bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein functional dynamics from the rigorous global analysis of DEER data:
Conditions, components, and conformations
Authors: Hustedt Eric J. , Stein Richard A. , Mchaourab Hassane S.
Published: September 2021

The potential of spin labeling to reveal the dynamic dimension of macromolecules has been recognized since the dawn of the methodology in the 1960s. However, it was the development of pulsed electron paramagnetic resonance spectroscopy to detect dipolar coupling between spin labels and the availability of turnkey instrumentation in the 21st century that realized the full promise of spin labeling. Double electron-electron resonance (DEER) spectroscopy has seen widespread applications to channels, transporters, and receptors. In these studies, distance distributions between pairs of spin labels obtained under different biochemical conditions report the conformational states of macromolecules, illuminating the key movements underlying biological function. These experimental studies have spurred the development of methods for the rigorous analysis of DEER spectroscopic data along with methods for integrating these distributions into structural models. In this tutorial, we describe a model-based approach to obtaining a minimum set of components of the distance distribution that correspond to functionally relevant protein conformations with a set of fractional amplitudes that define the equilibrium between these conformations. Importantly, we review and elaborate on the error analysis reflecting the uncertainty in the various parameters, a critical step in rigorous structural interpretation of the spectroscopic data.
Lateral β-Ga2O3 Schottky barrier diode fabricated on (–201) single crystal substrate and its temperature-dependent current–voltage characteristics
Authors: Ma Pei-Pei , Zheng Jun , Zhang Ya-Bao , Liu Xiang-Quan , Liu Zhi , Zuo Yu-Hua , Xue Chun-Lai , Cheng Bu-Wen
Published: September 2021

Lateral β-Ga2O3 Schottky barrier diodes (SBDs) each are fabricated on an unintentionally doped (-201) n-type β-Ga2O3 single crystal substrate by designing L-shaped electrodes. By introducing sidewall electrodes on both sides of the conductive channel, the SBD demonstrates a high current density of 223 mA/mm and low specific on-resistance of 4.7 mΩ⋅cm2. Temperature-dependent performance is studied and the Schottky barrier height is extracted to be in a range between 1.3 eV and 1.35 eV at temperatures ranging from 20 °C to 150 °C. These results suggest that the lateral β-Ga2O3 SBD has a tremendous potential for future power electronic applications.
Hybrid-anode structure designed for a high-performance quasi-vertical GaN Schottky barrier diode
Authors: Wang Qiliang , Wang Tingting , Pu Taofei , Cheng Shaoheng , Li Xiaobo , Li Liuan , Ao Jinping
Published: September 2021

A quasi-vertical GaN Schottky barrier diode with a hybrid anode structure is proposed to trade off the on-resistance and the breakdown voltage. By inserting a SiN dielectric between the anode metal with a relatively small length, it suppresses the electric field crowding effect without presenting an obvious effect on the forward characteristics. The enhanced breakdown voltage is ascribed to the charge-coupling effect between the insulation dielectric layer and GaN. On the other hand, the current density is decreased beneath the dielectric layer with the increasing length of the SiN, resulting in a high on-resistance. Furthermore, the introduction of the field plate on the side wall forms an metal-oxide-semiconductor (MOS) channel and decreases the series resistance, but also shows an obvious electric field crowding effect at the bottom of the mesa due to the quasi-vertical structure.
Generation of mid-infrared supercontinuum by designing circular photonic crystal fiber
Authors: Huang Ying , Yang Hua , Mao Yucheng
Published: September 2021

A circular photonic crystal fiber (C-PCF) based on As2Se3 is designed, which has three zero dispersion wavelengths and flat dispersion. Using this fiber, a wide mid-infrared supercontinuum (MIR-SC) can be generated by launching a femtosecond pulse in the first anomalous dispersion region. The simulation results show that the MIR-SC is formed by soliton self-frequency shift and direct soliton spectrum tunneling on the long wavelength side and self-phase modulation, soliton fission on the short wavelength side. Further, optical shocking and four-wave mixing (FWM) are not conducive to the long-wavelength extension of MIR-SC, while the number and intensity of fundamental solitons have a greater effect on the short-wavelength extension of MIR-SC. The generation of optical shocking waves, FWM waves and fundamental solitons can be obviously affected by changing the fiber length and input pulse parameters, so that the spectrum range and flatness can be adjusted with great freedom. Finally, under the conditions of 4000 W pulse peak power, 30 fs pulse width, 47 mm fiber length, and 0 initial chirp, a wide MIR-SC with a coverage range of 2.535 μm–16.6 μm is obtained. These numerical results are encouraging because they demonstrate that the spread of MIR-SC towards the red and blue ends can be manipulated by choosing the appropriate incident pulse and designing optimized fiber parameters, which contributes to applications in such diverse areas as spectroscopy, metrology and tomography.
Monthly river temperature trends across the US confound annual changes
Authors: Kelleher Christa A , Golden Heather E , Archfield Stacey A
Published: September 2021

Climate variations and human modifications of the water cycle continue to alter the Earth’s surface water and energy exchanges. It is therefore critical to ascertain how these changes impact water quality and aquatic ecosystem habitat metrics such as river temperatures. Though river temperature trend analyses exist in the literature, studies on seasonal trends in river temperatures across large spatial extents, e.g. the contiguous United States (US), are limited. As we show through both annual and monthly trend analyses for 20 year (n = 138 sites) and 40 year (n = 40 sites) periods, annual temperature trends across the US mask extensive monthly variability. While most sites exhibited annual warming trends, these annual trends obscured sub-annual cooling trends at many sites. Monthly trend anomalies were spatially organized, with persistent regional patterns at both reference and human-impacted sites. The largest warming and cooling anomalies happened at human impacted sites and during summer months. Though our analysis points to coherence in trends as well as the overall impact of human activity in driving these patterns, we did not investigate the impact of river temperature observation accuracy on reported trends, an area needed for future work. Overall, these patterns emphasize the need to consider sub-annual behavior when managing the ecological impacts of river temperature throughout lotic networks.
Quantum metasurfaces of arrays of Λ-emitters for photonic nano-devices
Authors: Ryzhov Igor V , Malikov Ramil F , Malyshev Andrey V , Malyshev Victor A
Published: September 2021

We address exotic optical response of a planar metasurface comprising a monolayer of regularly spaced quantum three-level emitters with a doublet in the ground state (the so-called Λ-emitters). All emitters are coupled by the retarded dipole field which depends on the current state of all emitters. This coupling introduces a feedback into the system. Complex interplay of the latter with the intrinsic nonlinearity of a three-level system results in several remarkable effects in the monolayer’s optical response, such as multistability, self-oscillations, and chaos. The peculiarity of the considered system is that some of the predicted nonlinear effects manifest themselves at very low excitation field intensities (on the order of 1 W/cm2), which is advantageous for possible applications: the monolayer can operate as a perfect reflector, a bistable mirror, and a THz or noise generator. It is argued therefore that the proposed system is a promising candidate for a building block for various photonic nano-devices.
Co-Topical Small Talk: Troubles-Telling in Traditional Chinese Medical Encounters
Authors: Jin Ying , Kim Younhee , Carlin Andrew P
Published: September 2021

Research has suggested that a rigid dichotomy between small and professional talk is misleading given the porous nature of ‘types’ of talk. Yet, other research considers this distinction helpful in understanding the functions of talk in situated contexts. This article contributes to this discussion by discussing one type of small talk—co-topical small talk (CST). Drawing from Hudak and Maynard’s (2011) understanding of CST as talk that combines instrumental and small talk, we further discuss the bigness of such talk in holistic medical encounters. Specifically, we focus on the ambiguity embedded in participants’ turns that allows the navigation of topics between the small/big talk distinctions. We use Conversation Analysis focusing on a routine traditional Chinese medicine doctor–patient encounter. Our data present a case where CST comfortably and appropriately emerges and develops into extensive troubles talk that forms the main activity in caring for older adults. We conclude that the smallness/bigness of talk is determined by the nature of the context and the relevancy of the topic to the encounter.
News in Astronomy & Geophysics – October 2021
Authors: Bowler Sue , Gunn Alastair
Published: September 2021

A digest of some of the big stories from the past two months
Lucinda Offer: RAS Education, Outreach & Events Officer
Authors: Johnson Paul
Published: September 2021

The daughter of a NASA engineer has spent her life advocating for sending humans to Mars. Interview by Paul Johnson
Wildlife pathogen detection: evaluation of alternative DNA extraction protocols
Authors: Mantzana-Oikonomaki Vasiliki , Maan Martine , Sabino-Pinto Joana
Published: September 2021

Accurate detection of wildlife pathogens is critical in wildlife disease research. False negatives or positives can have catastrophic consequences for conservation and disease-mitigation decisions. Quantitative polymerase chain reaction is commonly used for molecular detection of wildlife pathogens. The reliability of this method depends on the effective extraction of the pathogen’s DNA from host samples. A wildlife disease that has been in the centre of conservationist’s attention is the amphibian disease Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Here, we compare the efficiency of a spin column extraction kit (QIAGEN), commonly used in Bd DNA extraction, to an alternative spin column kit (BIOKÈ) used in extractions from other types of samples, which is considerably cheaper but not typically used for Bd DNA extraction. Additionally, we explore the effect of an enzymatic pre-treatment on detection efficiency. Both methods showed similar efficiency when extracting Bd DNA from zoospores from laboratory-created cell-cultures, as well as higher efficiency when combined with the enzymatic pre-treatment. Our results indicate that selecting the optimal method for DNA extraction is essential to ensure minimal false negatives and reduce project costs.
Collections Education: The Extended Specimen and Data Acumen
Authors: Monfils Anna K , Krimmel Erica R , Linton Debra L , Marsico Travis D , Morris Ashley B , Ruhfel Brad R
Published: September 2021

Biodiversity scientists must be fluent across disciplines; they must possess the quantitative, computational, and data skills necessary for working with large, complex data sets, and they must have foundational skills and content knowledge from ecology, evolution, taxonomy, and systematics. To effectively train the emerging workforce, we must teach science as we conduct science and embrace emerging concepts of data acumen alongside the knowledge, tools, and techniques foundational to organismal biology. We present an open education resource that updates the traditional plant collection exercise to incorporate best practices in twenty-first century collecting and to contextualize the activities that build data acumen. Students exposed to this resource gained skills and content knowledge in plant taxonomy and systematics, as well as a nuanced understanding of collections-based data resources. We discuss the importance of the extended specimen in fostering scientific discovery and reinforcing foundational concepts in biodiversity science, taxonomy, and systematics.
Postnephrectomy outcomes following en bloc resection of primary retroperitoneal sarcoma: multicentre study
Authors: Fairweather Mark , Lyu Heather , Conti Lorenzo , Callegaro Dario , Radaelli Stefano , Fiore Marco , Ng Deanna , Swallow Carol , Gronchi Alessandro , Raut Chandrajit P.
Published: September 2021

This article reports on postoperative renal function in the largest series of patients with primary retroperitoneal sarcoma undergoing nephrectomy at three high-volume sarcoma centres. Although half of patients develop chronic kidney disease of stage 3 or higher, rarely do patients develop acute renal failure requiring renal replacement therapy.
Quality of life in restorative versus non-restorative resections for rectal cancer: systematic review
Authors: Lawday Samuel , Flamey Nicholas , Fowler George E , Leaning Matthew , Dyar Nadine , Daniels Ian R , Smart Neil J , Hyde Christopher
Published: September 2021

Background

Low rectal cancers could be treated using restorative (anterior resection, AR) or non-restorative procedures with an end/permanent stoma (Hartmann’s, HE; or abdominoperineal excision, APE). Although the surgical choice is determined by tumour and patient factors, quality of life (QoL) will also influence the patient's future beyond cancer. This systematic review of the literature compared postoperative QoL between the restorative and non-restorative techniques using validated measurement tools.

Methods

The review was registered on PROSPERO (CRD42020131492). Embase and MEDLINE, along with grey literature and trials websites, were searched comprehensively for papers published since 2012. Inclusion criteria were original research in an adult population with rectal cancer that reported QoL using a validated tool, including the European Organization for Research and Treatment of Cancer QLQ-CR30, QLQ-CR29, and QLQ-CR38. Studies were included if they compared AR with APE (or HE), independent of study design. Risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. Outcomes of interest were: QoL, pain, gastrointestinal (GI) symptoms (stool frequency, flatulence, diarrhoea and constipation), and body image.

Results

Nineteen studies met the inclusion criteria with a total of 6453 patients; all papers were observational and just four included preoperative evaluations. There was no identifiable difference in global QoL and pain between the two surgical techniques. Reported results regarding GI symptoms and body image documented similar findings. The ROBINS-I tool highlighted a significant risk of bias across the studies.

Conclusion

Currently, it is not possible to draw a firm conclusion on postoperative QoL, pain, GI symptoms, and body image following restorative or non-restorative surgery. The included studies were generally of poor quality, lacked preoperative evaluations, and showed considerable bias in the data.
Infection With the USNeisseria meningitidisUrethritis Clade Does Not Lower Future Risk of Urethral Gonorrhea
Authors: Turner Abigail Norris , Carter Alexandria M , Tzeng Yih-Ling , Stephens David S , Brown Morgan A , Snyder Brandon M , Retchless Adam C , Wang Xin , Bazan Jose A
Published: September 2021

Background

Cross-protective immunity between Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) may inform gonococcal vaccine development. Meningococcal serogroup B (MenB) outer membrane vesicle (OMV) vaccines confer modest protection against gonorrhea. However, whether urethral Nm infection protects against gonorrhea is unknown. We examined gonorrhea risk among men with US Nm urethritis clade (US_NmUC) infections.

Methods

We conducted a retrospective cohort study of men with urethral US_NmUC (n = 128) between January 2015 and April 2018. Using diagnosis date as the baseline visit, we examined Ng status at return visits to compute urethral Ng risk. We compared these data to 3 referent populations: men with urethral Ng (n = 253), urethral chlamydia (Ct) (n = 251), and no urethral Ng or Ct (n = 255). We conducted sensitivity analyses to assess varied approaches to censoring, missing data, and anatomical site of infection. We also compared sequences of protein antigens in the OMV-based MenB-4C vaccine, US_NmUC, and Ng.

Results

Participants were primarily Black (65%) and heterosexual (82%). Over follow-up, 91 men acquired urethral Ng. Men with urethral US_NmUC had similar Ng risk to men with prior urethral Ng (adjusted hazard ratio [aHR]: 1.27; 95% CI: .65–2.48). Men with urethral US_NmUC had nonsignificantly increased Ng risk compared with men with urethral Ct (aHR: 1.51; 95% CI: .79–2.88), and significantly increased Ng risk compared with men without urethral Ng or Ct (aHR: 3.55; 95% CI: 1.27–9.91). Most of the protein antigens analyzed shared high sequence similarity.

Conclusions

Urethral US_NmUC infection did not protect against gonorrhea despite substantial sequence similarities in shared protein antigens.
Ultrasensitive and Quantitative Toxin Measurement Correlates With Baseline Severity, Severe Outcomes, and Recurrence Among Hospitalized Patients With Clostridioides difficile Infection
Authors: Alonso Carolyn D , Kelly Ciarán P , Garey Kevin W , Gonzales-Luna Anne J , Williams David , Daugherty Kaitlyn , Cuddemi Christine , Villafuerte-Gálvez Javier , White Nicole C , Chen Xinhua , Xu Hua , Sprague Rebecca , Barrett Caitlin , Miller Mark , Foussadier Agnès , Lantz Aude , Banz Alice , Pollock Nira R
Published: September 2021

Background

Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence.

Methods

We enrolled 615 hospitalized adults (≥18 years) with CDI (acute diarrhea, positive stool nucleic acid amplification testing, and decision to treat). Baseline stool toxin A and B concentrations were measured by single molecule array. Subjects were classified by baseline CDI severity (4 scoring methods) and outcomes within 40 days (death, intensive care unit stay, colectomy, and recurrence).

Results

Among 615 patients (median, 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P < .01). Nineteen subjects (3.1%) had a severe outcome primarily attributed to CDI (group 1). This group had higher median toxin A+B (14 303 pg/mL [interquartile range, 416.0, 141 967]) than subjects in whom CDI only contributed to the outcome (group 2, 163.2 pg/mL [0.0, 8423.3]), subjects with severe outcome unrelated to CDI (group 3, 158.6 pg/mL [0.0, 1795.2]), or no severe outcome (group 4, 209.5 pg/mL [0.0, 8566.3]) (P = .003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2–4 (60.5%–66.1%) (P = .02). Individuals with recurrence had higher toxin A+B (2266.8 pg/mL [188.8, 29411]) than those without (154.0 pg/mL [0.0, 5864.3]) (P < .001) and higher rates of detectable toxin (85.7% versus 64.0%, P = .004).

Conclusions

In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.
Chinese Positions on Global Constitutionalism, Community of Common Destiny for Mankind, and the Future of International Law
Authors: Ahl Björn
Published: September 2021

Global constitutionalism and the Chinese concept of a community of common destiny for mankind provide different master narratives for the future development of the international legal order. This study analyses Chinese legal scholarship and Chinese government statements that relate to elements of global constitutionalism and the community of common destiny in order to identify the values and structures of future international law envisaged by China. We argue that although authors and government statements refute or re-interpret the underlying values of global constitutionalism such as the rule of law, democracy and human rights, Chinese scholarship embraces the idea of a higher order of international norms that derive from the common values of the international community. However, the Chinese government’s position on jus cogens appears to reject a version of peremptory norms that empower non-state actors. We find that he principle of universal security and the principle of openness and inclusiveness that form part of the community of common destiny concept extend to international law the important regime-specific domestic doctrines of social stability and national conditions. In the legal interpretation of the community of common destiny concept, this study finds evidence of a dialectical process of norm-making that consists of both a confirmation of the normative status quo and the pursuit of far-reaching changes to the international legal order.
The Impact of Inflammatory Bowel Disease Clinic On-site Vaccination Services
Authors: Hussain Nadeen , Proctor Deborah , Al-Bawardy Badr
Published: September 2021

Background

Despite being susceptible to vaccine-preventable diseases, patients with inflammatory bowel disease (IBD) have low vaccination rates. The aims of this study are to examine the rates of vaccine discussion and completion among patients of an IBD clinic that offers on-site vaccinations.

Methods

This is a retrospective study from March 1, 2019 to February 1, 2020 comparing vaccination discussion and completion rates for patients with IBD who visited 2 clinics—1 that offers on-site vaccination (Clinic A) and 1 that does not (Clinic B). Both clinics are staffed by the same IBD physicians and utilize an identical IBD vaccine checklist.

Results

A total of 356 patients were included (64.6% Crohn’s, 31.7% ulcerative colitis, 1.1% indeterminate colitis, and 2.5% pouchitis). Overall vaccine discussion rate was 77.6% in Clinic A vs 70.9% in Clinic B (P = .15). Herpes zoster (HZ), pneumococcal, and tetanus–diphtheria–pertussis (Tdap) vaccine discussion rates were higher in Clinic A compared to Clinic B (17.8% vs 5%, P < .001, 56.3% vs 43.4%; P = .01, and 41.4% vs 21.4%, P < .001), respectively. Influenza vaccine completion and hepatitis A immunization rates were higher in Clinic A compared to Clinic B (67.8% vs 47.8%, P < .001 and 36.2% vs 22.5%, P = .005), respectively. A numerically higher percentage of patients completed the pneumococcal, HZ, and hepatitis B vaccination in Clinic A, but this difference did not reach statistical significance.

Conclusions

IBD clinic on-site vaccination services enhanced vaccine discussion and completion rates. IBD clinics should offer on-site vaccination services as part of the comprehensive care of the IBD patient.
EpiSurf: metadata-driven search server for analyzing amino acid changes within epitopes of SARS-CoV-2 and other viral species
Authors: Bernasconi Anna , Cilibrasi Luca , Al Khalaf Ruba , Alfonsi Tommaso , Ceri Stefano , Pinoli Pietro , Canakoglu Arif
Published: September 2021

EpiSurf is a Web application for selecting viral populations of interest and then analyzing how their amino acid changes are distributed along epitopes. Viral sequences are searched within ViruSurf, which stores curated metadata and amino acid changes imported from the most widely used deposition sources for viral databases (GenBank, COVID-19 Genomics UK (COG-UK) and Global initiative on sharing all influenza data (GISAID)). Epitopes are searched within the open source Immune Epitope Database or directly proposed by users by indicating their start and stop positions in the context of a given viral protein. Amino acid changes of selected populations are joined with epitopes of interest; a result table summarizes, for each epitope, statistics about the overlapping amino acid changes and about the sequences carrying such alterations. The results may also be inspected by the VirusViz Web application; epitope regions are highlighted within the given viral protein, and changes can be comparatively inspected. For sequences mutated within the epitope, we also offer a complete view of the distribution of amino acid changes, optionally grouped by the location, collection date or lineage. Thanks to these functionalities, EpiSurf supports the user-friendly testing of epitope conservancy within selected populations of interest, which can be of utmost relevance for designing vaccines, drugs or serological assays. EpiSurf is available at two endpoints.

Database URL: http://gmql.eu/episurf/ (for searching GenBank and COG-UK sequences) and http://gmql.eu/episurf_gisaid/ (for GISAID sequences).
Capital market development over the long run: the portfolios of UK life assurers over two centuries
Authors: Bogle David A , Coyle Christopher , Turner John D
Published: September 2021

What shapes and drives capital market development over the long run? In this paper, using the asset portfolios of UK life assurers, we examine the role of regulation, historical contingency, and political reactions to events on the long-run development of the UK capital market. Government response to events such as war, hegemony-secured peace, and the wider macroeconomic environment was the ultimate determinant of major changes in asset allocation since 1800. Furthermore, when we compare the UK with the United States, we find that regulation played a limited role in shaping the asset portfolios of the UK life assurance industry.
Do Birth Order Effects on Secondary School Track Placement Differ Between Natives and Migrants? A Within-Family Analysis in the German Educational System
Authors: Roth Tobias , Pforr Klaus , Mingham Sandra , Selbach Meike
Published: September 2021

While existing research has found negative birth order effects on competences and educational attainment in various Western countries with different educational systems, it is unclear whether these findings also hold in families with migration background. We argue that in migrant families where children were born in the host country, birth order effects on secondary school track placement should be weak or even reversed. In these families, parents’ host country-specific resources and knowledge of the education system are likely to be comparatively low. Consequently, older siblings who were born and educated in the host country can be an important source of information and support on educational matters for their younger siblings. Moreover, parental knowledge of the education system should increase with the educational career of each of their children. Family fixed-effects models based on representative data from the German Microcensus show negative birth order effects on secondary school track placement for native, first-generation migrant, and interethnic siblings, but not for second-generation migrant siblings. The empirical results indicate that negative birth order effects are not necessarily universal, but that children may even benefit from having older siblings under certain conditions.
The accountability of the private sector towards citizens in times of crisis: vaccines, medicines and equipment
Authors: Petelos Elena , Lingri Dimitra , Ghattas Jinane , Evers Silvia M A A , Paget Dineke Zeegers , de Waure Chiara
Published: September 2021

In this article, we examine what the role of the private sector in times of crises is and whether the private sector is, and can be held to be, accountable. COVID-19 has amplified the difficulties with public–private partnerships and this article addresses several aspects concerning business enterprises, in particular transnational corporations, human rights and health sector activities, highlighting the key aspects to understand and address accountability issues. The article also explores accountability for the private sector, the processes to ensure accountability, and the relevance of regulation and self-regulation.
The Association of Mobility Determinants and Life Space Among Older Adults
Authors: Dunlap Pamela M , Rosso Andrea L , Zhu Xiaonan , Klatt Brooke N , Brach Jennifer S
Published: September 2021

Background

It is important to understand the factors associated with life-space mobility so that mobility disability can be prevented/treated. The purpose of this study was to identify the association between mobility determinants and life space among older adults.

Methods

This study was a cross-sectional analysis of 249 community-dwelling older adults (mean age = 77.4 years, 65.5% female, 88% White), who were recruited for a randomized, controlled, clinical intervention trial. Associations between cognitive, physical, psychosocial, financial, and environmental mobility determinants and the life-space assessment (LSA) at baseline were determined using Spearman’s correlation coefficients and one-way analysis of variance. Multivariate analysis was performed using multivariable linear regression models.

Results

The mean LSA score for the sample was 75.3 (SD = 17.8). Personal factors (age, gender, education, comorbidities), cognitive (Trail Making Test A and B), physical (gait speed, lower extremity power, 6-Minute Walk Test, Figure of 8 Walk Test, tandem stance, energy cost of walking, and Late-Life Function and Disability Function Scale), psychosocial (Modified Gait Efficacy Scale), and financial (neighborhood socioeconomic status) domains of mobility were significantly associated with LSA score. In the final regression model, age (β = −0.43), lower extremity power (β = 0.03), gait efficacy (β = 0.19), and energy cost of walking (β = −57.41) were associated with life space (R2 = 0.238).

Conclusions

Younger age, greater lower extremity power, more confidence in walking, and lower energy cost of walking were associated with greater life space. Clinicians treating individuals with mobility disability should consider personal, physical, and psychosocial factors when assessing barriers to life-space mobility.
Aging in Zimbabwe: Reflections 41 Years After Independence
Authors: Hungwe Chipo
Published: September 2021

While Zimbabwe shares similar characteristics with other sub-Saharan countries that are generally regarded as “young populations,” the percentage of older adults has increased from 4.7% in 1982 to 6% in 2017. Research on aging is mainly on social protection, health, and quality of life. Emerging research points toward healthy aging, gender relations, and access to resources. The economic environment has been unstable for the greater part of the 41 years of independence. Poverty is increasing and the lives of older adults are vulnerable owing to inadequate and poorly targeted and funded social safety nets and social care services. The framework for addressing aging in the country is adequate but implementation is lacking. Zimbabwe lacks longitudinal data sets on aging; researchers mostly rely on data produced by Zimbabwe National Statistics Agency, United Nations agencies, and other international nongovernmental organizations.
Pre-conditioned BFGS-based uncertainty quantification in elastic full-waveform inversion
Authors: Liu Qiancheng , Beller Stephen , Lei Wenjie , Peter Daniel , Tromp Jeroen
Published: September 2021

Full-waveform inversion has become an essential technique for mapping geophysical subsurface structures. However, proper uncertainty quantification is often lacking in current applications. In theory, uncertainty quantification is related to the inverse Hessian (or the posterior covariance matrix). Even for common geophysical inverse problems its calculation is beyond the computational and storage capacities of the largest high-performance computing systems. In this study, we amend the Broyden–Fletcher–Goldfarb–Shanno (BFGS) algorithm to perform uncertainty quantification for large-scale applications. For seismic inverse problems, the limited-memory BFGS (L-BFGS) method prevails as the most efficient quasi-Newton method. We aim to augment it further to obtain an approximate inverse Hessian for uncertainty quantification in FWI. To facilitate retrieval of the inverse Hessian, we combine BFGS (essentially a full-history L-BFGS) with randomized singular value decomposition to determine a low-rank approximation of the inverse Hessian. Setting the rank number equal to the number of iterations makes this solution efficient and memory-affordable even for large-scale problems. Furthermore, based on the Gauss–Newton method, we formulate different initial, diagonal Hessian matrices as pre-conditioners for the inverse scheme and compare their performances in elastic FWI applications. We highlight our approach with the elastic Marmousi benchmark model, demonstrating the applicability of pre-conditioned BFGS for large-scale FWI and uncertainty quantification.
The relationship between cross correlations and Green’s functions in ambient noise interferometry with Bayesian constraints
Authors: Tsai Victor C , Sager Korbinian
Published: September 2021

Cross correlation of ambient seismic noise has begun to provide detailed images of the Earth that are not possible to attain using earthquake-based or active-source imaging techniques. However, the theoretical justification for the ambient noise correlation or seismic interferometry approach typically relies on an equipartition or diffuse field assumption that is not expected to be satisfied on Earth. Here we demonstrate that a Bayesian inference approach to calculating the expected cross correlation of seismic signals leads to an improved understanding of its relationship with the Green’s function. The Bayesian derivation is found to exactly replicate the equipartition result under a global energy constraint, and is able to accommodate any number of other constraints that typically cannot be utilized in other approaches. With these stronger constraints, the cross correlation is found to deviate more and more strongly from the ‘expected’ Green’s function, but nonetheless a specific prediction can be made regarding the expected cross correlation which can be used as a more reliable point of comparison with observations than the Green’s function. The approach therefore provides a path forward for how to use seismic cross correlation data under more and more realistic conditions and improvements in knowledge, and should eventually help improve the accuracy of resulting images of the Earth.
A genome-first approach to rare variants in hypertrophic cardiomyopathy genes MYBPC3 and MYH7 in a medical biobank
Authors: Park Joseph , Packard Elizabeth A , Levin Michael G , Judy Renae L ,   Regeneron Genetics Center, Damrauer Scott M , Day Sharlene M , Ritchie Marylyn D , Rader Daniel J
Published: September 2021

‘Genome-first’ approaches to analyzing rare variants can reveal new insights into human biology and disease. Because pathogenic variants are often rare, new discovery requires aggregating rare coding variants into ‘gene burdens’ for sufficient power. However, a major challenge is deciding which variants to include in gene burden tests. Pathogenic variants in MYBPC3 and MYH7 are well-known causes of hypertrophic cardiomyopathy (HCM), and focusing on these ‘positive control’ genes in a genome-first approach could help inform variant selection methods and gene burdening strategies for other genes and diseases. Integrating exome sequences with electronic health records among 41 759 participants in the Penn Medicine BioBank, we evaluated the performance of aggregating predicted loss-of-function (pLOF) and/or predicted deleterious missense (pDM) variants in MYBPC3 and MYH7 for gene burden phenome-wide association studies (PheWAS). The approach to grouping rare variants for these two genes produced very different results: pLOFs but not pDM variants in MYBPC3 were strongly associated with HCM, whereas the opposite was true for MYH7. Detailed review of clinical charts revealed that only 38.5% of patients with HCM diagnoses carrying an HCM-associated variant in MYBPC3 or MYH7 had a clinical genetic test result. Additionally, 26.7% of MYBPC3 pLOF carriers without HCM diagnoses had clear evidence of left atrial enlargement and/or septal/LV hypertrophy on echocardiography. Our study shows the importance of evaluating both pLOF and pDM variants for gene burden testing in future studies to uncover novel gene-disease relationships and identify new pathogenic loss-of-function variants across the human genome through genome-first analyses of healthcare-based populations.
Meta-GWAS of PCSK9 levels detects two novel loci atAPOBandTM6SF2
Authors: Pott Janne , Gådin Jesper R , Theusch Elizabeth , Kleber Marcus E , Delgado Graciela E , Kirsten Holger , Hauck Stefanie M , Burkhardt Ralph , Scharnagl Hubert , Krauss Ronald M , Loeffler Markus , März Winfried , Thiery Joachim , Silveira Angela , van't Hooft Ferdinand M , Scholz Markus
Published: September 2021

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player in lipid metabolism, as it degrades low-density lipoprotein (LDL) receptors from hepatic cell membranes. So far, only variants of the PCSK9 gene locus were found to be associated with PCSK9 levels. Here we aimed to identify novel genetic loci that regulate PCSK9 levels and how they relate to other lipid traits. Additionally, we investigated to what extend the causal effect of PCSK9 on coronary artery disease (CAD) is mediated by low-density lipoprotein–cholesterol (LDL–C).

Methods and Results

We performed a genome-wide association study meta-analysis of PCSK9 levels in up to 12 721 samples of European ancestry. The estimated heritability was 10.3%, which increased to 12.6% using only samples from patients without statin treatment. We successfully replicated the known PCSK9 hit consisting of three independent signals. Interestingly, in a study of 300 African Americans, we confirmed the locus with a different PCSK9 variant. Beyond PCSK9, our meta-analysis detected three novel loci with genome-wide significance. Co-localization analysis with cis-eQTLs and lipid traits revealed biologically plausible candidate genes at two of them: APOB and TM6SF2. In a bivariate Mendelian Randomization analysis, we detected a strong effect of PCSK9 on LDL-C, but not vice versa. LDL-C mediated 63% of the total causal effect of PCSK9 on CAD.

Conclusion

Our study identified novel genetic loci with plausible candidate genes affecting PCSK9 levels. Ethnic heterogeneity was observed at the PCSK9 locus itself. Although the causal effect of PCSK9 on CAD is mainly mediated by LDL-C, an independent direct effect also occurs.
Quantification of Viral RNA in Multiple Pieces of Explant Liver Tissue Shows Distinct Focal Differences in Hepatitis B Infection
Authors: Rydell Gustaf E , Prakash Kasthuri , Larsson Simon B , Skoglund Catarina , Ringlander Johan , Andersson Maria E , Castedal Maria , Norder Heléne , Lindh Magnus
Published: September 2021

Hepatitis B virus (HBV) DNA and RNA were quantified by digital PCR assays in 20–30 tissue pieces from each of 4 liver explants with cirrhosis caused by HBV. The within-patient variability of HBV RNA levels between pieces was up to a 1000-fold. Core RNA and S RNA levels were similar and correlated strongly when replication was high, supporting that transcription was from covalently closed circular DNA (cccDNA). By contrast, enhanced expression of S RNA relative to cccDNA and core RNA in patients with medium-high or low replication supports that HBV surface antigen (HBsAg) can be expressed mainly from integrated HBV DNA in such patients.
Waning Immunity After Receipt of Pertussis, Diphtheria, Tetanus, and Polio-Related Vaccines: A Systematic Review and Meta-analysis
Authors: Gao Huizhi , Lau Eric H Y , Cowling Benjamin J
Published: September 2021

Pertussis, diphtheria, and tetanus (DTP)–containing vaccines combined with polio vaccines are recommended by the World Health Organization as part of routine immunization programs. The decline of immunity after vaccination has been considered as a possible reason for the reemergence of vaccine-preventable diseases worldwide. In this study, we evaluated the potential duration of protective immunity of pertussis, diphtheria, tetanus, and polio through a systematic review and meta-analysis. We examined data on immunological and clinical outcomes. We observed evidence of waning postvaccination immunity for pertussis and diphtheria, whereas tetanus and polio vaccines provided sustained protection. Further research on the risk factors of waning immunity after vaccination and the optimal timing of booster doses for pertussis and diphtheria is needed.
Does procalcitonin have clinical utility in the management of paediatric community-acquired pneumonia? A PRO/CON debate
Authors: Chiotos Kathleen , Gerber Jeffrey S
Published: September 2021

Although the overwhelming majority of community-acquired pneumonia (CAP) in children is caused by viral infections, treatment of CAP is among the most common indications for antibiotic use in children. This is largely driven by the imprecision of clinical diagnostic tools to differentiate viral from bacterial pneumonia and highlights the need for improved approaches to optimizing management of CAP in children. In this issue of JAC-Antimicrobial Resistance, we present a PRO/CON debate that discusses the clinical utility of procalcitonin in children with CAP.
Microaggression clues from social media: revealing and counteracting the suppression of women’s health care
Authors: Ryu Hyeyoung , Pratt Wanda
Published: September 2021

Objective

The purpose of this study was to demonstrate how analyzing social media posts can uncover microaggressions and generate new cultural insights. We explore why Korean women hesitate to seek recommended gynecological care and how microaggressions visible in social media reveal insights for counteracting such harmful messaging.

Materials and Methods

We scraped the posts and responses on social media related to unmarried women’s uncomfortableness or unpleasantness in receiving gynecological care. We conducted content analyses of the posts and responses with the microaggression framework to identify both the types of microaggressions occurring within and outside the clinic as well as the responsible perpetrators. With an open-coding and subsequent deductive coding approach, we further investigated the socio-cultural context for receiving gynecological care as an unmarried woman in South Korea.

Results

Our analysis uncovered that mothers, male partners, and superficially supportive social media responders contribute to pre- and post-visit microaggressions toward unmarried women seeking gynecological care whereas healthcare providers contribute to only mid-visit microaggressions. We also exposed how social media was not only revealing but also reinforcing the suppression of women’s health care.

Discussion

Mid-visit microaggressions are currently addressed by cultural competence education, but pre- and post-visit microaggressions are overlooked. We uncover the gaps in current practices of informatics and public health methods and suggest ways to counteract online and offline microaggressions.

Conclusions

Social media provides valuable information about the cultural context of health care and should be used as a source of insights for targeted interventions to improve health care, in this case for unmarried Korean women.
Engineering sequence and selectivity of late-stage C-H oxidation in the MycG iterative cytochrome P450
Authors: Iizaka Yohei , Arai Ryusei , Takahashi Akari , Ito Mikino , Sakai Miho , Fukumoto Atsushi , Sherman David H , Anzai Yojiro
Published: September 2021

MycG is a multifunctional P450 monooxygenase that catalyzes sequential hydroxylation and epoxidation or a single epoxidation in mycinamicin biosynthesis. In the mycinamicin-producing strain Micromonospora griseorubida A11725, very low-level accumulation of mycinamicin V generated by the initial C-14 allylic hydroxylation of MycG is observed due to its subsequent epoxidation to generate mycinamicin II, the terminal metabolite in this pathway. Herein, we investigated whether MycG can be engineered for production of the mycinamicin II intermediate as the predominant metabolite. Thus, mycG was subject to random mutagenesis and screening was conducted in Escherichia coli whole-cell assays. This enabled efficient identification of amino acid residues involved in reaction profile alterations, which included MycG R111Q/V358L, W44R, and V135G/E355K with enhanced monohydroxylation to accumulate mycinamicin V. The MycG V135G/E355K mutant generated 40-fold higher levels of mycinamicin V compared to wild-type M. griseorubida A11725. In addition, the E355K mutation showed improved ability to catalyze sequential hydroxylation and epoxidation with minimal mono-epoxidation product mycinamicin I compared to the wild-type enzyme. These approaches demonstrate the ability to selectively coordinate the catalytic activity of multifunctional P450s and efficiently produce the desired compounds.
The Argument Flagging and Indexing Construction in the Jewish Arabic Dialect of Baghdad
Authors: Bar-Moshe Assaf
Published: September 2021

The Jewish dialect of Baghdad employs a particular construction to mark constituents of the clause as arguments. This construction typically marks the argument twice—once by the morpheme l- and once by a pronominal suffix that agrees with the argument. Syntactically, the former has the properties of a flag and the latter of a person index. The construction, which we call THE ARGUMENT FLAGGING AND indexing construction, primarily assigns the argument with the syntactic function of a direct or an indirect object, but it is also capable of marking oblique and genitive arguments. This paper focuses on the morpho-syntactic properties of the construction. It presents the mechanism by which the argument is marked and describes how the syntactic function is assigned.
Origin of cyanobacterial thylakoids via a non-vesicular glycolipid phase transition and their impact on the Great Oxygenation Event
Authors: Guéguen Nolwenn , Maréchal Eric
Published: September 2021

The appearance of oxygenic photosynthesis in cyanobacteria is a major event in evolution. It had an irreversible impact on the Earth, promoting the Great Oxygenation Event (GOE) ~2.4 billion years ago. Ancient cyanobacteria predating the GOE were Gloeobacter-type cells lacking thylakoids, which hosted photosystems in their cytoplasmic membrane. The driver of the GOE was proposed to be the transition from unicellular to filamentous cyanobacteria. However, the appearance of thylakoids expanded the photosynthetic surface to such an extent that it introduced a multiplier effect, which would be more coherent with an impact on the atmosphere. Primitive thylakoids self-organize as concentric parietal uninterrupted multilayers. There is no robust evidence for an origin of thylakoids via a vesicular-based scenario. This review reports studies supporting that hexagonal II-forming glucolipids and galactolipids at the periphery of the cytosolic membrane could be turned, within nanoseconds and without any external source of energy, into membrane multilayers. Comparison of lipid biosynthetic pathways shows that ancient cyanobacteria contained only one anionic lamellar-forming lipid, phosphatidylglycerol. The acquisition of sulfoquinovosyldiacylglycerol biosynthesis correlates with thylakoid emergence, possibly enabling sufficient provision of anionic lipids to trigger a hexagonal II-to-lamellar phase transition. With this non-vesicular lipid-phase transition, a framework is also available to re-examine the role of companion proteins in thylakoid biogenesis.