bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse t-complex protein 11 is important for progressive motility in sperm†
Authors: Castaneda Julio M , Miyata Haruhiko , Archambeault Denise R , Satouh Yuhkoh , Yu Zhifeng , Ikawa Masahito , Matzuk Martin M
Published: December 2019

The t-complex is defined as naturally occurring variants of the proximal third of mouse chromosome 17 and has been studied by mouse geneticists for decades. This region contains many genes involved in processes from embryogenesis to sperm function. One such gene, t-complex protein 11 (Tcp11), was identified as a testis-specific gene whose protein is present in elongating spermatids. Later work on Tcp11 localized TCP11 to the sperm surface and acrosome cap and implicated TCP11 as important for sperm capacitation through the cyclic AMP/Protein Kinase A pathway. Here, we show that TCP11 is cytoplasmically localized to elongating spermatids and absent from sperm. In the absence of Tcp11, male mice have severely reduced fertility due to a significant decrease in progressively motile sperm; however, Tcp11-null sperm continues to undergo tyrosine phosphorylation, a hallmark of capacitation. Interestingly, null sperm displays reduced PKA activity, consistent with previous reports. Our work demonstrates that TCP11 functions in elongated spermatids to confer proper motility in mature sperm.
Accelerated ovarian reserve depletion in female anti-Müllerian hormone knockout mice has no effect on lifetime fertility†
Authors: Guo Ruikang , Pankhurst Michael W
Published: December 2019

Anti-Müllerian hormone (AMH) inhibits the activation of primordial follicles in the ovary. This causes an increased rate of ovarian reserve depletion in Amh−/− mice. The depletion of the ovarian reserve is responsible for the onset of menopause but age-related infertility occurs in advance of ovarian reserve depletion. To determine whether accelerated loss of primordial follicles leads to earlier onset infertility, Amh−/− and Amh+/+ females were paired with Amh+/+ stud males and birth rates were recorded across the females’ reproductive lifespan. The number of primordial follicles remaining in the ovaries of Amh−/− and Amh+/+ females were quantified in two cohorts at 11–12 and 12–13 months of age. As expected, the ovarian reserve in the Amh−/− females became depleted approximately 1 month earlier than Amh+/+ females. However, no difference was observed in the cumulative number of births over the lifespan, nor were there any differences in mean littersize at any age. It is possible that the reproductive lifespan of mice is too short for sufficient divergence of primordial follicles numbers to cause differences in Amh−/− and Amh+/+ female fertility. An alternative explanation contradicts current thinking; the function of AMH may be unrelated to the longevity of the reproductive lifespan in female mice.
HPTLC Separation of a Hepatoprotective Combination in Pharmaceutical Formulation and Human Plasma
Authors: Magdy Maimana A , Abdelfatah Rehab M
Published: December 2019

A binary mixture of Silymarin (SR) and Vitamin E (VE) acetate, of an antioxidant and a hepatoprotective effect, has been analyzed using a sensitive, selective and economic high performance thin layer chromatographic (HPTLC) method in their pure forms, pharmaceutical formulation and spiked human plasma. SR and VE were separated on 60F254 silica gel plates using hexane:acetone:formic acid (7:3:0.15, v/v/v) as a developing system with UV detection at 215 nm. The method was evaluated for linearity, accuracy, precision, selectivity, limit of detection (LOD) and limit of quantification (LOQ). SR and VE were detected in the linear range of 0.2–2.5 and 0.2–4.5 μg/band, respectively. Method validation was done as per ICH guidelines and acceptable results of accuracy of 99.86 ± 1.190 and 100.22 ± 1.609 for SR and VE, respectively were obtained. The method has been successfully applied for determination of the studied drugs in their pharmaceutical formulation without any interference from excipients, and in spiked plasma samples. Results obtained by the developed HPTLC-densitometric method were statistically compared to those obtained by the reported HPLC methods and no significant difference was found between them.
Framing Lars von Trier’s Medea
Authors: Giannopoulou Zina
Published: December 2019

Lars von Trier’s Medea renders on the silver screen Carl Th. Dreyer’s unrealized script from Euripides’ play. Von Trier considers Dreyer one of his greatest cinematic influences and fashions his film as a ‘personal interpretation and homage to the master’. Two prominent narrative features of Dreyer’s cinematic oeuvre are a cause/effect logic and parallelism, which create formally rigid and closed worlds governed by an abstract, impersonal order. Von Trier applies these features especially to the frame of Medea in order to enhance the theodicy of Euripides’ tragedy and Dreyer’s adaptation of it. He also plays games of cinematic reflexivity in conscious or unconscious competition with Dreyer. Finally, his directorial virtuosity manifests itself most spectacularly in the editing of the film’s frame, which arranges the segments of the prologue and the epilogue so as to engage reception as a temporal activity rooted in the past, undertaken in the present, and directed to the future.
Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by in utero environmental contaminant exposure
Authors: Herst P M , Dalvai M , Lessard M , Charest P L , Navarro P , Joly-Beauparlant C , Droit A , Trasler J M , Kimmins S , MacFarlane A J , Benoit-Biancamano M-O , Bailey J L
Published: December 2019

Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) ± FA supplementation and subsequent F1–F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1–F4 generations, sperm miRNA profiles were less perturbed with POPs+FA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPs+FA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and cognition and brain development in F3. When the POPs treatment was combined with FA supplementation, however, these same miRNA-targeted gene pathways were perturbed to a lesser extend and only in F1 sperm. These findings suggest that FA partially mitigates the effect of POPs on paternally derived miRNA in a intergenerational manner.
Patterns of Home Environmental Modification Use and Functional Health: The Women’s Health Initiative
Authors: Welti Laura M , Beavers Kristen M , Mampieri Annie , Rapp Stephen R , Ip Edward , Shumaker Sally A , Beavers Daniel P
Published: December 2019

Background

We examined common patterns of home environmental modification (HEM) use and associated major (including disability-, cardiovascular-, and cancer-related) health conditions and events among older women.

Methods

Women, aged 78.6 ± 6.3 years (n = 71,257), self-reported utilization of nine types of HEMs (hand rails, grab bars, ramps, nonslip surfaces, tacking carpets/rugs, decreasing clutter, increasing lighting, raised sink/counter heights, other). Concurrent history of major health conditions and events was collected. Odds ratios (ORs) were estimated based on overall HEM use and four latent classes (low HEM use [56%], rails/grab bars [20%], lighting/decluttering [18%], high HEM use [5%]), adjusted for age, marital status, race/ethnicity, education, depression, and obesity.

Results

Fifty-five percent of women reported using any HEM (overall), with strongest associations among disability-related conditions. Activities of daily living limitations were strongly associated with high HEM use (OR = 8.16, 95% confidence interval [CI] = 6.62–10.05), railing/grab bar use (OR = 4.02, 95% CI = 3.26–4.95), and lighting/declutter use (OR = 1.87, 95% CI = 1.40–2.50) versus low HEM use. Recent falls were positively associated with overall HEM use (OR = 1.79, 95% CI = 1.72–1.87); high HEM use (OR = 2.89, 95% CI = 2.64–3.16), railings/grab bars use (OR = 2.32, 95% CI = 2.18–2.48), and lighting/declutter use (OR = 1.93, 95% CI = 1.79–2.08) were positively associated with recent falls. Modest associations were observed between HEM use and select (ie, atrial fibrillation, heart valve disease, stroke) cardiovascular outcomes.

Conclusions

Among older women, disability-related conditions, including functional limitations and recent falls, were strongly associated with overall HEM use, high HEM use, and railings/grab bar use.
Genes, Education, and Labor Market Outcomes: Evidence from the Health and Retirement Study
Authors: Papageorge Nicholas W , Thom Kevin
Published: December 2019

Recent advances have led to the discovery of specific genetic variants that predict educational attainment. We study how these variants, summarized as a linear index—known as a polygenic score—are associated with human capital accumulation and labor market outcomes in the Health and Retirement Study (HRS). We present two main sets of results. First, we find evidence that the genetic factors measured by this score interact strongly with childhood socioeconomic status in determining educational outcomes. In particular, although the polygenic score predicts higher rates of college graduation on average, this relationship is substantially stronger for individuals who grew up in households with higher socioeconomic status relative to those who grew up in poorer households. Second, the polygenic score predicts labor earnings even after adjusting for completed education, with larger returns in more recent decades. These patterns suggest that the genetic traits that promote education might allow workers to better accommodate ongoing skill biased technological change. Consistent with this interpretation, we find a positive association between the polygenic score and nonroutine analytic tasks that have benefited from the introduction of new technologies. Nonetheless, the college premium remains a dominant determinant of earnings differences at all levels of the polygenic score. Given the role of childhood SES in predicting college attainment, this raises concerns about wasted potential arising from limited household resources.
Seismic low-frequency amplitude analysis for identifying gas reservoirs within thinly layered media
Authors: Li Shengjie , Rao Ying
Published: December 2019

Seismic low-frequency amplitude anomalies can be correlated with the existence of hydrocarbon reservoirs, but the generation mechanism of these low-frequency amplitude anomalies is very complicated. We investigated the effect of the Biot slow P-waves on the seismic reflection amplitude at low frequencies from fluid-saturated porous media using techniques of both theoretical calculation and physical modelling. First, we used theoretical calculation to study the effects of the frequency, the fluid content and the heterogeneity of layered media on the conversion of the Biot slow waves, and the reflection coefficients. Then, we used physical modelling data to show a low-frequency shadow of the air-saturated layered model. The phenomenon was similar to that in the theoretical calculation. A combination of the theoretical calculation and physical modelling results provided a reasonable explanation of the low-frequency shadow. The conclusion is that whether the actual hydrocarbon reservoirs exhibit low-frequency shadow phenomena depends on the frequency, the consolidation, the thickness of the hydrocarbon reservoirs, the homogeneity of the porosity and the fluid distributions of the reservoirs. The proposed method can be used to analyse the low-frequency anomalies and to identify the fluid properties using seismic data.
Netta Syrett, Nobody’s Fault, and Female Decadence: The Story of a Wagnerite
Authors: Rainwater Crescent
Published: December 2019

Scholars have traditionally associated decadence with misogyny, and therefore it has typically been perceived as antithetical to feminism. Nobody’s Fault (1896), Netta Syrett’s first novel, complicates this perception through the way in which the self-assertive protagonist, Bridget Ruan, finds in the decadent music of Richard Wagner a liberating form of aesthetic experience. In this essay, I argue that encountering Wagner’s music marks Bridget’s immersion into a form of decadent culture that affirms her aesthetic longings and awakens her erotic desires. At the same time, the novel condemns an antifeminist form of decadence that is associated with elitist male artists who indulge in a superficial manipulation of language and treat women as art objects. The novel’s resistance to exclusionary forms of aesthetic experience is modelled in its straightforward narrative style and strategic engagement with familiar New Woman themes. This middlebrow narrative thus made Syrett’s intervention into debates about women and decadence accessible to a middle-class female audience. When we recognize that the history of decadence includes its appeal to feminist writers such as Syrett rather than an exclusively antifeminist legacy, we can begin to uncover a more nuanced history of feminism and decadence in England at the fin de siècle.
Costs for Colon Cancer Treatment Comparing Benefit Types and Care Sources in the US Military Health System
Authors: Eaglehouse Yvonne L , Georg Matthew W , Richard Patrick , Shriver Craig D , Zhu Kangmin
Published: December 2019

Introduction

Cancer is one of the leading causes of morbidity and mortality in the USA, contributing largely to US healthcare spending. Provision of services (direct or purchased) and insurance benefit type may impact cost for cancer care. As a common cause of cancer in both men and women, we aim to compare colon cancer treatment costs between insurance benefit types and care sources in the US Military Health System (MHS) to better understand whether and to what extent these system factors impact cancer care costs.

Materials and Methods

Department of Defense Central Cancer Registry records and MHS Data Repository administrative claims were used to identify MHS beneficiaries aged 18–64 who were diagnosed with primary colon adenocarcinoma and received treatment between 2003 and 2008. The data linkage was approved by the Institutional Review Boards of the Walter Reed National Military Medical Center, the Defense Health Agency, and the National Institutes of Health. Costs to the MHS for each claim related to cancer treatment were extracted from the linked data and adjusted to 2008 USD. We used quantile regression models to compare median cancer treatment costs between benefit types and care sources (direct, purchased, or both), adjusted for demographic, tumor, and treatment characteristics.

Results

The median per capita (n = 801) costs for colon cancer care were $60,321 (interquartile range $24,625, $159,729) over a median follow-up of 1.7 years. The model-estimated treatment costs were similar between benefit types. Patients using direct care had significantly lower estimated median costs [$34,145 (standard error $4,326)] than patients using purchased care [$106,395 ($10,559)] or both care sources [$82,439 ($13,330)], controlled for patient demographic, tumor, and treatment characteristics. Differences in cost by care source were noted for patients with later stage tumors and by treatment type. Relative costs were 2–3 times higher for purchased care compared to direct care for patients with late-stage tumors and for patients receiving chemotherapy or radiation treatment.

Conclusions

In the MHS, median cost for colon cancer treatment was lower in direct care compared to purchased care or patients using a combination of direct and purchased care. The variation in cancer treatment costs between care sources may be due to differences in treatment incentives or capabilities. Additional studies on cost differences between direct and purchased services are needed to understand how provision of care affects cancer treatment costs and to identify possible targets for cost reduction.
The Clinical Burden of Clostridioides difficile in Ontario, Canada
Authors: Pereira Jennifer A , McGeer Allison , Tomovici Antigona , Selmani Alex , Chit Ayman
Published: December 2019

Background

To understand the clinical burden of Clostridioides difficile infection (CDI), we analyzed health outcome data from Ontario, Canada for CDI associated with and manifested in acute care hospitals (ACH), long-term care facilities (LTCF), the community, or ACH-associated with community-onset.

Methods

We performed a retrospective analysis using individual-level data from Ontario databases (April 1, 2005 to March 31, 2015), identifying CDI cases ≥18 years requiring hospitalization, and stratifying into cohorts based on association and onset location. Cohort members were matched to controls on demographics and medical conditions at onset, for outcomes including 30- and 180-day all-cause mortality and rehospitalization.

Results

We stratified 22 617 individuals hospitalized with CDI during the study period: 13 152 (58.1%) ACH-associated/ACH-onset, 7116 (31.5%) community-associated/community-onset, 1847 (8.2%) ACH-associated/community-onset, and 502 (2.2%) LTCF-associated/LTCF-onset. Compared with controls, unadjusted 30-day rehospitalization rates were significantly higher (P < .0001) for ACH-associated/ACH-onset CDI (9.5% vs 0.4%), LTCF-associated/LTCF-onset (7.2% vs 1.1%), community-associated/community-onset (7.8% vs 0.8%), and ACH-associated/community-onset (10.9% vs 0.7%). One hundred eighty-day mortality rates were higher in the community-associated/community-onset and the LTCF-associated/LTCF-onset cohorts than controls: 66.3% vs 12.3% (P < .0001) and 30.9% vs 3.1% (P < .0001), respectively. All differences remained significant after adjusting for patient factors.

Conclusions

Clostridioides difficile infection is associated with higher rates of 30-day rehospitalization compared with controls. In addition, mortality rates within 180-days of hospital discharge are significantly higher for community-associated/community-onset and LTCF-associated/LTCF-onset CDI cohorts than controls. Clostridioides difficile infection warrants increased prevention and monitoring efforts.
Markers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL
Authors: Farhadian Shelli F , Mistry Hetal , Kirchwey Tobias , Chiarella Jennifer , Calvi Rachela , Chintanaphol Michelle , Patel Payal , Landry Marie L , Robertson Kevin , Spudich Serena S
Published: December 2019

The presence of quantifiable HIV RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART) can associate with central nervous system (CNS) pathology, but the significance of RNA detected below the limit of quantification (LOQ) on a standard assay during ART remains unknown. We compared CNS parameters between individuals with CSF RNA detected below the LOQ (20 copies/mL) with those with HIV RNA not detected. Detection of CSF HIV RNA associated with decreased blood–brain barrier integrity and with decreased executive function, but not with CNS immune activation or poorer performance in overall neuropsychological testing.
Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment
Authors: Ellis Kristen E , Nawas George T , Chan Connie , York Lawrence , Fisher Julia , Connick Elizabeth , Zangeneh Tirdad T
Published: December 2019

Background

Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic.

Methods

Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the effect of ART switch on HIV RNA over time.

Results

Eighty-three PWH had DNA GT performed, 66 (80%) switched ART, and 59 had postswitch follow-up. Data were analyzed pre-/postswitch for these 59 PWH (median age, 54 years; 71% LWH ≥10 years; 46% ≥2 previous regimens; 36% recent low-level viremia; 34% unknown medication history). On DNA GT, 58% had ≥1-class ART resistance, 34% ≥2-class, and 10% 3-class. Median follow-up (range) was 337 (34–647) days. There was no change in probability of HIV RNA ≥50 copies/mL over time (P > .05). At baseline, 76% had HIV RNA <50 vs 88% at last postswitch follow-up (P = .092). Protease inhibitor use decreased from 58% to 24% (P < .001). Average daily pills and dosing frequency decreased from 3.48 to 2.05 (P < .001) and 1.39 to 1.09 (P < .001), respectively; ART cost did not change.

Conclusions

DNA GT facilitated changes in ART in a treatment-experienced population without increases in HIV RNA. Decreased pill burden occurred without increased ART cost. Further studies to identify optimal use of DNA GT are needed.
Snoring: a source of noise pollution and sleep apnea predictor
Authors: Sowho Mudiaga , Sgambati Francis , Guzman Michelle , Schneider Hartmut , Schwartz Alan
Published: December 2019

Snoring is a highly prevalent condition associated with obstructive sleep apnea (OSA) and sleep disturbance in bed partners. Objective measurements of snoring in the community, however, are limited. The present study was designed to measure sound levels produced by self-reported habitual snorers in a single night. Snorers were excluded if they reported nocturnal gasping or had severe obesity (BMI > 35 kg/m2). Sound was measured by a monitor mounted 65 cm over the head of the bed on an overnight sleep study. Snoring was defined as sound ≥40 dB(A) during flow limited inspirations. The apnea hypopnea index (AHI) and breath-by-breath peak decibel levels were measured. Snore breaths were tallied to determine the frequency and intensity of snoring. Regression models were used to determine the relationship between objective measures of snoring and OSA (AHI ≥ 5 events/h). The area under the curve (AUC) for the receiver operating characteristic (ROC) was used to predict OSA. Snoring intensity exceeded 45 dB(A) in 66% of the 162 participants studied, with 14% surpassing the 53 dB(A) threshold for noise pollution. Snoring intensity and frequency were independent predictors of OSA. AUCs for snoring intensity and frequency were 77% and 81%, respectively, and increased to 87% and 89%, respectively, with the addition of age and sex as predictors. Snoring represents a source of noise pollution in the bedroom and constitutes an important target for mitigating sound and its adverse effects on bed partners. Precise breath-by-breath identification and quantification of snoring also offers a way to risk stratify otherwise healthy snorers for OSA.
Genetic and Epigenetic Intratumor Heterogeneity Impacts Prognosis of Lung Adenocarcinoma
Authors: Hua Xing , Zhao Wei , Pesatori Angela C. , Consonni Dario , Caporaso Neil E. , Zhang Tongwu , Zhu Bin , Wang Mingyi , Jones Kristine , Hicks Belynda , Song Lei , Sampson Joshua , Wedge David , Shi Jianxin , Landi Maria Teresa
Published: December 2019

Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). We investigated ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 LUAD patients. We found substantial SCNA and methylation ITH, and clonal architecture analyses showed congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Interestingly, methylation ITH mapping to gene promoter areas or tumor suppressor genes was low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes was found in several tumors. To quantify ITH for valid statistical association analyses we developed an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. APITH indexes for SCNAs and methylation aberrations were both significantly associated with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD.
Metabolomics pilot study identifies circadian desynchronization and distinct intra-patient variability patterns in critical illness
Authors: Lusczek Elizabeth R. , Parsons Lee , Elder Jesse , Harvey Stephen B. , Skube Mariya , Muratore Sydne , Beilman Greg , Cornelissen-Guillaume Germaine
Published: December 2019

Background

Synchronized circadian rhythms play a key role in coordinating physiologic health. Desynchronized circadian rhythms may predispose individuals to disease or be indicative of underlying disease. Intensive care unit (ICU) patients likely experience desynchronized circadian rhythms due to disruptive environmental conditions in the ICU and underlying pathophysiology. This observational pilot study was undertaken to determine if circadian rhythms are altered in ICU patients relative to healthy controls by profiling circadian rhythms in vital signs and plasma metabolites.

Methods

We monitored circadian rhythms in 5 healthy controls and 5 ICU patients for 24 hours. Heart rate and blood pressure were measured every 30 minutes, temperature was measured every hour, and blood was sampled for mass spectrometry-based plasma metabolomics every 4 hours. Bedside sound levels were measured every minute. Circadian rhythms were evaluated in vitals and plasma metabolites individually and in each group using the cosinor method.

Results

ICU patient rooms were significantly louder than healthy controls’ rooms and average noise levels were above EPA recommendations. Healthy controls generally had significant circadian rhythms individually and as a group. While a few ICU patients had significant circadian rhythms in isolated variables, no significant rhythms were identified in ICU patients as a group, except in cortisol. This indicates a lack of coherence in circadian phases and amplitudes among ICU patients. Finally, principal component analysis of metabolic profiles showed surprising patterns in plasma sample clustering. Each ICU patient’s samples were clearly discernable in individual clusters, separate from a single cluster of healthy controls.

Conclusions

ICU patients’ circadian rhythms show significant desynchronization compared to healthy controls. Clustering of plasma metabolic profiles suggests that metabolomics could be used to track individual patients’ clinical courses longitudinally. Our results show global disordering of metabolism and the circadian system in ICU patients which should be characterized further in order to determine implications for patient care.
A novel art of continuous non-invasive blood pressure measurement
Authors: Fortin Jürgen , Rogge Dorothea , Fellner Christian , Flotzinger Doris , Grond Julian , Lerche Katja , Saugel Bernd
Published: December 2019

Abstract

Wearable sensors to continuously measure blood pressure (BP) and derived cardiovascular variables have the potential to revolutionize patient monitoring. Current wearable methods analyzing time components (e.g., pulse transit time) still lack clinical accuracy, whereas existing technologies for direct BP measurement are too bulky. Here we present a new art of continuous non-invasive arterial blood pressure monitoring (CNAP2GO). It directly measures BP by using a new “volume control technique” and could be used for small wearable sensors integrated in a finger ring. As a software prototype, CNAP2GO showed excellent BP measurement performance in comparison with invasive BP in 46 patients having surgery. The resulting pulsatile BP signal carries information to derive cardiac output and other hemodynamic variables. We show that CNAP2GO can be miniaturized for wearable approaches. CNAP2GO potentially constitutes the breakthrough for wearable sensors for blood pressure and flow monitoring in both ambulatory and in-hospital clinical settings.
Considering the APOE locus in polygenic scores for Alzheimer’s disease
Authors: Ware Erin B. , Faul Jessica D. , Mitchell Colter M. , Bakulski Kelly M.
Published: December 2019

Polygenic scores are a strategy to aggregate the small, additive effects of single nucleotide polymorphisms across the genome. With phenotypes like Alzheimer’s disease, which have a strong and well established genomic locus (APOE), the cumulative effect of genetic variants outside of this area has not been well established in a population-representative sample. Here we examine the association between polygenic scores both with and without the APOE region at different P value thresholds. We also investigate the addition of APOE-ε4 carrier status and its effect on the polygenic score – dementia association. We found that including the APOE region through weighted variants in a polygenic score was insufficient to capture the large amount of risk attributed to this region. We recommend removing this region from polygenic score calculation and treating the APOE locus as an independent covariate.
Using Media to Promote Public Awareness of Early Detection of Kaposi’s Sarcoma in Africa
Authors: Laker-Oketta Miriam , Butler Lisa , Kadama-Makanga Philippa , Inglis Robert , Wenger Megan , Katongole-Mbidde Edward , Maurer Toby , Kambugu Andrew , Martin Jeffrey
Published: December 2019

Background

Despite its hallmark cutaneous presentation, most Kaposi’s sarcoma (KS) in Africa is diagnosed too late for effective treatment. Early diagnosis will only be achievable if patients with KS present earlier for care. We hypothesized that public awareness about KS can be enhanced through exposure to common media.

Methods

We developed educational messages regarding early detection of KS for the general African public portraying a three-part theme: “Look” (regularly examine one’s skin/mouth); “Show” (bring to the attention of a healthcare provider any skin/mouth changes); and “Test” (ask for a biopsy for definitive diagnosis). We packaged the messages in three common media forms (comic strips, radio, and video) and tested their effect on increasing KS awareness among adults attending markets in Uganda. Participants were randomized to a single exposure to one of the media and evaluated for change in KS-related knowledge and attitudes.

Results

Among 420 participants, media exposure resulted in increased ability to identify KS (from 0.95% pre-test to 46% post-test); awareness that anyone is at risk for KS (29% to 50%); belief that they may be at risk (63% to 76%); and knowledge that definitive diagnosis requires biopsy (23% to 51%) (all p<0.001). Most participants (96%) found the media culturally appropriate.

Conclusion

Exposure to media featuring a theme of “Look”, “Show”, “Test” resulted in changes in knowledge and attitudes concerning KS among the general public in Uganda. High incidence and poor survival of KS in Africa are an impetus to further evaluate these media, which are freely available online.
Prevalence and associated factors of pterygium among adults living in Kolla diba town, Northwest Ethiopia
Authors: Alemayehu Tibebu Kassie , Addis Yezinash , Bizuneh Zewdu Yenegeta , Tegegne Mebratu Mulusew , Alemayehu Abiy Maru
Published: December 2019

Introduction

Pterygium is a disfiguring disease that can potentially lead to blindness and has a significant public health problem in rural areas. It is more common in warm, windy and dry climates of tropical and sub-tropical “pterygium belt” regions of Africa, including Ethiopia. Globally, the prevalence ranging from 0.07% to 53%. Studies conducted on the prevalence of pterygium in developing countries like Ethiopia were limited with wider discrepancy between them.

Objective

The aim of this study was to assess the prevalence of pterygium and associated factors among adults in Kolla Diba town, Northwest Ethiopia, 2019.

Method

A community-based cross-sectional study was done in Kolla Diba town from May 30-June 16, 2019. Systematic random sampling technique was used to select 627 study participants. Data was collected through basic ophthalmic examination with portable slit lamp, 3x magnifying loop and torchlight and a pretested structured questionnaire was administered to collect the data. Then the data entered into EPI INFO version 7 and analyzed using SPSS version 20. Descriptive statistics and binary logistic regression analysis were employed. P-values of <0.05 was considered statistically significant.

Result

A total of 605 study participants were involved with a response rate of 96.5%. Among them 317 (52.4%) participants were males. The mean age of the respondents was 38.18 ± 15.56 with a range of (18-95) in years. The overall Prevalence of pterygium among adults living in Kolla Diba town was 112 (18.5% (95% CI (15.6-21.7)). Being widowed (AOR = 7.32 (95%CI: 2.88, 18.57)), outdoor occupation (AOR = 2.50 (95%CI: 1.46, 4.29)), sun exposure (AOR = 2.38 (95%CI: 1.28, 4.43)), wind exposure (AOR = 1.97 (95%CI: 1.04, 3.72)), alcohol drinking (AOR = 2.26 (95%CI: 1.48, 4.63)), and severe blepharitis (AOR = 2.45 (95%CI: 1.48, 4.05)) had statistically significant positive association with pterygium.

Conclusion

The prevalence of pterygium was relatively higher. Marital status (being widowed), outdoor occupation, sun exposure, wind exposure, alcohol drinking, and severe blepharitis were significantly associated with the development of pterygium.
Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood
Authors: Ojanen Xiaowei , Cheng Runtan , Törmäkangas Timo , Wu Na , Rappaport Noa , Wilmanski Tomasz , Yan Wei , Price Nathan D. , Cheng Sulin , Wiklund Petri
Published: December 2019

Cardiovascular diseases have their origin in childhood. Early biomarkers identifying individuals with increased risk for disease are needed to support early detection and to optimize prevention strategies. By applying machine learning approach on high throughput NMR-based metabolomics data, we identified metabolic predictors of cardiovascular risk in circulation in a cohort of 396 females, followed from childhood (mean age 11.2 years) to early adulthood (mean age 18.1 years). The identified childhood metabolic signature included three circulating biomarkers robustly associating with increased cardiovascular risk in early adulthood (AUC = 0.641 to 0.802, all p<0.01). These associations were confirmed in two validation cohorts including middle-aged women, with similar effect estimates. We subsequently applied random intercept cross-lagged panel model analysis, which suggested causal relationship between metabolites and cardio-metabolic risk score from childhood to early adulthood. These results provide evidence for the utility of circulating metabolomics panel to identify children and adolescents at risk for cardiovascular disease, to whom preventive measures and follow-up could be indicated.
Satellite glial cells promote regenerative growth in sensory neurons
Authors: Avraham Oshri , Deng Pan-Yue , Jones Sara , Kuruvilla Rejji , Semenkovich Clay F. , Klyachko Vitaly A. , Cavalli Valeria
Published: December 2019

Peripheral sensory neurons switch to a regenerative state after nerve injury to enable axon regeneration and functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, undergo injury-evoked transcriptional changes and contribute to nerve regeneration remains unexplored. This is largely due to the lack of molecular and genetic tools to study SGC. Using a single cell RNAseq approach to define the transcriptional profile of SGC in naïve and injured conditions, we reveal that these cells are distinct from Schwann cells and share similarities with astrocytes. We find that nerve injury elicits gene expression changes in SGC, which are related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of Fatty acid synthase (Fasn), the committed enzyme inde novofatty acid synthesis, in SGC, impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC, indicating that PPARα functions downstream of fatty acid synthesis in SGC to promote axon regeneration. These results identify fatty acid synthesis in SGC as a fundamental novel mechanism mediating axon regeneration in adult peripheral nerves. These results also highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.
Non-ionic CT Contrast Solutions Rapidly Alter Bovine Cartilage and Meniscus Mechanics
Authors: Baylon Eva G. , Crowder Hollis A. , Gold Garry E. , Levenston Marc E.
Published: December 2019

Objective

To evaluate effects of a common CT contrast agent (iohexol) on the mechanical behaviors of cartilage and meniscus.

Methods

Indentation responses of juvenile bovine cartilage and meniscus were monitored following exposure to undiluted contrast agent (100% CA), 50% CA/water, 50% CA/Phosphate Buffered Saline (PBS) or PBS alone, and during re-equilibration in PBS. The normalized peak force, effective osmotic strain (εosm), and normalized effective contact moduluswere calculated for every cycle, with time constants determined for both exposure and recovery via mono- or biexponential fits to.

Results

All cartilage CA groups exhibited long-term increases infollowing exposure, although the hyperosmolal 100% CA and 50% CA/PBS groups showed an initial transient decrease. Meniscus presented opposing trends, with decreasingfor all CA groups. Re-equilibration in PBS for 1hr after exposure to 100% CA did not produce recovery to baselinein either tissue. The recovery time for meniscus was substantially longer than that of cartilage.increased with CA exposure time for cartilage but decreased for meniscus, suggesting an increased effective stiffness for cartilage and decreased stiffness for meniscus. Long-term changes toεosmin both tissues were consistent with changes in.

Conclusion

Exposure to iohexol solutions affected joint tissues differentially, with increased cartilage stiffness, likely relating to competing hyperosmotic and hypotonic interactions with tissue fixed charges, and decreased meniscus stiffness, likely dominated by hyperosmolarity. These altered tissue mechanics could allow non-physiological deformation during ambulatory weight-bearing, resulting in an increased risk of tissue or cell damage.
Visual impairment, spectacle wear and academic performance among junior high school students in western China
Authors: Nie Jingchun , Nie Wei , Mu Ming , Zhang Lifang , Song Shuyi , Peng Lanxi , Gao Qiufeng , Yang Jie
Published: December 2019

In September 2013, 2248 students from 36 junior high schools in Shaanxi Province underwent assessment of visual acuity (VA), completed a questionnaire about their spectacle use and were administered a standardized mathematics examination. Among 2,248 students (mean age 13.6 years, 52% male), visual impairment was present in 699 (31%, 95% Confidence Interval 29-33%). Spectacle wear was observed in 360 of 966 children needing glasses (37%). Ownership of spectacles among children needing glasses was associated with poorer uncorrected vision in the better-seeing eye (P <0.001) and paternal educational (p=0.001), but not age, sex, boarding at school, both parents having out-migrated for work or maternal education. Spectacle ownership among children with visual impairment was associated with better test performance (P=0.035). Therefore, visual impairment and non-wear of spectacle were common. Wearing spectacles was associated with better academic performance in this cross-sectional analysis, consistent with recent trial results among younger children.
Hemocyte-targeted gene expression in the female malaria mosquito using thehemolectinpromoter fromDrosophila
Authors: Pondeville Emilie , Puchot Nicolas , Parvy Jean-Philippe , Carrissimo Guillaume , Poidevin Mickael , Waterhouse Robert M. , Marois Eric , Bourgouin Catherine
Published: December 2019

Hemocytes, the immune cells in mosquitoes, participate in immune defenses against pathogens including malaria parasites. Mosquito hemocytes can also be infected by arthropod-borne viruses but the pro- or anti-viral nature of this interaction is unknown. Although there has been progress on hemocyte characterization during pathogen infections in mosquitoes, the specific contribution of hemocytes to immune responses and the hemocyte-specific functions of immune genes and pathways remain unresolved due to the lack of genetic tools to manipulate gene expression in these cells specifically. Here, we used the Gal4-UAS system to characterize the activity of theDrosophilahemocyte-specifichemolectinpromoter in the adults ofAnopheles gambiae, the malaria mosquito. We established anhml-Gal4 driver line that we further crossed to a fluorescent UAS responder line, and examined the expression pattern in the adult progeny driven by thehmlpromoter. We show that thehmlregulatory region drives hemocyte-specific transgene expression in a subset of hemocytes, and that transgene expression is triggered after a blood meal. Thehmlpromoter drives transgene expression in differentiating prohemocytes as well as in differentiated granulocytes. Analysis of different immune markers in hemocytes in which thehmlpromoter drives transgene expression revealed that this regulatory region could be used to study phagocytosis as well as melanization. Finally, thehmlpromoter drives transgene expression in hemocytes in which o’nyong’nyong virus replicates. Altogether, thehmlpromoter constitutes a good tool to drive transgene expression in hemocyte only and to analyze the function of these cells and the genes they express during pathogen infection inAnopheles gambiae.
An Alignment-free Method for Phylogeny Estimation using Maximum Likelihood
Authors: Zahin Tasfia , Abrar Md. Hasin , Rahman Mizanur , Tasnim Tahrina , Bayzid Md. Shamsuzzoha , Rahman Atif
Published: December 2019

While alignment has traditionally been the primary approach for establishing homology prior to phylogenetic inference, alignment-free methods offer a simplified alternative, particularly beneficial when handling genome-wide data involving long sequences and complex events such as rearrangements. Moreover, alignment-free methods become crucial for data types like genome skims, where assembly is impractical. However, despite these benefits, alignment-free techniques have not gained widespread acceptance since they lack the accuracy of alignment-based techniques, primarily due to their reliance on simplified models of pairwise distance calculation. Here, we present a likelihood based alignment-free technique for phylogenetic tree construction. We encode the presence or absence ofk-mers in genome sequences in a binary matrix, and estimate phylogenetic trees using a maximum likelihood approach. We analyze the performance of our method on seven real datasets and compare the results with the state of the art alignment-free methods. Results suggest that our method is competitive with existing alignment-free tools. This indicates that maximum likelihood based alignment-free methods may in the future be refined to outperform alignment-free methods relying on distance calculation as has been the case in the alignment-based setting. A likelihood based alignment-free method for phylogeny estimation is implemented for the first time in a software named Peafowl, which is available at:https://github.com/hasin-abrar/Peafowlrepo.
The effect of feeding behavior ofMonochamus alternatus(Coleoptera: Cerambycidae) on the departure of pine wood nematode,Bursaphelenchus xylophilus(Nematoda: Aphelenchoididae)
Authors: Wang Yang , Chen Fengmao , Wang Lichao , Zhou Lifeng , Song Juan
Published: December 2019

In order to study the causes of pine wood nematode (PWN) departure fromMonochamus alternatus, the effects of the feeding behavior ofM. alternatuson the start date of the departure of PWN were studied. The start date of the departure of PWN carried by the directly fedM. alternatuswas 5—13 d after beetle emergence, mainly concentrated within 6—10 d, with a mean (±SD) of 8.02 ± 1.96 d. The start date of the departure of PWN carried by theM. alternatusfed after starvation was 5—14 d after beetle emergence, mainly concentrated within 6—9 d, with a mean of 7.76 ± 2.28 d. The results show that there was no significant difference in the start departure date of PWN between the two treatments. This shows that the feeding behavior ofM. alternatusis not the trigger for PWN departure. At the same time, it was found that the motility of the PWN carried byM. alternatusat 8 d after emergence was significantly greater than that of the PWN carried by the newly emergedM. alternatus.And the PWN carried byM. alternatusat 8 d after emergence was extracted more easily than the PWN carried by newly emerged beetles. These results show that greater motility was associated with easier departure of PWN fromM. alternatus.In addition, transcriptome sequencing found that the level of oxidative phosphorylation metabolism of PWN carried by beetles at 8 d after emergence was significantly higher than that in the PWN carried by newly emerged beetle. High oxidative phosphorylation was associated with increased energy production and motility by the PWN and were the internal cause of the start of nematode departure.
Deriving Ranges of Optimal Estimated Transcript Expression Due to Non-identifiability
Authors: Zheng Hongyu , Ma Cong , Kingsford Carl
Published: December 2019

Current expression quantification methods suffer from a fundamental but under-characterized type of error: the most likely estimates for transcript abundances are not unique. This means multiple estimates of transcript abundances generate the observed RNA-seq reads with equal likelihood, and the underlying true expression cannot be determined. This problem is called non-identifiability for probabilistic models, and is further exacerbated by incomplete reference transcriptome. That is, reads may be sequenced from unannotated expressed transcripts. Graph quantification is a generalization to transcript quantification, accounting for the reference incompleteness by allowing exponentially many unannotated transcripts to express reads. We propose methods to calculate a “confidence range of expression” for each transcript, representing its possible abundance across equally optimal estimates for both quantification models. This range informs both whether a transcript has potential estimation error due to non-identifiability and the extent of the error. Applying our methods to the Human Body Map data, we observe 35%–50% of transcripts potentially suffer from inaccurate quantification caused by non-identifiability. When comparing the expression between isoforms in one sample, we find that the degree of inaccuracy of 20%–47% transcripts can be so large that the ranking of expression between the transcript and its sibling isoforms cannot be determined. When comparing the expression of a transcript between two groups of RNA-seq samples in differential expression analysis, we observe that the majority of detected differentially expressed transcripts are reliable with a few exceptions after considering the ranges of the optimal expression estimates. The code for computing the range of expression is available athttps://github.com/Kingsford-Group/subgraphquant. The code for the involved analyses is available athttps://github.com/Kingsford-Group/subgraphquantanalysis.