bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of the cancer stem cell niche and therapeutic strategies
Authors: Ju Feng , Atyah Manar M. , Horstmann Nellie , Gul Sheraz , Vago Razi , Bruns Christiane J. , Zhao Yue , Dong Qiong-Zhu , Ren Ning
Published: June 2022

Distinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in the case of their healthy counterparts, these anatomical regions are termed “niche.” Thus far, a large volume of studies have shown that CSC niches take part in the maintenance, regulation of renewal, differentiation and plasticity of CSCs. In this review, we summarize and discuss the latest findings regarding CSC niche morphology, physical terrain, main signaling pathways and interactions within them. The cellular and molecular components of CSCs also involve genetic and epigenetic modulations that mediate and support their maintenance, ultimately leading to cancer progression. It suggests that the crosstalk between CSCs and their niche plays an important role regarding therapy resistance and recurrence. In addition, we updated diverse therapeutic strategies in different cancers in basic research and clinical trials in this review. Understanding the complex heterogeneity of CSC niches is a necessary pre-requisite for designing superior therapeutic strategies to target CSC-specific factors and/or components of the CSC niche.
Human amniotic mesenchymal stem cells-derived IGFBP-3, DKK-3, and DKK-1 attenuate liver fibrosis through inhibiting hepatic stellate cell activation by blocking Wnt/β-catenin signaling pathway in mice
Authors: Liu Quan-Wen , Ying Yan-Min , Zhou Jia-Xin , Zhang Wen-Jie , Liu Zhao-xiao , Jia Bing-Bing , Gu Hao-Cheng , Zhao Chu-Yu , Guan Xiao-Hui , Deng Ke-Yu , Xin Hong-Bo
Published: June 2022

Background

Liver fibrosis is an outcome of restoring process in chronic liver injury. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating liver fibrosis. This study aimed to explore the effect and mechanism of hAMSCs on liver fibrosis.

Methods

hAMSCs were transplanted into carbon tetrachloride (CCl4)-induced liver fibrosis mice via tail vein, and the effects of hAMSCs on hepatic fibrosis were assessed. The effects of hAMSCs and hAMSCs conditional medium (CM) on the activation of hepatic stellate cells (HSCs) were investigated in vivo and in vitro. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may inhibit the activation of HSCs. Finally, the underlying mechanisms were explored by assessing IGF-1R/PI3K/AKT and GSK3β/β-catenin signaling pathways in the activated HSCs (LX-2) with hAMSCs and hAMSCs transfected with corresponding siRNAs.

Results

Our results showed that hAMSCs possessed the characterizations of mesenchymal stem cells. hAMSCs significantly reduced liver fibrosis and improved liver function in mice by inhibiting HSCs activation in vivo. Both hAMSCs and hAMSC-CM remarkably inhibited the collagen deposition and activation of LX-2 cells in vitro. Antibody array assay showed that insulin-like growth factor binding protein-3 (IGFBP-3), Dickkopf-3 (DKK-3), and Dickkopf-1 (DKK-1) were highly expressed in the co-culture group and hAMSC-CM group compared with LX-2 group. Western blot assay demonstrated that IGFBP-3, DKK-3, and DKK-1 derived from hAMSCs inhibit LX-2 cell activation through blocking canonical Wnt signaling pathway.

Conclusions

Our results demonstrated that IGFBP-3, Dkk3, and DKK-1 secreted by hAMSCs attenuated liver fibrosis in mice through inhibiting HSCs activation via depression of Wnt/β-catenin signaling pathway, suggesting that hAMSCs or hAMSC-CM provides an alternative therapeutic approach for the treatment of liver fibrosis.
Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model
Authors: Chen Ying-Cheng , Lan Ying-Wei , Huang Shiaw-Min , Yen Chih-Ching , Chen Wei , Wu Wan-Ju , Staniczek Theresa , Chong Kowit-Yu , Chen Chuan-Mu
Published: June 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC.

Methods

To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft.

Results

An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice.

Conclusions

Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT.
Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the human developing kidney
Authors: Wu Hongwei , Liu Fanna , Shangguan Yu , Yang Yane , Shi Wei , Hu Wenlong , Zeng Zhipeng , Hu Nan , Zhang Xinzhou , Hocher Berthold , Tang Donge , Yin Lianghong , Dai Yong
Published: June 2022

Background

Research on spatiotemporal gene landscape can provide insights into the spatial characteristics of human kidney development and facilitate kidney organoid cultivation. Here, we profiled the spatiotemporal gene programs of the human embryonic kidneys at 9 and 18 post-conception weeks (PCW) by integrating the application of microarray-based spatial transcriptomics and single-cell transcriptomics.

Results

We mapped transcriptomic signatures of scRNA-seq cell types upon the 9 and 18 PCW kidney sections based on cell-type deconvolution and multimodal intersection analyses, depicting a spatial landscape of developing cell subpopulations. We established the gene characteristics in the medullary regions and revealed a strong mitochondrial oxidative phosphorylation and glycolysis activity in the deeper medullary region. We also built a regulatory network centered on GDNF-ETV4 for nephrogenic niche development based on the weighted gene co-expression network analysis and highlighted the key roles of Wnt, FGF, and JAG1-Notch2 signaling in maintaining renal branching morphogenesis.

Conclusions

Our findings obtained by this spatiotemporal gene program are expected to improve the current understanding of kidney development.
The evidence synthesis and meta-analysis in R conference (ESMARConf): levelling the playing field of conference accessibility and equitability
Authors: Haddaway Neal R. , Bannach-Brown Alexandra , Grainger Matthew J. , Hamilton W. Kyle , Hennessy Emily A. , Keenan Ciara , Pritchard Chris C. , Stojanova Jana
Published: June 2022

Rigorous evidence is vital in all disciplines to ensure efficient, appropriate, and fit-for-purpose decision-making with minimised risk of unintended harm. To date, however, disciplines have been slow to share evidence synthesis frameworks, best practices, and tools amongst one another. Recent progress in collaborative digital and programmatic frameworks, such as the free and Open Source software R, have significantly expanded the opportunities for development of free-to-use, incrementally improvable, community driven tools to support evidence synthesis (e.g. EviAtlas, robvis, PRISMA2020 flow diagrams and metadat). Despite this, evidence synthesis (and meta-analysis) practitioners and methodologists who make use of R remain relatively disconnected from one another. Here, we report on a new virtual conference for evidence synthesis and meta-analysis in the R programming environment (ESMARConf) that aims to connect these communities. By designing an entirely free and online conference from scratch, we have been able to focus efforts on maximising accessibility and equity—making these core missions for our new community of practice. As a community of practice, ESMARConf builds on the success and groundwork of the broader R community and systematic review coordinating bodies (e.g. Cochrane), but fills an important niche. ESMARConf aims to maximise accessibility and equity of participants across regions, contexts, and social backgrounds, forging a level playing field in a digital, connected, and online future of evidence synthesis. We believe that everyone should have the same access to participation and involvement, and we believe ESMARConf provides a vital opportunity to push for equitability across disciplines, regions, and personal situations.
On boundary value problems of Caputo fractional differential equation of variable order via Kuratowski MNC technique
Authors: Benkerrouche Amar , Souid Mohammed Said , Jarad Fahd , Hakem Ali
Published: June 2022

In this manuscript, we examine both the existence and the stability of solutions to the boundary value problem of Caputo fractional differential equations of variable order by converting it into an equivalent standard Caputo boundary value problem of the fractional constant order with the help of the generalized intervals and the piece-wise constant functions. All results in this study are established using Darbo’s fixed point theorem combined with the Kuratowski measure of noncompactness. Further, the Ulam–Hyers stability of the given problem is examined; and finally, we construct an example to illustrate the validity of the observed results.
Tolerance of biofilm of a carbapenem-resistant Klebsiella pneumoniae involved in a duodenoscopy-associated outbreak to the disinfectant used in reprocessing
Authors: Brunke Melanie S. , Konrat Katharina , Schaudinn Christoph , Piening Brar , Pfeifer Yvonne , Becker Laura , Schwebke Ingeborg , Arvand Mardjan
Published: June 2022

Background

One possible transmission route for nosocomial pathogens is contaminated medical devices. Formation of biofilms can exacerbate the problem. We report on a carbapenemase-producing Klebsiella pneumoniae that had caused an outbreak linked to contaminated duodenoscopes. To determine whether increased tolerance to disinfectants may have contributed to the outbreak, we investigated the susceptibility of the outbreak strain to disinfectants commonly used for duodenoscope reprocessing. Disinfection efficacy was tested on planktonic bacteria and on biofilm.

Methods

Disinfectant efficacy testing was performed for planktonic bacteria according to EN standards 13727 and 14561 and for biofilm using the Bead Assay for Biofilms. Disinfection was defined as ≥ 5log10 reduction in recoverable colony forming units (CFU).

Results

The outbreak strain was an OXA-48 carbapenemase-producing K. pneumoniae of sequence type 101. We found a slightly increased tolerance of the outbreak strain in planktonic form to peracetic acid (PAA), but not to other disinfectants tested. Since PAA was the disinfectant used for duodenoscope reprocessing, we investigated the effect of PAA on biofilm of the outbreak strain. Remarkably, disinfection of biofilm of the outbreak strain could not be achieved by the standard PAA concentration used for duodenoscope reprocessing at the time of outbreak. An increased tolerance to PAA was not observed in a K. pneumoniae type strain tested in parallel.

Conclusions

Biofilm of the K. pneumoniae outbreak strain was tolerant to standard disinfection during duodenoscope reprocessing. This study establishes for the first time a direct link between biofilm formation, increased tolerance to disinfectants, reprocessing failure of duodenoscopes and nosocomial transmission of carbapenem-resistant K. pneumoniae.
Lower risk of peripheral venous catheter-related bloodstream infection by hand insertion
Authors: Buetti Niccolò , Abbas Mohamed , Pittet Didier , Chraiti Marie-Noëlle , Sauvan Valérie , De Kraker Marlieke E. A. , Boisson Matthieu , Teixeira Daniel , Zingg Walter , Harbarth Stephan
Published: June 2022

Introduction

Little is known about the bloodstream infection (BSI) risk associated with short-term peripheral venous catheters (PVCs) and no large study investigated the insertion site-related risk for PVC-BSI.

Methods

We performed a cohort study at the University of Geneva Hospitals using the prospective hospital-wide BSI surveillance database. We analyzed the association between insertion site and risk of PVC-BSI on the upper extremity using univariable and multivariable marginal Cox models.

Results

Between 2016 and 2020, utilization of 403′206 peripheral venous catheters were prospectively recorded in a 2000-bed hospital consortium with ten sites. Twenty-seven percent of PVC (n = 109′686) were inserted in the hand. After adjustment for confounding factors, hand insertion was associated with a decreased PVC-BSI risk (adjusted hazard ratio [HR] 0.42, 95% CI 0.18–0.98, p = 0.046) compared to more proximal insertion sites. In a sensitivity analysis for PVCs with ≥ 3 days of dwell time, we confirmed a decreased PVC-BSI risk after hand insertion (HR 0.37, 95% CI 0.15–0.93, p = 0.035).

Conclusion

Hand insertion should be considered for reducing PVC infections, especially for catheters with an expected dwell time of more than 2 days.
Multi-platform quantitation of alpha-synuclein human brain proteoforms suggests disease-specific biochemical profiles of synucleinopathies
Authors: Moors Tim E. , Mona Daniel , Luehe Stefan , Duran-Pacheco Gonzalo , Spycher Liz , Mundigl Olaf , Kaluza Klaus , Huber Sylwia , Hug Melanie N. , Kremer Thomas , Ritter Mirko , Dziadek Sebastian , Dernick Gregor , van de Berg Wilma D. J. , Britschgi Markus
Published: June 2022

Based on immunostainings and biochemical analyses, certain post-translationally modified alpha-synuclein (aSyn) variants, including C-terminally truncated (CTT) and Serine-129 phosphorylated (pSer129) aSyn, are proposed to be involved in the pathogenesis of synucleinopathies such as Parkinson’s disease with (PDD) and without dementia (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, quantitative information about aSyn proteoforms in the human brain in physiological and different pathological conditions is still limited. To address this, we generated sequential biochemical extracts of the substantia nigra, putamen and hippocampus from 28 donors diagnosed and neuropathologically-confirmed with different synucleinopathies (PD/PDD/DLB/MSA), as well as Alzheimer’s disease, progressive supranuclear palsy, and aged normal subjects. The tissue extracts were used to build a reverse phase array including 65 aSyn antibodies for detection. In this multiplex approach, we observed increased immunoreactivity in donors with synucleinopathies compared to controls in detergent-insoluble fractions, mainly for antibodies against CT aSyn and pSer129 aSyn. In addition, despite of the restricted sample size, clustering analysis suggested disease-specific immunoreactivity signatures in patient groups with different synucleinopathies. We aimed to validate and quantify these findings using newly developed immunoassays towards total, 119 and 122 CTT, and pSer129 aSyn. In line with previous studies, we found that synucleinopathies shared an enrichment of post-translationally modified aSyn in detergent-insoluble fractions compared to the other analyzed groups. Our measurements allowed for a quantitative separation of PDD/DLB patients from other synucleinopathies based on higher detergent-insoluble pSer129 aSyn concentrations in the hippocampus. In addition, we found that MSA stood out due to enrichment of CTT and pSer129 aSyn also in the detergent-soluble fraction of the SN and putamen. Together, our results achieved by multiplexed and quantitative immunoassay-based approaches in human brain extracts of a limited sample set point to disease-specific biochemical aSyn proteoform profiles in distinct neurodegenerative disorders.
Variations of elements, pigments, amino acids and secondary metabolites in Vitis vinifera (L.) cv Garganega after 501 biodynamic treatment
Authors: Malagoli Mario , Sut Stefania , Kumar Gourav , Dall’Acqua Stefano
Published: June 2022

Background

There is a need for new approaches in agriculture to improve safety of final products as well as to increase environmental acceptability. In this paper, the biodynamic preparation 501 (horn silica) was sprayed onVitis vinifera(L.) cv Garganega plants in two vineyards located in Veneto region, North-East Italy. Leaf samples were collected on the day of 501-treatment and 11 days later, and berries were sampled at harvest time. Leaves and berries samples were analysed combining targeted and untargeted measurements related to primary metabolism (pigment, element and amino acid contents) and to secondary metabolism. Chlorophyll content in leaves, and amino acid and element (C, N, S) analysis in berries were combined with untargeted UPLC-QTOF metabolomics.

Results

The discriminant compounds related to the 501-treatment were annotated on the basis of accurate MS and fragmentation and were identified as secondary metabolites, namely phenolic constituents belonging to the shikimate pathway. The level of most of the identified compounds increased in plants treated with 501 preparation.

Conclusions

Results highlight the prominent value of the metabolomic approach to elucidate the role of the 501 applications on grapevine secondary metabolism.

Graphical Abstract
Fatigue and Recovery Time Course After Female Soccer Matches: A Systematic Review And Meta-analysis
Authors: Goulart Karine Naves Oliveira , Coimbra Cândido Celso , Campos Helton Oliveira , Drummond Lucas Rios , Ogando Pedro Henrique Madureira , Brown Georgia , Couto Bruno Pena , Duffield Rob , Wanner Samuel Penna
Published: June 2022

Background

This study aimed to analyze the extent of fatigue responses after female soccer matches and the ensuing recovery time course of performance, physiological, and perceptual responses.

Methods

Three databases (PubMed, Web of Science, and SPORTDiscus) were searched in October 2020 and updated in November 2021. Studies were included when participants were female soccer players, regardless of their ability level. Further, the intervention was an official soccer match with performance, physiological, or perceptual parameters collected pre- and post-match (immediately, 12 h, 24 h, 48 h, or 72 h-post).

Results

A total of 26 studies (n = 465 players) were included for meta-analysis. Most performance parameters showed some immediate post-match reduction (effect size [ES] = − 0.72 to − 1.80), apart from countermovement jump (CMJ; ES = − 0.04). Reduced CMJ performance occurred at 12 h (ES = − 0.38) and 24 h (ES = − 0.42) and sprint at 48 h post-match (ES = − 0.75). Inflammatory and immunological parameters responded acutely with moderate-to-large increases (ES = 0.58–2.75) immediately post-match. Creatine kinase and lactate dehydrogenase alterations persisted at 72 h post-match (ES = 3.79 and 7.46, respectively). Small-to-moderate effects were observed for increased cortisol (ES = 0.75) and reduced testosterone/cortisol ratio (ES = -0.47) immediately post-match, while negligible to small effects existed for testosterone (ES = 0.14) and estradiol (ES = 0.34). Large effects were observed for perceptual variables, with increased fatigue (ES = 1.79) and reduced vigor (ES = − 0.97) at 12 h post-match, while muscle soreness was increased immediately post (ES = 1.63) and at 24 h post-match (ES = 1.00).

Conclusions

Acute fatigue exists following female soccer matches, and the performance, physiological, and perceptual parameters showed distinctive recovery timelines. Importantly, physical performance was recovered at 72 h post-match, whereas muscle damage markers were still increased at this time point. These timelines should be considered when planning training and match schedules. However, some caution should be advised given the small number of studies available on this population.

Registration

The protocol for this systematic review was pre-registered on the International Prospective Register of Systematic Reviews (PROSPERO, Registration Number: CRD42021237857).
NIR-Mediated drug release and tumor theranostics using melanin-loaded liposomes
Authors: Kim Min Ah. , Lee Chang-Moon
Published: June 2022

Background

Heat generation in a drug delivery carrier by exposure to near-infrared (NIR) light with excellent tissue transmittance is an effective strategy for drug release and tumor therapy. Because liposomes have amphiphilic properties, they are useful as drug carriers. Liposomes are also very suitable for drug delivery strategies using heat generation by NIR laser because lipid bilayers are easily broken by heat. Thermally generated bubbles from liposomes not only induce drug release, but also enable ultrasound imaging.

Methods

Melanin, perfluorohexane (PFH), and 5-fluorouracil (5-FU)-loaded liposomes (melanin@PFH@5-FU-liposomes) that can generate heat and bubble by NIR laser irradiation were prepared by a thin film method. Conversion of light to heat and bubble generation of melanin@PFH@5-FU-liposomes were evaluated using an infrared (IR) thermal imaging camera and an ultrasound imaging system both
in vitro
and
in vivo
. To investigate tumor therapeutic effect, NIR laser of 808 nm was used to irradiate tumor site for 10 min after injecting melanin@PFH@5-FU-liposome into tail veins of CT26-bearing mice.

Results

Melanin@PFH@5-FU-liposomes showed a spherical shape with a size of 209.6 ± 4.3 nm. Upon NIR laser irradiation, melanin@PFH@5-FU-liposomes exhibited effective temperature increase both
in vitro
and
in vivo
. In this regard, temperature increase caused a phase transition of PFH to induce bubble generation dramatically, resulting in effective drug release behavior and ultrasound imaging. The temperature of the tumor site was increased to 52 t and contrast was greatly enhanced during ultrasound imaging due to the generation of bubble. More importantly, tumor growth was effectively inhibited by injection of melanin@PFH@5-FU-liposomes with laser irradiation.

Conclusions

Based on intrinsic photothermal properties of melanin and phase transition properties of PFH, melanin@PFH@5-FU-liposomes exhibited effective heat and bubble generation upon NIR laser irradiation. The elevated temperature induced bubble generation, resulting in contrast enhancement of ultrasound imaging. Melanin@PFH@5-FU-liposomes under NIR laser irradiation induced the death of cancer cells, thereby effectively inhibiting tumor growth. These results suggest that melanin@PFH@5-FU-liposomes can be utilized as a promising agent for photothermal tumor therapy and ultrasound imaging.
Primary headache disorders in epileptic adults
Authors: Osama Ahmed , Orabi Marwa , Yassine Imane , El-Hady Mohamed Elsayed Abd
Published: June 2022

Background

Epilepsy and primary headache disorders are two relatively common neurological disorders and their relationship is still a matter of debate. We aimed to estimate the prevalence and clinical features of primary headache disorders in patients with epilepsy.

Methods

62 subjects aged ≥ 18 years were recruited from the hospital’s neurology outpatient clinic in the period from January to April 2018. The subjects were further divided into two equal groups, epileptics and non-epileptics. They underwent a semi-structured interview including the ILAE 2017 epilepsy classification and the ICHD III-beta criteria for headache. Patients' demographic data and clinical characteristics of epilepsy and headache and temporal relationships between them were assessed. Patients who experienced headaches were grouped based on the type of headaches and on whether their headaches occurred in the pre-ictal, post-ictal or inter-ictal period.

Results

Primary headache disorders were more common in epileptic group (61.3%) than the non-epileptic group (32.2%) (p = 0.021). The tension-type headache was the most common (45.2%) followed by migraine-type headache (12.9%) in the epileptic group. Post-ictal headache was the most common type (29%). Inter-ictal headaches were significantly related to "focal to bilateral tonic–clonic" seizures (p = 0.046). The prevalence of headache among patients on polytherapy (69.2%) was higher than that of patients on monotherapy (52.9%).

Conclusions

In this study, headache was more common in epileptic patients. TTH was the most represented type of headache in patients with epilepsy. Headache occurred in patients with epilepsy most frequently during the post-ictal period.
Economic policy uncertainty and stock returns among OPEC members: evidence from feasible quasi-generalized least squares
Authors: Oyewole Oluwatomisin J. , Adubiagbe Idowu A. , Adekoya Oluwasegun B.
Published: June 2022

We examine the predictive ability of economic policy uncertainty on stock returns of selected OPEC countries. In order to deal with certain statistical properties of the predictors, which include serial correlation, persistence, conditional heteroskedasticity, and endogeneity effects, wse utilize the Feasible Quasi-Generalized Least Squares (FQGLS) estimator in order to obtain accurate forecast estimates. As a precondition for forecast analysis, we conduct the predictability test, which shows that economic policy uncertainty is significant only for five countries, namely Kuwait, Nigeria, Saudi Arabia, United Arab Emirates, and Venezuela. Hence, we proceed with the main forecast analysis for only this set of countries. Our results are twofold. We first account for asymmetries in forecasting stock returns by comparing the forecast performance of the symmetric economic policy uncertainty-based predictive model with its asymmetric variant. On the other hand, we compare the performance of the best model from above with the standard ARFIMA model using an alternative forecast test. In both cases, we find that the asymmetric model yields the most accurate forecast returns for stock returns of the five countries. In essence, neglecting the role of asymmetries in forecasting stock returns can lead to bias results. Our findings are not only robust to different sample sizes (i.e., 50%, and 75%) and different forecast horizons (4, 8, and 12 months) but have important policy implications for policymakers and potential investors.
Digital phenotyping correlations in larger mental health samples: analysis and replication
Authors: Currey Danielle , Torous John
Published: June 2022

Background

Smartphones can facilitate patients completing surveys and collecting sensor data to gain insight into their mental health conditions. However, the utility of sensor data is still being explored. Prior studies have reported a wide range of correlations between passive data and survey scores.

Aims

To explore correlations in a large data-set collected with the mindLAMP app. Additionally, we explored whether passive data features could be used in models to predict survey results.

Method

Participants were asked to complete daily and weekly mental health surveys. After screening for data quality, our sample included 147 college student participants and 270 weeks of data. We examined correlations between six weekly surveys and 13 metrics derived from passive data features. Finally, we trained logistic regression models to predict survey scores from passive data with and without daily surveys.

Results

Similar to other large studies, our correlations were lower than prior reports from smaller studies. We found that the most useful features came from GPS, call, and sleep duration data. Logistic regression models performed poorly with only passive data, but when daily survey scores were included, performance greatly increased.

Conclusions

Although passive data alone may not provide enough information to predict survey scores, augmenting this data with short daily surveys can improve performance. Therefore, it may be that passive data can be used to refine survey score predictions and clinical utility may be derived from the combination of active and passive data.
Oxytocin receptor gene, post-traumatic stress disorder and dissociation in a community sample of European American women
Authors: Lee Hyunhwa , King Anthony P. , Li Yang , Seng Julia S.
Published: June 2022

The aims of this study were: (a) to examine associations of oxytocin receptor gene (OXTR) single nucleotide polymorphisms (SNPs) with post-traumatic stress disorder (PTSD) and dissociative symptoms and (b) to investigate gene–environment (G × E) interaction with childhood maltreatment. Salivary DNA samples from 228 women of European ancestry were analysed. Two SNPs, rs237895 and rs237897, were associated with dissociative symptoms but not PTSD diagnosis. Another SNP (rs2254298) was associated with dissociation when interacting with history of childhood maltreatment. These results contribute to theorising and evidence suggesting that the oxytocin system and its genetics may be associated with risk for dissociation among European American women, including those with maltreatment history. Replication with larger patient samples, including men and other ancestry groups, is needed.
Drug Development in Low- and Middle-Income Countries: Opportunity or Exploitation?
Authors: Jalali Rakesh , Nogueira-Rodrigues Angelica , Das Arunangshu , Sirohi Bhawna , Panda Pankaj Kumar
Published: June 2022

Low- and middle-income countries (LMICs) represent a diverse group of regions with varied cancer presentation. Drug development and accessibility across these regions have primarily been dependent on the trials initiated and conducted across high-income countries. Representation of LMIC regions in these trials in terms of study population has been minimal, leading to inequitable distribution of optimal and affordable cancer care. In spite of many challenges, LMICs have now increasingly been able to contribute to anticancer drug development. The opportunities present in LMICs must be explored and used in conjunction with due collaborative efforts from high-income countries, health care planners, and regulatory agencies. Global drug development trials should not only factor in suitable representation of LMICs but also design studies with pragmatic objectives and endpoints so that the trial results lead to equitable and affordable cancer care. Strengthening collaboration between cancer researchers from LMICs and high-income countries and empowering the local investigator with adequate resources will help remove current disparities.
Gender- and Sexual Orientation– Based Inequities: Promoting Inclusion, Visibility, and Data Accuracy in Oncology
Authors: Alpert Ash B. , Scout N.F.N. , Schabath Matthew B. , Adams Spencer , Obedin-Maliver Juno , Safer Joshua D.
Published: June 2022

Sexual and gender minority (SGM) people, including agender, asexual, bisexual, gay, gender diverse, genderqueer, genderfluid, intersex, lesbian, nonbinary, pansexual, queer, and transgender people, comprise approximately 10% or more of the U.S. population. Thus, most oncologists see SGM patients whether they know it or not. SGM people experience stigma and structural discrimination that lead to cancer disparities. Because of the lack of systematic and comprehensive data collection, data regarding SGM cancer incidence, outcomes, and treatment responses are limited. Collection of data regarding sexual orientation, gender identity, transgender identity and/or experience, anatomy, and serum hormone concentrations in oncology settings would drastically increase collective knowledge about the impact of stigma and biologic markers on cancer outcomes. Increasing the safety of oncology settings for SGM people will require individual, institutional, and systems changes that will likely improve oncologic care for all patients.
TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study
Authors: Thiel Kristina W. , Devor Eric J. , Filiaci Virginia L. , Mutch David , Moxley Katherine , Alvarez Secord Angeles , Tewari Krishnansu S. , McDonald Megan E. , Mathews Cara , Cosgrove Casey , Dewdney Summer , Aghajanian Carol , Samuelson Megan I. , Lankes Heather A. , Soslow Robert A. , Leslie Kimberly K.
Published: June 2022

PURPOSE

The status of p53 in a tumor can be inferred by next-generation sequencing (NGS) or by immunohistochemistry (IHC). We examined the association between p53 IHC and sequence and whether p53 IHC alone, or integrated with TP53 NGS, predicts the outcome.

METHODS

From GOG-86P, a randomized phase II study of chemotherapy combined with either bevacizumab or temsirolimus in advanced endometrial cancer, 213 cases had p53 protein expression data measured by IHC and TP53 NGS data. An analysis was designed to integrate p53 expression by IHC with the presence or absence of a TP53 mutation. These variables were further correlated with progression-free survival (PFS) and overall survival (OS) in the chemotherapy plus bevacizumab arms versus the chemotherapy plus temsirolimus arm.

RESULTS

In the analysis of p53 IHC, the most striking treatment effect favoring bevacizumab was in cases where p53 was overexpressed (PFS hazard ratio [HR]: 0.46, 95% CI, 0.26 to 0.88; OS HR: 0.31, 95% CI, 0.16 to 0.62). On integrated analysis, patients with TP53 missense mutations and p53 protein overexpression had a similar treatment effect on PFS (HR: 0.41, 95% CI, 0.22 to 0.83) and OS (HR: 0.28, 95% CI, 0.14 to 0.59) favoring bevacizumab plus chemotherapy relative to temsirolimus plus chemotherapy. Concordance between TP53 NGS and p53 IHC was 88%. Concordance was 92% when cases with TP53 mutations and POLE mutations or mismatch repair deficiency were removed.

CONCLUSION

IHC for p53 alone or when integrated with sequencing for TP53 identifies a specific, high-risk tumor genotype/phenotype for which bevacizumab is particularly beneficial in improving outcomes when combined with chemotherapy.
Pancreatic Cancer Surveillance in Carriers of a Germline CDKN2A Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up
Authors: Klatte Derk C.F. , Boekestijn Bas , Wasser Martin N.J.M. , Feshtali Shahbazi Shirin , Ibrahim Isaura S. , Mieog J. Sven D. , Luelmo Saskia A.C. , Morreau Hans , Potjer Thomas P. , Inderson Akin , Boonstra Jurjen J. , Dekker Friedo W. , Vasen Hans F.A. , van Hooft Jeanin E. , Bonsing Bert A. , van Leerdam Monique E.
Published: June 2022

PURPOSE

Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A.

METHODS

Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound.

RESULTS

Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia.

CONCLUSION

This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.
Effects of spermidine on germination of Salix spp. after storage under controlled conditions
Authors: Wawrzyniak Mikołaj K. , Ley-López Juan Manuel , Kijowska-Oberc Joanna , Chmielarz Paweł , Ratajczak Ewelina
Published: June 2022

Willows produce fast germinating and short-lived seeds, difficult to store in the long-term under controlled conditions. The aim of this study was to examine the feasibility of storage of three Salix spp. at controlled temperatures (3°, −10°, −196 °C). We also analyzed the effect of spermidine (Spd) as an antioxidant factor in desiccated seeds. Collected seeds were either desiccated or hydrated to obtain 10 levels of moisture content (between app. 4% and 2%) and subjected to storage at temperatures 3°, −10°, or −196 °C (liquid nitrogen; LN). After two months, seeds were germinated on the light at 20 °C. Seeds desiccated below a safe range of moisture content were further tested and germinated on filter paper with additions of 0.25 mM Spd solution. After 7 days seedlings were examined for hydrogen peroxide content (H2O2) and total antioxidant capacity (TAC). Fresh seeds of three Salix species: Persian willow (S. aegyptiaca L.), heartleaf willow (S. cordata Michx.) and crack willow (S. ×fragilis L.) were successfully stored at temperature −10° and −196 °C for two months. After cryopreservation seed of S. aegyptiaca, S. cordata, and S. ×fragilis germinated without viability loss in moisture content ranging from 4.4–15.9%, 6.4–18.5%, and 7.1–11.5% respectively. The addition of Spd during germination of desiccated seed did not affect germination capacity. However, seedlings of S. aegyptiaca had lower hydrogen peroxide content in comparison with control (germination on water). Seedlings of S. cordata showed an increase in hydrogen peroxide content in control after storing in LN. In seedlings of Crack willow Spd increased hydrogen peroxide content. Seeds of tested species differ in response to storage conditions. Salix seeds can be stored successfully for two months at −10° or −196 °C without losing viability in the safe range of moisture content. Storing at 3 °C can be used for storage in the narrower range of seeds’ moisture content, however, seedlings stored at this temperature produce a higher level of reactive oxygen species. Germinating seeds in Spd did not increase their germination, however in S. aegyptiaca and S. cordata decreased hydrogen peroxide content
Two-Level Capacitated Discrete Location with Concave Costs
Authors: Malik Aditya , Contreras Ivan , Vidyarthi Navneet
Published: June 2022

In this paper, we study a general class of two-level capacitated discrete location problems with concave costs. The concavity arises from the economies of scale in production, inventory, or handling at the facilities and from the consolidation of flows for transportation and transshipment on the links connecting the facilities. Given the discrete nature of the problem, it is naturally formulated as a mixed-integer nonlinear program that uses binary variables for locational decisions and continuous variables for routing flows. We present an alternative formulation that only uses continuous variables and discontinuous functions, resulting in a nonlinear program with a concave objective function. Our main goal is to computationally compare these two modeling approaches under the same solution framework. In particular, we present an exact branch-and-bound algorithm that uses (integer) linear relaxations of the proposed formulations to optimally solve large-scale instances. The algorithm is enhanced with a cost-dependent spatial branching strategy and preprocessing step to improve its convergence. Extensive computational experiments are performed to assess the performance of the exact algorithm. Based on real location data from 3,109 counties in the contiguous United States, we also present a sensitivity analysis to showcase the impact of considering concave costs in location and assignment decisions.
Demonstration of a ring-core few-mode erbium-doped fiber for mode gain equalization based on layered doping
Authors: Zhao Qi , Pei Li , Zheng Jingjing , Wang Jianshuai , Xie Yuheng , Li Jing , Ning Tigang
Published: June 2022

A ring-core few-mode erbium-doped fiber (FM-EDF) with step refractive index is designed and proposed to realize the modal gain equalization of the amplifier. The layered-doping method is used to reduce the mode gain difference (DMG), and the doping radius and doping concentration are adjusted to obtain the best FM-EDF structure. When it is applied to the few-mode erbium-doped fiber amplifier (FM-EDFA), the DMG at 1550 nm is less than 0.44 dB. The gains of each mode in the entire C-band are greater than 16 dB. To further improve the gain equalization characteristics of the designed fiber, the DMG can be reduced to 0.03 dB by adding trenches at appropriate positions on the basis of the same core structure. The tolerances in the optical fiber manufacturing process are considered to verify the reliability of the FM-EDFA performance. The doping radius and doping concentration are changed by

±

15

%

based on the precise value to consider the tolerances in the fiber manufacturing process to verify the reliability of the FM-EDFA performance. Generally speaking, doping radius changes have a greater impact on DMG, so higher production accuracy is required. To explore the experimental structure and procedures of FM-EDFA, a preliminary experiment is carried out. The experimental results obtained have great reference significance for subsequent experiments. The characteristics of the FM-EDFA, such as all-fiber and low DMG, are difficult to implement by other methods.
Multiple Airy beam generation by a digital micro mirror device
Authors: Kichi Zahra Abedi , Sabouri Saeed Ghavami
Published: June 2022

The Airy beam is the solution of Maxwell's wave equation and since this equation is linear, a superposition of Airy beams still remains the solution of the wave equation. In this paper, we propose a method for generating multiple Airy beams that includes a desirable number of up to 6 individual Airy beams with desirable acceleration properties. By introducing a decenter into the designed diffractive optical element (DOE) of an Airy beam the problem of generating dual airy beams patterns by an amplitude-based spatial light modulator is solved. By superimposing the designed DOEs of individual Airy beams and scaling them to the proper gray level range, the DOE of the multiple Airy beams is generated. Displaying this DOE on a digital micromirror device, multiple Airy beams are experimentally produced. The experimental studies of these beams show good agreement with the performed simulations.
Membrane multiple quantum well electro-optical modulator employing low loss high-k radio-frequency slot waveguides
Authors: Xing Jianghao , Sun Changzheng , Xiong Bing , Wang Jian , Hao Zhibiao , Wang Lai , Han Yanjun , Li Hongtao , Luo Yi
Published: June 2022

A membrane multiple quantum well (MQW) electro-optical (EO) modulator exploiting low loss high-k radio-frequency (RF) slot waveguides is proposed for sub-terahertz bandwidth. By employing high-k barium titanate (BTO) claddings in place of doped InP cladding layers in traditional InP-based MQW modulators, the proposed modulator exhibits enhanced modulation efficiency and bandwidth as well as reduced insertion loss. A low half-wave voltage-length product of 0.24 V·cm is estimated, together with over 240 GHz bandwidth for a 2-mm-long modulation region, thus allowing sub-terahertz operation.
Optical fiber optofluidic laser based on surfactant solubilization of rhodamine B gain in an aqueous solution
Authors: Li Dongyang , Zhou Li , Yu Qiuhan , Pu Xiaoyun , Sun Yuze , Zhou Qing , Zhang Yuanxian
Published: June 2022

We report a whispering gallery mode (WGM)-based fiber optofluidic laser (FOFL), in which rhodamine B (RhB) in an aqueous surfactant solution of sodium dodecylbenzene sulfonate (SDBS) is used as the laser gain medium. Here, the role of SDBS is to scatter the RhB dye molecules to effectively prevent its self-association in the aqueous solution. Therefore, the fluorescence quantum yield of the used RhB dye is improved due to the enhanced solubilization, which results in a low lasing threshold of ∼2.2 µJ/mm2 when the concentration of SDBS aqueous solution reaches up to 20 mM, on par with or even better than most of the optofluidic dye lasers using RhB as the gain medium in an organic solution. We then establish a model of solubilization capacity of SDBS micelles, which successfully addresses the mechanisms of dye-surfactant interactions in the proposed FOFL system. We further apply this FOFL platform to the case of concentration sensing of the used SDBS, which exhibits a 2-order-of-magnitude improvement in sensitivity compared to the fluorescence measurement due to the signal amplification inherent to the lasing process. The proposed FOFL platform in combination with surfactant solubilization gain medium in an aqueous solution promises to enable chip-scale coherent light sources for various environmental and bio-chemical sensing applications.
Watt-level beam combined diode laser systems in a chip-scale hybrid photonic platform
Authors: Zeng Siwei , Zhao Xiaolei , Zhu Yeyu , Sweatt Lance , Zhu Lin
Published: June 2022

Scaling up the power of on-chip diode lasers is of great importance for many emerging applications, such as integrated nonlinear optics, remote sensing, free space communication, infrared countermeasure, and light detection and ranging (LIDAR). In this manuscript, we introduce and demonstrate photonic integrated circuits (PIC) based beam combining methods to create power scalable, integrated direct diode laser systems. Traditional laser beam combining, including coherent beam combining (CBC) and wavelength beam combining (WBC), usually requires free space or fiber optical components, leading to bulky and complex systems. Instead, PIC based beam combining methods can greatly reduce the cost, size, weight, and power consumption (CSWaP) of next generation direct diode laser systems. We experimentally demonstrate four channel chip-scale CBC and WBC with watt-level on-chip power by using III/V-Si3N4 hybrid integration. Our results show that PIC based beam combining is very suitable for power scaling in a chip-scale platform.
Experimental demonstration of an indoor optical wireless communication system with a waveform index modulated uplink
Authors: Wang Ke , Kandeepan Sithamparanathan
Published: June 2022

The optical wireless communication (OWC) technology has been widely studied to provide high-speed wireless connections in indoor environments. Compared with the downlink, the uplink faces more restrictions, such as the stringent power, complexity, and cost requirements. In this Letter, we propose a waveform index modulated OWC uplink with each waveform seen as a virtual transmitter. Extra data is transmitted via the index of selectively activated virtual transmitter, and the OWC uplink speed can be improved whilst achieving similar bit-error-rate (BER) performance. The waveform index modulated uplink is experimentally demonstrated in a near-infrared OWC system. Results show that up to 15 Gb/s data rate is achieved with the proposed waveform index modulated uplink, which increases the data rate significantly with similar power and BER.