bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Burden of Infant Deaths Due to Herpes Simplex Virus, Human Immunodeficiency Virus, and Congenital Syphilis: United States, 1995 to 2017
Authors: Slutsker Jennifer Sanderson , Schillinger Julia A.
Published: May 2021

Background

Despite advances in diagnosis and treatment, neonatal infection with herpes simplex virus (HSV) has a high case fatality rate. The national burden of neonatal HSV and associated deaths is unknown because this condition is not nationally notifiable. We investigated trends in HSV-related infant deaths compared with infant deaths from congenital syphilis (CS) and human immunodeficiency virus (HIV).

Methods

Linked birth-death files for infant deaths from 1995 to 2017 were obtained from the National Center for Health Statistics. These files include infants who were born alive and died in the first 365 days of life and exclude stillbirths. We searched death certificates for disease codes indicating HSV, CS, or HIV, and calculated the frequency and rate of deaths for each infection, overall, by infant sex, and birthing parent age and race/ethnicity.

Results

Nationally, 1591 deaths related to the infections of interest were identified: 1271 related to HSV (79.9%), 234 to HIV (14.7%), and 86 to CS (5.4%). Herpes simplex virus–related deaths increased significantly from 0.83/100,000 live births (95% confidence interval [CI], 0.57–1.17) in 1995 to 1.77 (95% CI, 1.37–2.24) in 2017. In contrast, HIV-related deaths declined: 1.64/100,000 (95% CI, 1.27–2.10) in 1995 to 0.00 in 2017. There was a median of 3 CS-related deaths/year, with elevated frequencies in 1995 to 1996 and 2017 (n = 8). Herpes simplex virus–related death rates were elevated among infants born to birthing parents younger than 20 years (4.17/100,000; 95% CI, 3.75–4.59) and to Black parents (2.86/100,000; 95% CI, 2.58–3.15).

Conclusions

Nationally, HSV-related infant deaths exceeded those caused by HIV and CS and seem to be increasing. Our findings underscore the need for an effective HSV vaccine, test technologies enabling rapid identification of infants exposed to HSV at delivery, and a focus on equity in prevention efforts.
Case Report: Modified Piggyback System to Treat Peripheral Iridotomies and Degenerative Myopia
Authors: Nadarajah Vakishan
Published: May 2021

SIGNIFICANCE

This report details how a case with degenerative myopia and symptoms secondary to laser peripheral iridotomies is managed with a modified piggyback contact lens system. The benefits of using a system with tinted and gas-permeable (GP) lenses are discussed.

PURPOSE

This study aimed to report the positive outcome of a modified piggyback system in the treatment of degenerative myopia and iris abnormalities.

CASE REPORT

A patient with degenerative myopia presented with visual disturbances secondary to laser peripheral iridotomies in both eyes. A modified piggyback system was trialed using a corneal GP lens overlaying a tinted soft contact lens to provide optimal vision and visual comfort in both eyes. After optimizing the fit, there was a reduction in glare and improved vision.

CONCLUSIONS

Hard contact lenses often provide superior optics and vision compared with soft lenses, especially to patients with high refractive errors. Patients who require hard lenses and also have visual disturbances secondary to iris abnormalities could be managed with a modified piggyback contact lens systems using a corneal GP lens and tinted soft lens.
Visual Performance with Spherical and Multifocal Contact Lenses in a Pediatric Population
Authors: Bickle Katherine M. , Mitchell G. Lynn , Walline Jeffrey J.
Published: May 2021

SIGNIFICANCE

This pilot study compared subjective and objective vision of children wearing single-vision and +2.00, +3.00, and +4.00 D add power soft multifocal contact lenses to determine whether the higher add power—thought to provide better myopia control—resulted in visual compromise.

PURPOSE

This study aimed to determine the maximum add power children wearing center-distance soft multifocal contact lenses could accept objectively and subjectively.

METHODS

Myopic children were assigned in random order to wear omafilcon A single-vision or multifocal “D” contact lenses with +2.00, +3.00, or +4.00 D add power for 1 week each. High-contrast distance and near visual acuity, low-contrast distance visual acuity, and contrast sensitivity were measured at each visit along with a quality of vision questionnaire to assess their vision. The Friedman test was performed to evaluate the impact of add power on all outcome measures.

Results

Eleven subjects were enrolled, and nine subjects completed the study. The median age of completed subjects was 11 years. Median logMAR low-contrast distance visual acuity was reduced in the +3.00 (+0.20) and +4.00 (+0.28) D add lenses compared with the +2.00 (+0.16) D add and single-vision lenses (+0.10, P < .001). All three multifocal lenses resulted in reduced contrast sensitivity (+1.35 to +1.40) compared with single-vision lenses (+1.60, P < .001). In general, +3.00 and +4.00 D add lenses resulted in worse glare/starbursts, ghost images, computer vision, changing fixation distance, and overall vision, but results varied. There were no differences among the lenses with respect to subjective assessments of distance vision, near vision, strain or tiredness, contact lens comfort, or sporting activities.

CONCLUSIONS

The +3.00 D and higher add powers result in more objective and subjective vision-related issues than single-vision lenses, but the +2.00 D add multifocal lenses were well tolerated.
Development and Evaluation of Deep Learning-Accelerated Single-Breath-Hold Abdominal HASTE at 3 T Using Variable Refocusing Flip Angles
Authors: Herrmann Judith , Nickel Dominik , Mugler John P. , Arberet Simon , Gassenmaier Sebastian , Afat Saif , Nikolaou Konstantin , Othman Ahmed E.
Published: May 2021

Objective

Deep learning (DL) reconstruction enables substantial acceleration of image acquisition while maintaining diagnostic image quality. The aims of this study were to overcome the drawback of specific absorption rate (SAR)–related limitations at 3 T and to develop a DL-accelerated single-breath-hold half-Fourier acquisition single-shot turbo spin echo (HASTE) sequence for 2-dimesional T2-weighted fat-suppressed magnetic resonance imaging of the abdomen at 3 T using a variable flip angle (FA) evolution for the refocusing radiofrequency pulses, as well as to evaluate its feasibility and image quality in comparison to state-of-the-art T2-weighted fat-suppressed imaging technique (BLADE).

Materials and Methods

First, a suitable FA evolution with low cardiac motion–related signal loss (CRSL) and low SAR was determined through a prospective volunteer study with 11 participants. Image quality and diagnostic confidence with 5 different FA evolutions of a HASTEDL were assessed to identify the most suitable FA evolution. Second, the identified FA evolution was implemented clinically and evaluated in 51 patients undergoing a clinically indicated liver magnetic resonance imaging at 3 T. Two radiologists assessed the HASTEDL and standard sequences regarding overall image quality, noise, contrast, sharpness, artifacts, CRSL, and diagnostic confidence using a Likert scale ranging from 1 to 4, with 4 being the best. Comparative analyses were conducted to assess the differences between HASTEDL (acquisition time, 21 seconds; single breath-hold) and the routinely used T2-weighted BLADE sequence (acquisition time, 4 minutes; respiratory triggering).

Results

From the volunteer study, the FA evolution characterized by the control points 130-90-110-130 degrees (HASTEDL) was identified as optimal among the 5 evolutions evaluated and was implemented in our clinical protocol. In all 51 patients, HASTEDL was successfully acquired at 3 T and showed excellent image quality (median, 4; interquartile range, 3–4). Although BLADE was rated significantly higher for overall image quality, noise, contrast, sharpness, artifacts, CRSL, and diagnostic confidence than HASTEDL, no differences were found concerning the number (n = 102) and measured diameter of the detected hepatic lesions between the 2 sequences BLADE and HASTEDL.

Conclusions

The proposed single-breath-hold abdominal HASTEDL with variable refocusing FAs is feasible at 3 T within SAR limits and yields high image quality and diagnostic confidence as compared with a standard T2-weighted acquisition technique, at a 10th of the acquisition time.
Guidelines for Perioperative Care for Liver Transplantation: Enhanced Recovery After Surgery (ERAS) Recommendations
Authors: Brustia Raffaele , Monsel Antoine , Skurzak Stefano , Schiffer Eduardo , Carrier François Martin , Patrono Damiano , Kaba Abdourahamane , Detry Olivier , Malbouisson Luiz , Andraus Wellington , Vandenbroucke-Menu Franck , Biancofiore Gianni , Kaido Toshimi , Compagnon Philippe , Uemoto Shinji , Rodriguez Laiz Gonzalo , De Boer Marieke , Orloff Susan , Melgar Paola , Buis Carlijn , Zeillemaker-Hoekstra Miriam , Usher Helen , Reyntjens Koen , Baird Emily , Demartines Nicolas , Wigmore Stephen , Scatton Olivier
Published: May 2021

Background.

Enhanced Recovery After Surgery (ERAS) is a multimodal, evidence-based, program of care developed to minimize the response to surgical stress, associated with reduced perioperative morbidity and hospital stay. This study presents the specific ERAS Society recommendations for liver transplantation (LT) based on the best available evidence and on expert consensus

Methods.

PubMed and ClinicalTrials.gov were searched in April 2019 for published and ongoing randomized clinical trials on LT in the last 15 y. Studies were selected by 5 independent reviewers and were eligible if focusing on each validated ERAS item in the area of adult LT. An e-Delphi method was used with an extended interdisciplinary panel of experts to validate the final recommendations.

Results.

Forty-three articles were included in the systematic review. A consensus was reached among experts after the second round. Patients should be screened for malnutrition and treated whenever possible. Prophylactic nasogastric intubation and prophylactic abdominal drainage may be omitted, and early extubation should be considered. Early oral intake, mobilization, and multimodal-balanced analgesia are recommended.

Conclusions.

The current ERAS recommendations were elaborated based on the best available evidence and endorsed by the e-Delphi method. Nevertheless, prospective studies need to confirm the clinical use of the suggested protocol.
COVID-19 Compromises in the Medical Practice and the Consequential Effect on Endometriosis Patients
Authors: Ashkenazi Shaked , Huseby Ole Linvåg , Kroken Gard , Soto-Mota Adrian , Pents Marius , Loschiavo Alessandra , Lewandowska Roksana , Tran Grace , Kwiatkowski Sebastian
Published: May 2021

Background and purpose

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, self-isolation practices aimed to curb the spread of COVID-19 have severely complicated the medical management of patients suffering from endometriosis and their physical and mental well- being. Endometriosis, the main cause for chronic pelvic pain (CPP), is a highly prevalent disease characterized by the presence of endometrial tissue in locations outside the uterine cavity that affects up to 10% of women in their reproductive age. This study aimed to explore the effects of the global COVID-19 pandemic on patients suffering from endometriosis across multiple countries, and to investigate the different approaches to the medical management of these patients based on their self-reported experiences.

Methods

A cross-sectional survey, partially based on validated quality of life questionnaires for endometriosis patients, was initially created in English, which was then reviewed by experts. Through the process of assessing face and content validity, the questionnaire was then translated to fifteen different languages following the WHO recommendations for medical translation. After evaluation, the questionnaire was converted into a web form and distributed across different platforms. An analysis of 2964 responses of participants from 59 countries suffering from self-reported endometriosis was then conducted.

Results

The data shows an association between COVID-19 imposed compromises with the reported worsening of the mental state of the participants, as well as with the aggravation of their symptoms. For the 1174 participants who had their medical appointments cancelled, 43.7% (n=513) reported that their symptoms had been aggravated, and 49.3% (n=579) reported that their mental state had worsened. In comparison, of the 1180 participants who kept their appointments, only 29.4% (n=347) stated that their symptoms had been aggravated, and 27.5% (n=325) stated their mental health had worsened. 610 participants did not have medical appointments scheduled, and these participants follow a similar pattern as the participants who kept their appointments, with 29.0% (n=177) reporting aggravation of symptoms and 28.2% (n=172) reporting that their mental state had worsened.

Conclusions

These findings suggest that COVID-19 pandemic has had a clinically significant negative effect on the mental and physical well-being of participants suffering from endometriosis based on their self-reported experiences. Thus, they show the importance of further assessment and reevaluation of the current and future management of this condition in medical practices worldwide.
Oral Vitamin D supplementation induces transcriptomic changes in rectal mucosa that are consistent with anti-tumour effects
Authors: Vaughan-Shaw P.G. , Grimes G. , Blackmur JP , Timofeeva M. , Walker M , Ooi L.Y , Svinti Victoria , Donnelly Kevin , Din FVN , Farrington S.M. , Dunlop M.G.
Published: May 2021

Background

Risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in-vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response.

Methods

Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks’. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D).

Results

629 genes were associated with 25-OHD level (P<0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P<1.0E-07; downregulated gene-set P<2.6E-05) and corresponding GO terms (P=2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P<0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI:0.66-1.00]), and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI:0.77-0.89]; PPP1CC AUC=0.91 [95%CI:0.86-0.95]).

Conclusions

Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumor transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.
Saudi Arabian SARS-CoV-2 genomes implicate a mutant Nucleocapsid protein in modulating host interactions and increased viral load in COVID-19 patients
Authors: Mourier Tobias , Shuaib Muhammad , Hala Sharif , Mfarrej Sara , Alofi Fadwa , Naeem Raeece , Alsomali Afrah , Jorgensen David , Subudhi Amit Kumar , Rached Fathia Ben , Guan Qingtian , Salunke Rahul P , Ooi Amanda , Esau Luke , Douvropoulou Olga , Nugmanova Raushan , Perumal Sadhasivam , Zhang Huoming , Rajan Issaac , Al-Omari Awad , Salih Samer , Shamsan Abbas , Mutair Abbas Al , Taha Jumana , Alahmadi Abdulaziz , Khotani Nashwa , Alhamss Abdelrahman , Mahmoud Ahmed , Alquthami Khaled , Dageeg Abdullah , Khogeer Asim , Hashem Anwar M. , Moraga Paula , Volz Eric , Almontashiri Naif , Pain Arnab
Published: May 2021

Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.
Identification of a novel FUS/ETV4 fusion and comparative analysis with other Ewing sarcoma fusion proteins
Authors: Boone Megann A. , Taslim Cenny , Crow Jesse C. , Selich-Anderson Julia , Watson Mike , Heppner Peter , Hamill James , Wood Andrew C. , Lessnick Stephen L. , Winstanley Mark
Published: May 2021

Ewing sarcoma is an aggressive pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to a member of the ETS transcription factor family. To date, there have been seven reported translocations, with the most recent translocation reported over a decade ago. We now report the first identification of a novel translocation occurring between the FUS gene and ETS family member ETV4 detected in a neonatal patient with Ewing sarcoma. Given its apparent rarity, we conducted an initial characterization of FUS/ETV4 function by performing genomic localization and transcriptional regulatory studies. We knocked down endogenous EWS/FLI in the A673 cell line, and expressed FUS/ETV4 in its stead, and performed CUT&Tag and RNA-sequencing analyses. We compared these data to similar “knock-down/rescue” analyses of other rare (non-EWS/FLI) Ewing sarcoma-associated translocation products. Through this comparative analysis in the same genetic background, we demonstrate significant similarities across these fusions, and in doing so, validate this novel FUS/ETV4 translocation as a bona fide Ewing sarcoma translocation. This study presents the first genomic comparisons of the rare Ewing sarcoma-associated translocation products, and reveals that the FET/ETS fusions share highly similar, but not identical, genomic localization and transcriptional regulation patterns. These data provide insights into the roles of both the FET and ETS sides of these fusions, and provide a generic strategy to provide further strength to the notion that FET/ETS fusions are key drivers of, and thus pathognomonic for, Ewing sarcoma.

Significance

Identification and initial characterization of the novel Ewing sarcoma fusion, FUS/ETV4, expands the family of Ewing-fusions and extends the diagnostic possibilities for this aggressive tumor of adolescents and young adults.
The Association Between Threatened Miscarriage And Development Of Gestational Hypertension/Pre-Eclampsia
Authors: Gunarathna S.M.S.G. , Ratnayake Naleen , Pallemulla Lakshman , Rasanjana D.P. Lanka , Abeysundara P.K. , Nishad A.A. Nilanga
Published: May 2021

Introduction

Gestational hypertension (GH)/Pre-eclampsia (PEC) is an important cause of direct maternal deaths in Sri Lanka. GH/PEC and threatened miscarriage (TM) share common pathophysiological mechanisms. This study was conducted to determine the association between TM and development of GH/PEC.

Methodology

A case control study was conducted at Castle Street Hospital for Women, Sri Lanka from April 2015 to October 2015. Cases consisted of patients with GH/PEC and compared with age and parity matched controls. A systematic random sampling method was used. Similar number of cases and controls were compared while each group consisted of 245 subjects. Data was obtained from medical records. It’s also important to note that mothers aged 20-35 years were included and medical disorders other than GH/PEC was excluded.

Results

There were 245 subjects in each group of the study. Among the cases, 56% had GH and the rest had PEC. There were 25 patients with TM in the study population and 64% of them subsequently developed GH or PEC. There is also a significant risk of developing PEC in a patient who had a history of threatened miscarriage (OR 3.31, 95% CI 1.35-8.11). Moreover the patients who had a history of TM tend to develop GH or PEC early, within 20-32 weeks of gestation (OR 11.49, 95% CI 3.88-33.99). As we identified, 62% of patients who had TM developed GH/PEC early (from 20 to 32 weeks) but among the cases who had no history of TM, only 12% developed GH/PEC between 20 to 32 weeks of gestation (O.R. 20.7 (5.66 to 91.96). There is a significant risk of developing severe GH/PEC in the group of patients who had a history of TM (OR 8.59, 95% CI 2.87-25.66). Eighty one percent (81%) of the cases, who had a history of TM, developed severe and moderate GH/PEC rather than mild. But the majority (63%) of the cases, who had no history of TM, developed mild GH/PEC (O.R. 7.6 (2.00 to 42.55).

Conclusions

Shared pathophysiological mechanisms of GH/PEC and TM may explain the observed association between these obstetric complications. Early onset, severe GH/PEC in cases with TM suggests temporality and a biological gradient which favors causality.
Respiratory cryptosporidiosis in Malawian children with diarrheal disease
Authors: Tam Pui-Ying Iroh , Chisala Mphatso , Nyangulu Wongani , Thole Herbert , Nyirenda James
Published: May 2021

Background

Respiratory cryptosporidiosis has been documented in children with diarrhea. We sought to describe the dynamics of respiratory involvement in children hospitalized with gastrointestinal (GI) diarrheal disease.

Methods

We conducted a prospective, observational longitudinal study of Malawian children 2-24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment.

Results

Of the 162 children recruited, participants had mild-moderate malnutrition, 36 (22%) were PCR-positive for cryptosporidium at enrollment (34 stool, 11 sputum, and 4 NP) and 27 completed the majority of follow-up visits (75%). Cryptosporidium was detected in all compartments over the 4 post-enrollment visits, most commonly in stool (94% at enrollment with mean cycle thresholds (Ct) of 28.8±4.3 to 44% at 8 weeks with Ct 29.9±4.1), followed by sputum (31% at enrollment with mean Ct 31.1±4.4 to 20% at 8 weeks with Ct 35.7±2.6), then NP (11% with mean Ct 33.5±1.0 to 8% with Ct 36.6±0.7). Participants with cryptosporidium detection in both the respiratory and GI tract over the study period reported respiratory and GI symptoms in 81% and 62% of study visits, respectively, compared to 68% and 27%, respectively, for those with only GI detection, and had longer GI shedding (17.5±6.6 v. 15.9±2.9 days).

Conclusion

Cryptosporidium was detected in both respiratory and GI tracts throughout the 8 weeks post-enrollment. The development of therapeutics for cryptosporidium in children should target the respiratory as well as GI tract. (255)

Author summary

We conducted a prospective, observational longitudinal study of Malawian children 2-24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment. Cryptosporidium was detected by PCR in 21%, 7% and 3% in stool, sputum and nasopharynx of children hospitalized with diarrhea. Of those positive at enrollment, detection was noted in 44%, 20%, and 8%, respectively, by 8 weeks post-enrollment. (87)
THE COST-EFFECTIVENESS OF DEPRESSION SCREENING FOR THE GENERAL ADULT POPULATION
Authors: Yildirim Melike , Gaynes Bradley N , Keskinocak Pinar , Pence Brian W , Swann Julie
Published: May 2021

Background

Depression is a treatable disease, and untreated depression can lead to serious health complications and decrease the quality of life. Therefore, prevention, early identification, and treatment efforts are essential. Screening has an essential role in preventive medicine in the general population. Ideally, screening tools detect patients early enough to manage the disease and reduce symptoms. We aimed to determine the cost-effectiveness of routine screening schedules.

Methods

We used a discrete-time nonstationary Markov model to simulate the progression of depression. We used Monte Carlo techniques to simulate the stochastic model for 20 years or during the lifetime of individuals. Baseline and screening scenario models with screening frequencies of annual, 2-year, and 5-year strategies were compared based on incremental cost-effectiveness ratios (ICER). Monte Carlo (MC) simulation and one-way sensitivity analysis were conducted to manage uncertainties.

Results

In the general population, all screening strategies were cost-effective compared to the baseline. However, male and female populations differed based on cost over quality-adjusted life years (QALY). Females had lower ICERs, and annual screening had the highest ICER for females, with 11,134$/QALY gained. In contrast, males had around three times higher ICER, with annual screening costs of 34,065$/QALY gained.

Limitations

We assumed that the screening frequency was not changing at any time during the screening scenario. In our calculations, false-positive cases were not taking into account.

Conclusions

Considering the high lifetime prevalence and recurrence rates of depression, detection and prevention efforts can be one critical cornerstone to support required care. Our analysis combined the expected benefits and costs of screening and assessed the effectiveness of screening scenarios. We conclude that routine screening is cost-effective for all age groups of females and young, middle-aged males.
Elevated nest temperature has opposing effects on host species infested with parasitic nest flies
Authors: Albert Lauren , Rumschlag Samantha , Parker Alexandra , Vaziri Grace , Knutie Sarah A.
Published: May 2021

Environmental factors, such as elevated temperature, can have varying effects on hosts and their parasites, which can have consequences for disease outcomes. The individual direct effects of temperature must be disentangled to determine the net-effect in host-parasite relationships, yet few studies have determined the net-effects in a multi-host system. To address this gap, we experimentally manipulated temperature and parasite presence in the nests of two host species infested by parasitic blowflies (Protocalliphora sialia). We conducted a factorial experiment by increasing temperature (or not) and removing all parasites (or not) in the nests of eastern bluebirds (Sialia sialis) and tree swallows (Tachycineta bicolor). We then measured nestling morphometrics, blood loss, and survival and quantified parasite abundance. We predicted that if temperature had a direct effect on parasite fitness, then elevated temperature would cause similar directional effects on parasite abundance across host species. If temperature had a direct effect on hosts, and therefore an indirect effect on the parasite, parasite abundance would differ across host species. Heated swallow nests had fewer parasites compared to non-heated nests. In contrast, heated bluebird nests had more parasites compared to non-heated nests. The results of our study demonstrate that elevated temperature can have differential effects on host species, which can impact infestation susceptibility. Furthermore, changing climates could have complex net-effects on parasite fitness and host health across multi-host-parasite interactions.
Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data
Authors: Arzalluz-Luque Angeles , Salguero Pedro , Tarazona Sonia , Conesa Ana
Published: May 2021

Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. However, the extent to which alternative isoforms establish co-expression networks that may relevant in cellular function has not been explored yet. Here, we presentacorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships. To achieve this, we developed and validated percentile correlations, a novel approach that overcomes data sparsity and yields accurate co-expression estimates from single-cell data. Next,acordeuses correlations to cluster co-expressed isoforms into a network, unraveling cell type-specific alternative isoform usage patterns. By selecting same-gene isoforms between these clusters, we subsequently detect and characterize genes with co-differential isoform usage (coDIU) across neural cell types. Finally, we predict functional elements from long read-defined isoforms and provide insight into biological processes, motifs and domains potentially controlled by the coordination of post-transcriptional regulation.
A Metric for Quantifying the Resolution of Molecular Assays
Authors: Wilson Brandon D. , Eisenstein Michael , Soh H. Tom
Published: May 2021

Many assay developers focus on limit of detection (LOD) as a primary performance metric, and LOD is indeed useful for assays designed to determine the presence or absence of an analyte. However, LOD is less useful for ‘continuous assays’ designed to discriminate between concentrations of an analyte—e.g., glucose monitoring in diabetes, where clinical care is guided by particular concentration ranges and thresholds. In such scenarios, it would be valuable to quantify discriminatory resolution—i.e., whether an assay can differentiate 1 pM from 10 pM— but no such standardized metric currently exists. Here, we propose a useful solution, termed ‘resolution of molecular concentration’ (RMC). RMC offers a simple means for characterizing quantitative resolution and quickly comparing the quantitative performance of assays. By raising awareness of the limitations of current metrics for evaluating assay performance, we hope to empower the molecular diagnostics community to evaluate their methods in a more application-appropriate manner.
RNA toxicity and perturbation ofrRNA processing in spinocerebellar ataxia type 2
Authors: Li Pan P. , Moulick Roumita , Feng Hongxuan , Sun Xin , Arbez Nicolas , Jin Jing , Marque Leonard O. , Hedglen Erin , Chan H.Y. Edwin , Ross Christopher A. , Pulst Stefan M. , Margolis Russell L. , Woodson Sarah , Rudnicki Dobrila D.
Published: May 2021

BACKGROUND

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of a CAG repeat inAtaxin-2(ATXN2) gene. The mutant ATXN2 protein with a polyglutamine tract is known to be toxic and contributes to the SCA2 pathogenesis.

OBJECTIVE

Here we tested the hypothesis that the mutantATXN2transcript with an expanded CAG repeat (expATXN2) is also toxic and contributes to SCA2 pathogenesis.

METHODS

The toxic effect ofexpATXN2transcripts on SK-N-MC neuroblastoma cells and primary mouse cortical neurons was evaluated by caspase 3/7 activity and nuclear condensation assay, respectively. RNA immunoprecipitation assay was performed to identify RNA binding proteins (RBPs) that bind toexpATXN2RNA. Quantitative PCR was used to examine if rRNA processing is disrupted in SCA2 and Huntington disease (HD) human brain tissue.

RESULTS

expATXN2RNA induces neuronal cell death, and aberrantly interacts with RBPs involved in RNA metabolism. One of the RBPs, transducin β-like protein 3 (TBL3), involved in rRNA processing, binds to bothexpATXN2and expandedhuntingtin(expHTT) RNAin vitro. rRNA processing is disrupted in both SCA2 and HD human brain tissue.

CONCLUSION

These findings provide the first evidence of a contributory role ofexpATXN2transcripts in SCA2 pathogenesis, and further support the roleexpHTTtranscripts in HD pathogenesis. The disruption of rRNA processing, mediated by aberrant interaction of RBPs withexpATXN2andexpHTTtranscripts, suggest a point of convergence in the pathogeneses of repeat expansion diseases with potential therapeutic implications.
Integrative Wireless Device for Remote Continuous Blood Biomarker Monitoring
Authors: Phan Dinh-Tuan , Zeming Kerwin Kwek , Lian Sophie Wan Mei , Jin Lin , Dinh Ngoc-Duy , Chen Chia-Hung
Published: May 2021

To perform precision medicine in real-time at home, a device capable of long-distance continuously monitoring target biomolecules in unprocessed blood under dynamic situations is essential. In this study, an integrative buffer-free wireless device is developed to measure drug concentrations in patient’s blood in real time for remote clinical healthcare. To demonstrate its capability, the drug molecules (i.e., small-molecule drug doxorubicin, DOX) are continuously measured in the unprocessed whole blood of live animals (e.g., rats). The dynamic changes of drug concentrations with sub-minute temporal resolution are recorded for an extended period of time (∼8 hours). As an advance in remote diagnosis, this device would benefit the public by enabling long-distance precision medicine to prevent pandemics in advance.
Mining endophytic microbiome information from plant and animal transcriptome data
Authors: Han Guomin , Wang Xianjin , Qiu Guiping
Published: May 2021

Endophytic microorganisms play important physiological functions in plants and animals. In this paper, we developed a method to obtain endophytic microbiome information directly by analyzing transcriptome sequencing data files of plants and animals. Compared with the use of amplicon analysis or whole-genome sequencing of animal and plant tissues to analyze microbial composition information, this method can obtain endophytic microbiome information in addition to obtaining gene expression information of host plants and animals.
Bibliometric analysis of parental anxiety and postpartum depression across the perinatal period from 1920-2020: A protocol
Authors: Dol Justine , Campbell-Yeo Marsha , Dennis Cindy-Lee , Leahy-Warren Patricia
Published: May 2021

Introduction

Throughout the perinatal period from pregnancy to the first year postpartum, both men and women experience significant physical, psychological, and social changes which may increase their risk of a mental illness, including anxiety and depression. There has been significant growth in the frequency literature around anxiety and depression across the perinatal period over the past decades with significant variation in definition, measurement outcomes, and populations. To focus future research and identify gaps, it is important to explore current patterns and trends in the current literature.

Objective

The objective of this bibliometric analysis is to analyze the characteristics and trends in published research on anxiety and depression across the perinatal period from January 1, 1920 to end of 2020.

Inclusion criteria

All published literature in Web of Science on perinatal anxiety and depression from January 1, 1920 to December 31, 2020.

Methods

Web of Science will be used to analyze bibliometric information through their built-in analysis feature and citation report that generates a list of leading publications, publication years, document types, authors, source titles, countries/regions, organizations, and research areas. VOSViewer will be utilized to analyze and visualize the networks of linkages between the identified reports, including bibliometric networks, including co-authorship, co-occurrence, and co-citation, as well as co-occurrence between keywords.

Conclusion

The findings from this study will provide useful information to guide future work on perinatal anxiety and depression. This bibliometric review will provide an overview of the work to date in perinatal mental health, identify key contributions to the field, and identify knowledge gaps and future directions.
The Core Human Fecal Metabolome
Authors: Haffner Jacob J. , Katemauswa Mitchelle , Kagone Thérèse S. , Hossain Ekram , Jacobson David , Flores Karina , Parab Adwaita R. , Obregon-Tito Alexandra J. , Tito Raul Y. , Reyes Luis Marin , Troncoso-Corzo Luzmila , Guija-Poma Emilio , Meda Nicolas , Carabin Hélène , Honap Tanvi P. , Sankaranarayanan Krithivasan , Lewis Cecil M. , McCall Laura-Isobel
Published: May 2021

Summary Paragraph

Among the biomolecules at the center of human health and molecular biology is a system of molecules that defines the human phenotype known as the metabolome. Through an untargeted metabolomic analysis of fecal samples from human individuals from Africa and the Americas—the birthplace and the last continental expansion of our species, respectively—we present the characterization of the core human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the core human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features like leucyl-leucine dipeptides and urobilin as major metabolic correlates of these behavioral shifts. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a core human fecal metabolome. This study represents the first characterization of the core human fecal metabolome through untargeted analyses of populations along an industrialization gradient.
Adapting to extremes: reconstructing evolution in response to changing climate over time and space in the diverse Australian plant genus Acacia
Authors: Hua Xia , Cardillo Marcel , Bromham Lindell
Published: May 2021

Aim

Macroevolutionary analysis is increasingly being used to study biodiversity responses to climate change, for example by using phylogenetic node ages to infer periods of diversification, or phylogenetic reconstruction of traits to infer adaptation to particular stresses. Here we apply a recently developed macroevolutionary method to investigate the responses of a diverse plant genus, Acacia, to increasing aridity and salinity in Australia from the Miocene to the present. We ask whether increase in tolerance of aridity and salinity coincided with periods of aridification, and if it allowed the radiation of Acacia into a wide range of niches.

Taxon

Acacia

Location

Australia

Methods

We applied the Niche Evolution Model (NEMo), which combines Environmental (or Ecological) Niche Modelling (ENM) with phylogenetic comparative methods (PCM) in a single statistical framework, to a large database of Acacia presence-only records and presence-absence survey sites in order to infer current environmental tolerances of Australia Acacia species and reconstruct the evolution of environmental tolerance to increasing aridity and salinity.

Results

We find that patterns in evolution of Acacia, over time and across different habitat types, are consistent with the aridification history of Australia and suggests substantial ability to adapt to high aridity and salinity.

Main conclusions

Our results suggest that many Acacia lineages have been able to exploit new environments created during the aridification of Australia through evolution of environmental tolerance, resulting in their current dominance of many habitats across the continent. This study demonstrates that phylogenetic studies of the evolution of responses to changing environment can move beyond application of simple trait-based models, allowing the underlying processes of speciation, adaptation and dispersal to be explicitly modelled in a macroecological and macroevolutionary context.

Statement of significance

Acacia species are found throughout Australia, from rainforests to deserts, and are striking in their environmental adaptability, so they are a perfect case study for understanding evolution of tolerance to environmental extremes in a changing climate. We use the largest database of spatial distribution records yet assembled, using both surveys and atlas data, and a new analytical method that combines the strengths of environmental niche modelling with phylogenetic comparative methods, to demonstrate rapid evolution in aridity and salinity tolerance in response to aridification of the Australian continent during the Neogene and Quaternary.
Multiple ancestral duplications of the red-sensitive opsin gene (LWS) in teleost fishes and convergent spectral shifts to green vision in gobies
Authors: Cortesi Fabio , Camacho Daniel Escobar , Luehrmann Martin , Sommer Gina Maria , Musilova Zuzana
Published: May 2021

Photopigments, consisting of an opsin protein bound to a light-sensitive chromophore, are at the centre of vertebrate vision. The vertebrate ancestor already possessed four cone opsin classes involved in colour perception during bright-light conditions, which are sensitive from the ultraviolet to the red-wavelengths of light. Teleosts experienced an extra round of whole genome duplication (3R) at their origin, and while most teleosts maintained only one long-wavelength-sensitive opsin gene (LWS1), the second ancestral copy (LWS2) persisted in characins and osteoglossomorphs. Following 3R, teleost opsins have continued to expand and diversify, which is thought to be a consequence of the different light environment fishes inhabit, from clear streams to the relative darkness of the deep-sea. Although many recent and a few ancestral opsin duplicates can be found, none predating the 3R were thought to exist. In this study we report on a second, previously unnoticed ancestral duplication of the red-sensitive opsin (LWS3), which predates the teleost-specific genome duplication and only persists in gobiid fishes. This is surprising, since it implies thatLWS3has been lost at least 19-20 times independently along the teleost phylogeny. Mining 109 teleost genomes we also uncover a third lineage, the elopomorphs, that maintained theLWS2copy. We identify convergent amino acid changes that green-shift ancestral and recentLWScopies, leading to adaptive differentiation and the functional replacement of the original green-sensitiveRH2opsin. Retinal transcriptomes and in-situ hybridisation show thatLWS3is expressed to various extents in gobies and in the case of the whitebarred goby,Amblygobius phalaena, it occurs in a separate photoreceptor toLWS1. Our study highlights the importance of comparative studies to comprehend evolution of gene function.
Structural and mechanistic basis of reiterative transcription initiation
Authors: Liu Yu , Winkelman Jared T. , Yu Libing , Pukhrambam Chirangini , Firlar Emre , Kaelber Jason T , Zhang Yu , Nickels Bryce E. , Ebright Richard H.
Published: May 2021

Reiterative transcription initiation, observed at promoters that contain homopolymeric sequences at the transcription start site, generates RNA products having 5’ sequences non-complementary to the DNA template. Here, using crystallography and cryo-EM to define structures, protein-DNA-photocrosslinking to map positions of RNAP leading and trailing edges relative to DNA, and single-molecule DNA nanomanipulation to assess RNAP-dependent DNA unwinding, we show that RNA extension in reiterative transcription initiation: (1) occurs without DNA scrunching, (2) involves a short, 2-3 bp RNA-DNA hybrid, and (3) generates RNA that exits RNAP through the portal by which scrunched nontemplate-strand DNA exits RNAP in standard transcription initiation. The results establish that, whereas RNA extension in standard transcription initiation proceeds through a scrunching mechanism, RNA extension in reiterative transcription initiation proceeds through a slippage mechanism, with slipping of RNA relative to DNA within a short RNA-DNA hybrid, and with extrusion of RNA from RNAP through an alternative RNA exit.
DETECTION OF ITALIAN NURSES’ THOUGHTS ON SEXUAL HEALTH AND THEIR KNOWLEDGE ON THE HIV-TRANSMISSION: A WEB SURVEY
Authors: Costanzo Italo
Published: May 2021

INTRODUCTION

Despite the prevention of sexually transmitted infections included HIV and promotion of sexual health are fundamental parts of human health, the education system in Italy does not seem to provide healthcare professionals with specific knowledge requested by the most recent discoveries on HIV transmission.

METHODS

A web survey was randomly administered to Italian nurses to collect their thoughts about the academic education they received and analyse their knowledge on one of the newest discoveries related to HIV transmission.

RESULTS

More than half of the participants never received any specific academic training on sexual health and sexually transmitted infections, and more than three-quarters of the respondents did not know that a gay couple where only one of the partners is HIV positive will not have to use condoms forever and for every sexual intercourse.

CONCLUSIONS

The survey suggests that training on sexual health and sexually transmitted infections of Italian nurses need to be reinforced and it also highlights the need of updating nurses on the  campaign.

KEY POINT

Knowledge related to sexual health and HIV needs to be expanded in Italian nurses.