bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ribavirin-induced ORF2 single-nucleotide variant produces defective hepatitis E virus particles with immune decoy function
Authors: Meister Toni Luise , Brüggemann Yannick , Nocke Maximilian K. , Ulrich Rainer G. , Schuhenn Jonas , Sutter Kathrin , Gömer André , Bader Verian , Winklhofer Konstanze F. , Broering Ruth , Verhoye Lieven , Meuleman Philip , Vondran Florian W. R. , Camuzet Charline , Cocquerel Laurence , Todt Daniel , Steinmann Eike 
Published: August 2022

Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically transmitted viral hepatitis worldwide. Ribavirin (RBV) is currently the only treatment option for many patients; however, cases of treatment failures or posttreatment relapses have been frequently reported. RBV therapy was shown to be associated with an increase in HEV genome heterogeneity and the emergence of distinct HEV variants. In this study, we analyzed the impact of eight patient-derived open reading frame 2 (ORF2) single-nucleotide variants (SNVs), which occurred under RBV treatment, on the replication cycle and pathogenesis of HEV. The parental HEV strain and seven ORF2 variants showed comparable levels of RNA replication in human hepatoma cells and primary human hepatocytes. However, a P79S ORF2 variant demonstrated reduced RNA copy numbers released in the supernatant and an impairment in the production of infectious particles. Biophysical and biochemical characterization revealed that this SNV caused defective, smaller HEV particles with a loss of infectiousness. Furthermore, the P79S variant displayed an altered subcellular distribution of the ORF2 protein and was able to interfere with antibody-mediated neutralization of HEV in a competition assay. In conclusion, an SNV in the HEV ORF2 could be identified that resulted in altered virus particles that were noninfectious in vitro and in vivo, but could potentially serve as immune decoys. These findings provide insights in understanding the biology of circulating HEV variants and may guide development of personalized antiviral strategies in the future.
Inferring gene regulation from stochastic transcriptional variation across single cells at steady state
Authors: Gupta Anika , Martin-Rufino Jorge D. , Jones Thouis R. , Subramanian Vidya , Qiu Xiaojie , Grody Emanuelle I. , Bloemendal Alex , Weng Chen , Niu Sheng-Yong , Min Kyung Hoi , Mehta Arnav , Zhang Kaite , Siraj Layla , Al' Khafaji Aziz , Sankaran Vijay G. , Raychaudhuri Soumya , Cleary Brian , Grossman Sharon , Lander Eric S. 
Published: August 2022

Regulatory relationships between transcription factors (TFs) and their target genes lie at the heart of cellular identity and function; however, uncovering these relationships is often labor-intensive and requires perturbations. Here, we propose a principled framework to systematically infer gene regulation for all TFs simultaneously in cells at steady state by leveraging the intrinsic variation in the transcriptional abundance across single cells. Through modeling and simulations, we characterize how transcriptional bursts of a TF gene are propagated to its target genes, including the expected ranges of time delay and magnitude of maximum covariation. We distinguish these temporal trends from the time-invariant covariation arising from cell states, and we delineate the experimental and technical requirements for leveraging these small but meaningful cofluctuations in the presence of measurement noise. While current technology does not yet allow adequate power for definitively detecting regulatory relationships for all TFs simultaneously in cells at steady state, we investigate a small-scale dataset to inform future experimental design. This study supports the potential value of mapping regulatory connections through stochastic variation, and it motivates further technological development to achieve its full potential.
Research Spotlight—Insect Polarization Vision: Peripheral And Central Mechanisms
Authors: Warrant Eric , Homberg U. 
Published: August 2022

AbstractThe ability to detect linearly polarized light is used by insects for spatial orientation, object identification and, in a few cases, sexual signalling. The use of polarization vision for sky compass orientation has received particular attention. Scattering of sunlight by air molecules generates a pattern of skylight polarization, which insects can use, just like the sun itself, as a visual celestial compass. Polarized skylight is detected by specialized ommatidia in the so-called dorsal rim area of the eye. In this eye region, ommatidial photoreceptors have highly aligned rhodopsin-bearing microvilli, resulting in high polarization sensitivity. Photoreceptors are homochromatic and occur in each ommatidium as sets of receptors with orthogonal microvillar orientations. Antagonistic input from these photoreceptors likely results in polarization-opponency in neurons of the polarization vision pathway in the brain. Studies in locusts, monarch butterflies, and a few other species have shown that convergence of signals from both eyes occurs in the central complex, a group of midline-spanning neuropils in the brain. Here, bilateral integration results in a compass-like topographic representation of zenithal E-vectors, which may be used as a frame of reference for spatial memory, path integration, and other spatial tasks. Integration of other celestial cues, such as the sky chromatic contrast, occurs at central stages of the polarization vision system, presumably to increase the robustness of the sky compass signal.
Exploring Ageism as a Structure of Consciousness Across the Female Life Course Through the Work of Simone de Beauvoir
Authors: Pickard Susan 
Published: August 2022

Abstract
Drawing on the work of Simone de Beauvoir, this paper considers ageism as a structure of consciousness, with important convergences with, as well as departures from, those associated with gender. Specifically, it explores the double consciousness through which the self is experienced negatively as old, at 2 points in a woman’s life course, namely midlife and “old age.” The first kind of ageism works through the double standard of aging and the gender hierarchy, whereby women can no longer successfully comply with the objectification of the male gaze. This is a moment of intense age consciousness, tainted by a gendered narrative of decline, working jointly from the outside in and from the inside out. The second form of ageism has its source in the social world, in the reactions of other people to old age, resulting in an uneasy dialectic between one’s own sense of an ageless or youthful self and the alien view of self as old. The paper proceeds as follows. After a brief account of Beauvoir’s general philosophical approach, I compare and contrast the doubled consciousness associated with aging as a woman and with aging in a more general sense as described in The Second Sex and The Coming of Age, respectively. I then flesh out this conceptual framework by drawing on fiction and autofiction written by Beauvoir herself. Together, this approach vividly illuminates the important interconnections and intersections between ageism and sexism, the way they work together, as well as separately, across the female life course.
Expected Impact of Universal Immunization With Nirsevimab Against RSV-Related Outcomes and Costs Among All US Infants in Their First RSV Season: A Static Model
Authors: Kieffer Alexia , Beuvelet Matthieu , Sardesai Aditya , Musci Robert , Milev Sandra , Roiz Julie , Lee Jason K H 
Published: August 2022

Abstract

Background
Respiratory syncytial virus (RSV) is associated with substantial morbidity in the United States, especially among infants. Nirsevimab, an investigational long-acting monoclonal antibody, was evaluated as an immunoprophylactic strategy for infants in their first RSV season and for its potential impact on RSV-associated, medically attended lower respiratory tract illness (RSV-MALRTI) and associated costs.

Methods
A static decision-analytic model of the US birth cohort during its first RSV season was developed to estimate nirsevimab’s impact on RSV-related health events and costs; model inputs included US-specific costs and epidemiological data. Modelled RSV-related outcomes included primary care and emergency room visits, hospitalizations including intensive care unit admission and mechanical ventilations, and RSV-related mortality.

Results
Under current standard of care, RSV caused 529 915 RSV-MALRTIs and 47 281 hospitalizations annually, representing $1.2 billion (2021 US dollars [USD]) in costs. Universal immunization of all infants with nirsevimab is expected to reduce 290 174 RSV-MALRTI, 24 986 hospitalizations, and expenditures of $612 million 2021 USD.

Conclusions
An all-infant immunization strategy with nirsevimab could substantially reduce the health and economic burden for US infants during their first RSV season. While this reduction is driven by term infants, all infants, including palivizumab-eligible and preterm infants, would benefit from this strategy.
Magnetic Resonance Imaging Is Inadequate to Assess Cervical Sagittal Alignment Parameters
Authors: Goh Brian C. , Lightsey Harry M. , Lopez Wylie Y. , Tobert Daniel G. , Fogel Harold A. , Cha Thomas D. , Schwab Joseph H. , Bono Christopher M. , Hershman Stuart H. 
Published: August 2022

Study Design:
Retrospective radiographic study.

Objective:
To evaluate cervical sagittal alignment measurement reliability and correlation between upright radiographs and magnetic resonance imaging (MRI).

Summary of Background Data:
Cervical sagittal alignment (CSA) helps determine the surgical technique employed to treat cervical spondylotic myelopathy. Traditionally, upright lateral radiographs are used to measure CSA, but obtaining adequate imaging can be challenging. Utilizing MRI to evaluate sagittal parameters has been explored; however, the impact of positional change on these parameters has not been determined.

Methods:
One hundred seventeen adult patients were identified who underwent laminoplasty or laminectomy and fusion for cervical spondylotic myelopathy from 2017 to 2019. Two clinicians independently measured the C2–C7 sagittal angle, C2–C7 sagittal vertical axis (SVA), and the T1 tilt. Interobserver and intraobserver reliability were assessed by intraclass correlation coefficient.

Results:
Intraobserver and interobserver reliabilities were highly correlated, with correlations greater than 0.85 across all permutations; intraclass correlation coefficients were highest with MRI measurements. The C2–C7 sagittal angle was highly correlated between x-ray and MRI at 0.76 with no significant difference (P=0.46). There was a weaker correlation with regard to C2–C7 SVA (0.48) and T1 tilt (0.62) with significant differences observed in the mean values between the 2 modalities (P<0.01).

Conclusions:
The C2–C7 sagittal angle is highly correlated and not significantly different between upright x-ray and supine MRIs. However, cervical SVA and T1 tilt change with patient position. Since MRI does not accurately reflect the CSA in the upright position, upright lateral radiographs should be obtained to assess global sagittal alignment when planning a posterior-based cervical procedure.
Risk factors for future osteoporosis in perimenopausal Japanese women
Authors: Kanto Akiko , Kotani Yasushi , Murakami Kosuke , Tamaki Junko , Sato Yuho , Kagamimori Sadanobu , Matsumura Noriomi , Iki Masayuki 
Published: August 2022

Abstract

Objective
The aims of this study were to investigate trends in bone mineral density (BMD) loss and related factors in early postmenopausal women in Japan, identify risk factors for future osteoporosis, and predict osteoporosis before it occurs.

Methods
The study population consisted of women who were 50 to 54 years old at the time of the survey in 2002 or 2006. The study included a questionnaire and physical measurement findings (BMD, height, body weight [WT], body mass index [BMI], and handgrip strength). One hundred sixty-seven women continued to participate in the study and had BMD measurements at the 9- or 10-year follow-up of the Japanese Population-based Osteoporosis study. Statistical analyses were performed using Pearson correlation to examine each factor of physical measurement and BMD for lumbar spine (LS) and femoral neck (FN). The receiver operating characteristic curve of this data was also predictive of osteoporosis in 2011 for 2002 data; BMD at the age of 50 to 54 years was then used to predict the likelihood of being diagnosed with osteoporosis 9 and 10 years later.

Results
At the baseline in 2002 and 2006, WT, BMI, height, and handgrip strength were positively correlated with BMD. The optimal cutoff values for BMD in 2006 to predict osteoporosis in 2016 were LS less than 0.834 g/cm2 and FN less than 0.702 g/cm2. These data were also predictive of osteoporosis in 2011 for 2002 data; applying this to the 2002 data, LS/FN had a sensitivity of 92%/100%, a specificity of 87%/81%, a positive predictive value of 55%/48%, and a negative predictive value of 98%/100%. The larger WT and BMI also resulted in a greater decrease in BMD of FN after 9 or 10 years.

Conclusions
We have identified a cutoff value for BMD to predict future osteoporosis in menopausal women and found a negative correlation between WT and BMI in menopausal women and changes in BMD of the FN over the next 10 years.
Association between equol production and metabolic syndrome in Japanese women in their 50s-60s
Authors: Takahashi Atsushi , Kokubun Masae , Anzai Yukio , Kogre Atsuko , Ogata Takashi , Imaizumi Hiromichi , Fujita Masashi , Hayashi Manabu , Abe Kazumichi , Ohira Hiromasa 
Published: August 2022

Abstract

Objective
Equol is an active metabolite of soy isoflavone. As a phytoestrogen, equol has the potential to prevent metabolic disorders such as hyperglycemia, hyperlipidemia, and obesity. This study aimed to determine the association between equol production and metabolic syndrome (METS) in postmenopausal women.

Methods
This cross-sectional study included 1,345 women aged 50 to 69 years who underwent health checkups from February 2018 to November 2021 at four health centers in Fukushima, Japan. Equol producers were defined as those with a urinary equol concentration of 1.0 μM or more. METS was defined based on Japanese diagnostic criteria including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and glucose intolerance. The association between equol production and METS was estimated by logistic regression analysis, with adjustments for age, exercise, physical activity, and fast walking.

Results
Of the 1,345 women, 378 (28.1%) were equol producers. The proportion of women who had METS (6.6% vs 10.9%) was significantly lower in the equol-producing group than in the nonproducing group. Multivariable logistic regression analysis revealed that equol production was significantly associated with METS (odds ratio, 0.60; 95% CI, 0.38-0.95).

Conclusions
Equol production was associated with a lower prevalence of METS among women aged 50 to 69 years.
Pleural Pustule—a Novel Thoracoscopic Appearance of Pleural Tuberculosis
Authors: Maturu Venkata Nagarjuna , Prasad Virender Pratibh , Biradar Mahendra , Narahari Narendra Kumar 
Published: August 2022

Background:
Thoracoscopic pleural biopsy is the gold standard for diagnosing tubercular pleural effusion (TPE). Various thoracoscopic appearances like sago grain nodules, caseous necrosis, and adhesions have been described in TPE. However, none of these have high specificity for diagnosing TPE. In this study we evaluate a novel finding on thoracoscopy, the “Pleural Pustule.”

Methods:
This is a retrospective analysis of patients who underwent thoracoscopy for undiagnosed pleural effusion. Visual inspection of the pleura was performed to identify abnormalities. Biopsies were obtained from those areas and sent for histopathology, acid fast bacillus (AFB) smear, culture, and Xpert MTB/Rif assay. Pleural pustule was defined as a pus filled nodule on the pleural surface.

Results:
Of the 259 patients included, 92 were diagnosed with TPE. Pleural pustule(s) were identified in 16 patients with TPE. Presence of pleural pustule had a sensitivity, specificity, positive predictive value, and negative predictive value of 17.4%, 100%, 100% and 68.7%, respectively, for diagnosing TPE. Histopathology of pleural pustule demonstrated necrotizing granulomas in all. In patients with pleural pustule, a microbiological diagnosis of tuberculosis was achieved in 93.7% patients (AFB smear, Xpert MTB/Rif assay, and MTB culture positive in 31.3%, 93.7%, and 43.7% cases, respectively). There is a strong association between pleural pustule and positive Xpert MTB/Rif assay (P=0.002) and microbiologic confirmation of diagnosis (P=0.017).

Conclusion:
The presence of pleural pustule on thoracoscopy has a high positive predictive value for TPE. In tuberculosis-endemic countries, this can be considered suggestive for TPE. When identified, a biopsy from the pleural pustule should be performed as it will likely yield a positive microbiologic diagnosis.
Toward Personalized Diagnosis and Therapy for Hearing Loss: Insights From Cochlear Implants
Authors: Sagi Varun , Stankovic Konstantina M. 
Published: August 2022

Abstract:
Sensorineural hearing loss (SNHL) is the most common sensory deficit, disabling nearly half a billion people worldwide. The cochlear implant (CI) has transformed the treatment of patients with SNHL, having restored hearing to more than 800,000 people. The success of CIs has inspired multidisciplinary efforts to address the unmet need for personalized, cellular-level diagnosis, and treatment of patients with SNHL. Current limitations include an inability to safely and accurately image at high resolution and biopsy the inner ear, precluding the use of key structural and molecular information during diagnostic and treatment decisions. Furthermore, there remains a lack of pharmacological therapies for hearing loss, which can partially be attributed to challenges associated with new drug development. We highlight advances in diagnostic and therapeutic strategies for SNHL that will help accelerate the push toward precision medicine. In addition, we discuss technological improvements for the CI that will further enhance its functionality for future patients. This report highlights work that was originally presented by Dr. Stankovic as part of the Dr. John Niparko Memorial Lecture during the 2021 American Cochlear Implant Alliance annual meeting.
Tympanoplasty With and Without Mastoidectomy for Chronic Otitis Media Without Cholesteatoma: A Systematic Review and Meta-analysis
Authors: Poupore Nicolas S. , Gordis Tamar M. , Nguyen Shaun A. , Meyer Ted A. , Carroll William W. , Lambert Paul R. 
Published: August 2022

Objective
This study aimed to compare surgical and audiometric outcomes of tympanoplasty alone (T) to tympanoplasty and mastoidectomy (T&M) in patients without cholesteatoma.

Databases Reviewed
According to PRISMA guidelines, English articles in PubMed, Scopus, CINAHL, and Cochrane Library databases from inception to 7/29/2021 were searched.

Methods
Studies describing a comparison of patients who underwent T to patients who underwent T&M were included. Studies describing patients with cholesteatoma were excluded. Patient demographics, graft failure rates, and preoperative and postoperative audiological findings were collected. Mean differences (MD) and risk difference (RD) were calculated using RevMan 5.4. Heterogeneity was assessed using Q test and I
2 statistic. Risk of bias was assessed using both version 2 of the Cochrane risk-of-bias tool for randomized trials and Risk of Bias in Non-randomized Studies of Interventions.

Results
A total of 27 studies fulfilled eligibility with T (n = 1,711) and T&M (n = 1,186). When pooling the data, mean differences between T versus T&M for air bone gap (−0.3 dB: 95% CI = −1.9 to 1.3, p = 0.730) and pure tone average (1.9 dB: 95% CI = −0.3 to 4.2, p = 0.090) were not statistically significant. Graft failure was higher with T only (16.4% versus 14.2%) than T&M (RD = −0.04, 95% CI = −0.07 to −0.00, p = 0.030, I
2 = 35%].

Conclusion
This study endorses clinically similar audiological outcomes and a reduced risk difference of graft failure with mastoidectomy. Although these data suggest that adding a mastoidectomy could decrease the risk of graft failure, the risk reduction is minimal. More research on the cost-effectiveness and the specific patient clinical characteristics and comorbidities that would benefit from adding a mastoidectomy is warranted.
Refining epidemiological forecasts with simple scoring rules
Authors: Moore Robert E. , Rosato Conor , Maskell Simon 
Published: August 2022

Estimates from infectious disease models have constituted a significant part of the scientific evidence used to inform the response to the COVID-19 pandemic in the UK. These estimates can vary strikingly in their bias and variability. Epidemiological forecasts should be consistent with the observations that eventually materialize. We use simple scoring rules to refine the forecasts of a novel statistical model for multisource COVID-19 surveillance data by tuning its smoothness hyperparameter.This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.
The Royal Society RAMP modelling initiative
Authors: Ackland G. J. , Panovska-Griffiths J. , Waites W. , Cates M. E. 
Published: August 2022

Normally, science proceeds following a well-established set of principles. Studies are done with an emphasis on correctness, are submitted to a journal editor who evaluates their relevance, and then undergo anonymous peer review by experts before publication in a journal and acceptance by the scientific community via the open literature. This process is slow, but its accuracy has served all fields of science well. In an emergency situation, different priorities come to the fore. Research and review need to be conducted quickly, and the target audience consists of policymakers. Scientists must jostle for the attention of non-specialists without sacrificing rigour, and must deal not only with peer assessment but also with media scrutiny by journalists who may have agendas other than ensuring scientific correctness. Here, we describe how the Royal Society coordinated efforts of diverse scientists to help model the coronavirus epidemic.This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.