bluuebunny/crossref_metadata_2025 huggingface dataset:
Nightmare disorder and low back pain in veterans: cross-sectional association and effect over time
Authors: Taylor Kenneth A , Schwartz Skai W , Alman Amy C , Goode Adam P , Dagne Getachew A , Sebastião Yuri V , Foulis Philip R
Published: September 2022

Low back pain (LBP) disproportionately impacts US military veterans compared with nonveterans. Although the effect of psychological conditions on LBP is regularly studied, there is little published to date investigating nightmare disorder (NMD) and LBP. The purpose of this study was to (1) investigate whether an association exists between NMD and LBP and (2) estimate the effect of NMD diagnosis on time to LBP. We used a retrospective cohort design with oversampling of those with NMD from the Veterans Health Administration (n = 15 983). We used logistic regression to assess for a cross-sectional association between NMD and LBP and survival analysis to estimate the effect of NMD on time to LBP, up to 60-month follow-up, conditioning on age, sex, race, index year, Charlson Comorbidity Index, depression, anxiety, insomnia, combat exposure, and prisoner of war history to address confounding. Odds ratios (with 95% confidence intervals [CIs]) indicated a cross-sectional association of 1.35 (1.13 to 1.60) and 1.21 (1.02 to 1.42) for NMD and LBP within 6 months and 12 months pre- or post-NMD diagnosis, respectively. Hazard ratios (HRs) indicated the effect of NMD on time to LBP that was time-dependent—HR (with 95% CIs) 1.27 (1.02 to 1.59), 1.23 (1.03 to 1.48), 1.19 (1.01 to 1.40), and 1.10 (0.94 to 1.29) in the first 3, 6, 9, and 12 months post-diagnosis, respectively—approximating the null (1.00) at >12 months. The estimated effect of NMD on LBP suggests that improved screening for NMD among veterans may help clinicians and researchers predict (or intervene to reduce) risk of future back pain.
Blurring the Borders of Reentry: Socioeconomic Reintegration among Noncitizens Following Release from Immigration Detention
Authors: Patler Caitlin
Published: September 2022

An established literature demonstrates that formerly imprisoned people experience barriers to finding work. However, no research has analyzed how noncitizens experience socioeconomic reintegration following imprisonment. Additionally, while we know many immigrants find work in co-ethnic labor markets, we know little about how these networks respond to individuals with a criminal record. I analyze 321 longitudinal, semi-structured interviews collected between 2013–2016 from 121 noncitizens who were detained by U.S. immigration authorities for six months or longer and then released back into their communities on bond. Results reveal a complex set of socioeconomic reintegration experiences that are shaped by ethnic, legal, generational, and gender stratification in immigrant integration outcomes more broadly. These findings have important implications as immigration laws have become increasingly punitive and intertwined with criminal laws.
Belonging and Boundaries at an Elite University
Authors: Jack Anthony Abraham , Black Zennon
Published: September 2022

Scholars posit that lower-income undergraduates experience “cultural mismatch,” which undermines their sense of belonging, promotes withdrawal from campus, and limits mobility upon graduation. Drawing on in-depth interviews with 103 undergraduates at an elite university, we examine how students’ diverse trajectories to college affect how they identify as members of the community and modulate the relationship between social class and sense of belonging. While upper-income undergraduates find commonalities between themselves and college peers and integrate into the community, lower-income students offer divergent accounts. The doubly disadvantaged—lower-income undergraduates who attended local, typically distressed public high schools—felt a heightened sense of difference, drew moral boundaries, and withdrew from campus life. Alternatively, the privileged poor—lower-income undergraduates who attended boarding, day, and preparatory high schools—adopted a cosmopolitan approach focused on continued expansion of horizons and integrated into campus. Through detailing this overlooked diversity among lower-income undergraduates, our findings expand theoretical frameworks for examining sense of belonging to include boundary work that shapes students’ agendas, thereby deepening our understanding of the reproduction of inequality in college.
The Uses and Abuses of ‘Community Art’ on an Inner-City Estate
Authors: Romyn Michael
Published: September 2022

This article traces the history of ‘community art’ on the Aylesbury Estate, a mass municipal housing development in inner-city London. Established by local artists soon after the Aylesbury’s opening in 1974, the Walworth and Aylesbury Community Arts Trust (WACAT) ran a multifaceted arts project on the estate until the early 1990s. Through an examination of WACAT’s changing aims, outputs and engagements with tenants, this article presents new ways of thinking about life on an inner urban estate. For many participants, the project was not only a focus of sociability and creative expression, but a way of making sense of rapidly changing material and social circumstances. The article further shows how art-making was used to both facilitate and oppose the estate’s ongoing demolition, and of contesting stereotypical representations of the estate that went hand in hand with the process of state-led ‘regeneration’.
Smoke propagation characteristics and influencing factors of high-temperature spiral tunnel fire
Authors: Song Yang , Wang Huibin , Guo Chao , Pan Sitong , Wu Yan
Published: September 2022

A tunnel fire may cause great damage to people, vehicles, facilities and tunnel structures if it is not effectively controlled. Therefore, it is very important to clarify the smoke propagation characteristics and influencing factors that can help to accelerate the removal of fire smoke and reduce casualties and property losses. In order to study the influence of slope, curvature radius and ambient temperature on smoke propagation during the tunnel operation period, based on the high-temperature spiral tunnel in Midi village, Yunnan Province, the internal and external environmental parameters of the tunnel were measured on site and the numerical simulation model was established by using the simulation software FDS, and the control variable method was used to study the fire smoke propagation characteristics of the tunnel with different characteristics. The results show that: the influence of slope on smoke migration velocity is non-linear, the greater the slope is, the greater the change of smoke spreading speed is; the smaller the curvature radius is, the greater the obstruction to smoke migration is, and the slower the smoke migration speed is; high temperature speeds up the smoke exhaust rate in the tunnel but has less promotion of the fire smoke migration.
Workplace Disclosure Decisions of Older Workers Wanting to Remain Employed: A Qualitative Study of Factors Considered When Contemplating Revealing or Concealing Support Needs
Authors: Gignac Monique A M , Bowring Julie , Shahidi Faraz V , Kristman Vicki , Cameron Jill I , Jetha Arif
Published: September 2022

Many older workers want to work longer. However, we understand little about the different workplace support needs they may have and whether workers choose to share their needs with others. The objective of this research was to qualitatively examine workplace disclosure-support decisions among workers aged 50 years and older. Sixty-eight participants from diverse employment sectors and with a range of personal experiences and circumstances (e.g., health conditions, caregiving responsibilities, job experiences) participated in 1 of 10 focus groups within the greater Toronto area. Recruitment drew on an existing cohort of Canadians from a survey research firm. Participants were asked about their work experiences, age-related changes, and disclosure decisions and experiences. Focus group discussions were audio-taped and transcribed. Qualitative content analysis was used analyze the data and identify emerging themes. There was variability in disclosure decisions with many participants being reluctant to share their needs at work. Four inter-related themes guided participants’ communication decisions: the need to communicate information; the desire to maintain one’s reputation; trust in others and perceived support; and perceived job insecurity. In discussing job insecurity, participants noted challenges in finding a new job, perceptions held by others of the cost-benefits of employing older workers, and labor market insecurity. The findings highlight challenges experienced by older adults in remaining employed and barriers to communicating their needs. Results underscore the importance of greater attention to ageism within organizations, the need for age-inclusive policies, and workplace flexibility to promote job sustainability across the life course.
Three in one: molecular phylogeny of the genusHelodrilus(Crassiclitellata: Lumbricidae) with a description of two new genera and two new species
Authors: Szederjesi Tímea , Marchán Daniel F , Csuzdi Csaba , Sarbu Serban M , Pavlíček Tomáš , Krízsik Virág , Martin Patrick , Domínguez Jorge
Published: September 2022

The earthworm genus Helodrilus comprises about 20 species with distributions ranging from the Iberian Peninsula to the Caucasus, through Central Europe, the Balkans, Anatolia and the Levant. The species prefer moist habitats and are often found in the mud of river banks, in swamps or in caves. Although a high degree of morphological variability is observed in the taxonomic characters, the genus shares a common feature: the absence of nephridial bladders. In this study, we clarify the phylogeny and taxonomy of the genus Helodrilus using an integrated approach including a multilocus molecular phylogenetic analysis and thorough morphological examination of several species across the putative Helodrilus area of distribution. The findings of this study have led to the genus Helodrilus being split and to the description of two new genera and two new species: Coventina Szederjesi, Sarbu & Csuzdi gen. nov. and Imetescolex movilensis Szederjesi, Sarbu & Csuzdi gen. & sp. nov. The highly homoplasic nature of the absence of nephridial bladders was also revealed.
A curriculum to improve knowledge and skills of nurse practitioners and physician assistants in the pediatric emergency department
Authors: Yusuf Shabana , Hagan Joseph L. , Stone Suzette
Published: September 2022

Nurse practitioners (NPs) and physician assistants (PAs) have an important role in delivery of care in a tertiary children's hospital emergency department (ED). Most NPs and PAs have not had any formal training to work in a pediatric ED; although our NPs and PAs had no formal ED training, some were acute care certified. We describe a curriculum designed to improve knowledge and skills of NPs and PAs in the pediatric ED. The curriculum consists of three modules, namely, online lecture series, procedural workshops, and case scenarios in a simulated setting. Module 1 consisted of online lecture on 10 common ED diagnoses. The second module consisted of procedural workshops on lumbar puncture, incision and drainage of abscesses, gastrostomy insertion, and laceration repair. The third module included simulation scenarios on ED-specific cases of seizure in an infant, bronchiolitis and ruptured appendicitis with shock. Each module was evaluated by a survey. Participants rated each item on the survey using a Likert scale response (1 = disagree completely to 5 = agree completely). Both NPs and PAs demonstrated increase in knowledge scores in posttest 1 vs pretest (p < .001) and did not show a significant decline in posttest 2 (p = .073). The mean ratings of components of the online lecture series, workshops, and simulation scenarios were 4.5–4.7, 4.4–4.8, and 4.5–4.7, respectively, with positive comments. This novel curriculum meets the educational needs of NPs and PAs at our institution and can be used as a model to train them at other tertiary care pediatric EDs.
Pediatric Emergency Medicine Faculty Response to Point-of-Care Ultrasound Credentialing Curriculum
Authors: Nti Benjamin K. , Kennedy Sarah , Sarmiento Elisa , Weinstein Elizabeth , Russell Frances
Published: September 2022

Objectives

As point-of-care ultrasound (POCUS) continues to evolve in pediatric emergency medicine (PEM), new protocols and curricula are being developed to help establish the standards of practice and delineate training requirements. New suggested guidelines continue to improve, but a national standard curriculum for training and credentialing PEM providers is still lacking. To understand the barriers and perception of curriculum implementation for PEM providers, we created an ultrasound program at our institution and observed attitudes and response to training.

Methods

Fourteen PEM-fellowship–trained faculty with limited to no previous experience with POCUS underwent training within a 12-month time frame using a modified practice-based training that included didactics, knowledge assessment, and hands-on practice. As part of the curriculum, the faculty completed a 3-phase survey before, after, and 6 months after completion of the curriculum.

Results

There was a 100%, 78.6%, and 71.4% response rate for the presurvey, postsurvey, and 6 months postsurvey, respectively. Lack of confidence with using POCUS went from 100% on the presurvey to 57% on the postsurvey and down to 30% on the 6th month postsurvey. All other barriers also decreased from precurriculum to postcurriculum, except for length of time to perform POCUS. Participants rated the curriculum highly, with a mean Likert score and standard error of the mean at 3.9 ± 0.73, respectively. The average rating for whether POCUS changed clinical practice was low (2.6 ± 1.34).

Conclusion

These results show that a simplified structured curriculum can improve perception of POCUS and decrease barriers to usage while helping to understand obstacles for implementation of POCUS among PEM-fellowship–trained faculty.
Boldness predicts divorce rates in wandering albatrosses (
Diomedea exulans
)
Authors: Sun Ruijiao , Van de Walle Joanie , Patrick Samantha C. , Barbraud Christophe , Weimerskirch Henri , Delord Karine , Jenouvrier Stéphanie
Published: September 2022

Personality predicts divorce rates in humans, yet how personality traits affect divorce in wild animals remains largely unknown. In a male-skewed population of wandering albatross (
Diomedea exulans
), we showed that personality predicts divorce; shyer males exhibited higher divorce rates than bolder males but no such relationship was found in females. We propose that divorce may be caused by the intrusion of male competitors and shyer males divorce more often because of their avoidance of territorial aggression, while females have easier access to mates regardless of their personality. Thus, personality may have important implications for the dynamics of social relationships.
Anti-oxidative and muscle cell protective effects of ginger extract
according to the extraction conditions
Authors: Choi Sang Yoon , Kim Kyung-Tack
Published: September 2022

Ginger (Zingiber officinale Rosc.) root is known to have
anti-oxidative effects. However, studies on the extraction conditions to obtain
ginger extract (GE) with high antioxidant power have not yielded satisfactory
results. Therefore, the effects of extraction temperature and time on the
anti-oxidative effects of GE were investigated. The content of 6-gingerol and
6-shogaol in the GE was also analyzed. The results revealed that extraction
carried out at 50°C for 5 h was optimal for maintaining the
anti-oxidative activity of the GE. Further, GE obtained under these optimal
conditions exhibited the highest DPPH and ABTS+ radical
scavenging activities and cytoprotective effect against oxidative damage in L6
skeletal muscle cells and was rich in active compounds. Thus, the GE obtained
under the optimal conditions could be useful for the development of functional
food materials.
Anti-adipogenic effects of Maclura tricuspidata
twig extract in 3T3-L1 pre-adipocytes
Authors: Lee Hyo-Jeong , Park Se-Eun , Kim Seung
Published: September 2022

This study was conducted to evaluate the anti-adipogenic effects of
Maclura tricuspidate twig extract (MTE) in 3T3-L1
pre-adipocytes. 3T3-L1 pre-adipocytes were differentiated with adipogenic
regents (dexamethsone, 3-isobutyl-methylxanthine, insulin) by incubation for 8
days in the absence or presence of MTE. The accumulation of lipid droplets and
triglycerides in cells was dose-dependently suppressed by MTE. MTE caused an
increase in the release of adiponectin and inhibited the release of leptin.
Consistent with these results, MTE attenuated the protein expression of
peroxisome proliferator-activated receptor gamma
(PPARγ), CCATT/enhancer binding protein alpha
(C/EBPα), fatty acid synthase (FAS) and adipocyte
Protein 2 (aP2), all of which are associated with adipogenesis in cells.
Treatment with MTE also dose-dependently increased the release of free glycerol.
Additionally, MTE increased the protein expression of hormone-sensitive lipase
(HSL) and adipose triglyceride lipase (ATGL), which are associated with
lipolysis. These results showed that MTE inhibits adipogenesis by regulating the
expression of proteins involved in adipogenesis. Therefore, the results suggest
that MTE has the potential to be used as a functional ingredient in the food
industry to prevent obesity.
Effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines against SARS-CoV-2 Omicron BA. 2 variant infection, severe illness, and death
Authors: Huang Zhuoying , Xu Shuangfei , Liu Jiechen , Wu Linlin , Qiu Jing , Wang Nan , Ren Jia , Li Zhi , Guo Xiang , Tao Fangfang , Chen Jian , Lu Donglei , Sun Xiaodong , Wang Weibing
Published: September 2022

Background

Limited data are available on effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines in real-world use - especially against Omicron variants in SARS-CoV-2 infection-naïve population. During an outbreak in Shanghai’s SARS-CoV-2 infection-naïve population, we evaluated vaccine effectiveness (VE) against Omicron infection, severe or critical COVID-19, and COVID-19-related death.

Methods

A matched case-control study was conducted among people aged ≥3 years between 2 December 2021 through 13 May 2022. Cases were SARS-CoV-2 infected individuals, individuals with severe/critical COVID-19, or COVID-19-related deaths. Controls were selected from consecutively test negative individuals at the same time as cases were diagnosed and were exact-matched on year-of-age, gender, birthplace, illness onset date, and residency district in ratios of 1:1 with infected individuals and 4:1 with severe/critical COVID-19 and COVID-19-related deaths.

Results

Our study included 612597 documented SARS-CoV-2 infections, among which 1485 progressed to severe or critical illness and 568 died. Inactivated vaccine was 16.3% (95% CI: 15.4%-17.2%) effective against infection, 88.6% (95% CI: 85.8%-90.9%) effective against severe/critical COVIID-19 and 91.7% (95% CI: 86.9%-94.7%) against COVID-19 death. Ad5-vectored vaccine was 13.2% (95% CI: 10.9%-15.5%) effective against infection and 77.9% (95% CI: 15.6%-94.2%) effective against severe/critical COVIID-19. Booster vaccination with inactivated vaccines enhanced protection against severe COVID-19 (92.7%, 95% CI: 90.1%-94.6%) and COVID-19 death (95.9%, 95% CI: 91.4%-98.1%). Inactivated VE against infection began to wane 12 weeks after the last dose but two- and three-dose sustained high protection levels (>80%) against severe/critical illness and death.

Conclusions

Our real-world study found high and durable two- and three-dose inactivated VE against Omicron-associated severe/critical illness and death across all age groups, but lower effectiveness against Omicron infection. High direct protection from severe/fatal Omicron COVID-19 provided by inactivated vaccines, and a consequent potential reduction in health-care utilization, reinforces the critical importance of full-series vaccination and timely booster dose administration for all eligible individuals.
Probing Local Force Propagation in Tensed Fibrous Gels
Authors: Goren Shahar , Levin Maayan , Brand Guy , Lesman Ayelet , Sorkin Raya
Published: September 2022

Fibrous hydrogels are a key component of soft animal tissues. They support cellular functions and facilitate efficient mechanical communication between cells. Due to their nonlinear mechanical properties, fibrous materials display non-trivial force propagation at the microscale, that is enhanced compared to that of linear-elastic materials. In the body, tissues are constantly subjected to external loads that tense or compress them, modifying their micro-mechanical properties into an anisotropic state. However, it is unknown how force propagation is modified by this isotropic-to-anisotropic transition. Here, we directly measure force propagation in tensed fibrin hydrogels. Local perturbations are induced by oscillating microspheres using optical tweezers. We use both 1-point and 2-point microrheology to simultaneously measure both the shear modulus and force propagation. We suggest a mathematical framework to quantify anisotropic force propagation trends. We show that force propagation becomes anisotropic in tensed gels, with, surprisingly, stronger response to perturbations perpendicular to the axis of tension. Our results suggest that under external loads, there are favoured directions of mechanical communication between cells in a tissue. Importantly, we also find that external tension increases the range of force transmission by altering the power-law exponent governing the decay of oscillations with distance from the perturbation. We end with a discussion of possible implications and future directions for research.
SCING: Single Cell INtegrative Gene regulatory network inference elucidates robust, interpretable gene regulatory networks
Authors: Littman Russell , Wang Ning , Peng Chao , Yang Xia
Published: September 2022

Gene regulatory network (GRN) inference is an integral part of understanding physiology and disease. Single cell/nuclei RNAseq (scRNAseq/snRNAseq) data has been used to elucidate cell-type GRNs; however, the accuracy and speed of current scRNAseq-based GRN approaches are suboptimal. Here, we present Single Cell INtegrative Gene regulatory network inference (SCING), a gradient boosting and mutual information based approach for identifying robust GRNs from scRNAseq, snRNAseq, and spatial transcriptomics data. Performance evaluation using held-out data, Perturb-seq datasets, and the mouse cell atlas combined with the DisGeNET database demonstrates the improved accuracy and biological interpretability of SCING compared to existing methods. We applied SCING to the entire mouse single cell atlas, human Alzheimer’s disease (AD), and mouse AD spatial transcriptomics. SCING GRNs reveal unique disease subnetwork modeling capabilities, have intrinsic capacity to correct for batch effects, retrieve disease relevant genes and pathways, and are informative on spatial specificity of disease pathogenesis.
A cross-sectional study of low birth satisfaction among Iranian postpartum women during COVID-19 epidemics’ fifth wave
Authors: Mortazavi Forough , Mehrabadi Maryam
Published: September 2022

Background

Birth dissatisfaction may increase the risk for postpartum depression and requests for an elective cesarean for the next birth. The outbreak of COVID-19 pandemic has had a considerable impact on the healthcare systems and their users in many aspects. We investigated predictors of birth satisfaction in a sample of Iranian postpartum women during the COVID-19 epidemics’ fifth wave.

Methods

This cross-sectional study was conducted on 601 postpartum women admitted to postpartum wards of Mobini maternity hospital using a convenience sampling method between 2 Aug and 18 September 2021. We collected data on socio-demographic, obstetric, labor and birth, and psychological variables. We used the general linear model and multiple linear regression analyses to determine predictors of birth satisfaction.

Results

The mean birth satisfaction score was 28.6±7.3. The percentages of mothers who gave birth by elective and emergency cesarean were 19.5% and 10.8%, respectively. Overall predictors of birth satisfaction were emergency cesarean [-7.463(-9.310, -5.616), instrumental birth [-3.571(-6.907, -0.235)], episiotomy [-2.227 (-3.591, -0.862)], Entonox analgesia [-1.548(-2.726, -0.371)], Well-being score < 50 [-1.812(-3.146, -0.478)], fear of COVID-19 [-1.216(-2.288,, -0.144)], low satisfaction with pregnancy -2.539(-3.952, -1.127) and low satisfaction with spouse’s support [-2.419(-4.598, -0.240)].

Conclusions

During the pandemic, fear of COVID-19, low level of well-being, low satisfaction with pregnancy and low satisfaction with spouse’s support as well as women’s experience of emergency cesarean, instrumental birth, episiotomy, and Entonox analgesia, are exerting negative influences on birth satisfaction. To improve birth satisfaction and thus maternal mental health interventions to lower fear of contracting COVID-19 and reduce rates of episiotomy, emergency cesarean, and instrumental birth are recommended.
Brain Volumes, Thicknesses, and Surface Areas as Mediators of Genetic Factors and Childhood Adversity on Intelligence
Authors: Williams Camille M. , Peyre Hugo , Ramus Franck
Published: September 2022

Although genetic and environmental factors influence general intelligence (g-factor), few studies examined the neuroanatomical measures mediating environmental and genetic effects on intelligence. Therefore, we investigate the brain volumes, cortical mean thicknesses, and cortical surface areas mediating the effects of the g-factor polygenic score (gPGS) and childhood adversity on the g-factor in the UK Biobank.

We first identified the global and regional brain measures for the mediation models that contribute to the g-factor independently of global brain size and regional associations. Most regions contributed to the g-factor through global brain size. Parieto-Frontal Integration Theory (P-FIT) regions were not more associated with the g-factor than non-PFIT regions. Adjusting for global brain size and regional associations, only a few regions, such as the right olfactory sulcus and the right mediodorsal thalamic nuclei volumes, the right orbital inferior frontal gyrus surface area, and the anterior cingulate gyrus mean thicknesses, predicted intelligence and were included in the mediation analyses.

We conducted mediation analyses on global measures, regional volumes, mean thicknesses, and surface areas, separately. Total brain volume mediated 7.04% of the gPGS’ effect on the g-factor and 2.50% of childhood adversity’s effect on the g-factor. In comparison, the fraction of the gPGS and childhood adversity’s effects mediated by individual regional volumes, surfaces, and mean thicknesses was 10-15 times smaller. Our findings suggest that genetic and environmental effects on general intelligence must be mediated to a larger extent by other structural brain properties.

Significance Statement

Genes and environmental factors, such as childhood adversity, influence our cognitive abilities via the brain. Our results show that genetic and environmental effects on intelligence are mediated to some extent by neuroanatomical properties. However, we find that global brain measures (e.g., total brain volume) are the largest mediators and that regional volumes, surfaces, and mean thicknesses only mediated a fraction of a person’s genetic predisposition to intelligence and childhood adversity’s effect on intelligence. This suggests that genetic and environmental effects on general intelligence are to a large extent mediated by other kinds of brain structural properties.
Environmental selection influences the microbiome of subsurface petroleum reservoirs
Authors: Gittins Daniel A. , Bhatnagar Srijak , Hubert Casey R. J.
Published: September 2022

Petroleum reservoirs within the deep biosphere are extreme environments inhabited by diverse microbial communities creating biogeochemical hotspots in the subsurface. Despite their ecological and industrial importance, systematic studies of core microbial taxa and associated genomic attributes of the oil reservoir microbiome are limited. This study compiles and compares 343 16S rRNA gene amplicon libraries and 25 shotgun metagenomic libraries from oil reservoirs in different parts of the world. Taxonomic composition varies among reservoirs with different physicochemical characteristics, and with geographic distance. Despite oil reservoirs lacking a taxonomic core microbiome in these datasets, gene-centric metagenomic analysis reveals a functional core featuring carbon acquisition and energy conservation strategies consistent with other deep biosphere environments. Genes for anaerobic hydrocarbon degradation are observed in a subset of the samples and are therefore not considered to represent core biogeochemical functions in oil reservoirs. Metabolic redundancy within the petroleum reservoir microbiome reveals these to be deep biosphere systems poised to respond to changes in redox biogeochemistry. This highlights the potential to use microbial genomics for predicting microbial responses to (bio)engineering perturbations to these subsurface habitats.
A systematic review and comparison of automated tools for quantification of fibrous networks
Authors: de Vries Judith J. , Laan Daphne M. , Frey Felix , Koenderink Gijsje H. , de Maat Moniek P.M.
Published: September 2022

Fibrous networks are essential structural components of biological and engineered materials. Accordingly, many approaches have been developed to quantify their structural properties, which define their material properties. However, a comprehensive overview and comparison of methods is lacking. Therefore, we systematically searched for automated tools quantifying network characteristics in confocal, stimulated emission depletion (STED) or scanning electron microscopy (SEM) images and compared these tools by applying them to fibrin, a prototypical fibrous network in thrombi. Structural properties of fibrin such as fiber diameter and alignment are clinically relevant, since they influence the risk of thrombosis. Based on a systematic comparison of the automated tools with each other, manual measurements, and simulated networks, we provide guidance to choose appropriate tools for fibrous network quantification depending on imaging modality and structural parameter. These tools are often able to reliably measure relative changes in network characteristics, but absolute numbers should be interpreted with care.
High-resolution structures map the metal import pathway in an Nramp transporter
Authors: Ray Shamayeeta , Berry Samuel P. , Wilson Eric A. , Zhang Casey H. , Shekhar Mrinal , Singharoy Abhishek , Gaudet Rachelle
Published: September 2022

Transporters of the Nramp (Natural resistance-associated macrophage protein) family import divalent transition metal ions into cells of most organisms. By supporting metal homeostasis, Nramps prevent disorders related to metal insufficiency or overload. Previous studies revealed that Nramps take on a LeuT fold and identified the metal-binding site. We present high- resolution structures ofDeinococcus radioduransNramp in three stable conformations of the transport cycle revealing that global conformational changes are supported by distinct coordination geometries of its physiological substrate, Mn2+, across conformations and conserved networks of polar residues lining the inner and outer gates. A Cd2+-bound structure highlights differences in coordination geometry for Mn2+and Cd2+. Measurements of metal binding using isothermal titration calorimetry indicate that the thermodynamic landscape for binding and transporting physiological metals like Mn2+is different and more robust to perturbation than for transporting the toxic Cd2+metal.
Effectiveness of incentivized peer referral to increase enrollment in a community-based chlamydia screening and treatment study among young Black men
Authors: Campbell Mary Beth , Ratnayake Aneeka , Gomes Gérard , Stoecker Charles , Kissinger Patricia
Published: September 2022

Purpose

Incentivized peer referral (IPR) has been shown to be an effective method of recruitment for men who have sex with men but has not been studied extensively in men who have sex with women (MSW), particularly among Black MSW. We aimed to determine if IPR was more effective than uncompensated peer referral for recruiting young Black men into a community STI screening study.

Methods

We used data from the Check It study, a chlamydia (Ct) screening and treatment program for young Black men ages 15-26 in New Orleans, LA. Enrollment was compared before and after IPR was implemented using Multiple Series Analysis (MTSA). IPR was introduced to increase recruitment that had been severely diminished because of the COVID-19 shutdown.

Results

Of 1527 men enrolled, 1399 (91.6%) were enrolled pre-IPR and 128 (8.4%) were enrolled post-IPR. The percentage of men referred by a friend or peer was higher in the post-IPR period than in the pre-IPR period (45.7% vs. 19.7%, p<0.001). Post-pandemic, we observed a statistically significant increase of 2.007 more recruitments (p=0.044, 95% CI (0.0515, 3.964)) at the start of the post-IPR era, compared to the pre-IPR era. Overall, we also observed a trending increase in recruitments in the IPR era relative to the pre-IPR era (0.0174 recruitments/week, p=0.285, 95% CI (−0.0146, 0.0493)) with less recruitment decay in the post-IPR compared to pre-IPR.

Conclusions

IPR may be an effective means of engaging young Black men in community based STI research and prevention programs, particularly when clinic access is limited.
CURE: A Pre-training Framework on Large-scale Patient Data for Treatment Effect Estimation
Authors: Liu Ruoqi , Chen Pin-Yu , Zhang Ping
Published: September 2022

Treatment effect estimation (TEE) refers to the estimation of causal effects, and it aims to compare the difference among treatment strategies on important outcomes. Current machine learning based methods are mainly trained on labeled data with specific treatments or outcomes of interest, which can be sub-optimal if the labeled data are limited. In this paper, we propose a novel transformer-based pre-training and fine-tuning framework called CURE for TEE from observational data. CURE is pre-trained on large-scale unlabeled patient data to learn representative contextual patient representations, and then fine-tuned on labeled patient data for TEE. We design a new sequence encoding for longitudinal (or structured) patient data and we incorporate structure and time into patient embeddings. Evaluated on 4 downstream TEE tasks, CURE outperforms the state-of-the-art methods in terms of an average of 3.8% and 6.9% absolute improvement in Area under the ROC Curve (AUC) and Area under the Precision-Recall Curve (AUPR), and 15.7% absolute improvement in Influence function-based Precision of Estimating Heterogeneous Effects (IF-PEHE). We further demonstrate the data scalability of CURE and verify the results with corresponding randomized clinical trials. Our proposed method provides a new machine learning paradigm for TEE based on observational data.
SARS-CoV-2 Serosurveys: How antigen, isotype and threshold choices affect the outcome
Authors: Binder Raquel A. , Fujimori Gavin F. , Forconi Catherine S. , Reed George W. , Silva Leandro S. , Lakshmi Priya Saikumar , Higgins Amanda , Cincotta Lindsey , Dutta Protiva , Salive Marie-Claire , Mangolds Virginia , Anya Otuwe , Calle J. Mauricio Calvo , Nixon Thomas , Tang Qiushi , Wessolossky Mireya , Wang Yang , Ritacco Dominic A. , Bly Courtney S. , Fischinger Stephanie , Atyeo Caroline , Oluoch Peter O. , Odwar Boaz , Bailey Jeffrey A. , Maldonado-Contreras Ana , Haran John P. , Schmidt Aaron G. , Cavacini Lisa , Alter Galit , Moormann Ann M.
Published: September 2022

Background

Evaluating the performance of SARS-CoV-2 serological assays and clearly articulating the utility of selected antigen, isotypes and thresholds is crucial to understanding the prevalence of infection within selected communities.

Methods

This cross-sectional study, implemented in 2020, screened PCR-confirmed COVID-19 patients (n=86), banked pre-pandemic and negative donors (n=96), health care workers and family members (n=552), and university employees (n=327) for anti-SARS-CoV-2 receptor-binding domain (RBD), trimeric spike protein (S), and nucleocapsid protein (N) IgG and IgA antibodies with a laboratory developed Enzyme-Linked Immunosorbent Assay (ELISA) and tested how antigen, isotype and threshold choices affected the seroprevalence. The following threshold methods were evaluated: (i) mean + 3 standard deviations of the negative controls; (ii) 100% specificity for each antigen/isotype combination; and (iii) the maximal Youden index.

Results

We found vastly different seroprevalence estimates depending on selected antigens, isotypes and the applied threshold method, ranging from 0.0% to 85.4%. Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3% to 25.9%.

Conclusions

This study revealed the importance of evaluating serosurvey tools for antigen, isotype, and threshold-specific sensitivity and specificity, in order to interpret qualitative serosurvey outcomes reliably and consistently across studies.
Genome analysis of Parmales, a sister group of diatoms, reveals the evolutionary specialization of diatoms from phago-mixotrophs to photoautotrophs
Authors: Ban Hiroki , Sato Shinya , Yoshikawa Shinya , Yamada Kazumasa , Nakamura Yoji , Ichinomiya Mutsuo , Sato Naoki , Blanc-Mathieu Romain , Endo Hisashi , Kuwata Akira , Ogata Hiroyuki
Published: September 2022

The order Parmales (Bolidophyceae) is a minor group of pico-sized eukaryotic marine phytoplankton that contains species with cells surrounded by silica plates. Previous studies revealed that Parmales is a member of ochrophytes and sister to diatoms (Bacillariophyta), the most successful phytoplankton group in the modern ocean. Therefore, parmalean genomes can serve as a reference to elucidate both the evolutionary events that differentiated these two lineages and the genomic basis for the ecological success of diatoms vs. the more cryptic lifestyle of parmaleans. Here, we compared the genomes of eight parmaleans and five diatoms to explore their physiological and evolutionary differences. Parmaleans were predicted to be phago-mixotrophs. By contrast, diatoms have undergone loss of genes related to phagocytosis, indicating the ecological specialization from phago-mixotroph to photoautotroph in the early evolution of diatoms. Furthermore, diatoms showed significant enrichment in gene sets involved in silica metabolism, nutrient uptake capacity, carbon concentrating mechanisms, and iron uptake in comparison with parmaleans. Overall, our results suggest a strong evolutionary link between the loss of phago-mixotrophy and specialization to a silicified photoautotrophic life stage early in diatom evolution after diverging from the Parmales lineage.
Enhanced Golden Gate Assembly: Evaluating Overhang Strength for Improved Ligation Efficiency
Authors: Strzelecki Patryk , Joly Nicolas , Hébraud Pascal , Hoffmann Elise , Cech Grzegorz M. , Kloska Anna , Busi Florent , Grange Wilfried
Published: September 2022

Molecular cloning, a routine yet essential technique, relies heavily on efficient ligation, which can be significantly improved using Golden Gate Assembly (GGA). A key component of GGA is the use of type IIS enzymes, which uniquely cleave downstream of their recognition sequences to generate various overhangs, including non-palindromic ones. Recent advancements in GGA include the development of newly engineered enzymes with enhanced activity. Additionally, high-throughput GGA assays, which allow for the simultaneous study of all possible overhangs, have identified optimal GGA substrates with high efficiencies and fidelities, greatly facilitating the design of complex assemblies. Interestingly, these assays reveal unexpected correlations between ligation efficiencies and overhang stabilities. One hypothesis for this observation is that newly hydrolyzed DNA fragments with strong overhangs can readily re-ligate, thereby slowing down the overall process. In this paper, we employ a combination of gel electrophoresis and numerical calculations to test this hypothesis, ultimately determining that it does not hold true under the conditions established by conventional GGA assays. Using an assembly of 10 fragments, we demonstrate that strong overhangs yield higher GGA efficiency, while weak overhangs result in lower efficiency. These findings enable us to propose optimal overhangs for efficient GGA assays, significantly increasing yield.
Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design
Authors: Moussaoui Dihia , Robblee James P. , Auguin Daniel , Fisher Fabio , Fagnant Patricia M. , Macfarlane Jill E. , Schaletzky Julia , Wehri Eddie , Mueller-Dieckmann Christoph , Baum Jake , Robert-Paganin Julien , Trybus Kathleen M. , Houdusse Anne
Published: September 2022

Malaria is responsible for more than a half million deaths per year. The Plasmodium parasites responsible continue to develop resistance to all known agents, despite treatment with different antimalarial combinations. The atypical Myosin A motor (PfMyoA) is part of a core macromolecular complex called the glideosome, essential for Plasmodium parasite mobility and therefore an attractive drug target. Here, we characterize the interaction of a small molecule (KNX-002) with PfMyoA. KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage growth of merozoites, one of three motile Plasmodium life-cycle stages. Combining biochemical assays, X-ray crystallography and molecular dynamics, we demonstrate that KNX-002 targets a novel pocket in PfMyoA, sequestering it in a post-rigor state detached from actin. KNX-002 binding affects Mg2+ coordination near ATP, preventing ATP hydrolysis and thus inhibiting motor activity. This first-in-class small-molecule inhibitor of PfMyoA paves the way for developing a new generation of antimalarial treatments.
SARS-CoV-2 polyprotein substrate regulates the stepwise Mpro cleavage reaction
Authors: Narwal Manju , Armache Jean-Paul , Edwards Thomas , Murakami Katsuhiko S.
Published: September 2022

Processing of polyproteins pp1a and pp1ab in Coronaviruses by main protease Mpro is a crucial event in virus replication and a promising target for antiviral drug development. Mpro recognizes multiple recognition sites within polyproteins in a defined order, but its mechanism remains enigmatic due to lack of structural information of the polyprotein substrate bound Mpro complex. Here, we present the cryo-EM structures of the SARS-CoV-2 Mpro in an apo-form and in complex with the nsp7-10 region of pp1a polyprotein. The structure shows that the interaction of Mpro with polyproteins is limited to the recognition site connecting nsp9 and nsp10 proteins without any tight association with the rest of polyprotein structure or sequence. Comparison between the apo-form and the polyprotein bound structures of Mpro highlights the flexible nature of active site region allowing the Mpro to accommodate various recognition sites connecting series of nsp proteins. These observations suggest that the role of Mpro for selecting a preferred cleavage site within the polyprotein is limited and underscore the structure, conformation and/or dynamics of polyprotein determining the sequential polyprotein cleavage by Mpro.
A structural dendrogram of the actinobacteriophage major capsid proteins provides important structural insights into the evolution of capsid stability
Authors: Podgorski Jennifer M. , Freeman Krista , Gosselin Sophia , Huet Alexis , Conway James F. , Bird Mary , Grecco John , Patel Shreya , Jacobs-Sera Deborah , Hatfull Graham , Gogarten Johann Peter , Ravantti Janne , White Simon
Published: September 2022

Many double-stranded DNA viruses, including tailed bacteriophages (phages) and herpesviruses, use the HK97-fold in their major capsid protein to make the capsomers of the icosahedral viral capsid. Following the genome packaging at near-crystalline densities, the capsid is subjected to a major expansion and stabilization step that allows it to withstand environmental stresses and internal high pressure. Several different mechanisms for stabilizing the capsid have been structurally characterized, but how these mechanisms have evolved is still not understood. Using cryo-EM structure determination, structural comparisons, phylogenetic analyses, and Alphafold predictions, we have constructed a detailed structural dendrogram describing the evolution of capsid structural stability within the actinobacteriophages. The cryo-EM reconstructions of ten capsids solved to resolutions between 2.2 and 4 Ångstroms revealed that eight of them exhibit major capsid proteins that are linked by a covalent cross-linking (isopeptide bond) between subunits that was first described in the HK97 phage. Those covalent interactions ultimately lead to the formation of mutually interlinked capsomers that has been compared to the structure of chain mail. However, three of the closely related phages do not exhibit such an isopeptide bond as demonstrated by both our cryo-EM maps and the lack of the required residue. This work raises questions about the importance of previously described capsid stabilization mechanisms.
Endogenous Plasmids and Reductive Genome Evolution in Host-Associated Bacteria
Authors: Xiong Qing , Fung Cathy Sin-Hang , Xiao Xiaojun , Wan Angel Tsz-Yau , Wang Mingqiang , Ren Yaning , Yang Kevin Yi , Cui Yubao , Liu Xiaoyu , Tsui Stephen Kwok-Wing
Published: September 2022

Reductive genome evolution is commonly observed among host-associated bacteria including many important pathogens, such as Mycobacterium leprae but its molecular mechanism is not well understood 1–5. One of the most widely accepted hypotheses to explain bacterial genome reduction is Muller’s ratchet, in which the associated bacteria tend to accumulate deleterious mutations for reduction in the absence of chromosomal recombination inside the eukaryotic host organism 1,2. Cardinium species belong to the family Amoebophilaceae of the CFB group bacteria, which are a group of endosymbiont bacteria widely distributed among arthropods, that along with Wolbachia can cause cytoplasmic incompatibility 6,7. In this study, we explored bacterial reductive evolution within the de novo assembled genomes of Cardinium endosymbionts in two astigmatic mites 8,9. Our results shed light on the reduction mechanism driven by endogenous plasmids and their encoded enzymes.