bluuebunny/crossref_metadata_2025 huggingface dataset:
Microresonator-based spectral translation of a gain-switched semiconductor laser comb
Authors: Weng Wenle , Kaszubowska-Anandarajah Aleksandra , Anandarajah Prince M. , Luiten Andre N.
Published: March 2023

Gain-switched semiconductor laser technology provides a simple and low-cost method to generate optical frequency combs. However, the spectral coverage of these compact comb sources has been limited to the near-infrared range. Here, we combine a gain-switched laser comb with a continuous-wave translation laser within a periodically poled lithium niobate microresonator and demonstrate efficient and broadband sum-frequency conversion, spectrally translating the near-infrared comb to the visible domain. The broadband nature of the nonlinear conversion arises from a chirping of the domain inversion grating period along the microresonator circumference. We also validate the coherence of the visible-wavelength comb teeth which underlines the general applicability of this spectral translation approach.
Olver plasmon: an accelerating surface wave with various orders
Authors: Chen Yanru , Tu Zhifeng , Hu Hongcheng , Zhang Junxi , Feng Zien , Wang Ziyu , Hong Weiyi , Deng Dongmei
Published: March 2023

In this Letter, we introduce a new, to the best of our knowledge, class of accelerating surface plasmonic wave: the Olver plasmon. Our research reveals that such a surface wave propagates along self-bending trajectories at the silver–air interface with various orders, among which Airy plasmon is regarded as the zeroth-order one. We demonstrate a plasmonic autofocusing hot-spot by the interference of Olver plasmons and the focusing properties can be controlled. Also, a scheme for the generation of this new surface plasmon is proposed with the verification of finite difference time-domain numerical simulations.
Efficient continuous wave and passively Q switched Er:GdScO3 laser using Fe:ZnSe at 2.8 µm
Authors: Hou Wentao , Xue Yanyan , Qin Zhipeng , Tang Huili , Xie Guoqiang , Wang Qingguo , Xu Xiaodong , Xu Jun
Published: March 2023

We report on diode-pumped continuous wave and passively Q switched Er:GdScO3 crystal lasers at around 2.8 µm. A continuous wave output power of 579 mW was obtained with a slope efficiency of 16.6%. Using Fe:ZnSe as a saturable absorber, a passively Q switched laser operation was realized. A maximum output power of 32 mW was generated with the shortest pulse duration of 286 ns at a repetition rate of 157.3 kHz, leading to a pulse energy of 204 nJ and a pulse peak power of 0.7 W.
TDP-43 and other hnRNPs regulate cryptic exon inclusion of a key ALS/FTD risk gene, UNC13A
Authors: Koike Yuka , Pickles Sarah , Estades Ayuso Virginia , Jansen-West Karen , Qi Yue A. , Li Ziyi , Daughrity Lillian M. , Yue Mei , Zhang Yong-Jie , Cook Casey N. , Dickson Dennis W. , Ward Michael , Petrucelli Leonard , Prudencio Mercedes
Published: March 2023

A major function of TAR DNA-binding protein-43 (TDP-43) is to repress the inclusion of cryptic exons during RNA splicing. One of these cryptic exons is in UNC13A, a genetic risk factor for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of cryptic UNC13A in disease is heightened by the presence of a risk haplotype located within the cryptic exon itself. Here, we revealed that TDP-43 extreme N-terminus is important to repress UNC13A cryptic exon inclusion. Further, we found hnRNP L, hnRNP A1, and hnRNP A2B1 bind UNC13A RNA and repress cryptic exon inclusion, independently of TDP-43. Finally, higher levels of hnRNP L protein associate with lower burden of UNC13A cryptic RNA in ALS/FTD brains. Our findings suggest that while TDP-43 is the main repressor of UNC13A cryptic exon inclusion, other hnRNPs contribute to its regulation and may potentially function as disease modifiers.
Role of Nesprin-2 and RanBP2 in BICD2-associated brain developmental disorders
Authors: Yi Julie , Zhao Xiaoxin , Noell Crystal R. , Helmer Paige , Solmaz Sozanne R. , Vallee Richard B.
Published: March 2023

Bicaudal D2 (BICD2) is responsible for recruiting cytoplasmic dynein to diverse forms of subcellular cargo for their intracellular transport. Mutations in the human BICD2 gene have been found to cause an autosomal dominant form of spinal muscular atrophy (SMA-LED2), and brain developmental defects. Whether and how the latter mutations are related to roles we and others have identified for BICD2 in brain development remains little understood. BICD2 interacts with the nucleoporin RanBP2 to recruit dynein to the nuclear envelope (NE) of Radial Glial Progenitor cells (RGPs) to mediate their well-known but mysterious cell-cycle-regulated interkinetic nuclear migration (INM) behavior, and their subsequent differentiation to form cortical neurons. We more recently found that BICD2 also mediates NE dynein recruitment in migrating post-mitotic neurons, though via a different interactor, Nesprin-2. Here, we report that Nesprin-2 and RanBP2 compete for BICD2-binding in vitro. To test the physiological implications of this behavior, we examined the effects of known BICD2 mutations using in vitro biochemical and in vivo electroporation-mediated brain developmental assays. We find a clear relationship between the ability of BICD2 to bind RanBP2 vs. Nesprin-2 in controlling of nuclear migration and neuronal migration behavior. We propose that mutually exclusive RanBP2-BICD2 vs. Nesprin-2-BICD2 interactions at the NE play successive, critical roles in INM behavior in RGPs and in post-mitotic neuronal migration and errors in these processes contribute to specific human brain malformations.
The prophage-encoded transcriptional regulator AppY has pleiotropic effects on E. coli physiology
Authors: Derdouri Naoual , Ginet Nicolas , Denis Yann , Ansaldi Mireille , Battesti Aurélia
Published: March 2023

Bacterial genome diversity is influenced by prophages, which are viral genomes integrated into the bacterial chromosome. Most prophage genes are silent but those that are expressed can provide unexpected properties to their host. Using as a modelE.coliK-12 that carries 9 defective prophages in its genome, we aimed at highlighting the impact of genes encoded by prophages on host physiology. We focused our work on AppY, a transcriptional regulator encoded on the DLP12 prophage. By performing RNA-Seq experiments, we showed that AppY production modulates the expression of more than 200 genes. Among them, 11 were identified by ChIP-Seq as direct AppY targets. AppY directly and positively regulates several genes involved in the acid stress response including the master regulator genegadEbut alsonhaRandgadY, two genes important for biofilm formation. Moreover, AppY indirectly and negatively impacts bacterial motility by favoring the degradation of FlhDC, the master regulator of the flagella biosynthesis. As a consequence of these regulatory effects, AppY increases acid stress resistance and biofilm formation while also causing a strong defect in motility. Our research shed light on the importance to consider the genetic interactions occurring between prophages and bacteria to fully understand bacterial physiology. It also highlights how a prophage-encoded transcriptional regulator integrates in a complex manner into the host regulatory network and how it benefits its host, allowing it to cope with changing environmental conditions.
Multimodal CRISPR perturbations of GWAS loci associated with coronary artery disease in vascular endothelial cells
Authors: Wünnemann Florian , Fotsing Tadjo Thierry , Beaudoin Mélissa , Lalonde Simon , Lo Ken Sin , Kleinstiver Benjamin P. , Lettre Guillaume
Published: March 2023

Genome-wide association studies have identified >250 genetic variants associated with coronary artery disease (CAD), but the causal variants, genes and molecular mechanisms remain unknown at most loci. We performed pooled CRISPR screens to test the impact of sequences at or near CAD-associated genetic variants on vascular endothelial cell functions. Using CRISPR knockout, inhibition and activation, we targeted 1998 variants at 83 CAD loci to assess their effect on three adhesion proteins (E-selectin, ICAM1, VCAM1) and three key endothelial functions (nitric oxide and reactive oxygen species production, calcium signalling). At a false discovery rate ≤10%, we identified significant CRISPR perturbations near 42 variants located within 26 CAD loci. We used base editing to validate a putative causal variant in the promoter of the FES gene. Although a few of the loci include genes previously characterized in endothelial cells (e.g. AIDA, ARHGEF26, ADAMTS7), most are implicated in endothelial dysfunction for the first time. Detailed characterization of one of these new loci implicated the RNA helicase DHX38 in vascular endothelial cell senescence. While promising, our results also highlighted several limitations in using CRISPR perturbations to functionally dissect GWAS loci, including an unknown false negative rate and potential off-target effects.
The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo
Authors: Tirgar Reyhaneh , Davies Jonathan P. , Plate Lars , Nordman Jared T.
Published: March 2023

Histones are essential for chromatin packaging, and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones, but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila homolog of NASP, is a H3-H4-specific chaperone in the early embryo. We demonstrate that, while a NASP null mutant is viable in Drosophila, NASP is a maternal effect gene. Embryos laid by NASP mutant mothers have a reduced rate of hatching and show defects in early embryogenesis. Critically, soluble H3-H4 pools are degraded in embryos laid by NASP mutant mothers. Our work identifies NASP as the critical H3-H4 histone chaperone in the Drosophila embryo.
Stigma as a barrier and sex work as a protective factor for HIV testing among trans women in Nepal
Authors: Wilson Erin C. , Turner Caitlin M. , Dhakal Manisha , Sharma Sanjay , Rai Anuj , Lama Rajesh , Banik Swagata , Arayasirikul Sean
Published: March 2023

Stigma towards trans women in Nepal creates individual and system-level risks for HIV. A critical protective factor is access to HIV prevention. Research is needed to determine the impact of stigma on HIV testing among trans women in Nepal. We conducted a secondary analysis of data collected using respondent driven sampling in 2019 on HIV risk among trans women in Nepal. Data analysis was restricted to trans women who were HIV negative at testing through the parent study. Descriptive statistics, tests for bivariable associations between HIV testing and stigma variables, and binomial Poisson regression were conducted to examine HIV testing outcomes. There were 173 participants who tested negative for HIV in our sample. The majority were under age 35 (59%) and most had a grade school education or less (64.7%). No trans women were homeless and most rented a room (70.5%) or owned their home (19.7%). The majority were currently sex workers (57.8%). Almost all HIV-negative trans women had ever been tested for HIV (90.8%), but only 53.5% in the last 3 months. The most frequently cited reason for not having been tested was thinking they were at low risk for HIV (40.9%) and being afraid of receiving a positive test result (22.7%). HIV and anti-trans stigma were high across most measures, including that almost all (94.2%) believed that most people in Nepal would discriminate against people with HIV. And most participants thought trans women were not accepted in Nepali Society (65.9%). Most participants also reported high social support (70.5%). Social cohesion among participants varied, with most experiencing medium (41.6%) or high (33.5%) social cohesion. Just over half had high social participation (55.5%). Participants who reported current sex work had lower prevalence of not testing for HIV in the last 3 months (prevalence ratio, PR = 0.54, 95% confidence interval, 95%CI = 0.32–0.92, p = 0.02). Every one-unit increase in social cohesion was associated with 1.05 times the prevalence of not testing for HIV in the last 3 months (95%CI = 1.01–1.09, p-value = 0.02). Trans women who did sex work were more likely to be HIV tested while those who were more socially connected to peers were less likely to have recently been tested for HIV. HIV stigma may result in fear of social rejection from peers if one tests positive. Interventions that focus on addressing stigma within trans women’s social networks and strategies to mitigate HIV stigma in society may result in increased frequency of HIV testing among trans women in Nepal.
Knowledge and attitudes toward complete diagnostic autopsy and minimally invasive autopsy: A cross-sectional survey in Hanoi, Vietnam
Authors: Dieu Ngan Ta Thi , Phuong Nhung Doan , Le Thao My Nguyen , Chambers Mary , Nguyen Duy Manh , Nguyen Ha Thi Lien , Vu Huong Thi Thu , Pham Thach Ngoc , van Doorn Rogier , Van Nuil Jennifer Ilo
Published: March 2023

Knowing the cause of death (CoD) plays an important role in developing strategies and interventions to prevent early mortality. In Vietnam, the CoD of the majority of patients who acquired infectious diseases remains unknown. While there are challenges that hinder the use of complete diagnostic autopsy (CDA) in practice, minimally invasive autopsy (MIA) might be a promising alternative to establish CoD in Vietnam. The current study aims to explore knowledge of and attitudes toward CDA and MIA in the wider population in Vietnam. The study was cross-sectional, using structured questionnaires that were disseminated electronically via several websites and as paper-based forms in a national level hospital in Vietnam. Descriptive analyses were performed and where appropriate, comparisons between the healthcare workers and the general public were performed. We included 394 questionnaires in the analysis. The majority of participants were under age 40, living in major cities and currently practicing no religion. 76.6% of respondents were aware of CDA and among them, 98% acknowledged its importance in medicine. However, most participants thought that CDA should only be performed when the CoD was suspicious or unconfirmed because of its the invasive nature. For MIA, only 22% were aware of the method and there was no difference in knowledge of MIA between healthcare workers and the wider public. The questionnaire results showed that there are socio-cultural barriers that hinder the implementation of CDA in practice. While the awareness of MIA among participants was low, the minimally invasive nature of the method is promising for implementation in Vietnam. A qualitative study is needed to further explore the ethical, socio-cultural and/or religious barriers that might hinder the implementation of MIA in Vietnam.
Standardized evaluation of Zika nucleic acid tests used in clinical settings and blood screening
Authors: Stone Mars , Bakkour Sonia , Grebe Eduard , Emperador Devy M. , Escadafal Camille , Deng Xutao , Dave Honey , Kelly-Cirino Cassandra , Lackritz Eve , Rojas Diana P. , Simmons Graham , Rabe Ingrid B. , Busch Michael P.
Published: March 2023

Early detection of Zika virus (ZIKV) transmission within geographic regions informs implementation of community mitigation measures such as vector reduction strategies, travel advisories, enhanced surveillance among pregnant women, and possible implementation of blood and organ donor screening or deferral. Standardized, comparative assessments of ZIKV assay and testing lab performance are important to develop optimal approaches to ZIKV diagnostic testing and surveillance. We conducted an expanded blinded panel study to characterize and compare the analytical performance of fifteen diagnostic and blood screening ZIKV NAT assays, including detection among single- and multiplex assays detecting ZIKV, dengue virus (DENV) and chikungunya virus (CHIKV). A 300 member blinded panel was constructed, consisting of 11 serial half-log dilutions ranging from ~104 to 10−1 genome equivalents/mL in 25 replicates each of the Tahitian Asian ZIKV isolate in ZIKV-negative human serum. Additionally, clinical samples from individuals with DENV-like syndrome or suspected ZIKV infection in Brazil were evaluated. The majority of assays demonstrated good specificity. Analytical sensitivities varied 1–2 logs, with a substantially higher limit of detection (LOD) in one outlier. Similar analytical sensitivity for ZIKV RNA detection in singleplex and multiplex assays of the Grifols and ThermoFisher tests were observed. Coefficient of Assay Efficiency (CE), calculated to characterize assays’ RNA extraction and amplification efficiency, ranged from 0.13 for the Certest VIASURE multiplex and 0.75 for the Grifols multiplex assays. In general, assays using transcription mediated amplification (TMA) technology had greater CE compared to assays using conventional PCR technology. Donor screening NAT assays were significantly more sensitive than diagnostic RT-qPCR assays, primarily attributable to higher sample input volumes. However, ideal assays to maximize sensitivity and throughput may not be a viable option in all contexts, with other factors such as cost, instrumentation, and regulatory approval status influencing assay availability and selection, particularly in resource constrained settings.
Mapping of cholera hotspots in Kenya using epidemiologic and water, sanitation, and hygiene (WASH) indicators as part of Kenya’s new 2022–2030 cholera elimination plan
Authors: Kiama Catherine , Okunga Emmanuel , Muange Annastacia , Marwanga Doris , Langat Daniel , Kuria Francis , Amoth Patrick , Were Ian , Gachohi John , Ganda Nolluscus , Martinez Valiente Marion , Njenga M. Kariuki , Osoro Eric , Brunkard Joan
Published: March 2023

Cholera is an issue of major public health importance. It was first reported in Kenya in 1971, with the country experiencing outbreaks through the years, most recently in 2021. Factors associated with the outbreaks in Kenya include open defecation, population growth with inadequate expansion of safe drinking water and sanitation infrastructure, population movement from neighboring countries, crowded settings such as refugee camps coupled with massive displacement of persons, mass gathering events, and changes in rainfall patterns. The Ministry of Health, together with other ministries and partners, revised the national cholera control plan to a multisectoral cholera elimination plan that is aligned with the Global Roadmap for Ending Cholera. One of the key features in the revised plan is the identification of hotspots. The hotspot identification exercise followed guidance and tools provided by the Global Task Force on Cholera Control (GTFCC). Two epidemiological indicators were used to identify the sub-counties with the highest cholera burden: incidence per population and persistence. Additionally, two indicators were used to identify sub-counties with poor WASH coverage due to low proportions of households accessing improved water sources and improved sanitation facilities. The country reported over 25,000 cholera cases between 2015 and 2019. Of 290 sub-counties, 25 (8.6%) sub-counties were identified as a high epidemiological priority; 78 (26.9%) sub-counties were identified as high WASH priority; and 30 (10.3%) sub-counties were considered high priority based on a combination of epidemiological and WASH indicators. About 10% of the Kenyan population (4.89 million) is living in these 30-combination high-priority sub-counties. The novel method used to identify cholera hotspots in Kenya provides useful information to better target interventions in smaller geographical areas given resource constraints. Kenya plans to deploy oral cholera vaccines in addition to WASH interventions to the populations living in cholera hotspots as it targets cholera elimination by 2030.
Smoking and healthcare expenditure reductions associated with the California Tobacco Control Program, 1989 to 2019: A predictive validation
Authors: Lightwood James M. , Anderson Steve , Glantz Stanton A.
Published: March 2023

Background

Previous research used data through 2008 to estimate a model for the effect of the California Tobacco Control Program (CTCP) that used cumulative real per capita tobacco control expenditure to predict smoking behavior (current adult smoking prevalence and mean cigarette consumption per current smoker). Predicted changes in smoking behavior due to the CTCP were used to predict its effect on health care expenditure. This research updates the model using the most recently available data and estimates CTCP program effect through 2019.

Methods

The data used in the previous research were updated, and the original model specification and a related predictive forecast model were re-estimated. The updated regression estimates were compared to those previously published and used to update estimates of CTCP program effect in 2019 dollars.

Results

There was no evidence of structural change in the previously estimated model. The estimated effect of the CTCP program expenditures on adult current smoking prevalence and mean consumption per adult current smoker has remained stable over time. Over the life of the program, one additional dollar per capita of program expenditure was associated with a reduction of current adult smoking prevalence by about 0.05 percentage point and mean annual consumption per adult current smoker by about 2 packs. Using updated estimates, the program prevented 9.45 (SE 1.04) million person-years of smoking and cumulative consumption of 15.7 (SE 3.04) billion packs of cigarettes from 1989 to 2019. The program produced cumulative savings in real healthcare expenditure of $544 (SE $82) billion using the National Income and Product Accounts (NIPA), and $816 (SE $121) billion using the Center for Medicare and Medicaid Services (CMS) measure of medical costs. During this time, the CTCP expenditure was $3.5 billion.

Conclusion

A simple predictive model of the effectiveness of the CTCP program remained stable and retains its predictive performance out-of-sample. The updated estimates of program effect suggest that CTCP program has retained its effectiveness over its 31-year life and produced a return on investment of 231 to 1 in direct CMS medical expenditure.
Combining cash transfers and cognitive behavioral therapy to reduce antisocial behavior in young men: A mediation analysis of a randomized controlled trial in Liberia
Authors: Carpena Marina Xavier , Paula Cristiane Silvestre , Loret de Mola Christian , Hessel Philipp , Avendano Mauricio , Evans-Lacko Sara , Matijasevich Alicia
Published: March 2023

Background

Interventions that combine cognitive behavioral therapy (CBT) with unconditional cash transfers (UCT) reduce the risk of antisocial behavior (ASB), but the underlying mechanisms are unclear. In this paper, we test the role of psychological and cognitive mechanisms in explaining this effect. We assessed the mediating role of executive function, self-control, and time preferences.

Methods

We used data from the Sustainable Transformation of Youth in Liberia, a community-based randomized controlled trial of criminally engaged men. The men were randomized into: Group-1: control (n = 237); and Group-2: CBT+UCT (n = 207). ASB was measured 12–13 months after the interventions were completed, and the following mediators were assessed 2–5 weeks later: (i) self-control, (ii) time preferences and (iii) executive functions. We estimated the natural direct effect (NDE) and the natural indirect effect (NIE) of the intervention over ASB.

Results

Self-control, time preferences and a weighted index of all three mediators were associated with ASB scores, but the intervention influenced time preferences only [B = 0.09 95%CI (0.03; 0.15)]. There was no evidence that the effect of the intervention on ASB was mediated by self-control [BNIE= 0.007 95%CI (-0.01; 0.02)], time preferences [BNIE= -0.02 95%CI (-0.05; 0.01)], executive functions [BNIE= 0.002 95%CI (-0.002; 0.006)] or the weighted index of the mediators [BNIE= -0.0005 95%CI (-0.03; 0.02)].

Conclusions

UCT and CBT lead to improvements in ASB, even in the absence of mediation via psychological and cognitive functions. Findings suggest that the causal mechanisms may involve non-psychological pathways.
Purification and biochemical analysis of native AMPA receptors from three different mammalian species
Authors: Rao Prashant , Gouaux Eric
Published: March 2023

The majority of fast, excitatory synaptic transmission in the central nervous system (CNS) is mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), which are glutamate-activated ion channels integral to synaptic plasticity, motor coordination, learning, and memory. Native AMPARs are multiprotein assemblies comprised of a tetrameric receptor core that co-assembles with a broad range of peripheral auxiliary proteins which shape subcellular localization and signaling properties of the resulting complexes. Structure determination of AMPARs has traditionally relied on recombinant expression systems; however, these methods are not well suited to elucidate the diverse array of AMPAR assemblies that are differentially expressed in mammalian brains. While recent studies of native receptor complexes have advanced our understanding of endogenous assemblies, receptors thus far have only been isolated from rodent brain tissue. Here, we employed an immunoaffinity purification strategy to isolate native AMPARs from the brains of three different mammals–pigs, sheep, and cows. Compared to rodents, pigs, sheep, and cows are ungulate mammals, animals with closer genomic identity with humans. Here we determined the molecular size, overall yield, and purity of native AMPARs isolated from these three mammals, thereby demonstrating that structural determination and biochemical analysis is possible from a clade of mammals evolutionarily distinct from rodents.
MOPA: An integrative multi-omics pathway analysis method for measuring omics activity
Authors: Jeon Jaemin , Han Eon Yong , Jung Inuk
Published: March 2023

Pathways are composed of proteins forming a network to represent specific biological mechanisms and are often used to measure enrichment scores based on a list of genes in means to measure their biological activity. The pathway analysis is a de facto standard downstream analysis procedure in most genomic and transcriptomic studies. Here, we present MOPA (Multi-Omics Pathway Analysis), which is a multi-omics integrative method that scores individual pathways in a sample wise manner in terms of enriched multi-omics regulatory activity, which we refer to mES (multi-omics Enrichment Score). The mES score reflects the strength of regulatory relations between multi-omics in units of pathways. In addition, MOPA is able to measure how much each omics contribute to mES that may be used to observe what kind of omics are active in a pathway within a sample group (e.g., subtype, gender), which we refer to OCR (Omics Contribution Rate). Using nine different cancer types, 93 clinical features and three types of omics (i.e., gene expression, miRNA and methylation), MOPA was used to search for clinical features that were explainable in context of multi-omics. By evaluating the performance of MOPA, we showed that it yielded higher or at least equal performance compared to previous single and multi-omics pathway analysis tools. We find that the advantage of MOPA is the ability to explain pathways in terms of omics relation using mES and OCR. As one of the results, the TGF-beta signaling pathway was captured as an important pathway that showed distinct mES and OCR values specific to the CMS4 subtype in colon adenocarcinoma. The mES and OCR metrics suggested that the mRNA and miRNA expressions were significantly different from the other subtypes, which was concordant with previous studies. The MOPA software is available at https://github.com/jaeminjj/MOPA.
Type II endometrial cancer: Incidence, overall and disease-free survival in Martinique
Authors: Ebring Coralie , Marlin Régine , Macni Jonathan , Vallard Alexis , Bergerac Sébastien , Beaubrun-Renard Murielle , Joachim Clarisse , Jean-Laurent Mehdi
Published: March 2023

Background and study aims

In Martinique, about 33 new cases of endometrial cancer are diagnosed per year with a high mortality rate (world standardised rate of 4.9/100,000 versus 2.3/100,000 in mainland France). The present study aimed to determine the incidence and mortality of type I and type II endometrial cancers (ECs), their overall survival (OS) and disease-free survival (DFS) between 2012 and 2016.

Patients and methods

This retrospective observational cohort study used data from the Martinique Cancer Registry (MCR). 191 patients with corpus uterine cancer were extracted between 2012 and 2016. Patients with either endometrioid endometrial carcinoma (EEC), uterine papillary serous carcinomas (UPSC), uterine clear cell carcinomas (UCCC) or uterine carcinosarcomas (UCS) were included. All other uterine cancers were excluded.

Results

Among the 163 included patients, 97 (60%) were type I and 66 (40%) were type II. The standardized incidence rate is 4.50/100,000 for type I vs. 2.66/100,000 for type II. Three years DFS for all types, type I and type II was 81.5% [74.2–86.9], 84.9% [75.4–91] and 76.7% [63.8–85.5] respectively. The five-years OS for all types, type I and type II was 47.0% [38.9–54.7] vs. 58.8% [47.3–68.5] vs. 22.8% [15.0–37.7] respectively.

Conclusions

In Martinique, we report a high proportion of type II ECs, which has a poor prognosis with few treatment options.
Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice
Authors: Sugita Yoshito , Takada Shigeki , Tanigaki Kenji , Muraki Kazue , Uemura Munehiro , Hojo Masato , Miyamoto Susumu
Published: March 2023

Anti-vascular endothelial growth factor (VEGF) therapy has been developed for the treatment of a variety of cancers. Although this therapy may be a promising alternative treatment for refractory pituitary adenomas and pituitary carcinomas, the effects of anti-VEGF agents on the pituitary gland are not yet well understood. Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland. This is the first report that anti-VEGF therapy can cause pituitary apoplexy. C57BL/6 mice were daily injected intraperitoneally with 100 mg/kg body weight of OSI-930 for one to six days. Pituitary glands were immunohistochemically examined. Four of six mice treated for three days and all of five mice treated for six days exhibited hemorrhage in the pituitary gland. In all cases, the hemorrhage occurred just around Rathke’s cleft. In OSI-930-administered mice, the vascular coverage and branching were reduced in the anterior lobe, and capillary networks were also decreased in the intermediate lobe in a treatment-day dependent manner. Few blood vessels around Rathke’s cleft of the intermediate lobe express VE-cadherin and are covered with platelet-derived growth factor receptor-β (PDGFR-β)-positive cells, which suggests that capillaries around Rathke’s cleft of the intermediate lobe were VE-cadherin-negative and not covered with pericytes. The reduction of capillary plexus around Rathke’s cleft was observed at the site where hemorrhage occurred, suggesting a causal relationship with the pathogenesis of pituitary hemorrhage. Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy.
Delirium in older hospitalized patients—A prospective analysis of the detailed course of delirium in geriatric inpatients
Authors: Wilke Skadi , Steiger Edgar , Bärwolff Tanja L. , Kleine Justus F. , Müller-Werdan Ursula , Rosada Adrian
Published: March 2023

Background

Delirium in older hospitalized patients (> 65) is a common clinical syndrome, which is frequently unrecognized.

Aims

We aimed to describe the detailed clinical course of delirium and related cognitive functioning in geriatric patients in a mainly non-postoperative setting in association with demographic and clinical parameters and additionally to identify risk factors for delirium in this common setting.

Methods

Inpatients of a geriatric ward were screened for delirium and in the case of presence of delirium included into the study. Patients received three assessments including Mini-Mental-Status-Examination (MMSE) and the Delirium Rating Scale Revised 98 (DRS-R-98). We conducted correlation and linear mixed-effects model analyses to detect associations.

Results

Overall 31 patients (82 years (mean)) met the criteria for delirium and were included in the prospective observational study. Within one week of treatment, mean delirium symptom severity fell below the predefined cut-off. While overall cognitive functioning improved over time, short- and long-term memory deficits remained. Neuroradiological conspicuities were associated with cognitive deficits, but not with delirium severity.

Discussion

The temporal stability of some delirium symptoms (short-/long-term memory, language) on the one hand and on the other hand decrease in others (hallucinations, orientation) shown in our study visualizes the heterogeneity of symptoms attributed to delirium and their different courses, which complicates the differentiation between delirium and a preexisting cognitive decline. The recovery from delirium seems to be independent of preclinical cognitive status.

Conclusion

Treatment of the acute medical condition is associated with a fast decrease in delirium severity. Given the high incidence and prevalence of delirium in hospitalized older patients and its detrimental impact on cognition, abilities and personal independence further research needs to be done.
A predictive model for understanding the role of emotion for the formation of presence in virtual reality
Authors: Jicol Crescent , Cheng Hoi Ying , Petrini Karin , O’Neill Eamonn
Published: March 2023

Users’ emotions may influence the formation of presence in virtual reality (VR). Users’ expectations, state of arousal and personality may also moderate the relationship between emotions and presence. An interoceptive predictive coding model of conscious presence (IPCM) considers presence as a product of the match between predictions of interoceptive emotional states and the actual states evoked by an experience (Seth et al. 2012). The present paper aims to test this model’s applicability to VR for both high-arousal and low-arousal emotions. The moderating effect of personality traits on the creation of presence is also investigated. Results show that user expectations about emotional states in VR have an impact on presence, however, expression of this relationship is moderated by the intensity of an emotion, with only high-arousal emotions showing an effect. Additionally, users’ personality traits moderated the relationship between emotions and presence. A refined model is proposed that predicts presence in VR by weighting emotions according to their level of arousal and by considering the impact of personality traits.
Artificial intelligence-based point-of-care lung ultrasound for screening COVID-19 pneumoniae: Comparison with CT scans
Authors: Kuroda Yumi , Kaneko Tomohiro , Yoshikawa Hitomi , Uchiyama Saori , Nagata Yuichi , Matsushita Yasushi , Hiki Makoto , Minamino Tohru , Takahashi Kazuhisa , Daida Hiroyuki , Kagiyama Nobuyuki
Published: March 2023

Background

Although lung ultrasound has been reported to be a portable, cost-effective, and accurate method to detect pneumonia, it has not been widely used because of the difficulty in its interpretation. Here, we aimed to investigate the effectiveness of a novel artificial intelligence-based automated pneumonia detection method using point-of-care lung ultrasound (AI-POCUS) for the coronavirus disease 2019 (COVID-19).

Methods

We enrolled consecutive patients admitted with COVID-19 who underwent computed tomography (CT) in August and September 2021. A 12-zone AI-POCUS was performed by a novice observer using a pocket-size device within 24 h of the CT scan. Fifteen control subjects were also scanned. Additionally, the accuracy of the simplified 8-zone scan excluding the dorsal chest, was assessed. More than three B-lines detected in one lung zone were considered zone-level positive, and the presence of positive AI-POCUS in any lung zone was considered patient-level positive. The sample size calculation was not performed given the retrospective all-comer nature of the study.

Results

A total of 577 lung zones from 56 subjects (59.4 ± 14.8 years, 23% female) were evaluated using AI-POCUS. The mean number of days from disease onset was 9, and 14% of patients were under mechanical ventilation. The CT-validated pneumonia was seen in 71.4% of patients at total 577 lung zones (53.3%). The 12-zone AI-POCUS for detecting CT-validated pneumonia in the patient-level showed the accuracy of 94.5% (85.1%– 98.1%), sensitivity of 92.3% (79.7%– 97.3%), specificity of 100% (80.6%– 100%), positive predictive value of 95.0% (89.6% - 97.7%), and Kappa of 0.33 (0.27–0.40). When simplified with 8-zone scan, the accuracy, sensitivity, and sensitivity were 83.9% (72.2%– 91.3%), 77.5% (62.5%– 87.7%), and 100% (80.6%– 100%), respectively. The zone-level accuracy, sensitivity, and specificity of AI-POCUS were 65.3% (61.4%– 69.1%), 37.2% (32.0%– 42.7%), and 97.8% (95.2%– 99.0%), respectively.

Interpretation

AI-POCUS using the novel pocket-size ultrasound system showed excellent agreement with CT-validated COVID-19 pneumonia, even when used by a novice observer.
Many roads lead to Rome: How improvisation and absorptive capacity affect entrepreneurial orientation and new venture performance relationship
Authors: Sun Wei , Hou Xilin , Liang Li , Bi Xiaoliang
Published: March 2023

This paper develops and tests a model that highlights the roles of improvisation and absorptive capacity as important mediating mechanisms through which entrepreneurial orientation (EO) influences new venture performance. Furthermore, we examine the interactive effect of improvisation and absorptive capacity on new venture performance. The results show that (a) improvisation and absorptive capacity both mediate the relationship between EO and new venture performance; (b) the interaction between improvisation and absorptive capacity is positively related to new venture performance; (c) improvisation moderates the indirect relationship between EO and new venture performance via absorptive capacity; and (d) absorptive capacity moderates the mediation of improvisation in the relationship between EO and new venture performance. With these findings, this paper provides insights into how different learning modes can enhance the EO-performance relationship.
Development, refinement, and characterization of a nonhuman primate critical care environment
Authors: Bozzay Joseph D. , Walker Patrick F. , Atwood Rex E. , DeSpain Robert W. , Parker William J. , Chertow Daniel S. , Mares John A. , Leonhardt Crystal L. , Elster Eric A. , Bradley Matthew J.
Published: March 2023

Background

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated a critical care phase without the use of general anesthesia. We describe the development of a prolonged critical care environment with sedation and ventilation support, and also report corresponding NHP biologic and inflammatory markers.

Methods

Eight adult male rhesus macaques underwent ventilation with sedation for 48–96 hours in a critical care setting. Three of these NHPs underwent “sham” procedures as part of trauma control model development. Blood counts, chemistries, coagulation studies, and cytokines/chemokines were collected throughout the study, and histopathologic analysis was conducted at necropsy.

Results

Eight NHPs were intentionally survived and extubated. Three NHPs were euthanized at 72–96 hours without extubation. Transaminitis occurred over the duration of ventilation, but renal function, acid-base status, and hematologic profile remained stable. Chemokine and cytokine analysis were notable for baseline fold-change for Il-6 and Il-1ra (9.7 and 42.7, respectively) that subsequently downtrended throughout the experiment unless clinical respiratory compromise was observed.

Conclusions

A NHP critical care environment with ventilation support is feasible but requires robust resources. The inflammatory profile of NHPs is not profoundly altered by sedation and mechanical ventilation. NHPs are susceptible to the pulmonary effects of short-term ventilation and demonstrate a similar bioprofile response to ventilator-induced pulmonary pathology. This work has implications for further development of a prolonged care NHP model.
Assessing suicidality during the SARS-CoV-2 pandemic: Lessons learned from adaptation and implementation of a telephone-based suicide risk assessment and response protocol in Malawi
Authors: Landrum Kelsey R. , Akiba Christopher F. , Pence Brian W. , Akello Harriet , Chikalimba Hamis , Dussault Josée M. , Hosseinipour Mina C. , Kanzoole Kingsley , Kulisewa Kazione , Malava Jullita Kenala , Udedi Michael , Zimba Chifundo C. , Gaynes Bradley N.
Published: March 2023

The SARS-CoV-2 pandemic led to the rapid transition of many research studies from in-person to telephone follow-up globally. For mental health research in low-income settings, tele-follow-up raises unique safety concerns due to the potential of identifying suicide risk in participants who cannot be immediately referred to in-person care. We developed and iteratively adapted a telephone-delivered protocol designed to follow a positive suicide risk assessment (SRA) screening. We describe the development and implementation of this SRA protocol during follow-up of a cohort of adults with depression in Malawi enrolled in the Sub-Saharan Africa Regional Partnership for Mental Health Capacity Building (SHARP) randomized control trial during the COVID-19 era. We assess protocol feasibility and performance, describe challenges and lessons learned during protocol development, and discuss how this protocol may function as a model for use in other settings. Transition from in-person to telephone SRAs was feasible and identified participants with suicidal ideation (SI). Follow-up protocol monitoring indicated a 100% resolution rate of SI in cases following the SRA during this period, indicating that this was an effective strategy for monitoring SI virtually. Over 2% of participants monitored by phone screened positive for SI in the first six months of protocol implementation. Most were passive risk (73%). There were no suicides or suicide attempts during the study period. Barriers to implementation included use of a contact person for participants without personal phones, intermittent network problems, and pre-paid phone plans delaying follow-up. Delays in follow-up due to challenges with reaching contact persons, intermittent network problems, and pre-paid phone plans should be considered in future adaptations. Future directions include validation studies for use of this protocol in its existing context. This protocol was successful at identifying suicide risk levels and providing research assistants and participants with structured follow-up and referral plans. The protocol can serve as a model for virtual SRA development and is currently being adapted for use in other contexts.
Study protocol: Neuro-inflammatory parameters as mediators of the relationship between social anxiety and itch intensity: A cross-sectional, controlled laboratory study in patients with psoriasis and healthy skin controls
Authors: Schepko Marcel , Stumpf Katharina C. , Tumala Susanne , Peters Eva M. , Kupfer Jörg P. , Schut Christina
Published: March 2023

Introduction

Psoriasis (PSO) is a disease that in the majority of patients is accompanied by itch, which imposes a great burden and positively relates to anxiety. Social anxiety, a facet of anxiety associated with social withdrawal, may be a predictor of itch intensity in this patient group. Moreover, anxiety is linked to the secretion of neuroendocrine and inflammatory parameters such as substance P (SP), interleukin (IL)-6 and IL-17, which are also related to itch. In this research project, we investigate first, whether there is a direct relationship between social anxiety and itch intensity in patients with PSO and second whether the secretion of SP, IL-6 and IL-17 in the skin mediates this relationship. Additionally, PSO-patients are compared to healthy skin controls regarding their level of social anxiety, itch intensity and the secretion of SP, IL-6 and IL-17.

Methods and analyses

For study 1, we aim to recruit 250 psoriasis patients and 250 healthy skin controls who complete questionnaires to assess social anxiety, itch intensity and control variables (e.g. sociodemographic variables and severity of PSO). A linear hierarchic regression will be used to determine whether social anxiety significantly contributes to itch intensity. In study 2, we plan to apply the suction blister method to 128 patients and healthy skin controls recruited from study 1 to determine SP, IL-6 and IL-17 in tissue fluid extracted from the skin. A mediation analysis will be conducted using the SPSS-macro PROCESS to test whether the relationship between social anxiety and itch is mediated by SP, IL-6 and IL-17.

Trial registration numbers

DRKS00023621 (study 1) and DRKS00023622 (study 2).
A deep reinforcement learning algorithm for the rectangular strip packing problem
Authors: Fang Jie , Rao Yunqing , Shi Mingliang
Published: March 2023

As a branch of the two-dimensional (2D) optimal blanking problem, rectangular strip packing is a typical non-deterministic polynomial (NP-hard) problem. The classical packing solution method relies on heuristic and metaheuristic algorithms. Usually, it needs to be designed with manual decisions to guide the solution, resulting in a small solution scale, weak generalization, and low solution efficiency. Inspired by deep learning and reinforcement learning, combined with the characteristics of rectangular piece packing, a novel algorithm based on deep reinforcement learning is proposed in this work to solve the rectangular strip packing problem. The pointer network with an encoder and decoder structure is taken as the basic network for the deep reinforcement learning algorithm. A model-free reinforcement learning algorithm is designed to train network parameters to optimize the packing sequence. This design can not only avoid designing heuristic rules separately for different problems but also use the deep networks with self-learning characteristics to solve different instances more widely. At the same time, a piece positioning algorithm based on the maximum rectangles bottom-left (Maxrects-BL) is designed to determine the placement position of pieces on the plate and calculate model rewards and packing parameters. Finally, instances are used to analyze the optimization effect of the algorithm. The experimental results show that the proposed algorithm can produce three better and five comparable results compared with some classical heuristic algorithms. In addition, the calculation time of the proposed algorithm is less than 1 second in all test instances, which shows a good generalization, solution efficiency, and practical application potential.