai , Li Changxing , Zeng Kang
Published: May 2020

Pemphigus vulgaris (PV) is a regulatory T cell (Treg)‐associated autoimmune disease. Treg cells maintain immunosuppression by expressing the signature transcription factor FOXP3. MicroRNAs (miRNAs) have frequently emerged as regulators in Treg‐mediated immunosuppression. We previously found that miR‐338‐3p was overexpressed in the peripheral blood mononuclear cells of patients with PV. Herein, we explored the role of miR‐338‐3p in Treg‐mediated immunosuppression by quantitative real‐time polymerase chain reaction, analysis of public microarray data, miRNA transfection, Western blotting, flow cytometry, and luciferase reporter assays. Increased expression of miR‐338‐3p was detected in CD4+ T cells of active PV patients compared with those in healthy controls. Moreover, the miR‐338‐3p level was positively related to disease severity. Bioinformatics prediction revealed that Runt‐related transcription factor 1 (RUNX1), a gene activating FOXP3 expression, was a putative target of miR‐338‐3p. There was a reduction of FOXP3 and RUNX1 expression in the CD4+ T cells of patients with PV, along with significant correlations with the level of miR‐338‐3p. MiRNA transfection, mRNA and protein analysis, and luciferase reporter assays verified that miR‐338‐3p attenuated FOXP3 expression by targeting RUNX1. This study suggests that excessive expression of miR‐338‐3p attenuates the expression of FOXP3 by targeting RUNX1, contributing to Treg dysfunction in PV.
Attenuation of canonical NF‐κB signaling maintains function and stability of human Treg
Authors: Ziegler Liesa S. , Gerner Marlene C. , Schmidt Ralf L. J. , Trapin Doris , Steinberger Peter , Pickl Winfried F. , Sillaber Christian , Egger Gerda , Schwarzinger Ilse , Schmetterer Klaus G.
Published: May 2020

Nuclear factor ‘κ‐light‐chain‐enhancer’ of activated B cells (NF‐κB) signaling is a signaling pathway used by most immune cells to promote immunostimulatory functions. Recent studies have indicated that regulatory T cells (Treg) differentially integrate TCR‐derived signals, thereby maintaining their suppressive features. However, the role of NF‐κB signaling in the activation of human peripheral blood (PB) Treg has not been fully elucidated so far. We show that the activity of the master transcription factor forkhead box protein 3 (FOXP3) attenuates p65 phosphorylation and nuclear translocation of the NF‐κB proteins p50, p65, and c‐Rel following activation in human Treg. Using pharmacological and genetic inhibition of canonical NF‐κB signaling in FOXP3‐transgenic T cells and PB Treg from healthy donors as well as Treg from a patient with a primary NFKB1 haploinsufficiency, we validate that Treg activation and suppressive capacity is independent of NF‐κB signaling. Additionally, repression of residual NF‐κB signaling in Treg further enhances interleukin‐10 (IL‐10) production. Blockade of NF‐κB signaling can be exploited for the generation of in vitro induced Treg (iTreg) with enhanced suppressive capacity and functional stability. In this respect, dual blockade of mammalian target of rapamycin (mTOR) and NF‐κB signaling was accompanied by enhanced expression of the transcription factors FOXP1 and FOXP3 and demethylation of the Treg‐specific demethylated region compared to iTreg generated under mTOR blockade alone. Thus, we provide first insights into the role of NF‐κB signaling in human Treg. These findings could lead to strategies for the selective manipulation of Treg and the generation of improved iTreg for cellular therapy.
Gastric microbiota and Helicobacter pylori in Indonesian population
Authors: Miftahussurur Muhammad , Waskito Langgeng Agung , El‐Serag Hashem B , Ajami Nadim J. , Nusi Iswan Abbas , Syam Ari Fahrial , Matsumoto Takashi , Rezkitha Yudith Annisa Ayu , Doohan Dalla , Fauzia Kartika Afrida , Maimunah Ummi , Sugihartono Titong , Uchida Tomohisa , Yamaoka Yoshio
Published: May 2020

Background

The profile of gastric mucosal microbiota has not yet been described in the Indonesian population where the prevalence of Helicobacter pylori is low.

Methods

This is a cross‐sectional study analyzing 16S rRNA of 137 gastric biopsy specimens. We analyzed the association between gastric microbiota, H. pylori infection, and gastric mucosal damage.

Result

Among 137 analyzed samples, 27 were H. pylori‐positive and 110 were H. pylori ‐negative based on culture, histology, and 16S rRNA gene analysis. Significantly lower α‐diversity parameters, including Pielou's index, was observed in H. pylori‐infected individuals compared with noninfected individuals (all P < .001). Among H. pylori‐negative individuals, the permutational analysis of variance of Bray‐Curtis dissimilarity distances showed a significant association with different ethnicities, suggesting some ethnic groups had specific microbiota profiles based on the presence of different operational taxonomic units. The linear discriminant analysis effect size (LEfSe) of the H. pylori‐negative group showed significant associations between the presence of Micrococcus luteus and Sphingomonas yabuuchiae with Timor and Papuan ethnicities, respectively. The presence of Bulledia sp and Atopobium sp was associated with the Javanese ethnicity. We observed lower α‐diversity scores in individuals with gastric mucosal damage and profiles with high abundances of Paludibacter sp and Dialister sp based on LEfSe analysis.

Conclusion

Our findings suggest the presence of H. pylori is more correlated with a distinct microbiome profile than ethnic precedence.
Nesting outcomes under anthropogenic change – effects of changing climate and nestbox provision on the reproduction of Great TitsParus major
Authors: Bodey Thomas W. , Barnett Russell , du Feu Christopher R. , Clark John R. , Bearhop Stuart
Published: May 2020

Global anthropogenic changes are significantly impacting the ecology and evolution of many species. Among temperate taxa, changes to reproductive phenology as a result of warming springs are apparent. However, how such responses to abiotic change interact with biotic impacts resulting from human management interventions are less clear. Here we examine the response of a range of breeding metrics (laying date, clutch size, hatching and fledging success) to interactions between climatic variables and changes in conspecific density (and hence intraspecific competition) resulting from changes in nestbox provision. Using a 37‐year dataset on the Great TitParus majorwe found little evidence for interacting effects of these two drivers. Instead we found that either climatic or competitive effects were the key influence on different metrics. Annual mean laying date substantially advanced with a warming climate, whereas clutch size, hatching success and fledging success were significantly inversely associated with conspecific density. Annual variance in clutch size and hatching success increased weakly with measures of conspecific density, but there was no association between either climatic or density measures and the annual variance in laying date or fledging success. Increasing conspecific densities therefore resulted in years with lower, but more variable, reproductive rates. These results highlight the importance of adaptive provisioning of nestboxes to enhance reproductive output of hole‐nesting birds regardless of climate‐induced phenological change. Such management is likely to be appropriate for assisting with sustaining populations responding to a changing climate.
Brain Drain Losses – A Case Study of Serbia
Authors: Radonjić Ognjen , Bobić Mirjana
Published: May 2020

The focus of this paper is on an attempt to quantify economic losses due to ongoing and vast brain drain emigration from Serbia. We claim that socio‐economic losses in terms of implicit and explicit costs related to upbringing and education of emigrants as well as lost production are paramount. Therefore, the main argument is in line with pessimistic stances on migration and its effect on Serbian development. Massive emigration, especially of educated individuals, results in a great number of incalculable deficits for the country, which cannot be expressed and measured in monetary terms only. The authors argue that these are even more striking when viewed from a holistic perspective factoring in demographic, social, political, cultural and intellectual impacts. It is also shown how emigration of the highly educated greatly undermines local democracy and social cohesion in Serbia. Nevertheless, the authors also take note of contemporary transnational perspectives on migration and development and present possible policies aimed at exploiting advantages of human capital and social networks of migrants and diaspora, circular mobility and returns.
Holistic Mission in a Wounded World
Authors: Kääriäinen Jukka A.
Published: May 2020

Holistic mission, while widely used as a helpful articulation of the missio Dei, contains within itself a dilemma: if everything is mission, then nothing is mission (Anglican Bishop Stephen Neill). In its adoption of development studies language and practice of diakonia and development, contemporary holistic mission runs the ironic risk of not being holistic enough. To the extent that holistic mission “flattens” a holistic view of the scriptural, narrative arc of salvation into an immanent dimension, to the extent that it focuses on human injustice and structural manifestations of evil at the expense of personal, cosmic, and spiritual evil, to that extent holistic mission runs the risk of oversimplifying the challenge facing missions and risks offering a Band‐Aid to deep, life‐threatening wounds in a dying world. Miroslav Volf's distinction of primary and secondary, ultimate and penultimate flourishing is helpful in maintaining a clear vision of the whole arc of Christian salvation, including creation, sin, fall, redemption, and final consummation. Martin Luther's pastoral theology of holistic evil is helpful in delineating the breadth of personal, structural, and cosmic evil which Christian mission hopes to address.

Missiology has responded to the deep trauma of the 20th century by emphasizing missio ad vulnera, mission to the wounded. In the construction of an adequate mission to the wounds, the interweaving of a spiritual imagination, robust Christology, and theology of holistic evil are needed. Using Luther's insights into holistic evil can serve the construction of a robust missio ad vulnera, a missiology sufficiently rigorous in breadth and depth to face the multifaceted wounds and extensive evil in today's world. Holistic mission desperately needs a holistic vision of evil. Luther will serve as an unexpected, helpful ally in this regard.
The Catholic Church’s Mission with the Marginalized
Authors: Alva Reginald
Published: May 2020

The Catholic Church’s primary mission is to spread the kingdom of God. In the broader sense, the kingdom of God means the reign of righteousness, justice, and peace. However, widespread social, political, and economic inequity tramples the rights of the weak. The church wields tremendous power and influence in the world. However, at times it has failed miserably to protect the weakest. The various scandals within the church call for thorough introspection and repentance. Church authorities need to alter power structures radically to empower the poor and the marginalized. In this paper, I shall refer to Pope Francis’s Apostolic Exhortation Evangelii gaudium to propose concrete steps the church could take to reach out to the marginalized, heal their wounds, and collaborate with them to spread the kingdom of righteousness, justice, and peace in this world. Apart from Evangelii gaudium, I shall also refer to the documents on the social teachings of the Catholic Church and the views of experts in this field.
Pricing and order quantity of substitutes in two inventory‐related markets
Authors: Rasouli Nadia , Amin‐Naseri Mohammad Reza , Zaccour Georges
Published: May 2020

We determine optimal pricing and order quantity of two substitute products in two markets, one of them is seasonal, with a decreasing market potential over time, and the other is nonseasonal. The two markets are sealed, that is, the prices in one market are irrelevant to consumers in the other market. Still, the two markets are linked through inventories and the order quantity policy. In the paper, we develop a nonlinear model, in which seasonal demand depends on time and on both products' prices, while nonseasonal demand is time‐invariant and is the function of both products' prices. Then, we provide an algorithm to compute the optimal solution. An illustrative example is given along with a sensitivity analysis. Among other results, we obtain that dynamic pricing and accounting for substitution effect lead to more profit. Also, when both ordering and holding costs are high, it is beneficial for the firm to order fewer times in large sizes.
The provably good parallel seeding algorithms for the k‐means problem with penalties
Authors: Li Min , Xu Dachuan , Zhang Dongmei , Zhou Huiling
Published: May 2020

As a classic NP‐hard problem in machine learning and computational geometry, the k‐means problem aims to partition the given points into k sets to minimize the within‐cluster sum of squares. The k‐means problem with penalties (k‐MPWP), as a generalizing problem of the k‐means problem, allows a point that can be either clustered or penalized with some positive cost. In this paper, we mainly apply the parallel seeding algorithm to the k‐MPWP, and show sufficient analysis to bound the expected solution quality in the case where both the number of iterations and the number of points sampled in each iteration can be given arbitrarily. The approximate guarantee can be obtained as , where is a polynomial function involving the maximal ratio M between the penalties. On one hand, this result can be viewed as a further improvement on the parallel algorithm for k‐MPWP given by Li et al., where the number of iterations depends on other factors. On the other hand, our result also generalizes the one solving the k‐means problem presented by Bachem et al., because k‐MPWP is a variant of the k‐means problem. Moreover, we present a numerical experiment to show the effectiveness of the parallel algorithm for k‐means with penalties.
Optimal seat allocation strategy for e‐sports gaming center
Authors: Kwag Sungil , Lee Woo Jin , Ko Young Dae
Published: May 2020

This paper investigates the seat allocation issues for an e‐sports gaming center where people generally visit in groups to play games while eating. According to the data analysis, as the number of customers in a group gets larger, the revenue per person tends to get higher. The data analysis to identify the information, such as revenue and the stay time of customers is conducted, and operations research is applied to derive the optimal seat allocation strategy. Through a numerical experiment with actual data, it is discovered that small groups of customers can also be prioritized in the same way as groups with larger numbers due to the fluctuating revenue generated by each group of customers during every timeslot. Furthermore, the opportunity cost that occurs by blocking customers even if there are available seats to accommodate the larger groups of customers who provide bigger revenue at various timeslots is considered.
They should have known: Hindsight and outcome biases in child abduction cases
Authors: McDermott Christine M. , Miller Monica K. , DeVault Alicia
Published: May 2020

Two cognitive biases might partially account for public support of the ineffective AMBER Alert system. Hindsight bias is a cognitive error in which people with outcome knowledge overestimate the likelihood that this particular outcome would occur; outcome bias is an error made in evaluating the quality of a decision once the outcome is known. Two experiments assessed whether hindsight and outcome bias occur in child abduction scenarios. Study 1 was a pre/posttest experiment that examined whether hindsight bias occurs in situations in which the identity of the abductor (stranger or parent) is manipulated between groups, and all participants are told the child was killed. Study 2, a between‐subjects experiment, examined whether hindsight and outcome biases occur in situations in which no AMBER Alert was issued (because the situation did not meet the legal requirements to issue an Alert), and manipulated the identity of the abductor and the outcome (child safely returned, killed, or not outcome provided). Hindsight and outcome biases occurred in both studies, given the correct set of circumstances. Abductor identity also impacted outcome estimates. Results from the two studies indicate that hindsight and outcome bias occur, but this is dependent on the outcome (child killed, child returned safely, no outcome provided) and the identity of the abductor (stranger, dangerous parent, non‐dangerous parent). Limitations and future directions are discussed.
Experience counts: The role of female age in morning incubation and brooding behavior in relation to temperature
Authors: Williams Kelly , Sudnick Madeline , Anderson Rachel , Fitschen‐Brown Meredith
Published: May 2020

Reproductive experience can impact how individuals allocate time and energy to reproduction and generate differences in reproductive behavior that leads to experience dependent variation in reproductive success. In order to understand if individual variation in parental behavior is related to environmental temperature and breeding experience, we observed the timing and duration of the first morning off bout in a wild, open cup nesting passerine bird during the incubation and early nestling period. We compared incubation behaviors and nest temperature of inexperienced (second year = first breeding season) and experienced (after second year) female hooded warblers Setophaga citrina. Females left the nest earlier on colder mornings suggesting an energetic constraint due to the long overnight on bout during colder temperatures. During incubation, females increased the duration of the first morning off bout with increasing temperature. Similarly, during the early nestling period, experienced females had shorter off bout duration on colder mornings and increased duration with warmer temperatures. In contrast, inexperienced females increased off bout duration with colder morning temperatures. Experienced females maintained higher nest temperatures and higher minimum nest temperatures compared to inexperienced females. We also found evidence that experienced females nested in microhabitats with higher minimum morning temperature which may buffer older females from colder daily extremes and enable older females to maintain higher nest temperatures. While we found no relationship between incubation and brooding behaviors and fledging success, the proportion of the clutch that hatched was positively related to minimum nest temperature. The ability of experienced females to maintain higher minimum nest temperatures and to adjust brooding behaviors during colder mornings is a potential mechanism that has consequences for nestling condition in a wild population. Our results highlight the need to examine experience‐related parental care behaviors in responding to environmental variation.
Lung CSC‐derived exosomal miR‐210‐3p contributes to a pro‐metastatic phenotype in lung cancer by targeting FGFRL1
Authors: Wang Li , He Jun , Hu Haoyue , Tu Li , Sun Zhen , Liu Yanyang , Luo Feng
Published: May 2020

Lung cancer has the highest mortality rate among human cancers, and the majority of deaths can be attributed to metastatic spread. Lung cancer stem cells (CSCs) are a component of the tumour microenvironment that contributes to this process. Exosomes are small membrane vesicles secreted by all types of cells that mediate cell interactions, including cancer metastasis. Here, we show that lung CSC‐derived exosomes promote the migration and invasion of lung cancer cells, up‐regulate expression levels of N‐cadherin, vimentin, MMP‐9 and MMP‐1, and down‐regulate E‐cadherin expression. Moreover, we verified that these exosomes contribute to a pro‐metastatic phenotype in lung cancer cells via miR‐210‐3p transfer. The results of bioinformatics analysis and dual‐luciferase reporter assays further indicated that miR‐210‐3p may bind to fibroblast growth factor receptor‐like 1 (FGFRL1); silencing FGFRL1 enhanced the metastatic ability of lung cancer cells, whereas overexpressing FGFRL1 suppressed metastasis. Taken together, our results provide new insights into a potential molecular mechanism whereby lung CSC‐derived exosomal miR‐210‐3p targets FGFRL1 to promote lung cancer metastasis. FGFRL1 may be a promising therapeutic target in lung cancer.