bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers
Authors: Viswanadhapalli Suryavathi , Ma Shihong , Sareddy Gangadhara Reddy , Lee Tae-Kyung , Li Mengxing , Gilbreath Collin , Liu Xihui , Luo Yiliao , Pratap Uday P. , Zhou Mei , Blatt Eliot B. , Kassees Kara , Arteaga Carlos , Alluri Prasanna , Rao Manjeet , Weintraub Susan T. , Tekmal Rajeshwar Rao , Ahn Jung-Mo , Raj Ganesh V. , Vadlamudi Ratna K.
Published: December 2019

Background

CDK4/6 inhibitors in combination with endocrine therapy (AE/AI/SERDs) are approved for the treatment of ER+ advanced breast cancer (BCa). However, not all patients benefit from CDK4/6 inhibitors therapy. We previously reported a novel therapeutic agent, ERX-11, that binds to the estrogen receptor (ER) and modulates ER-coregulator interactions. Here, we tested if the combination of ERX-11 with agents approved for ER+ BCa would be more potent.

Methods

We tested the effect of combination therapy using BCa cell line models, including those that have acquired resistance to tamoxifen, letrozole, or CDK4/6 inhibitors or have been engineered to express mutant forms of the ER. In vitro activity was tested using Cell Titer-Glo, MTT, and apoptosis assays. Mechanistic studies were conducted using western blot, reporter gene assays, RT-qPCR, and mass spectrometry approaches. Xenograft, patient-derived explants (PDEs), and xenograft-derived explants (XDE) were used for preclinical evaluation and toxicity.

Results

ERX-11 inhibited the proliferation of therapy-resistant BCa cells in a dose-dependent manner, including ribociclib resistance. The combination of ERX-11 and CDK4/6 inhibitor was synergistic in decreasing the proliferation of both endocrine therapy-sensitive and endocrine therapy-resistant BCa cells, in vitro, in xenograft models in vivo, xenograft-derived explants ex vivo, and in primary patient-derived explants ex vivo. Importantly, the combination caused xenograft tumor regression in vivo. Unbiased global mass spectrometry studies demonstrated profound decreases in proliferation markers with combination therapy and indicated global proteomic changes in E2F1, ER, and ER coregulators. Mechanistically, the combination of ERX-11 and CDK4/6 inhibitor decreased the interaction between ER and its coregulators, as evidenced by immunoprecipitation followed by mass spectrometry studies. Biochemical studies confirmed that the combination therapy significantly altered the expression of proteins involved in E2F1 and ER signaling, and this is primarily driven by a transcriptional shift, as noted in gene expression studies.

Conclusions

Our results suggest that ERX-11 inhibited the proliferation of BCa cells resistant to both endocrine therapy and CDK4/6 inhibitors in a dose-dependent manner and that the combination of ERX-11 with a CDK4/6 inhibitor may represent a viable therapeutic approach.
Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer
Authors: Nederlof Iris , De Bortoli Davide , Bareche Yacine , Nguyen Bastien , de Maaker Michiel , Hooijer Gerrit K. J. , Buisseret Laurence , Kok Marleen , Smid Marcel , Van den Eynden Gert G. G. M. , Brinkman Arie B. , Hudecek Jan , Koster Jan , Sotiriou Christos , Larsimont Denis , Martens John W. M. , van de Vijver Marc J. , Horlings Hugo M. , Salgado Roberto , Biganzoli Elia , Desmedt Christine
Published: December 2019

Background

Breast cancer (BC) immune infiltrates play a critical role in tumor progression and response to treatment. Besides stromal tumor infiltrating lymphocytes (sTILs) which have recently reached level 1B evidence as a prognostic marker in triple negative BC, a plethora of methods to assess immune infiltration exists, and it is unclear how these compare to each other and if they can be used interchangeably.

Methods

Two experienced pathologists scored sTIL, intra-tumoral TIL (itTIL), and 6 immune cell types (CD3+, CD4+, CD8+, CD20+, CD68+, FOXP3+) in the International Cancer Genomics Consortium breast cancer cohort using hematoxylin and eosin-stained (n = 243) and immunohistochemistry-stained tissue microarrays (n = 254) and whole slides (n = 82). The same traits were evaluated using transcriptomic- and methylomic-based deconvolution methods or signatures.

Results

The concordance correlation coefficient (CCC) between pathologists for sTIL was very good (0.84) and for cell-specific immune infiltrates slightly lower (0.63–0.66). Comparison between tissue microarray and whole slide pathology scores revealed systematically higher values in whole slides (ratio 2.60–5.98). The Spearman correlations between microscopic sTIL and transcriptomic- or methylomic-based assessment of immune infiltrates were highly variable (r = 0.01–0.56). Similar observations were made for cell type-specific quantifications (r = 0.001–0.54). We observed a strong inter-method variability between the omics-derived estimations, which is further cell type dependent. Finally, we demonstrated that most methods more accurately identify highly infiltrated (sTIL ≥ 60%; area under the curve, AUC, 0.64–0.99) as compared to lowly infiltrated tumors (sTIL ≤ 10%; AUC 0.52–0.82).

Conclusions

There is a lower inter-pathologist concordance for cell-specific quantification as compared to overall infiltration quantification. Microscopic assessments are underestimated when considering small cores (tissue microarray) instead of whole slides. Results further highlight considerable differences between the microscopic-, transcriptomic-, and methylomic-based methods in the assessment of overall and cell-specific immune infiltration in BC. We therefore call for extreme caution when assessing immune infiltrates using current methods and emphasize the need for standardized immune characterization beyond TIL.
Establishment of an innovative and sustainable PCR technique for 1534 locus mutation of the knockdown resistance (kdr) gene in the dengue vector Aedes albopictus
Authors: Zhu Cai-Ying , Zhao Chun-Chun , Wang Yi-Guan , Ma De-Ling , Song Xiu-Ping , Wang Jun , Meng Feng-Xia
Published: December 2019

Background

Mutation of the voltage-gated sodium channel (VGSC) gene, or knockdown resistance (kdr) gene, is an important resistance mechanism against DDT and pyrethroids for dengue vectorAedes albopictus. A phenylalanine to serine (F1534S), leucine (F1534L) and cysteine (F1534C) substitution were detected in manyAe. albopictuspopulations around the world, and the mutant allele frequencies have been increasing in recent years. Therefore, it is essential to establish a simple, time-saving and cost-effective procedure to monitor the alleles in large-scale studies.

Methods

Based on the mutation genotypes of the 1534 locus in thekdrgene, F/F, F/S, F/C, F/L, S/S, C/C, L/L and S/C, we designed specific forward and reverse primers and optimized the reaction conditions for establishing of the allele-specific PCR(AS-PCR) detection technique. DNA sequencing in this study was taken as the gold standard, and used to determine the accuracy of AS-PCR.

Results

The designed AS-PCR technique showed high specificity for distinguishing the mutations at the 1534 locus, as the accuracy for F/F, F/S, F/C, F/L, S/S, C/C and S/C were 100%, 95.35%, 100%, 100%, 100%, 100% and 100%, respectively.

Conclusions

The designed AS-PCR technique effectively distinguished individual genotypes for the mutations at the 1534 locus in thekdrgene, which could facilitate the knockdown resistance surveillance inAe. albopictusin large-scale studies.
Draft genome of Ompok bimaculatus (Pabda fish)
Authors: Dhar Ruby , Pethusamy Karthikeyan , Singh Sunil , Mukherjee Indrani , Seethy Ashikh , Sengupta Bharoti , Srivastava Tryambak , Sarkar Sajib , Mandal Vikramjit , Karmakar Madhumita , Gupta Sandipan , Ghosh Arpita , Karmakar Subhradip
Published: December 2019

Objective

Pabda (Ompok bimaculatus) is a freshwater catfish, largely available in Asian countries, especially in Bangladesh, India, Pakistan and Nepal. This fish is highly valued for its fabulous taste and high nutritional value and is very popular as a rich source of proteins, omega-3 and omega-6 fatty acids, vitamins and mineral for growing children, pregnant females and elders. We performed de-novo sequencing of Ompok bimaculatus using a hybrid approach and present here a draft assembly for this species for the first time.

Data Description

The genome of Ompok bimaculatus (Fig. 1: Table 1, Data file 3) from Ganges river, has been sequenced by hybrid approach using Illumina short reads and PacBio long reads followed by structural annotations. The draft genome assembly was found to be 718 Mb with N50 size of 81 kb. MAKER gene annotation tool predicted 21,371 genes.
Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients
Authors: Delacrétaz Aurélie , Glatard Anaïs , Dubath Céline , Gholam-Rezaee Mehdi , Sanchez-Mut Jose Vicente , Gräff Johannes , von Gunten Armin , Conus Philippe , Eap Chin B.
Published: December 2019

Background

Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples.

Results

Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03).

Conclusions

These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.
Positive bound state solutions for the nonlinear Schrödinger–Poisson systems with potentials
Authors: Yang Jing
Published: December 2019

In this paper, we study the following Schrödinger–Poisson system in $\mathbb{R} ^{3}$R3$$ \textstyle\begin{cases} (-\Delta )^{\sigma }u+A(y)u+B(y)\phi (y)u=b(y) \vert u \vert ^{p-1}u, & y \in \mathbb{R} ^{3}, \\ (-\Delta )^{\sigma }\phi =B(y)u^{2}, & y\in \mathbb{R} ^{3}, \end{cases} $${(−Δ)σu+A(y)u+B(y)ϕ(y)u=b(y)|u|p−1u,y∈R3,(−Δ)σϕ=B(y)u2,y∈R3, with $\frac{3}{4}<\sigma <1$34<σ<1, $p\in (3,\frac{3+2\sigma }{3-2 \sigma })$p∈(3,3+2σ3−2σ). Then, under some suitable assumptions on the coefficients not requiring any symmetry property, we prove the existence of a bound state solution of the above problem.
Egg rejection behavior does not explain the lack of cowbird parasitism on an eastern North American population of Red-winged Blackbirds
Authors: Reel Justin J. , Underwood Todd J.
Published: December 2019

Background

Red-winged Blackbirds (Agelaius phoeniceus), hereafter red-wings, are much less frequently parasitized by Brown-headed Cowbirds (Molothrus ater) in eastern North America than in central North America and had not been recorded as hosts in our study area in southeastern Pennsylvania. Although hosts of Old World cuckoos (Cuculidae) often show geographic variation in egg rejection behavior, cowbird hosts typically exhibit uniform responses of all acceptance or all rejection of cowbird eggs. Thus, geographic variation in cowbird parasitism frequencies might reflect a different behavioral response to parasitism by hosts where only some populations reject parasitism. In this study, we tested whether egg rejection behavior may explain the lack of parasitism observed in our eastern red-wing population, which may provide insight into low parasitism levels across eastern North America.

Methods

We parasitized red-wing nests with model cowbird eggs to determine their response to parasitism. Nests were tested across three nest stages and compared to control nests with no manipulations. Because rejection differed significantly by stage, we compared responses separately for each nest stage. We also monitored other songbird nests to identify parasitism frequencies on all potential hosts.

Results

Red-wings showed significantly more rejections during the building stage, but not for the laying and incubation stages. Rejections during nest building involved mostly egg burials, which likely represent a continuation of the nest building process rather than true rejection of the cowbird egg. Excluding these responses, red-wings rejected 15% of cowbird eggs, which is similar to rejection levels from other studies and populations. The overall parasitism frequency on 11 species surveyed in our study area was only 7.4%.

Conclusions

Egg rejection behavior does not explain the lack of parasitism on red-wings in our eastern population. Alternatively, we suggest that cowbird preference for other hosts and the low abundance of cowbirds in the east might explain the lack of parasitism. Future research should also explore cowbird and host density and the makeup of the host community to explain the low levels of parasitism on red-wings across eastern North America because egg rejection alone is unlikely to explain this broad geographic trend.
Quantitative implications of the updated EARL 2019 PET–CT performance standards
Authors: Kaalep Andres , Burggraaff Coreline N. , Pieplenbosch Simone , Verwer Eline E. , Sera Terez , Zijlstra Josee , Hoekstra Otto S. , Oprea-Lager Daniela E. , Boellaard Ronald
Published: December 2019

Purpose

Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET–CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1).

Methods

Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET–CT studies were used to derive four image datasets—the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4).

Results

We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23–30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed.

Conclusions

Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data.
Towards standardization of absolute SPECT/CT quantification: a multi-center and multi-vendor phantom study
Authors: Peters Steffie M. B. , van der Werf Niels R. , Segbers Marcel , van Velden Floris H. P. , Wierts Roel , Blokland Koos A. K. , Konijnenberg Mark W. , Lazarenko Sergiy V. , Visser Eric P. , Gotthardt Martin
Published: December 2019

Absolute quantification of radiotracer distribution using SPECT/CT imaging is of great importance for dosimetry aimed at personalized radionuclide precision treatment. However, its accuracy depends on many factors. Using phantom measurements, this multi-vendor and multi-center study evaluates the quantitative accuracy and inter-system variability of various SPECT/CT systems as well as the effect of patient size, processing software and reconstruction algorithms on recovery coefficients (RC).

Methods

Five SPECT/CT systems were included: Discovery™ NM/CT 670 Pro (GE Healthcare), Precedence™ 6 (Philips Healthcare), Symbia Intevo™, and Symbia™ T16 (twice) (Siemens Healthineers). Three phantoms were used based on the NEMA IEC body phantom without lung insert simulating body mass indexes (BMI) of 25, 28, and 47 kg/m2. Six spheres (0.5–26.5 mL) and background were filled with 0.1 and 0.01 MBq/mL 99mTc-pertechnetate, respectively. Volumes of interest (VOI) of spheres were obtained by a region growing technique using a 50% threshold of the maximum voxel value corrected for background activity. RC, defined as imaged activity concentration divided by actual activity concentration, were determined for maximum (RCmax) and mean voxel value (RCmean) in the VOI for each sphere diameter. Inter-system variability was expressed as median absolute deviation (MAD) of RC. Acquisition settings were standardized. Images were reconstructed using vendor-specific 3D iterative reconstruction algorithms with institute-specific settings used in clinical practice and processed using a standardized, in-house developed processing tool based on the SimpleITK framework. Additionally, all data were reconstructed with a vendor-neutral reconstruction algorithm (Hybrid Recon™; Hermes Medical Solutions).

Results

RC decreased with decreasing sphere diameter for each system. Inter-system variability (MAD) was 16 and 17% for RCmean and RCmax, respectively. Standardized reconstruction decreased this variability to 4 and 5%. High BMI hampers quantification of small lesions (< 10 ml).

Conclusion

Absolute SPECT quantification in a multi-center and multi-vendor setting is feasible, especially when reconstruction protocols are standardized, paving the way for a standard for absolute quantitative SPECT.
A case of subcutaneous emphysema/mediastinal emphysema during the use of humidified high-flow nasal cannula
Authors: Sonobe Shota , Inoue Satoki , Nishiwada Tadashi , Egawa Junji , Kawaguchi Masahiko
Published: December 2019

Background

Heated, humidified, high-flow nasal cannula (HHFNC) oxygen therapy allows optimal humidification of inspired gas at high flows and creates a distending pressure similar to nasal continuous positive airway pressure [1]. It has been safely used in adults with moderate hypoxemia with few complications [2, 3]. Hereby, we report serious complications occurred during HHFNC oxygen therapy.

Case presentation

A 53-year-old female with hemophagocytic lymphohistiocytosis (HLH) was admitted to the intensive care unit because of respiratory failure. After weaning from mechanical ventilation which lasted for 2 weeks, HHFNC therapy at 40 L/min with an FiO2 of 0.5 was started for hypoxemia. Four days later, dyspnea and hypoxemia occurred and chest X-ray and CT scan revealed localized pneumothorax, subcutaneous emphysema, and massive pneumomediastinum. After cessation of HHFNC, respiratory condition improved.

Conclusion

Subcutaneous emphysema, pneumothorax, and pneumomediastinum should be notified as a serious complication during HHFNC therapy.
Response of two seed-grown artichoke cultivars to GA3 and melatonin treatments
Authors: Ezzo M. I. , Saleh Said A. , Abd El-Naby Saied K. M. , Khalifa Ramadan K. M.
Published: December 2019

Background

Globe artichokeCynara scolymusL. is an important vegetable crop. Poor crop stand due to the low ratio of stumps surviving is the common problem which occurs with using vegetative parts. The current study evaluated two seed-propagated cultivars of artichoke: treated by GA3and melatonin applications in newly reclaimed land.

Results

Results showed that Imperial Star produced higher values of vegetative growth, yield productivity, and chemical contents, compared with Romanesco cultivar. GA3foliar application treatment ranked the first to increase vegetative growth, yield productivity, and chemical contents, followed by melatonin treatment, compared with untreated control.

Conclusion

It could be concluded that the use of GA3and melatonin were favorable for the production of both artichoke cultivars: Imperial Star and Romanesco. The highest productivity was achieved by foliar application of GA3to Imperial Star cultivar.
Outcome of Men With Relapses After Adjuvant Bleomycin, Etoposide, and Cisplatin for Clinical Stage I Nonseminoma
Authors: Fischer Stefanie , Tandstad Torgrim , Cohn-Cedermark Gabriella , Thibault Constance , Vincenzi Bruno , Klingbiel Dirk , Albany Costantine , Necchi Andrea , Terbuch Angelika , Lorch Anja , Aparicio Jorge , Heidenreich Axel , Hentrich Marcus , Wheater Matthew , Langberg Carl W. , Ståhl Olof , Fankhauser Christian Daniel , Hamid Anis A. , Koutsoukos Konstantinos , Shamash Jonathan , White Jeff , Bokemeyer Carsten , Beyer Jörg , Gillessen Silke ,   on behalf of the Global Germ-Cell Cancer Group
Published: December 2019

PURPOSE

Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment.

PATIENTS AND METHODS

Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses.

RESULTS

Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last follow-up, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes.

CONCLUSION

Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (< 2 years), and late viable NS relapse (> 2 years).
Bromodomain and Extraterminal Inhibition by JQ1 Produces Divergent Transcriptional Regulation of Suppressors of Cytokine Signaling Genes in Adipocytes
Authors: Mota de Sá Paula , Richard Allison J , Stephens Jacqueline M
Published: December 2019

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway has cell-specific functions. Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK-STAT signaling. STAT5 plays a significant role in adipocyte development and function, and bromodomain and extraterminal (BET) proteins may be involved in STAT5 transcriptional activity. We treated 3T3-L1 adipocytes with the BET inhibitor JQ1 and observed that growth hormone (GH)-induced expression of 2 STAT5 target genes from the SOCS family, Socs3 and Cish, were inversely regulated (increased and decreased, respectively) by BET inhibition. Chromatin immunoprecipitation analyses revealed that changes in STAT5 binding did not correlate with gene expression changes. GH promoted the recruitment of the BET protein BRD2 to the Cish, but not Socs3, promoter. JQ1 treatment ablated this effect as well as the GH-induced binding of ribonucleic acid polymerase II (RNA Pol II) to the Cish transcription start site. BRD2 knockdown also suppressed GH induction of Cish, further supporting the role of BRD2 in Cish transcriptional activation. In contrast, JQ1 increased the binding of activated Pol II to the Socs3 coding region, suggesting enhanced messenger RNA (mRNA) elongation. Our finding that JQ1 transiently reduced the interaction between the positive transcription elongation factor (P-TEFb) and its inhibitor hexamethylene bis-acetamide inducible 1 (HEXIM1) is consistent with a previously described off-target effect of JQ1, whereby P-TEFb becomes more available to be recruited by genes that do not depend on BET proteins for activating transcription. These results demonstrate substantially different transcriptional regulation of Socs3 and Cish and suggest distinct roles in adipocytes for these 2 closely related proteins.
The Autophagy Gene Atg16L1 is Necessary for Endometrial Decidualization
Authors: Oestreich Arin K , Chadchan Sangappa B , Popli Pooja , Medvedeva Alexandra , Rowen Marina N , Stephens Claire S , Xu Ran , Lydon John P , Demayo Francesco J , Jungheim Emily S , Moley Kelle H , Kommagani Ramakrishna
Published: December 2019

Uterine receptivity is critical for establishing and maintaining pregnancy. For the endometrium to become receptive, stromal cells must differentiate into decidual cells capable of secreting factors necessary for embryo survival and placental development. Although there are multiple reports of autophagy induction correlated with endometrial stromal cell (ESC) decidualization, the role of autophagy in decidualization has remained elusive. To determine the role of autophagy in decidualization, we utilized 2 genetic models carrying mutations to the autophagy gene Atg16L1. Although the hypomorphic Atg16L1 mouse was fertile and displayed proper decidualization, conditional knockout in the reproductive tract of female mice reduced fertility by decreasing the implantation rate. In the absence of Atg16L1, ESCs failed to properly decidualize and fewer blastocysts were able to implant. Additionally, small interfering RNA knock down of Atg16L1 was detrimental to the decidualization response of human ESCs. We conclude that Atg16L1 is necessary for decidualization, implantation, and overall fertility in mice. Furthermore, considering its requirement for human endometrial decidualization, these data suggest Atg16L1 may be a potential mediator of implantation success in women.
Injured Runners Do Not Replace Lost Running Time with Other Physical Activity
Authors: DAVIS JOHN J. , GRUBER ALLISON H.
Published: December 2019

Running-related injuries are common and may pose a barrier to maintaining high levels of overall physical activity.

Purpose

The aim of this study was to determine whether recreational runners remain physically active while experiencing running-related pain or running-related injury.

Methods

Recreational runners (n= 49) participated in a year-long observational cohort study. Subjects were issued a commercial activity monitor to measure daily physical activity level, quantified by the total minutes of moderate to vigorous physical activity (MVPA). Subjects also completed a weekly survey inquiring about running-related pain and any modifications made to planned running sessions. A week was classified as an “injured week” if a runner reported a reduction or cancellation of at least three planned training sessions, otherwise, it was categorized as an “uninjured week.” Separately, pain level was assessed for each week using a 0 to 10 scale. Survey responses were used to longitudinally track pain levels and injury status for each runner. Mixed-effect linear models were used to quantify whether sustaining an injury or reporting running-related pain during a given week were associated with changes in MVPA levels for that week.

Results

Compared with uninjured weeks, runners engaged in 14.1 fewer minutes of MVPA per day (95% confidence interval, −22.5 to −6.0) during weeks in which they reported a running-related injury. Lost MVPA during injured weeks was primarily replaced by sedentary activity. There was no significant association between running-related pain and MVPA.

Conclusions

Injured runners do not replace lost running time with other forms of MVPA. Running-related injury and running-related pain should not be conflated; although reporting injury is associated with a reduction in physical activity in recreational runners, high pain levels are not.
Endurance Athletes Are at Increased Risk for Early Acute Mountain Sickness at 3450 m
Authors: SAREBAN MAHDI , SCHIEFER LISA M. , MACHOLZ FRANZISKA , SCHÄFER LARISSA , ZANGL QUIRIN , INAMA FRANCISCUS , REICH BERNHARD , MAYR BARBARA , SCHMIDT PETER , HARTL ARNULF , BÄRTSCH PETER , NIEBAUER JOSEF , TREFF GUNNAR , BERGER MARC M.
Published: December 2019

Introduction

Acute mountain sickness (AMS) may develop in nonacclimatized individuals after exposure to altitudes ≥2500 m. Anecdotal reports suggest that endurance-trained (ET) athletes with a high maximal oxygen uptake (V˙O2max) may be at increased risk for AMS. Possible underlying mechanisms include a training-induced increase in resting parasympathetic activity, higher resting metabolic rate (RMR), and lower hypoxic ventilatory response (HVR).

Methods

In 38 healthy, nonacclimatized men (19 ET and 19 untrained controls [UT], V˙O2max 66 ± 6 mL·min−1·kg−1 vs 45 ± 7 mL·min−1·kg−1; P < 0.001) peripheral oxygen saturation (SpO2), heart rate variability, RMR, and poikilocapnic HVR were assessed at 424 m and during 48 h at 3450 m after passive ascent by train (~2 h). Acute mountain sickness was evaluated by AMS cerebral (AMS-C) score.

Results

On day 1 at altitude, ET presented with a higher AMS incidence (42% vs 11%; P < 0.05) and severity (AMS-C score: ET, 0.48 ± 0.5 vs UT, 0.21 ± 0.2; P = 0.03), but no group difference was found on days 2 and 3. SpO2 decreased upon arrival at altitude (ET: 82% ± 6% vs UT: 83% ± 4%; p
time <0.001) with a significantly different time course between ET and UT (p
time × group = 0.045). Parasympathetic activity decreased at altitude (P < 0.001) but was always higher in ET (P < 0.05). At altitude RMR increased (P < 0.001) and was higher in ET (P < 0.001). Hypoxic ventilatory response increased only in ET (P < 0.05) and was greater than in UT after 24 and 48 h (P < 0.05).

Conclusions

Endurance-trained athletes are at higher risk for developing AMS on the first day after passive and rapid ascent to 3450 m, possibly due to an increased parasympathetic activity and an increased RMR, while HVR appeared to be of minor importance. Differences in AMS time course and physiological responses should be taken into consideration when ET are planning high-altitude sojourns.
Physical Activity, Sedentary Behavior, and White Matter Microstructure in Children with Overweight or Obesity
Authors: RODRIGUEZ-AYLLON MARÍA , Esteban-Cornejo IRENE , VERDEJO-ROMÁN JUAN , Muetzel RYAN L. , Migueles JAIRO H. , Mora-Gonzalez JOSE , Solis-Urra PATRICIO , Erickson KIRK I. , Hillman CHARLES H. , Catena ANDRÉS , Tiemeier HENNING , Ortega FRANCISCO B.
Published: December 2019

Purpose

This study aimed to investigate the associations of objectively measured and self-reported physical activity (PA) and sedentary behavior with white matter microstructure in children with overweight or obesity.

Methods

In a sample of 103 participants (age, 10.02 ± 1.15 yr; 42 girls) from the ActiveBrains project, we assessed PA and sedentary behavior using accelerometers (GT3X+; ActiGraph, Pensacola, FL), and the Youth Activity Profile-Spain questionnaire. Objectively measured PA and sedentary behavior were classified into different intensities following the hip- and wrist-based cutoff points for the Euclidean Norm Minus One metric by Hildebrand et al., wrist-based cutoff points for counts metric by Chandler et al., and hip-based cutoff points for counts metric for Romanzini et al. and Evenson et al. Magnetic resonance imaging of white matter microstructure, fractional anisotropy (FA), and mean diffusivity (MD) were derived from diffusion tensor imaging. Linear regression models were used to examine the associations of objectively measured and self-reported PA and sedentary behavior with global and tract-specific FA and MD.

Results

Self-reported total PA was positively associated with global FA (β = 0.236,P= 0.038), whereas watching television was negatively associated with global FA (β = −0.270,P= 0.014). In regard to the objective measures, using single regression models, light PA (β = 0.273,P= 0.016), moderate-to-vigorous PA (β = 0.257,P= 0.035), and total PA (β = 0.294,P= 0.013) were positively associated with global FA only when Hildebrand–Euclidean Norm Minus One hip cut points were used for analyses. Lastly, no association was found between PA and sedentary behavior and FA and MD within individual tracts.

Conclusions

Our results suggest that PA and watching television are related to white matter microstructure in children with overweight or obesity. However, longitudinal large-scale studies are needed to confirm and expand these findings.
Teaching Object Play to Young Children With Disabilities: A Systematic Review of Methods and Rigor
Authors: Barton Erin E. , Murray Rebecca , O'Flaherty Cecelia , Sweeney Erin M. , Gossett Stephanie
Published: December 2019

In this systematic review, we examined the rigor and outcomes across 27 object play intervention studies using single-case research methodology. We focused on studies including children age 5 years or younger and examined several descriptive characteristics including materials, instructional packages, and settings. We also analyzed the facilitation and measurement of generalized play and several methodological features including quality, rigor, and visual analysis procedures. Overall, the identified studies demonstrated positive outcomes, although quality and rigor limited interpretations of the outcomes. Previous reviews also have noted strong outcomes and weak to moderate quality for single-case studies. Our results should be interpreted with caution given previous reviews of play intervention studies identified strong outcomes and quality from group-design studies. Additional replications testing robust interventions using single-case research with strong methodological rigor are warranted.
Associated Risk Factors for Depression and Anxiety in Adults With Intellectual and Developmental Disabilities: Five-Year Follow Up
Authors: Hsieh Kelly , Scott Haleigh M. , Murthy Sumithra
Published: December 2019

A better understanding of the factors associated with depression and anxiety in people with intellectual and developmental disabilities (IDD) is needed to provide guidelines for service providers, clinicians, and researchers as well as to improve the diagnostic process. The current study used a longitudinal dataset to explore demographic, health, and psychosocial risk factors of anxiety and depression in adults with IDD. Women were more likely to have depression while older adults, people with autism, and people with hearing impairments, were more likely to have anxiety. Chronic health conditions were associated with both anxiety and depression, while changes in stressful life events were associated with an increased risk of anxiety. Clinical and research contributions are discussed.
Providers' Guidance to Parents and Service Use for Latino Children With Developmental Disabilities
Authors: Son Esther , Magaña Sandy , Pedraza Frances D. Martínez , Parish Susan L.
Published: December 2019

To better understand disparities between Latino and White children with autism or other developmental disabilities (ASD/DD), we examined whether Latino ethnicity predicted the number of specialty care services received by children with severe functional limitations depending on medical providers' responses to parents' initial concerns about their child's development. Through linkage of the Pathways and NS-CSHCN datasets, we found ethnic disparities in the receipt of specialty services associated with providers' responsiveness to parent-reported concerns among children with ASD/DD. Among children with significant functional limitations, Latino children whose parents received passive/reassuring responses from their providers were less likely to receive specialty services than White children with ASD/DD. Providers' guidance to parents may be a promising point of intervention for future disparity reduction efforts.
Preliminary Characterization of Parent-Child Interaction in Preschoolers With Prader-Willi Syndrome: The Relationship Between Engagement and Parental Stress
Authors: Zyga Olena , Dimitropoulos Anastasia
Published: December 2019

Early parent-child interactions (PCI) impact social cognitive development. Relatedly, children with various developmental disorders exhibit abnormal parental attachment relationships. Parental characteristics and behaviors can impact PCI and socioemotional development as well. No research has examined the parent-child dynamic in Prader-Willi syndrome (PWS), a neurodevelopmental disorder that presents with social cognitive deficits. This article provides a preliminary characterization of PCI quality and parenting stress in 17 PWS parent-child dyads, children ages 3–5 years, in comparison to 20 typically developing children and their parent. Results suggest early PCI disruption in preschoolers with PWS and their parents report increased levels of stress in various domains. These findings have important implications not only on parent well-being in PWS but its impact on child development.
Speed-up coherent Ising machine with a squeezed feedback system
Authors: Luo Lihaonan , Liu Hongjun , Huang Nan , Wang Zhaolu
Published: December 2019

As a solver for non-deterministic polynomial time (NP)-hard combinatorial optimization problems, the coherent Ising machine (CIM) is in the early stages of research, and the potential of this innovative physical system will be developed. Here, we propose a speed-up coherent Ising machine with a squeezed feedback system, which we call S-CIM. We couple squeezed feedback pulses generated by the squeezed feedback system into the degenerate optical parametric oscillator (DOPO) network. Simulations indicate that quantum inseparability of the coupled DOPO network is further enhanced during the whole optimization process, and quantum fluctuations are significantly smaller around the oscillation threshold. Computation experiments are performed on MAX-CUT problems of order between 4 and 20000. Numerical results demonstrate that S-CIM increases the optimal normalized output by 2.27% and significantly reduces the optimal computation time by 75.12%.
Development of self-tuned diamond milling system for fabricating infrared micro-optics arrays with enhanced surface uniformity and machining efficiency
Authors: Sun Zhanwen , To Suet , Wang Sujuan , Du Jianjun
Published: December 2019

Infrared micro-optics arrays (MOAs) featuring large numbers of micro-freeform lenslet are required increasingly in advanced infrared optical systems. Ultra-precision diamond cutting technologies have been widely used to fabricate MOAs with high form accuracy. However, the existing technologies can easily cause the non-uniformly fractured surface of infrared MOAs, due to the inherent low fracture toughness and high anisotropy of infrared materials as well as the time-varying chip thickness induced by ever-changing height and slope of the desired MOAs. In this study, a novel self-tuned diamond milling (STDM) system is proposed to achieve the ductile cutting of infrared MOAs with enhanced the surface uniformity and machining efficiency, and the corresponding toolpath planning algorithm is developed. In STDM system, a dual-axial fast servo motion platform is integrated into a raster milling system to self-adaptively match the maximum chip thickness for each tool rotational cycle with the critical depth of cut of the infrared material according to the local surface topography, thereby obtaining crack-free lenslet with high surface uniformity. Practically, micro-aspheric MOAs free from fractures are successfully machined on single-crystal silicon, a typical infrared material, to validate the proposed cutting concept. Compared with the conventional diamond milling, the proposed STDM is demonstrated to be able to avoid the non-uniform fractures without needing to reduce feed rate, and a smaller surface roughness of 4 nm and nearly double machining efficiency are achieved.
Comparison of nonlinear equalizers for high-speed visible light communication utilizing silicon substrate phosphorescent white LED
Authors: Zhou Yingjun , Wei Yiran , Hu Fangchen , Hu Jian , Zhao Yiheng , Zhang Jianli , Jiang Fengyi , Chi Nan
Published: December 2019

Compared with multicolor-chip integrated white LEDs, phosphor-based white LEDs are more attractive for daily illumination due to lower cost and complexity, and thus they are preferable for future commercial use of visible light communication (VLC) systems. However, the application of phosphorescent white LEDs has a lower data rate than multicolor-chip integrated LEDs because of severe nonlinear impairments and limited bandwidth caused by the slow-responding phosphor. In this paper, for the first time we propose to employ phosphorescent white LEDs based on silicon substrate with adaptive bit-loading discrete multitone (DMT) modulation and a memoryless polynomial based nonlinear equalizer to achieve a high-speed VLC system. We also present a comprehensive comparison among nonlinear equalizers based on the Volterra series model, memory polynomial model, memoryless polynomial model and deep neural network (DNN) with experimental results utilizing a silicon substrate phosphorescent white LED, and provide detailed suggestions on how to choose the most suitable nonlinear mitigation scheme considering different practical conditions and the tradeoff between complexity and performance. Beyond 3.00 Gb/s DMT VLC transmission over 1-m indoor free space is successfully demonstrated with bit error rate (BER) under the 7% forward error correction (FEC) limit of 3.8×10−3. As far as we know, this is the highest data rate ever reported for VLC systems based on a single high-power phosphorescent white LED.
Pasteurellaceae members with similar morphological patterns associated with respiratory manifestations in ducks
Authors: Eid Samah , Marouf Sherif , Hefny Hefny Y. , Al-Atfeehy Nayera M.
Published: December 2019

Aim: A total of 112 freshly dead ducks aged from 2 to 20 weeks old with a history of respiratory manifestations were investigated for the implication of Pasteurellaceae family members..

Materials and Methods: Isolation and identification to the family level were conducted by conventional bacteriological methods, including microscopic examination and biochemical characterization. Identification to the species level was conducted by polymerase chain reaction (PCR) and analytical profile index (API) 20E kits.

Results: Conventional bacteriological isolation and biochemical characterization revealed the infection of 16/112 examined birds with a prevalence rate of 14.3%. PCR confirmed the detection of Pasteurellaceae family conserved genes RpoB and Bootz in 16/16 (100%) isolates. PCR was also used for genus and species identification of the isolated Pasteurellaceae members; the results revealed that 5/16 (31.3%) of isolates were Gallibacterium anatis and 2/16 of isolates (12.5%) were Pasteurella multocida. Riemerella anatipestifer, Mannheimia haemolytica, and Avibacterium paragallinarum were not detected by PCR. Biotyping by API 20E successfully identified 5/16 (31.3%) isolates that could not be typed by PCR and confirmed their belonging to Pasteurella pneumotropica. Neither the available PCR primer sets nor API 20E succeeded for species identification of 4/16 (25%) isolates. Antibiotic susceptibility profiling of isolates revealed that 16/16 (100%) of isolates demonstrated multidrug resistance (MDR) phenotypes. Moreover, 16/16 (100%) of isolates demonstrated a phenotypic resistance pattern to neomycin.

Conclusion: Combined genotypic, phenotypic, biotyping, and virulence characterizations are required for laboratory identification of pathogenic Pasteurellaceae. Moreover, P. multocida was not the prevailed member implicated in respiratory problems in ducks as P. pneumotropica, G. anatis, and unidentified strains were involved with higher prevalence. Chloramphenicol and ampicillin demonstrated the highest in vivo effects on the studied Pasteurellaceae. Furthermore, the prevalence of multidrug-resistant isolates signified the demand to implement targeted surveillance in the ducks' production sector, and MDR survey in poultry sectors in Egypt to apply effective control measures.
A Comprehensive Review: Development of Biosensors Based on
Graphene-Mesoporous Combined Materials
Authors: Fatema Kamrun Nahar , Oh Won-Chun
Published: December 2019

Reliable data obtained from analysis of DNA, proteins, bacteria and other disease-related molecules or organisms in biological samples have become a fundamental and crucial part of human health diagnostics and therapy. After a brief summary of the implication of template based ordered mesoporous materials in electrochemical science, the various types of inorganic and organic-inorganic hybrid mesostructured used to date in electroanalysis and the corresponding electrode configurations are
described. The development of non-invasive tests that are rapid, sensitive, specific and simple would allow patient discomfort to be prevented, delays in diagnosis to be avoided and the status of a disease to be followed up. The use of biosensors for the early diagnosis of diseases has become widely accepted as a point-of-care diagnosis with appropriate specificity in a short time. To allow a reliable diagnosis of a disease at an early stage, highly sensitive biosensors are required as the corresponding biomarkers are generally expressed at very low concentrations. In past 50 years, various biosensors have been researched and developed encompassing a wide range of applications. This contrasts the limited number of commercially available biosensors. Lately, graphene-based materials have been considered as superior over other nanomaterials for the development of sensitive biosensors. The advantages of graphenebased sensor interfaces are numerous, including enhanced surface loading of desired ligand due to the high surface-to-volume ratio, excellent conductivity and a small band gap that is beneficial for sensitive electrical and electrochemical read-outs, as well as tunable optical properties for optical read-outs such as fluorescence and plasmonics. In this paper, we review the advances made in recent years on graphenebased biosensors in the field of medical diagnosis.