bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of COVID-19 on daily travel behaviour: a literature review
Authors: Paul Tonmoy , Chakraborty Rohit , Anwari Nafis
Published: June 2022

The coronavirus disease 2019 (COVID-19) pandemic made a perceptible impact on daily travel behaviour worldwide, especially through mode shifts and changes in trip frequencies with possible long-term repercussions. Non-therapeutic interventions adopted worldwide (e.g. lockdowns and travel restrictions) to reduce viral contagion need to be understood holistically because it is challenging for people to follow through these policies and stay home in developing nations. In this context, it is important to have a clear idea of how COVID-19 is shaping the mobility pattern and what policies must be taken (if not yet) to minimize viral transmission as well as develop a sustainable transportation system. To this end, this study presents a systematically analysed review of 56 international literatures from academic sources (Google Scholar, Scopus and Web of Science) on the impacts of COVID-19 on travel behaviour and focuses on policymaking measures. This article illustrates the modal shift, variation in frequencies of different trips and how sociodemographic characteristics have influenced the mobility pattern in response to COVID-19. Innate changes in travel patterns compared to the pre-COVID-19 era were observed. A noticeable apprehension on viral transmission in public transit has reduced public transit usage while increasing that of private vehicles. This poses challenges to develop sustainable transportation. This study concludes by discussing intervention measures to support transportation planners and policymakers to deal with the current pandemic as well as any future pandemics.
Elder Mistreatment Prevention Rounds in Nursing Homes
Authors: Fulmer Terry , Bonner Alice , Chandra Shreya , Le Tim
Published: June 2022

This new prevention paradigm could benefit all.
New Adjuvant Treatment for High-Risk Early Breast Cancer
Authors: Aschenbrenner Diane S.
Published: June 2022

Olaparib (Lynparza) is now approved for the adjuvant treatment of adult patients who have, or are suspected to have, the germline variation of BRCA-mutated human epidermal growth factor receptor 2–negative high-risk early breast cancer and who were previously treated with neoadjuvant or adjuvant chemotherapy.
Promoting Goals-of-Care Discussions in Seriously Ill Patients
Authors: Todd Betsy
Published: June 2022

Patient-specific guides were effective in promoting documented goals-of-care discussions and were feasible and acceptable to patients, surrogate decision makers, and clinicians.
First-year experience of transitioning from registered nurse to nurse practitioner
Authors: Cheng Ju-Fen , Wang Tsae-Jyy , Huang Xuan-Yi , Han Hui-Chun
Published: June 2022

Background:

Transitioning to advanced practice, novice nurse practitioners need to take on new roles, learn new practice areas, and develop new skills. This process requires breaking old practices and work habits and facing new challenges.

Purpose:

To explore the nature of nurse practitioners' work experiences during the first year of transition from registered nurse to nurse practitioner.

Methods:

This qualitative study was based on Husserl's phenomenological methodology. A purposive sample of 16 first-year nurse practitioners was recruited. Data were collected through in-depth interviews and analyzed by thematic content analysis. The approaches of Lincoln & Guba were applied to improve the validity of the study.

Results:

Results showed that the first-year experience of transitioning from registered nurse to nurse practitioner fell into two overarching themes: challenge and adjustment. The challenge consists of five subthemes: “facing the expectation-reality gap,” “managing others' expectations,” “striving to acquire professional skills,” “handling situational variability,” and “bearing emotional burdens” subthemes. The adjustment includes five subthemes: “finding resources,” “gaining experiences,” “building relationships,” “relieving stress,” and “overcoming obstacles.”

Implications for practice:

Novice nurse practitioners face many challenges as they adjust to a new role during their first year on the job. New nurse practitioners develop coping strategies to help themselves adjust to their work. They also gradually gain new resources and experiences to help them stay positive in stressful situations and restore work–life balance. The challenges of transitioning from a registered nurse to a nurse practitioner cannot be overlooked. Novice nurse practitioners need appropriate support measures to adapt to advanced practice roles.
State Policies Relevant to Disease Intervention Specialists in the United States
Authors: Cramer Ryan , Ludovic Jennifer A.
Published: June 2022

Background

The functions of disease intervention specialists (DIS) represent core infectious disease control practices and have legal foundations in the United States. Although important for state and local health departments to understand this authority, these policies have not been systematically collected and analyzed. We analyzed the authority for investigation of sexually transmitted infections (STIs) across all 50 US states and the District of Columbia.

Methods

In January 2022, we collected state policies addressing the investigation of STIs using a legal research database. We coded these policies into a database on variables of interest: (1) whether the policy authorized/required investigation, (2) what type of infection triggers an investigation, (3) and the entity who is authorized/required to perform the investigation.

Results

All 50 US states and District of Columbia explicitly authorize/require investigation of cases of STI. Of these jurisdictions, 62.7% require investigations, 41% authorize investigations, and 3.9% both authorize and require investigations. Sixty-seven percent authorize/require investigations for cases of communicable disease (inclusive of an STI), 45.1% authorize/require investigations for cases of STIs generally, and 3.9% authorize/require investigations for cases of a specific STI. Eighty-two percent of jurisdictions authorize/require the state to investigate, 62.7% authorize/require local governments to investigate, and 39.2% authorize/require investigations by both state and local governments.

Conclusions

State laws that establish authority or duties regarding the investigation of STIs differ across states. It may be useful for state and local health departments to examine these policies relative to the morbidity of their jurisdiction and their STI prevention priorities.
Improving Hepatitis B Vaccination Rates among At-risk Children and Adolescents with Inflammatory Bowel Disease
Authors: Megan McNicol Megan , Donegan Amy , Hawa Kate , Boutzoukas Angelique E. , Drobnic Barb , Oates Melanie , Orraca-Tetteh Maudie , Michel Hilary K. , Maltz Ross M. , Dotson Jennifer L. , Buckingham Don , Boyle Brendan , Ardura Monica I.
Published: June 2022

Introduction:

Patients with inflammatory bowel disease (IBD) receiving tumor necrosis factor alpha inhibitors (TNFai) may be at higher risk for hepatitis B virus (HBV) infection. We conducted a quality improvement (QI) initiative to improve HBV vaccination rates in seronegative children with IBD.

Methods:

This QI initiative implemented an HBV vaccination strategy from September 2018 to March 2020 in patients with newly diagnosed IBD with hepatitis B surface antibody (HBsAb) <10 mIU/mL. The project aimed to (1) increase HBV vaccination rates in seronegative patients and (2) document immunogenicity after completing a three-dose vaccine series. Outcome measures included the percentage of seronegative patients who received HBV vaccines (dose 1 and three-dose series). Interventions included applying a standardized vaccination protocol, and creating a vaccine workflow in two clinical areas, previsit planning and stakeholder engagement.

Results:

One hundred seventy-four children and adolescents with IBD were evaluated during the study period, and 132 (76%) were HBsAb negative. After plan-do-study-act (PDSA) 1, the proportion of eligible patients who received HBV vaccine dose 1 increased from a baseline of 7% to 100% and was sustained for over 12 months. During PDSA 2, the proportion of patients completing the three-dose vaccine series improved from a baseline of 0% to 82% (n = 100); among 93 children in this subgroup who had repeat serology performed, 86 (92%) demonstrated serologic evidence of HBV protection.

Conclusions:

A multidisciplinary approach applying QI methodology allowed for improved and sustained HBV vaccination rates in at-risk seronegative children and adolescents with IBD. A three-dose HBV vaccine series proved immunogenic in 92% of eligible patients.
“Oncologic Safety of Staged Pre-Pectoral Implant Reconstruction Following Nipple-Sparing Mastectomy: a Mean 9-Year Follow-Up.”
Authors: Salibian Arthur H. , Harness Jay K.
Published: June 2022

Background:

Prepectoral reconstruction following nipple-sparing mastectomy has recently gained popularity as an alternative to total or partial submuscular reconstruction. In the absence of long-term follow-up, concerns have been raised over the oncologic safety of using mastectomy flaps that preserve the entire thickness of the subcutaneous fat and its circulation. In this article we present our average 9-year oncologic follow-up of patients who underwent nipple-sparing mastectomy and 2-stage prepectoral implant reconstruction without acellular dermal matrix.

Methods:

In this retrospective study, a group of previously reported 151 consecutive breast cancer patients [246 breasts, (160 therapeutic, 86 preventative)] who underwent nipple-sparing mastectomy and staged prepectoral implant reconstruction between 2005 and 2015 were followed up for an average of 109 months (range, 14 to 192 months). Tumor related data, oncologic markers, staging, neoadjuvant/adjuvant therapy, and radiation therapy were evaluated to determine local recurrence, overall survival, and disease-free survival rates.

Results:

Local recurrence rate in 151 patients was 2.6 percent. Eleven patients (7.3 percent) died from metastatic disease and 3 patients from unrelated causes. The average 109-month overall survival rate was 92.9 percent and disease-free survival rate was 87.8 percent. Over the same period nine patients (6 percent) were alive with distant disease.

Conclusion:

Our 9-year two-stage prepectoral reconstruction study of nipple-sparing mastectomy shows that the procedure is oncologically safe, having comparable recurrence, overall survival, and disease-free survival rates as total mastectomy.
Partial Recovery of Amblyopia After Fellow Eye Ischemic Optic Neuropathy
Authors: Resnick Hannah H. , Bear Mark F. , Gaier Eric D.
Published: June 2022

Background:

Recovery from amblyopia in adulthood after fellow eye (FE) vision loss is a well-known phenomenon. Incidence of recovery varies widely following different FE pathologies, and the rate of recovery after FE ischemic optic neuropathy (ION) has not been examined. We aimed to determine the frequency and degree of improvement in amblyopic eye (AE) visual function after ION in the FE.

Methods:

We performed a retrospective chart review of patients between 2007 and 2021 confirmed to have amblyopia and ischemic optic neuropathy in different eyes. Patients with unstable ocular pathology potentially limiting vision were excluded. We compared the best-corrected visual acuity (VA) in each eye before and after FE ION over time. For patients with available data, we examined change in perimetric performance over time.

Results:

Among the 12 patients who met the inclusion criteria (mean age 67 ± 8 years), 9 (75%) improved ≥1 line and 2 (17%) improved ≥3 lines. The median time from ION symptom onset to maximal improvement was 6 months (range: 2–101 months). Reliable perimetric data were available for 6 patients. Mean sensitivity improved in the AE for all patients, with mean improvement of 1.9 ± 1.1 dB. There was no correspondence between foci of ION-related field loss and gains in field sensitivity in the AE.

Conclusions:

A high proportion of patients with amblyopia and contralateral ION experience improvement in AEVA. Modest gains in perimetric sensitivity in the AE may accompany FE ION. These findings support the view that residual plasticity in the adult visual cortex can be tapped to support functional improvement in amblyopia.
Phosphorylation of the Autographa californica multiple nucleopolyhedrovirus polyhedron envelope protein plays an important role in the formation of the occlusion body envelope
Authors: Wang Jia , Yang Jian , Lei Chengfeng , Sun Xiulian , Hu Jia
Published: June 2022

During the life cycle of a baculovirus, a crystallized protein matrix, formed by polyhedrin (POLH), is produced. The protein matrix is surrounded by a multilayered protein/carbohydrate envelope, and matrix and envelope together form a mature occlusion body (OB). The polyhedron envelope plays an important role in resistance against adverse external environments. The polyhedron envelope protein (PEP) is the main protein that forms the polyhedron envelope, but the mechanism of formation of the polyhedron envelope is unclear. Here, through immunofluorescence localization observations, we found that PEP interacted with both POLH and P10 during formation of the polyhedron envelope in the late stages of infection, and PEP was also required for P10 incorporation on the surface of OBs. In this process, the phosphorylation of PEP played an important role. PEP was determined to be a phosphorylated protein using the Phos-tag technique, and PK1 was determined to be the phosphokinase of PEP by co-immunoprecipitation and in vitro phosphorylation. Immunofluorescence localization revealed that PEP was continuously phosphorylated by PK1 after PEP entered the nucleus until PEP was correctly packaged on the OB surface. Multi-point mutations of PEP conservative potential phosphorylation sites showed that the simultaneous mutation of S85, T86 and Y92 caused changes in the location of PEP and P10 in the late stages of infection, and resulted in an OB surface that lacked the polyhedron envelope. These data suggested that the phosphorylation of PEP at particular sites, i.e. S85, T86 and Y92, plays an important role in the formation of the polyhedron envelope.
Population genomics of pneumococcal carriage in South Africa following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) immunization
Authors: Javaid Nida , Olwagen Courtney , Nzenze Susan , Hawkins Paulina , Gladstone Rebecca , McGee Lesley , Breiman Robert F. , Bentley Stephen D. , Madhi Shabir A. , Lo Stephanie
Published: June 2022

Streptococcus pneumoniae

is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, respectively, a decrease in both invasive pneumococcal infections and asymptomatic carriage of vaccine-type pneumococci were reported. In this study, we described the changing epidemiology of the pneumococcal carriage population in South Africa, by sequencing the genomes of 1825 isolates collected between 2009 and 2013. Using these genomic data, we reported the changes in serotypes, Global Pneumococcal Sequence Clusters (GPSCs), and antibiotic resistance before and after the introduction of PCV13. The pneumococcal carriage population in South Africa has a high level of diversity, comprising of 126 GPSCs and 49 serotypes. Of the ten most prevalent GPSCs detected, six were predominantly found in Africa (GPSC22, GPSC21, GPSC17, GPSC33, GPSC34 and GPSC52). We found a significant decrease in PCV7 serotypes (19F, 6B, 23F and 14) and an increase in non-vaccine serotypes (NVT) (16F, 34, 35B and 11A) among children <2 years of age. The increase in NVTs was driven by pneumococcal lineages GPSC33, GPSC34, GPSC5 and GPSC22. Overall, a decrease in antibiotic resistance for 11 antimicrobials was detected in the PCV13 era. Further, we reported a higher resistance prevalence among vaccine types (VTs), as compared to NVTs; however, an increase in penicillin resistance among NVT was observed between the PCV7 and PCV13 eras. The carriage isolates from South Africa predominantly belonged to pneumococcal lineages, which are endemic to Africa. While the introduction of PCV resulted in an overall reduction of resistance in pneumococcal carriage isolates, an increase in penicillin resistance among NVTs was detected in children aged between 3 and 5 years, driven by the expansion of penicillin-resistant clones associated with NVTs in the PCV13 era.
Peripheral Blood Gene Expression at 3 to 24 Hours Correlates with and Predicts 90-Day Outcome Following Human Ischemic Stroke
Authors: Amini Hajar , Knepp Bodie , Rodriguez Fernando , Jickling Glen C , Hull Heather , Carmona-Mora Paulina , Bushnell Cheryl , Ander Bradley P , Sharp Frank R , Stamova Boryana
Published: June 2022

This study identified early immune gene responses in peripheral blood associated with 90-day ischemic stroke (IS) outcomes and an early gene profile that predicted 90-day outcomes. Peripheral blood from the CLEAR trial IS patients was compared to vascular risk factor matched controls. Whole-transcriptome analyses identified genes and networks associated with 90-day IS outcome (NIHSS-NIH Stroke Scale, mRS-modified Rankin Scale). The expression of 467, 526, and 571 genes measured at ≤3, 5 and 24 hours after IS, respectively, were associated with poor 90-day mRS outcome (mRS=3-6), while 49, 100 and 35 associated with good mRS 90-day outcome (mRS=0-2). Poor outcomes were associated with up-regulatedMMP9,S100A12, interleukin-related and STAT3 pathways. Weighted Gene Co-Expression Network Analysis (WGCNA) revealed modules significantly associated with 90-day outcome. Poor outcome modules were enriched in down-regulated T cell and monocyte-specific genes plus up-regulated neutrophil genes and good outcome modules were associated with erythroblasts and megakaryocytes. Using the difference in gene expression between 3 and 24 hours, 10 genes correctly predicted 100% of patients with Good 90-day mRS outcome and 67% with Poor mRS outcome (AUC=0.88) in a validation set. The predictors includedAVPR1A, which mediates platelet aggregation, release of coagulation factors and exacerbates the brain inflammatory response; andKCNK1(TWIK-1), a member of a two-pore potassium channel family, which like other potassium channels likely modulates stroke outcomes. This study suggests the immune response after stroke impacts long-term functional outcomes. Furthermore, early post-stroke gene expression may predict stroke outcomes and outcome-associated genes could be targets for improving outcomes.
First Point-of-Care Diagnostic Test for Beta-Thalassemia
Authors: An Ran , Avanaki Alireza , Thota Priyaleela , Nemade Sai , Mehta Amrish , Gurkan Umut A.
Published: June 2022

Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world’s population. Among various Hb disorders, approximately 1.5% of the world population carry β-thalassemia (β-Thal), affecting 40,000 newborns every year. Early screening and timely diagnosis are essential in β-thalassemia patients for prevention and management of later clinical complications. However, in Africa to Southern Europe, Middle East, and Southeast Asia, where β-thalassemia is most prevalent, diagnosis and screening of β-thalassemia is still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, a paper-based microchip electrophoresis platform, that enables the first point-of-care diagnostic test for β-thalassemia. We evaluated the accuracy of Gazelle for β-Thal screening in 372 subjects in the age range of 4 – 63 years at Apple Diagnostics labin Mubai, India. Additionally, 30 blood samples were prepared to mimic β-Thal intermediate and β-Thal major samples. The Gazelle detected levels of Hb A, Hb F, and Hb A2 demonstrated high correlations with the results reported by the laboratory gold standard, high performance liquid chromatography (HPLC) yielding a Pearson Correlation Coefficient = 0.99. The ability to obtain rapid and accurate results suggest that Gazelle can be suitable for large-scale screening and diagnosis of β-Thal.
From individual to population disease risk: population-averaged polygenic risk scores
Authors: He Simin , Peng Liuqing , Jing Jiarui , Wang Juping , Wang Tong
Published: June 2022

Polygenic risk score (PRS) is a tool to quantify the susceptibility of an individual to a disease by using the results of individual gene sequencing to calculate the cumulative effect of genetic susceptibility loci. In this study, we extend the individual-based PRS to the population-based mean polygenic risk score (PMPRS), Further more, we constructed the risk score ratio (RSR) for etiology exploration. In the case study, we applied above method to explore the relationship between study six inflammatory factors and coronary heart disease (CHD). Our studies have shown that tumor necrosis factor-α (TNF-α) and procalcitonin (PCT) are potential risk factors for CHD. The RSR corresponding to TNF-α is 4.97 (prediction interval: 2.99, 10.548); the RSR corresponding to PCT is 21.87 (prediction interval: 2.29, 232.28), and controlling the levels of TNF-α and PCT can be used as a primary preventive measure to reduce the occurrence of coronary heart disease.
LGBTQ+ Affirming Care May Increase Awareness and Understanding of Undetectable=Untransmittable among Midlife and Older Gay and Bisexual Men in the US South
Authors: McKay Tara , Akré Ellesse-Roselee , Henne Jeff , Conway Adam , Gothelf Isabel , Kari Nitya
Published: June 2022

One of the most significant innovations in HIV prevention is the use of HIV treatment to prevent HIV transmission. This information has been disseminated as the “Undetectable = Untransmittable” (U=U) message. Despite evidence of effectiveness, U=U awareness, belief, and understanding remains limited in some communities. In this study we examine whether having an LGBTQ affirming healthcare provider increases U=U awareness, belief, and understanding among midlife and older gay and bisexual men in the US South, an understudied and underserved population and region where new HIV infections are increasing. We use data from the Vanderbilt University Social Networks Aging and Policy Study (VUSNAPS) on sexual minority men aged 50 to 76 from four Southern US states collected in 2020-2021. We find that only one in four men report prior awareness of U=U, but awareness is higher among HIV negative and HIV positive men who have an LGBTQ affirming provider. Having an affirming provider significantly increases U=U belief and understanding, improves risk perception accuracy, and increases the likelihood of having ever tested for HIV among HIV negative men. Improving access to LGBTQ affirming healthcare may improve U=U awareness, belief, and understanding, which could help to curb HIV transmission in the US South.
Semantic novelty modulates neural responses to visual change across the human brain
Authors: Nentwich Maximilian , Leszczynski Marcin , Russ Brian E. , Hirsch Lukas , Markowitz Noah , Sapru Kaustubh , Schroeder Charles E. , Mehta Ashesh , Bickel Stephan , Parra Lucas C
Published: June 2022

Our continuous visual experience in daily life is dominated by change. Previous research has focused on visual change due to stimulus motion, eye movements or unfolding events, but not their combined impact across the brain, or their interactions with semantic novelty. We investigate the neural responses to these sources of novelty during film viewing. We analyzed intracranial recordings in humans across 6328 electrodes from 23 individuals. Responses associated with saccades and film cuts were dominant across the entire brain. Film cuts at semantic event boundaries were particularly effective in the temporal and medial temporal lobe. Saccades to visual targets with high visual novelty were also associated with strong neural responses. Specific locations in higher-order association areas showed selectivity to either high or low-novelty saccades. We conclude that neural activity associated with film cuts and eye movements is widespread across the brain and is modulated by semantic novelty.
Phylogenomic Analysis of Protein-Coding Genes Resolves Complex Gall Wasp Relationships
Authors: Hearn Jack , Gobbo Erik , Nieves-Aldrey José Luis , Branca Antoine , Nicholls James A. , Koutsovoulos Georgios , Lartillot Nicolas , Stone Graham N. , Ronquist Fredrik
Published: June 2022

The phylogeny of gall wasps (Cynipidae) and their parasitic relatives has attracted considerable attention in recent years. The family is now widely recognized to fall into thirteen natural lineages, designated tribes, but the relationships among them have remained elusive. This has stymied any progress in understanding how cynipid gall inducers evolved from insect parasitoids, and what role inquilinism (development as a herbivore inside galls induced by other cynipids) might have played in this transition. A recent analysis of ultraconserved elements (UCEs) represents the first attempt at resolving these questions using phylogenomics. Here, we present the first analysis based on protein-coding sequences from genome and transcriptome assemblies. To address potential problems due to model misfit, we focus on models that accommodate site-specific amino-acid profiles and that are less sensitive than standard models to long-branch attraction. Our results show that the Cynipidae as previously circumscribed are not monophyletic. Specifically, the Paraulacini and a clade formed by Diplolepidini + Pediaspidini both fall outside a core clade (Cynipidae s. str.), which is more closely related to Figitidae. This result is robust to the exclusion of long-branch taxa that could potentially mislead the analysis, and it is consistent with the UCE analysis. Given this, we propose that the Cynipidae be divided into three families: the Paraulacidae, Diplolepididae and Cynipidae (s. str.). Our results suggest that the Eschatocerini are the sister group of the remaining Cynipidae (s. str.). Within the latter, our results are consistent with the UCE analysis but place two additional tribes: (1) the Aylacini (s. str.), more closely related to the oak gall wasps (Cynipini) and some of their inquilines (Ceroptresini) than to other herb gallers (Aulacideini and Phanacidini); and (2) the Qwaqwaiini, likely the sister group to Synergini (s. str.) + Rhoophilini. Several alternative scenarios for the evolution of cynipid life histories are compatible with the relationships suggested by our analysis, but all are complex and require multiple shifts between parasitoids, inquilines and gall inducers. Linking the different types of life-history transitions to specific genomic signatures may be one of the best ways of differentiating among these alternative scenarios. Our study represents the first step towards enabling such analyses.
In vivo base editing rescues photoreceptors in a mouse model of retinitis pigmentosa
Authors: Su Jing , She Kaiqin , Song Li , Jin Xiu , Li Ruiting , Zhao Qinyu , Xiao Jianlu , Chen Danian , Cheng Hui , Lu Fang , Wei Yuquan , Yang Yang
Published: June 2022

Retinitis pigmentosa (RP) is a group of retinal diseases that cause the progressive death of retinal photoreceptor cells and eventually blindness. Mutations in the β-domain of the phosphodiesterase 6 (Pde6b) gene are among the most identified causes of autosomal recessive RP. Here, we report a base editing approach in which adeno-associated virus (AAV)-mediated adenine base editor (ABE) delivery to postmitotic photoreceptors is used to correct the Pde6b mutation in a retinal degeneration 10 (rd10) mouse model of RP. Subretinal delivery of AAV8-ABE corrects Pde6b mutation with up to 37.41% efficiency at the DNA level and up to 91.95% efficiency at the cDNA level, restores PDE6B expression, preserves photoreceptors and rescues visual function. RNA-seq reveals upregulation of genes associated with phototransduction and photoreceptor survival. Our data demonstrate that base editing is a potential gene therapy that could provide durable protection against RP.
Cable-free brain imaging with miniature wireless microscopes
Authors: Wang Yangzhen , Ma Zhongtian , Li Wenzhao , Su Feng , Wang Chong , Xiong Wei , Li Changhui , Zhang Chen
Published: June 2022

The invention of the miniaturized microscope has enabled neuroscientists to investigate neural mechanisms in freely moving mice. A lot of efforts have been made to optimize performance of the miniaturized microscope. However, the tethered cables limit the ability of mini-microscope systems to record neural activity from multiple mice simultaneously. Here, we present a wireless mini-microscope (wScope) that enables both real-time remote control and data preview during animal behavior; this design also supports simultaneous recording from up to 8 mice. The wScope has a mass of 2.7 g and a maximum frame rate of 25 Hz at 750 μm by 450 μm field of view with 1.8 μm resolution. We validated the wScopes in video-recording of the cerebral blood flow (CBF) and the activity of neurons in the primary visual cortex (V1) of different mice. The wScope provides a powerful tool for brain imaging of free moving animals, including large primates, in their much larger spaces and more naturalistic environments.
Species-specific protein-protein interactions govern the humanization of the 20S proteasome in yeast
Authors: Sultana Sarmin , Abdullah Mudabir , Li Jianhui , Hochstrasser Mark , Kachroo Aashiq H.
Published: June 2022

Yeast and humans share thousands of genes despite a billion years of evolutionary divergence. While many human genes can functionally replace their yeast counterparts, nearly half of the tested shared genes cannot. For example, most yeast proteasome subunits are humanizable, except subunits comprising the β-ring core, including β2 (HsPSMB7). We developed a high-throughput pipeline to humanize yeast proteasomes by generating a large library of Hsβ2 mutants and screening them for complementation of yeast β2 (ScPup1). Variants capable of replacing ScPup1 included (1) those impacting local protein-protein interactions (PPIs), with most affecting interactions between the β2 C-terminal tail and the adjacent β3 subunit, and (2) those affecting β2 proteolytic activity. Exchanging the full-length tail of human β2 with that of ScPup1 enabled complementation. Moreover, wild-type human β2 replaced yeast β2 if the adjacent human β3 subunit was also provided. Unexpectedly, yeast proteasomes bearing a catalytically inactive HsPSMB7-T44A variant blocking precursor autoprocessing were viable, suggesting an intact propeptide stabilizes late assembly intermediates. Our data reveal roles for specific PPIs governing functional replaceability across vast evolutionary distances.
Route-dependent spatial engram tagging in mouse dentate gyrus
Authors: Wilmerding Lucius K. , Kondratyev Ivan , Ramirez Steve , Hasselmo Michael E.
Published: June 2022

The dentate gyrus (DG) of hippocampus is hypothesized to act as a pattern separator that distinguishes between similar input patterns during memory formation and retrieval. Sparse ensembles of DG cells associated with learning and memory, i.e. engrams, have been labeled and manipulated to recall novel context memories. Functional studies of DG cell activity have demonstrated the spatial specificity and stability of DG cells during navigation. To reconcile how the DG contributes to separating global context as well as individual navigational routes, we trained mice to perform a delayed-non-match-to-position (DNMP) T-maze task and labeled DG neurons during performance of this task on a novel T-maze. The following day, mice navigated a second environment: the same T-maze, the same T-maze with one route permanently blocked but still visible, or a novel open field. We found that the degree of engram reactivation across days differed based on the traversal of maze routes, such that mice traversing only one arm had higher ensemble overlap than chance but less overlap than mice running the full two-route task. Mice experiencing the open field had similar ensemble sizes to the other groups but only chance-level ensemble reactivation. Ensemble overlap differences could not be explained by behavioral variability across groups, nor did behavioral metrics correlate to degree of ensemble reactivation. Together, these results support the hypothesis that DG contributes to spatial navigation memory and that partially non-overlapping ensembles encode different routes within the context of different environments.

Highlights

Immediate-early-gene labeling strategy revealed spatial navigation ensembles in DG

Sub-ensembles encode separate maze routes within a larger task context

Ensemble reactivation does not correlate with behavioral variables
Across atoms to crossing continents: application of similarity measures to biological location data
Authors: Schuhmann Fabian , Ryvkin Leonie , McLaren James D. , Gerhards Luca , Solov’yov Ilia A.
Published: June 2022

Biological processes involve movements across all measurable scales. Similarity measures can be applied to compare and analyze these movements but differ in how differences in movement are aggregated across space and time. The present study reviews frequently-used similarity measures, such as the Hausdorff distance, Frechet distance, Dynamic Time Warping, and Longest Common Subsequence, jointly with several measures less used in biological applications (Wasserstein distance, weak Fréchet distance, and Kullback-Leibler divergence), and provides computational tools for each of them that may be used in computational biology. We illustrate the use of the selected similarity measures in diagnosing differences within two extremely contrasting sets of biological data, which, remarkably, may both be relevant for magnetic field perception by migratory birds. Specifically, we assess and discuss cryptochrome protein conformational dynamics and extreme migratory trajectories of songbirds between Alaska and Africa. We highlight how similarity measures contrast regarding computational complexity and discuss those which can be useful in noise elimination or, conversely, are sensitive to spatiotemporal scales.
Quantifying the number of translatable transcripts through the use of OMICs involved in post-transcriptional regulation
Authors: Ochoteco Asensio Juan , Kleinjans Jos , Caiment Florian
Published: June 2022

Transcriptomics is nowadays frequently used as an analytical tool to study the extent of cell expression changes between two phenotypes or between different conditions. However, an important portion of the significant changes observed in transcriptomics at the gene level is usually not consistently detected at the protein level by proteomics. This poor correlation between the measured transcriptome and proteome is probably mainly due to post-transcriptional regulation, among which miRNA and circRNA have been proposed to play an important role. Therefore, since both miRNA and circRNA are also quantified by transcriptomics, we proposed to build a model taking those factors into account to estimate, for each transcript, the fraction of transcripts that would be available for translation. Using a dataset of cells exposed to diverse compounds, we evaluated how our model was able to improve the correlation between the assessed transcriptome and proteome expression level. The results show that the model improved the correlation for a subset of genes, probably due to the regulation of different miRNAs across the genome.
Hippocampal 4-Hz oscillations emerge during stationary running in a wheel and are resistant to medial septum inactivation
Authors: de Lima Ivan Alisson Cavalcante Nunes , Belchior Hindiael
Published: June 2022

Recent studies described 2-4 Hz oscillations in the hippocampus of rats performing stationary locomotion on treadmills and other apparatus. Since the 2-4 Hz rhythm shares common features with hippocampal theta (5-12 Hz) oscillations - such as a positive running speed-amplitude relationship and modulation of spiking activity - many have questioned whether these rhythms are related or independently generated. To answer this question, we analyzed local field potentials (LFP) and spiking activity from the dorsal CA1 of rats executing a spatial alternation task and running for ∼15 s in a wheel during the intertrial intervals both before and after muscimol injection into the medial septum. We observed 4-Hz oscillations during wheel runs, but not during maze runs. The 4-Hz amplitude positively correlated with wheel speed and negatively with maze speed. Also, the amplitude of 4-Hz and theta oscillations were inversely related. Medial septum inactivation abolished hippocampal theta but preserved 4-Hz oscillations. It also affected the entrainment of pyramidal cells and interneurons by 4-Hz rhythmic activity. In all, these results dissociate the underlying mechanism of 4-Hz and theta oscillations in the rat hippocampus.

Highlights

4-Hz oscillations emerge in the rat hippocampus during wheel running and correlate with speed

4-Hz and theta amplitude are inversely correlated

4-Hz oscillations are resistant to medial septum inactivation

Rhythmic discharge of interneurons and pyramidal cells at 4-Hz are reduced by medial septum inactivation

In brief

Lima and Belchior tested whether the pharmacological inactivation of the medial septum affects hippocampal 4-Hz oscillations associated with stationary running. They found that septal inactivation preserved 4-Hz oscillations while abolished theta, which dissociate the underlying mechanisms of these rhythms in the rat hippocampus.
Resource-Rational Account of Sequential Effects in Human Prediction
Authors: Prat-Carrabin Arthur , Meyniel Florent , da Silveira Rava Azeredo
Published: June 2022

An abundant literature reports on ‘sequential effects’ observed when humans make predictions on the basis of stochastic sequences of stimuli. Such sequential effects represent departures from an optimal, Bayesian process. A prominent explanation posits that humans are adapted to changing environments, and erroneously assume nonstationarity of the environment, even if the latter is static. As a result, their predictions fluctuate over time. We propose a different explanation in which sub-optimal and fluctuating predictions result from cognitive constraints (or costs), under which humans however behave rationally. We devise a framework of costly inference, in which we develop two classes of models that differ by the nature of the constraints at play: in one case the precision of beliefs comes at a cost, resulting in an exponential forgetting of past observations, while in the other beliefs with high predictive power are favored. To compare model predictions to human behavior, we carry out a prediction task that uses binary random stimuli, with probabilities ranging from .05 to .95. Although in this task the environment is static and the Bayesian belief converges, subjects’ predictions fluctuate and are biased toward the recent stimulus history. Both classes of models capture this ‘attractive effect’, but they depart in their characterization of higher-order effects. Only the precision-cost model reproduces a ‘repulsive effect’, observed in the data, in which predictions are biased away from stimuli presented in more distant trials. Our experimental results reveal systematic modulations in sequential effects, which our theoretical approach accounts for in terms of rationality under cognitive constraints.
Immune evasion impacts the selective landscape of driver genes during tumorigenesis
Authors: Gourmet Lucie , Sottoriva Andrea , Secrier Maria , Zapata Luis
Published: June 2022

Carcinogenesis is an evolutionary process fueled by the interplay of somatic mutations and the local microenvironment. In recent years, hundreds of cancer related genes have been discovered using cancer cohorts. However, these cohorts are heterogenous mixtures of different molecular phenotypes, which hampers the identification of driver genes associated to a specific cancer hallmark or microenvironment. Here, we compared the landscape of positively selected somatic mutations in immune-escaped (escape+) versus non-escaped (escape-) tumors. We applied the ratio of non-synonymous to synonymous mutations (dN/dS) to 9896 individuals from 31 primary tumor tissues from the Cancer Genome Atlas (TCGA) separated by escape status. Altogether, we found 85 driver genes, including 27 and 16 novel driver genes in escape- and escape+ tumors, respectively. Overall, driver dN/dS of escape+ tumors (dN/dS=1.23) was significantly lower and closer to neutrality than driver dN/dS of escape-tumors (dN/dS=1.62), suggesting a relaxation of positive selection in driver genes, a relaxation of negative selection on immunogenic driver sites, or a combination of both fueled by immune escape. We also found that the proportion of unique sites mutated in escape+ tumors is almost double than in escape-tumors, and that immune evasion allows for a more diverse repertoire of mutational signatures. We also identified that strong immunoediting in the absence of escape leads to a better overall survival in tumors enriched by an inflamed phenotype. Ultimately, our findings reveal differences in the evolutionary strategies used by cancer cells to establish tumorigenesis and highlight the need for better patient stratification to develop tailored treatments based on molecular targets.
Ancestral sex-role plasticity facilitates the evolution of same-sex sexual behaviour
Authors: Mizumoto Nobuaki , Bourguignon Thomas , Bailey Nathan W.
Published: June 2022

Recent attempts to explain the evolutionary prevalence of same-sex sexual behaviour (SSB) have focused on the role of indiscriminate mating. However, in many cases, SSB involves plastically adjusting sex roles to achieve successful courtship or pairing. To evaluate this overlooked factor, we tested whether ancestral sex-role plasticity facilitated the evolution of SSB in the termite Reticulitermes speratus. Male termites follow females in paired ‘tandems’ before mating, and movement patterns are sexually dimorphic. Adaptive same-sex tandems occur in both sexes. We show that in such cases, one partner adopts the other sex’s movement patterns, resulting in behavioural dimorphism. Data-based simulations confirmed that this socially-cued plasticity contributes to pair maintenance because dimorphic movements improve reunion success upon accidental separation. Phylogenetic analysis indicated that the ancestors of modern termites lack consistent sex roles during pairing, indicating that R. speratus inherited the plasticity from the ancestor. Socio-environmental induction of ancestral behavioural potential may be of widespread importance to the evolutionary maintenance of SSB.
Changes in benthic and pelagic production interact with warming to drive responses to climate change in a temperate coastal ecosystem
Authors: Audzijonyte Asta , Delius Gustav , Stuart-Smith Rick D. , Novaglio Camilla , Edgar Graham J. , Barrett Neville S. , Blanchard Julia L.
Published: June 2022

Changing sea temperatures and primary productivity are rapidly altering marine ecosystems, but with considerable uncertainty in our understanding of the relative importance of these drivers and how their interactions may affect fisheries yield through complex food webs. Such outcomes are more difficult to predict for shallow coastal ecosystems than those in pelagic and shelf habitats, because coastal food webs are fuelled by a combination of separate pelagic and benthic energy pathways. Using long-term, empirical field data, we developed a novel multispecies size spectrum model for shallow coastal reefs. We include size-structured benthic and pelagic resources and trophic structures, allowing us to explore potential climate change scenarios that involve varying combinations of warming with changes in benthic and pelagic resources. Our model predicts that changes in resource levels will have much stronger impacts on fish biomass and yields than changes driven by physiological responses to temperature. Under increased plankton abundance, species in all trophic groups were predicted to increase in biomass, average size and yields. By contrast, changes in benthic resource produced variable responses across coastal trophic groups. Increased benthic resource led to increasing benthivorous and piscivorous fish biomass, yields and mean body sizes, but decreases in herbivores and planktivores. When resource changes were combined with warming seas, physiological responses generally decreased species’ biomass and yields. Our results suggest that the source, size and abundance of primary and secondary producers are critical to understanding impacts of warming seas on coastal fish communities. Understanding changes in benthic production and its implications for coastal fisheries requires urgent attention. Our modified size spectrum model provides a framework for further study of benthic and pelagic energy pathways that can be easily adapted to other ecosystems.
Associations of functional HLA class I groups with HIV viral load in a heterogeneous cohort
Authors: Zucco Adrian G. , Bennedbæk Marc , Ekenberg Christina , Gabrielaite Migle , Leung Preston , Polizzotto Mark N. , Kan Virginia , Murray Daniel D. , Lundgren Jens D. , Macpherson Cameron R. ,   the INSIGHT START study group
Published: June 2022

Human Leucocyte Antigen (HLA) class I alleles are the main host genetic factors involved in controlling HIV-1 viral load (VL). Nevertheless, HLA diversity has proven a significant challenge in association studies. We assessed how accounting for binding affinities of HLA class I alleles to HIV-1 peptides facilitate association testing of HLA with HIV-1 VL in a heterogeneous cohort from the Strategic Timing of AntiRetroviral Treatment (START) study. We imputed HLA class I alleles from host genetic data (2,546 HIV+ participants) and sampled immunopeptidomes from 2,079 host-paired viral genomes (targeted amplicon sequencing). We predicted HLA class I binding affinities to HIV-1 and unspecific peptides, grouping alleles into functional clusters through consensus clustering. These functional HLA class I clusters were used to test associations with HIV VL. We identified four clades totalling 30 HLA alleles accounting for 11.4% variability in VL. We highlight HLA-B*57:01 and B*57:03 as functionally similar but yet overrepresented in distinct ethnic groups, showing when combined a protective association with HIV+ VL (log, β −0.25; adj. p-value < 0.05). We further demonstrate only a slight power reduction when using unspecific immunopeptidomes, facilitating the use of the inferred functional HLA groups in other studies. The outlined computational approach provides a robust and efficient way to incorporate HLA function and peptide diversity, aiding clinical association studies in heterogeneous cohorts. To facilitate access to the proposed methods and results we provide an interactive application for exploring data.

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