bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelvic Avulsion Fractures in Adolescent Athletes: Analyzing the Effect of Delay in Diagnosis
Authors: Moeller James L.
Published: September 2021

Objective:

To evaluate whether delay in the diagnosis of pelvic avulsion fractures in young athletes leads to prolonged treatment and prolonged return toward sport activities, whether fractures at certain locations are associated with a greater risk of diagnostic delay, and what reasons may exist for delay in diagnosis.

Design:

Retrospective chart review of young patients who presented with pelvic region avulsion fracture to a community-based sports medicine clinic over a 19-year period.

Setting:

Private practice, primary care sports medicine clinic.

Patients:

Patients younger than 20 years diagnosed with pelvic region avulsion fracture.

Interventions:

None, this was a retrospective study.

Main Outcome Measures:

Clearance for return toward sport activities.

Results:

Two hundred twenty-five cases were reviewed for reasons for delay in diagnosis; 208 cases met criteria for the duration of treatment and return to play activities portions of the study. The mean time from date of injury diagnosis was 19.59 days, and the mean duration from date of injury to clearance for return to play advancement was 67.20 days. Duration of treatment varied slightly depending on timing of diagnosis, whereas duration from date of injury to clearance for return to play advancement varied greatly depending on diagnostic delay. Those who did not sense a “pop” at the time of injury were more likely to experience diagnostic delay, as were athletes with ischial tuberosity fractures. The most common cause of diagnostic delay was patient/family decision on when to seek care; misdiagnosis as a muscle strain was also common.

Conclusions:

Diagnostic delay of adolescent pelvic avulsion fractures may unnecessarily prevent athletes from returning to play within an optimal time frame. Our observations highlight a need for educating athletes and their families on when to seek initial or follow-up medical care as well as educating medical providers regarding the diagnosis of pelvic avulsion fractures.
Role of deceased donor kidney procurement biopsies in organ allocation
Authors: Jadav Paresh , Mohan Sumit , Husain Syed Ali
Published: September 2021

Purpose of review

There has been an increased emphasis by the transplant community and the federal government to increase the utilization of deceased donor kidneys. Procurement biopsies during allocation are the most common reason for kidney discards. This manuscript reviews the evidence of procurement biopsies practices and utility.

Recent findings

Procurement biopsies are performed in over half of all the kidneys recovered in the United States and account for more than one third of the kidney discards. However, there is a significant heterogeneity across the organ procurement organizations regarding the indications for biopsy, biopsy techniques and their reporting. Procurement biopsy findings are not reproducible and poorly correlate to postimplantation histology, although reasons for these limitations are not clear. Procurement biopsy findings are not associated with posttransplant outcomes after accounting for readily available donor clinical characteristics.

Procurement biopsies contribute to deceased donor kidney discards but do not predict posttransplant outcomes. Research to establish the best practices for procurement biopsies is needed to improve organ utilization.
Transition of Care from Pediatric to Adult Care in Eosinophilic Esophagitis
Authors: Robinson Jane , Furuta Glenn T. , Hadker Nandini , Kolev Irana , Williams James , Juethner Salomé , Falk Gary W.
Published: September 2021

Eosinophilic esophagitis (EoE) is a chronic immune‐mediated disease. Patients with a childhood diagnosis require ongoing disease management in adulthood; however, knowledge of the patient experience during pediatric to adult healthcare transition is lacking. Here, an online survey captured patient perceptions of the challenges faced by patients with EoE in the United States during transition to adult healthcare, and which resources, if implemented, could better support transition. Of 67 respondents, 91% (n = 61) were under adult care at the time of survey completion. Aspects that respondents struggled with most included meal planning, food shopping, cooking/finding foods that did not exacerbate their condition, and knowledge of insurance coverage. Although most respondents reported confidence in having the knowledge to manage their EoE, almost half of the respondents worried about managing their condition in the future. Resources detailing diet, medication and insurance management strategies could support the transition to adult healthcare for patients with EoE.
Swallowing difficulty in the older adults: presbyphagia or dysphagia with sarcopenia?
Authors: Yiğman Zeynep Aykin , Umay Ebru , Cankurtaran Damla , Güzel Şükran
Published: September 2021

Oropharyngeal dysphagia is an important cause of mortality and morbidity in older adults. It has been reported in the literature that 11–68% of older adults experience swallowing difficulties. This study aimed to investigate the presence of dysphagia in older adults, whether this dysphagia is related to age (presbyphagia) or sarcopenia by comparing it with adults. Two hundred twenty-five patients were included in this cross-sectional study. The participants were divided into two groups by age as ‘adults’ and ‘older adults’. Sarcopenia, dysphagia and malnutrition evaluations were performed. Older adult and adult groups were compared in terms of malnutrition, dysphagia and sarcopenia. The number of patients with dysphagia was significantly higher (P = 0.007) in the older adults. In older adults, all sarcopenic evaluation parameters were found significantly lower than adults (P < 0.05). The number of older adults with malnutrition was significantly lower in patients with normal swallowing (P < 0.05). The swallowing difficulty can be detected in older adults even if it does not cause any complaint. While most swallowing disorders may be due to age-related changes, about a third may be accompanied by sarcopenia.
Prevalence of High-Risk Human Papillomavirus by RNA Assay in Home Self-Collected Samples Among Underscreened People in North Carolina
Authors: Lee Fan , Bukowski Alexandra , Spees Lisa P. , Wheeler Stephanie B. , Brewer Noel T. , Sanusi Busola , Hudgens Michael G. , Jackson Sarah , Barclay Lynn , Carter Alicia , Tang Jennifer H. , Smith Jennifer S.
Published: September 2021

Background

Low-income and uninsured people with a cervix (PWC) are at the highest risk of being underscreened for cervical cancer. We evaluated the prevalence of high-risk human papillomavirus (hrHPV) on home self-collected samples, as well as rates of in-clinic follow-up and risk factors associated with hrHPV positivity in this at-risk population.

Methods

My Body My Test 3 was conducted between 2016 and 2019 in North Carolina among individuals aged 25 to 64 years, overdue for cervical cancer screening, and with incomes of <250% of the US Federal Poverty Level. Our analytic sample included participants randomized to the self-collection arm who returned self-collected cervicovaginal brush samples for HPV testing (n = 329). Samples were tested for 14 hrHPV types by an HPV RNA assay and further genotyped for HPV-16 and HPV-18/45. We examined behavioral risk factors for hrHPV positivity using logistic regression and between-subject t tests.

Results

High-risk HPV RNA prevalence was 16% (n = 52/329) in self-collected samples. Of the hrHPV-positive participants, 24 (46%) presented for in-clinic cervical cancer screening, compared with 56 (20%) of hrHPV-negative participants. Those with ≥2 sexual partners in the past year were twice as likely to be hrHPV positive in adjusted analyses (adjusted odds ratio, 2.00 [95% confidence interval, 1.03–3.88]). High-risk HPV-positive and HPV-negative participants had similar attitudes toward screening, with the exception of hrHPV-positive participants who reported a lower perceived risk of cervical cancer than those who were hrHPV negative (P < 0.05).

Conclusion

The hrHPV RNA prevalence was similar to findings in other underscreened PWC in the United States. Efforts to reach underscreened PWC are critical for cervical cancer prevention. Future studies aimed at home self-collection should address methods of increasing clinic attendance and completion of treatment among those with HPV-positive results.
Elevated Expressions of BTN3A1 and RhoB in Psoriasis Vulgaris Lesions by an Immunohistochemical Study
Authors: Tian Zhen , Wong Wenghong , Wu Qiong , Zhou Jiaqing , Yan Kexiang , Chen Jia , Zhang Zhenghua
Published: September 2021

Psoriasis is a chronic, immune-mediated inflammatory disease which pathogenesis is closely linked to γδ T cells. Recently, a critical role for butyrophilin 3A1 (BTN3A1) in mediating the activation of Vγ9Vδ2 T cells, which are reported to redistribute from blood to the perturbed skin lesions in psoriasis, has been proposed. Additional molecular partners, including RhoB and periplakin, have also been speculated to interact with BTN3A1 in modulating Vγ9Vδ2 T-cell activation. Immunohistochemical staining was performed to examine the expressions of BTN3A1, RhoB, and the plakin family members, including periplakin, epiplakin, and envoplakin in the psoriasis vulgaris lesions as compared with the normal control. The expressions of BTN3A1 and RhoB were found significantly upregulated in the psoriatic lesions. Besides, a downregulation of periplakin and an upregulation of epiplakin were noticed in the psoriasis vulgaris lesions. Our data suggest that BTN3A1 and RhoB might participate in the pathogenesis of psoriasis through Vγ9Vδ2 T-cell responses. In addition, a potential involvement of the plakin protein family, especially periplakin and epiplakin, in psoriasis pathology was proposed.
Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
Authors: Aguilar Mitzi , Chen Hao , Rivera-Colon Glorimar , Niu Shuang , Carrick Kelley , Gwin Katja , Cuevas Ileana C. , Sahoo Subhransu S. , Li Hao-Dong , Zhang Song , Zheng Wenxin , Lucas Elena , Castrillon Diego H.
Published: September 2021

The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually—and more importantly as a group—has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, β-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), β-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or β-catenin. A focused panel of only 3 markers (Pax2, Pten, and β-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN.
Eyebrow Reconstruction With Temporal Hairline Relay Flap
Authors: Gu Cong-Min , Chen Wen , Yang Ming-Yong
Published: September 2021

Eyebrow is one of the most important features of the face; the absence of eyebrows will cause a heavy psychological burden to patients. Existing brow reconstruction techniques are not perfect for every case of eyebrow defect. In this study, a patient who suffered from eyebrows loss after radiotherapy for hemangioma underwent eyebrow reconstruction with the relay transfer of a temporal hairline flap. The entire procedure was performed in the outpatient operating room. The temporal hairline flap was transferred to the eyebrow region in a relay and survived well without necrosis. In the 2-month follow-up, the shape and density of the reconstructed eyebrows were satisfactory. The operation showed this technique was innovative, economic, and recommended as a suitable choice for eyebrow reconstruction, especially in those patients with poor hair transplantation recipient area.
Brief exposure to systemic hypoxia enhances plasticity of the central nervous system in spinal cord injured animals and man
Authors: Sandhu Milap S. , Rymer William Z.
Published: September 2021

Purpose of review

We have known for many decades that animals that sustain injuries to the neuraxis, which result in respiratory impairment, are able to develop rapid neural compensation for these injuries. This compensation, which is linked to the systemic hypoxia resulting from damage to the respiratory apparatus, is a potent manifestation of neural plasticity. Hypoxia-induced plasticity is also applicable to somatic neural systems that regulate motor activity in extremity muscles. We report on recent developments in our understanding of the mechanisms underlying this seemingly beneficial action of acute intermittent hypoxia (AIH).

Recent findings

AIH improves breathing in animal models of spinal cord injury, and increases strength and endurance in individuals with incomplete spinal injuries. The role of AIH as a therapeutic intervention remains to be confirmed but it has proved to be well tolerated for use in humans with no adverse effects reported to date. The effects of AIH emerge rapidly and persist for several hours raising the possibility that the intervention may serve as a priming mechanism for facilitating rehabilitation and promoting recovery after neurologic injury in man.

AIH is emerging as a potent and relatively inexpensive modality for inducing neuroplasticity, so it may prove feasible to use AIH in a clinical setting.
Timing of spring departure of long distance migrants correlates with previous year's conditions at their breeding site
Authors: Amélineau Françoise , Delbart Nicolas , Schwemmer Philipp , Marja Riho , Fort Jérôme , Garthe Stefan , Elts Jaanus , Delaporte Philippe , Rousseau Pierre , Duraffour Françoise , Bocher Pierrick
Published: September 2021

Precise timing of migration is crucial for animals targeting seasonal resources at locations encountered across their annual cycle. Upon departure, long-distance migrants need to anticipate unknown environmental conditions at their arrival site, and they do so with their internal annual clock. Here, we tested the hypothesis that long-distance migrants synchronize their circannual clock according to the phenology of their environment during the breeding season and therefore adjust their spring departure date according to the conditions encountered at their breeding site the year before. To this end, we used tracking data of Eurasian curlews from different locations and combined movement data with satellite-extracted green-up dates at their breeding site. The spring departure date was better explained by green-up date of the previous year, while arrival date at the breeding site was better explained by latitude and longitude of the breeding site, suggesting that other factors impacted migration timing
en route
. On a broader temporal scale, our results suggest that long-distance migrants may be able to adjust their migration timing to advancing spring dates in the context of climate change.
Nonomuraea nitratireducens Qu et al. 2020 is a later heterotypic synonym of Nonomuraea phyllanthi Klykleung et al. 2020
Authors: Wu Yong , Peng Miaomiao , Gao Yuxin , Pei Jiahao , Zhang Yan , Li Sicong , Fang Jiasong , Wei Yuli
Published: September 2021

Nonomuraea nitratireducens

WYY166T was compared with

Nonomuraea phyllanthi

PA1-10T to examine the taxonomic relationship between the two type strains. The 16S rRNA gene sequence of

N. nitratireducens

WYY166T had high similarity (99.9 %) to that of

N. phyllanthi

PA1-10T. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the two strains formed a tight cluster within the genus

Nonomuraea

. Draft genomic comparison between the two strains revealed an average nucleotide identity of 99.3 % and a digital DNA–DNA hybridization estimate of 94.4±1.8 %, strongly indicating that the two strains represented a single species. In addition, neither strain displayed any striking difference in metabolic, physiological or chemotaxonomic features. Therefore, we propose

Nonomuraea nitratireducens

as a later heterotypic synonym of

Nonomuraea phyllanthi

.
Proteomic landscape of Japanese encephalitis virus-infected fibroblasts
Authors: Sharma Kiran Bala , Chhabra Simran , Aggarwal Suruchi , Tripathi Aarti , Banerjee Arup , Yadav Amit Kumar , Vrati Sudhanshu , Kalia Manjula
Published: September 2021

Advances in proteomics have enabled a comprehensive understanding of host–pathogen interactions. Here we have characterized Japanese encephalitis virus (JEV) infection-driven changes in the mouse embryonic fibroblast (MEF) proteome. Through tandem mass tagging (TMT)-based mass spectrometry, we describe changes in 7.85 % of the identified proteome due to JEV infection. Pathway enrichment analysis showed that proteins involved in innate immune sensing, interferon responses and inflammation were the major upregulated group, along with the immunoproteasome and poly ADP-ribosylation proteins. Functional validation of several upregulated anti-viral innate immune proteins, including an active cGAS–STING axis, was performed. Through siRNA depletion, we describe a crucial role of the DNA sensor cGAS in restricting JEV replication. Further, many interferon-stimulated genes (ISGs) were observed to be induced in infected cells. We also observed activation of TLR2 and inhibition of TLR2 signalling using TLR1/2 inhibitor CU-CPT22-blocked production of inflammatory cytokines IL6 and TNF-α from virus-infected N9 microglial cells. The major proteins that were downregulated by infection were involved in cell adhesion (collagens), transport (solute carrier and ATP-binding cassette transporters), sterol and lipid biosynthesis. Several collagens were found to be transcriptionally downregulated in infected MEFs and mouse brain. Collectively, our data provide a bird’s-eye view into how fibroblast protein composition is rewired following JEV infection.
Improved detection of SBDS gene mutation by a new method of next-generation sequencing analysis based on the Chinese mutation spectrum
Authors: Wu Dong , Zhang li , Qiang Yuzhen , Wang Kaiyu
Published: September 2021

Next-generation sequencing (NGS) is a useful molecular diagnostic tool for genetic diseases. However, due to the presence of highly homologous pseudogenes, it is challenging to use short-read NGS for analyzing mutations of the Shwachman-Bodian-Diamond syndrome (SBDS) gene. The SBDS mutation spectrum was analyzed in the Chinese population, which revealed that SBDS variants were primarily from sequence exchange between SBDS and its pseudogene at the base-pair level, predominantly in the coding region and splice junction of exon two. The c.258+2T>C and c.185_184TA>GT variants were the two most common pathogenic SBDS variants in the Chinese population, resulting in a total carrier frequency of 1.19%. When analyzing pathogenic variants in the SBDS gene from the NGS data, the misalignment was identified as a common issue, and there were different probabilities of misalignment for different pathogenic variants. Here, we present a novel mathematical method for identifying pathogenic variants in the SBDS gene from the NGS data, which utilizes read-depth of the paralogous sequence variant (PSV) loci of SBDS and its pseudogene. Combined with PCR and STR orthogonal experiments, the results of SBDS gene mutation analysis were improved in 40% of clinical samples, and various types of mutations such as homozygous, compound heterozygous, and uniparental diploid were explored. The findings effectively reduce the impact of misalignment in NGS-based SBDS mutation analysis and are helpful for the clinical diagnosis of SBDS-related diseases, the research into population variation, and the carrier screening.
Distributed Counterfactual Modeling Approach for Investigating Hospital-Associated Racial Disparities in COVID-19 Mortality
Authors: Edmondson Mackenzie , Luo Chongliang , Islam Nazmul , Asch David , Bian Jiang , Chen Yong
Published: September 2021

Several studies have found that black patients are more likely than white patients to test positive for or be hospitalized with COVID-19, but many of these same studies have found no difference in in-hospital mortality. These studies may have underestimated racial differences due to reliance on data from a single hospital system, as adequate control of patient-level characteristics requires aggregation of highly granular data from several institutions. Further, one factor thought to contribute to disparities in health outcomes by race is site of care. Several differences between black and white patient populations, such as access to care and referral patterns among clinicians, can lead to patients of different races largely attending different hospitals. We sought to develop a method that could study the potential association between attending hospital and racial disparity in mortality for COVID-19 patients without requiring patient-level data sharing among collaborating institutions. We propose a novel application of a distributed algorithm for generalized linear mixed modeling (GLMM) to perform counterfactual modeling and investigate the role of hospital in differences in COVID-19 mortality by race. Our counterfactual modeling approach uses simulation to randomly assign black patients to hospitals in the same distribution as those attended by white patients, quantifying the difference between observed mortality rates and simulated mortality risk following random hospital assignment. To illustrate our method, we perform a proof-of-concept analysis using data from four hospitals within the OneFlorida Clinical Research Consortium. Our approach can be used by investigators from several institutions to study the impact of admitting hospital on COVID-19 mortality, a critical step in addressing systemic racism in modern healthcare.
SARS-CoV-2 variants in Paraguay: Detection and surveillance with a readily modifiable, multiplex real-time RT-PCR
Authors: Martinez Magaly , Nguyen Phuong-Vi , Su Maxwell , Cardozo Fátima , Valenzuela Adriana , Franco Laura , Galeano María Eugenia , Rojas Leticia Elizabeth , Díaz Acosta Chyntia Carolina , Fernández Jonás , Ortiz Joel , Puerto Florencia del , Mendoza Laura , Nara Eva , Rojas Alejandra , Waggoner Jesse J.
Published: September 2021

Objectives

The objective of the current study was to develop a lower-cost and scalable protocol to identify and monitor SARS-CoV-2 variants in Paraguay by pairing real-time RT-PCR detection of spike mutations with amplicon Sanger sequencing and whole-genome Nanopore sequencing.

Methods

201 acute-phase nasopharyngeal samples from SARS-CoV-2-positive individuals were tested with two rRT-PCRs: 1) N2RP assay to confirm SARS-CoV-2 RNA detection (CDC N2 target), and 2) the Spike SNP assay to detect mutations in thespikereceptor binding domain. The assay was performed with probes to identify mutations associated with the following variants: alpha (501Y), beta/gamma (417variant/484K/501Y), delta (452R/478K), and lambda (452Q/490S).

Results

All samples were positive for SARS-CoV-2 in the N2RP assay (mean Ct, 20.8; SD 5.6); 198/201 (98.5%) tested positive in the Spike SNP assay. The most common genotype was 417variant/484K/501Y, detected in 102/198 samples (51.5%) and most consistent with P.1 lineage (gamma variant) in Paraguay. No mutations (K417 only) were found in 64/198 (32.3%); and K417/484K was identified in 22/198 (11.1%), consistent with P.2 (zeta). Seven samples (3.5%) tested positive for 452R without 478K, and one sample with genotype K417/501Y was confirmed as B.1.1.7 (alpha). Results were confirmed by Sanger sequencing in 181/181 samples (100%) with high-quality amplicon sequences, and variant calls were consistent with Nanopore sequencing in 29/29 samples.

Conclusions

The Spike SNP assay provides accurate detection of mutations associated with SARS-CoV-2 variants. This can be implemented in laboratories performing rRT-PCR to improve population-level surveillance for these mutations and inform the judicious use of scarce sequencing resources.
Detection of SARS-CoV-2 in the community by nucleic acid amplification testing of saliva
Authors: Fronza Filippo , Groff Nelli , Martinelli Angela , Passerini Beatrice Zita , Rensi Nicolò , Cortelletti Irene , Vivori Nicolò , Adami Valentina , Helander Anna , Bridi Simone , Pancher Michael , Greco Valentina , Garritano Sonia Iolanda , Piffer Elena , Stefani Lara , De Sanctis Veronica , Bertorelli Roberto , Pancheri Serena , Collini Lucia , Quattrone Alessandro , Capobianchi Maria Rosaria , Icardi Giancarlo , Poli Guido , Caciagli Patrizio , Ferro Antonio , Pizzato Massimo
Published: September 2021

Efficient wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) swabs, which requires the intervention of trained personnel. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here we describe the set-up of a laboratory, in an academic context, for the high-throughput screening of SARS-CoV-2 in the saliva from the community. A novel saliva collection device was designed to favour the safe and correct acquisition of the sample as well as the processivity of the downstream molecular analysis. To test the performance of the system,1025 paired saliva and nasopharyngeal samples were collected from individuals recruited at a public drive through testing facility and analysed in parallel. An overall moderate concordance (68%) between the two tests was found, with evidence that neither test can diagnose the infection in 100% of the cases. While the two tests performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent individuals. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study, therefore, indicates that saliva testing can be a reliable tool for wide-scale COVID-19 screening in the community.
Correlates of COVID-19 vaccination status among college students
Authors: Nicolo Michele , Kawaguchi Eric , Ghanem-Uzqueda Angie , Kim Andre E. , Soto Daniel , Deva Sohini , Shanker Kush , Rogers Christopher , Lee Ryan , Gilliland Frank , Klausner Jeffery , Kovacs Andrea , Conti David , Hu Howard , Unger Jennifer B.
Published: September 2021

Objectives

Despite the widespread availability of COVID-19 vaccines in the United States, vaccine hesitancy remains high among certain groups. This study examined the correlates of being unvaccinated among a sample of university students (N=2900) during the spring and summer of 2021, when the campus had been closed for over a year and students were preparing to return to in-person learning.

Methods

Students responded to an email invitation and completed electronic surveys. Results. In multivariable logistic regression analyses, students were more likely to be unvaccinated if they were African American, identified with any political affiliation other than Democrat, were undergraduates or international students, had not traveled outside the Los Angeles during the pandemic, and/or had previously been ill with COVID-19.

Conclusion

Findings indicate that culturally resonant educational interventions, and possibly vaccine requirements, are needed to promote vaccination among university students.
Lifelong musical activity is associated with multi-domain cognitive and brain benefits in older adults
Authors: Böttcher Adriana , Zarucha Alexis , Köbe Theresa , Gaubert Malo , Höppner Angela , Fabel Klaus , Altenstein Slawek , Bartels Claudia , Buerger Katharina , Dechent Peter , Dobisch Laura , Ewers Michael , Fliessbach Klaus , Freiesleben Silka Dawn , Frommann Ingo , Haynes John Dylan , Janowitz Daniel , Kilimann Ingo , Kleineidam Luca , Laske Christoph , Maier Franziska , Metzger Coraline , Munk Matthias , Perneczky Robert , Peters Oliver , Priller Josef , Rauchmann Boris-Stephan , Roy Nina , Scheffler Klaus , Schneider Anja , Spottke Annika , Teipel Stefan J. , Wiltfang Jens , Wolfsgruber Steffen , Yakupov Renat , Duzel Emrah , Jessen Frank , Röske Sandra , Wagner Michael , Kempermann Gerd , Wirth Miranka ,   for the DELCODE study group
Published: September 2021

1

Abstract

Regular musical activity as a highly-stimulating lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease (AD). This study investigated associations between lifelong regular musical instrument playing, late-life cognitive abilities and brain morphology in older adults. We show that musical activity over the life course is associated with better global cognition, working memory, executive functions, language, and visuospatial abilities accounting for reserve proxies. Playing music is not significantly associated with gray matter volume in regions most affected by aging and AD. Selectively in the musically active participants, multi-domain cognitive abilities were enhanced with preserved gray matter volume in frontal and temporal regions. Our correlational findings suggest that playing a musical instrument may improve the recruitment of existing brain resources to facilitate late-life cognitive capacities. We propose that engaging in regular musical activity could serve as a low-threshold multimodal enrichment strategy that may promote cognitive resilience in advanced age.
Pre-copulatory reproductive behaviours are preserved in Drosophila melanogaster infected with bacteria
Authors: Rose Saloni , Beckwith Esteban J. , Burmester Charlotte , May Robin C. , Dionne Marc S. , Rezaval Carolina
Published: September 2021

Reproduction and immunity are crucial traits that determine an animal’s fitness. Terminal investment hypothesis predicts that reproductive investment should increase in the face of a mortality risk caused by infection. However, due to competitive allocation of energetic resources, individuals fighting infections are expected to decrease reproductive efforts. While there is evidence for both hypotheses, the factors that determine the choice between these strategies are poorly understood. Here, we assess the impact of bacterial infection on pre-copulatory behaviours in the fruit fly Drosophila melanogaster. We found that male flies infected with six different bacteria, including pathogenic and non-pathogenic strains, show no significant differences in courtship intensity and mating success. Similarly, bacterial infections did not affect sexual receptivity in female flies. Our data suggest that pre-copulatory reproductive behaviours remain preserved in infected animals, despite the huge metabolic cost of infection.
Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad
Authors: Mayère Chloé , Regard Violaine , Perea-Gomez Aitana , Bunce Corey , Neirijnck Yasmine , Djari Cyril , Sararols Pauline , Reeves Richard , Greenaway Simon , Simon Michelle , Siggers Pam , Condrea Diana , Kühne Françoise , Gantar Ivana , Tang Furong , Stévant Isabelle , Batti Laura , Ghyselinck Norbert B. , Wilhelm Dagmar , Greenfield Andy , Capel Blanche , Chaboissier Marie-Christine , Nef Serge
Published: September 2021

Gonadal sex determination represents a unique model for studying cell fate decisions. However, a complete understanding of the different cell lineages forming the developing testis and ovary remains elusive. Here, we investigated the origin, specification and subsequent sex-specific differentiation of a previously uncharacterized population of supporting-like cells (SLC) in the developing mouse gonads. The SLC lineage is closely related to the coelomic epithelium and specified as early as E10.5, making it the first somatic lineage to be specified in the bipotential gonad. SLC progenitors are localized within the genital ridge at the interface with the mesonephros and initially co-expressWnt4andSox9. SLCs become sexually dimorphic around E12.5, progressively acquire a Sertoli- or granulosa-like identity and contribute to the formation of the rete testis and rete ovarii. Finally, we found that WNT4 is a crucial regulator of the SLC lineage and is required for the formation of the rete testis.

Teaser

Description of an uncharacterized multipotent gonadal cell lineage involved in testis and ovary development
High-order functional interactions in ageing explained via alterations in the connectome in a whole-brain model
Authors: Gatica Marilyn , Rosas Fernando E. , Mediano Pedro A.M. , Diez Ibai , Swinnen Stephan P. , Orio Patricio , Cofré Rodrigo , Cortes Jesus M.
Published: September 2021

The human brain generates a rich repertoire of spatio-temporal activity patterns, which support a wide variety of motor and cognitive functions. These patterns of activity change with age in a multi-factorial manner. One of these factors is the variations in the brain’s connectomics that occurs along the lifespan. However, the precise relationship between high-order functional interactions and connnectomics, as well as their variations with age are largely unknown, in part due to the absence of mechanistic models that can efficiently map brain connnectomics to functional connectivity in aging. To investigate this issue, we have built a neurobiologically-realistic whole-brain computational model using both anatomical and functional MRI data from 161 participants ranging from 10 to 80 years old. We show that the age differences in high-order functional interactions can be largely explained by variations in the connectome. Based on this finding, we propose a simple neurodegeneration model that is representative of normal physiological aging. As such, when applied to connectomes of young participant it reproduces the age-variations that occur in the high-order structure of the functional data. Overall, these results begin to disentangle the mechanisms by which structural changes in the connectome lead to functional differences in the ageing brain. Our model can also serve as a starting point for modelling more complex forms of pathological ageing or cognitive deficits.

Author summary

Modern neuroimaging techniques allow us to study how the human brain’s anatomical architecture (a.k.a. structural connectome) changes under different conditions or interventions. Recently, using functional neuroimaging data, we have shown that complex patterns of interactions between brain areas change along the lifespan, exhibiting increased redundant interactions in the older population. However, the mechanisms that underlie these functional differences are still unclear. Here, we extended this work and hypothesized that the variations of functional patterns can be explained by the dynamics of the brain’s anatomical networks, which are known to degenerate as we age. To test this hypothesis, we implemented a whole-brain model of neuronal activity, where different brain regions are anatomically wired using real connectomes from 161 participants with ages ranging from 10 to 80 years old. Analyzing different functional aspects of brain activity when varying the empirical connectomes, we show that the increased redundancy found in the older group can indeed be explained by precise rules affecting anatomical connectivity, thus emphasizing the critical role that the brain connectome plays for shaping complex functional interactions and the efficiency in the global communication of the human brain.
Modelling potential range expansion of an underutilised food security crop in Sub-Saharan Africa
Authors: Koch O. , Mengesha W.A. , Pironon S. , Pagella T. , Ondo I. , Rosa I. , Wilkin P. , Borrell J.S.
Published: September 2021

Despite substantial growth in global agricultural production, food and nutritional insecurity is rising in Sub-Saharan Africa. Identification of underutilised indigenous crops with useful food security traits may provide part of the solution. Enset (Ensete ventricosum) is a perennial banana relative with cultivation restricted to southwestern Ethiopia, where high productivity and harvest flexibility enables it to provide a starch staple for ~20 million people. An extensive wild distribution suggests that a much larger region may be climatically suitable for cultivation. Here we use ensemble ecological niche modelling to predict the potential range for enset cultivation within southern and eastern Africa. We find contemporary bioclimatic suitability for a 12-fold range expansion, equating to 21.9% of crop land and 28.4% of the population in the region. Integration of crop wild relative diversity, which has broader climate tolerance, could enable a 19-fold expansion, particularly to dryer and warmer regions. Whilst climate change may cause a 37% – 52% reduction in potential range by 2070, large centres of suitability remain in the Ethiopian Highlands, Lake Victoria region and the Drakensberg Range. We combine our bioclimatic assessment with socioeconomic data to identify priority areas with high population density, seasonal food deficits and predominantly small-scale subsistence agriculture, where integrating enset may be particularly feasible and deliver climate resilience. When incorporating the genetic potential of wild populations, enset cultivation might prove feasible for an additional 87.2 - 111.5 million people, 27.7 – 33 million of which are in Ethiopia outside of enset’s current cultivation range. Finally, we consider explanations why enset cultivation has not expanded historically, and ethical implications of expanding previously underutilised species.
Hippocampus maintains a flexible and coherent map under reward flavor-landmark cue conflict
Authors: Nair Indrajith R. , Roy Dipanjan
Published: September 2021

Animals predominantly use salient visual cues (landmarks) for efficient navigation over other sensory modalities. When the relative position of the visual cues is altered, the hippocampal population exhibits heterogeneous responses and constructs context-specific spatial maps. Another critical factor that can strongly modulate spatial representation is the presence of reward. Reward features can drive behavior and are known to bias spatial attention. However, it is unclear whether reward flavors are used for spatial reference in the presence of distal cues and how the hippocampus population dynamics changes when the association between reward flavors and distal cues is altered. We investigated these questions by recording place cells from the CA1 while the rats ran in an environment with the conflicting association between reward flavors and distal cues. We report that the hippocampal place cells coherently and dynamically bind to reward flavors or distal cues across sessions, but not simultaneously suggesting the use of a single spatial map. We found that place cells maintained their spatial offset in the cue conflict conditions, thus showing a robust spatial coupling featuring an attractor-like property in the CA1. When the textures were added on the track, the coherency of the CA1 is degraded, as the hippocampus showed a heterogeneous response and weak spatial coupling of co-recorded cells suggesting a break away from the attractor network. These results indicate that reward flavors alone may be used for spatial reference but may not cause sufficient input difference to create context-specific spatial maps in the CA1.
Adipocyte-specific modulation of KLF14 expression in mice leads to sex-dependent impacts in adiposity and lipid metabolism
Authors: Yang Qianyi , Hinkle Jameson , Reed Jordan N. , Aherrahrou Redouane , Xu Zhiwen , Harris Thurl E. , Stephenson Erin J. , Musunuru Kiran , Keller Susanna R. , Civelek Mete
Published: September 2021

Genome-wide association studies identified single nucleotide polymorphisms on chromosome 7 upstream of KLF14 to be associated with metabolic syndrome traits and increased risk for Type 2 Diabetes (T2D). The associations were more significant in women than in men. The risk allele carriers expressed lower levels of the transcription factor KLF14 in adipose tissues than non-risk allele carriers. To investigate how adipocyte KLF14 regulates metabolic traits in a sex-dependent manner, we characterized high-fat diet fed male and female mice with adipocyte-specific Klf14 deletion or overexpression. Klf14 deletion resulted in increased fat mass in female mice and decreased fat mass in male mice. Female Klf14-deficient mice had overall smaller adipocytes in subcutaneous fat depots but larger adipocytes in parametrial depots, indicating a shift in lipid storage from subcutaneous to visceral fat depots. They had reduced metabolic rates and increased respiratory exchange ratios consistent with increased utilization of carbohydrates as an energy source. Fasting and isoproterenol-induced adipocyte lipolysis was defective in female Klf14-deficient mice and concomitantly adipocyte triglycerides lipase mRNA levels were downregulated. Female Klf14-deficient mice cleared blood triglyceride and NEFA less efficiently than wild type. Finally, adipocyte-specific overexpression of Klf14 resulted in lower total body fat in female but not male mice. Taken together, consistent with human studies, adipocyte KLF14 deficiency in female but not in male mice causes increased adiposity and redistribution of lipid storage from subcutaneous to visceral adipose tissues. Increasing KLF14 abundance in adipocytes of females with obesity and T2D may provide a novel treatment option to alleviate metabolic abnormalities.
Long-term Motor Learning in the Wild with High Volume Video Game Data
Authors: Listman Jennifer B. , Tsay Jonathan S. , Kim Hyosub E. , Mackey Wayne E. , Heeger David J.
Published: September 2021

Motor learning occurs over long periods of practice during which motor acuity – the ability to execute actions more accurately, precisely, and within a shorter amount of time – improves. Laboratory-based motor learning studies are typically limited to a small number of participants and a time frame of minutes to several hours per participant. Thus, there is a need to assess the generalizability of theories and findings from lab-based motor learning studies on much larger samples across longer time scales. In addition, laboratory-based studies of motor learning use relatively simple motor tasks which participants are unlikely to be intrinsically motivated to learn, limiting the interpretation of their findings in more ecologically valid settings. We studied the acquisition and longitudinal refinement of a complex sensorimotor skill embodied in a first-person shooter video game scenario, with a large sample size (N = 7174 participants, 682,564 repeats of the 60 sec game) over a period of months. Participants voluntarily practiced the gaming scenario for as much as several hours per day up to 100 days. We found improvement in performance accuracy (quantified as hit rate) was modest over time but motor acuity (quantified as hits per second) improved considerably, with 40-60% retention from one day to the next. We observed steady improvements in motor acuity across multiple days of video game practice, unlike most motor learning tasks studied in the lab that hit a performance ceiling rather quickly. Learning rate was a nonlinear function of baseline performance level, amount of daily practice, and to a lesser extent, number of days between practice sessions. In addition, we found that the benefit of additional practice on any given day was non-monotonic; the greatest improvements in motor acuity were evident with about an hour of practice and 90% of the learning benefit was achieved by practicing 30 minutes per day. Taken together, these results provide a proof-of-concept in studying motor skill acquisition outside the confines of the traditional laboratory and provide new insights into how a complex motor skill is acquired in an ecologically valid setting and refined across much longer time scales than typically explored.
Particle foraging strategies promote microbial diversity in marine environments
Authors: Ebrahimi Ali , Goyal Akshit , Cordero Otto X.
Published: September 2021

Microbial foraging in patchy environments, where resources are fragmented into particles or pockets embedded in a large matrix, plays a key role in natural environments. In the oceans and freshwater systems, particle-associated bacteria can interact with particle surfaces in different ways: some colonize only during short transients, while others form long-lived, stable colonies. We do not yet understand the ecological mechanisms by which both short-term and long-term colonizers can coexist. Here, we address this problem with a mathematical model that explains how marine populations with different detachment rates from particles can stably coexist. In our model, populations grow only while on particles, but also face the increased risk of mortality by predation and sinking. Key to coexistence is the idea that detachment from particles modulates both net growth and mortality, but in opposite directions, creating a trade-off between them. While slow-detaching populations show the highest growth return (i.e., produce more net offspring), they are more susceptible to suffer higher rates of mortality than fast-detaching populations. Surprisingly, fluctuating environments, manifesting as blooms of particles (favoring growth) and predators (favoring mortality) significantly expand the likelihood that populations with different detachment rates can coexist. Our study shows how the spatial ecology of microbes in the ocean can lead to a predictable diversification of foraging strategies and the coexistence of multiple taxa on a single growth-limiting resource.