bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative Radiation Performed at a Nonsarcoma Center May Lead to Increased Wound Complications Following Resection in Patients With Soft Tissue Sarcomas
Authors: Ellison Ciani , King David M. , Neilson John C. , Wooldridge Adam , Charlson John A. , Hackbarth Donald A. , Johnstone Candice , Bedi Meena
Published: November 2021

Objectives:

Preoperative radiation therapy (RT) followed by wide-local excision with or without chemotherapy is widely accepted as management for soft tissue sarcomas (STS). Although studies have demonstrated excellent local control with this technique, there can be significant morbidity with the development of wound complications. It has been shown that sarcoma resections performed at a high-volume center lead to improved survival and functional outcomes. It is unclear, however, if radiation performed in a high-volume center leads to improved outcomes especially related to morbidity. The goal of this study was to determine whether preoperative RT performed at an academic cancer center have lower rates of wound complication compared with RT performed in community cancer centers.

Materials and Methods:

A total of 204 patients with STS were treated with preoperative RT±chemotherapy followed by limb-sparing resection. Of these, 150 patients had preoperative RT performed at an academic sarcoma center. wound complication were defined as those requiring secondary operations or prolonged wound care for 4 months following surgery. Predictors for wound complication were evaluated using a Fisher exact test for univariate analysis and logistic regression for multivariate analysis.

Results:

The overall incidence of wound complication was 28.3%. Significant predictors for wound complication include tumor location and radiation delivered at a community hospital. The postoperative incidence of wound complication was 21% when the preoperative RT was performed at an academic cancer center versus 39% when performed at a community cancer center (P=0.009). On multivariate analysis, both tumor location (P=0.0012, 95% confidence interval: 0.03-0.45, odds ratio: 0.13) and RT performed at a community cancer center (P=0.02, 95% confidence interval: 1.13-4.48, odds ratio: 2.25) remained significant in correlation with postoperative wound complication.

Conclusions:

Preoperative RT performed at an academic cancer center led to lower rates of postoperative wound complication. This may support the recommendation that preoperative RT and resection of STS be performed at an experienced sarcoma center.
Socioeconomic Determinants of the Use of Molecular Testing in Stage IV Colorectal Cancer
Authors: Punekar Salman R. , Griffin Megan M. , Masri Lena , Roman Stefanie D. , Makarov Danil V. , Sherman Scott E. , Becker Daniel J.
Published: November 2021

Objectives:

Treatment with epidermal growth factor receptor monoclonal antibodies extends life for patients with advanced colorectal cancers (CRCs) whose tumors exhibit wild-type KRAS, but KRAS testing may be underused. We studied the role of socioeconomic factors in the application of KRAS testing.

Materials and Methods:

We identified subjects with stage IV colorectal adenocarcinoma diagnosed 2010-2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We used multivariable logistic regression models to evaluate associations between clinical/demographic factors and the rate of KRAS testing. We used multivariable-adjusted Cox proportional hazards models to assess survival.

Results:

We identified 37,676 patients with stage IV CRC, 31.1% of whom were tested for KRAS mutations, of those who had documented KRAS testing, 44% were KRAS mutant. Patients were more likely to be tested if they were younger (odds ratio [OR]=5.10 for age 20 to 29 vs. 80+, 95% confidence interval [CI]: 3.99-6.54, P<0.01), diagnosed more recently (OR=1.92 for 2015 vs. 2010, 95% CI: 1.77-2.08, P<0.01), or lived in an area of high median household income (OR=1.24 for median household income of >$69,311 vs. <$49,265, 95% CI: 1.14-1.35, P<0.01). Patients were less likely to be tested if they had Medicaid (OR=0.83, 95% CI: 0.77-0.88, P<0.01) or were unmarried (OR=0.78, 95% CI: 0.75-0.82, P<0.0001). The risk of death was decreased in patients who received KRAS testing (hazard ratio=0.77, 95% CI: 0.75-0.80, P<0.01).

Conclusions:

We found a low rate of KRAS testing in CRC patients with those living in low-income areas less likely to be tested, even after controlling for Medicaid insurance. Our study suggests that socioeconomic disparities persist despite Medicaid insurance.
Safety and Experience With Combined Antiretroviral Prophylaxis in Newborn at High-risk of Perinatal HIV Infection, in a Cohort of Mother Living With HIV-infant Pairs
Authors: Illán Ramos Marta , Soto Sánchez Beatriz , Mazariegos Orellana Diana , Prieto Tato Luis Manuel , Guillén Martín Sara , Navarro Gómez Mª Luisa , del Rosal Rabes Teresa , Escosa García Luis , Roa Francia Miguel Ángel , Beceiro Mosquera José , Olabarrieta Arnal Iciar , Muñoz Gálligo Eloy , Viñuela Beneitez Mª Carmen , Regidor Sáez Francisco Javier , Serrano García Irene , Berzosa Sánchez Arantxa , Callejas Caballero Ignacio , Ramos Amador José Tomás
Published: November 2021

Background:

Perinatal transmission of HIV has dramatically decreased in high-income countries in the last few years with current rates below 1%, but it still occurs in high-risk situations, mainly pregnant women with late diagnosis of infection, poor antiretroviral adherence and a high viral load (VL). In these high-risk situations, many providers recommend combined neonatal prophylaxis (CNP). Our aim was to evaluate the safety and toxicity of CNP in infants deemed at high-risk of HIV infection among mother-infant pairs in the Madrid Cohort.

Materials and Methods:

Prospective, multicenter, observational cohort study between years 2000 and 2019. The subgroup of newborns on CNP and their mothers were retrospectively selected (cohort A) and compared with those who received monotherapy with zidovudine (cohort B). Infants with monotherapy were classified according to treatment regimes in long (6 weeks) and short (4 weeks) course.

Results:

We identified 227 newborns (33.3% preterm and 7 sets of twins) with CNP. A maternal diagnosis of HIV-1 infection was established during the current pregnancy in 72 cases (36.4%) and intrapartum or postpartum in 31 cases (15.7%). Most infants received triple combination antiretroviral therapy (65.6%; n = 149). The perinatal transmission rate in cohort A was 3.5% (95% confidence interval: 1.13%–5.92%). Infants from cohort A developed anemia (26.1% vs. 19.4%, P = 0.14) and neutropenia more frequently at 50–120 days (21.4% vs. 10.9%, P < 0.01), without significant differences in grade 3 and 4 anemia or neutropenia between the two cohorts. There were no differences in increased alanine aminotransferase. Neutropenia was more common in the long zidovudine regimes.

Conclusions:

Our findings provide further evidence of the safety of CNP in infants with high-risk of HIV-1 perinatal transmission.
Self-rated quality of vision and optical phenomena intensity of diffractive presbyopia-correcting IOLs: EDoF, trifocal vs panfocal
Authors: Böhm Myriam , Hemkeppler Eva , Kohnen Thomas
Published: November 2021

Purpose:

To investigate the self-rated quality of vision (SQV) and optical phenomena intensity of 3 diffractive multifocal intraocular lenses (mIOLs).

Setting:

Department of Ophthalmology, Goethe University Frankfurt, Germany.

Design:

Prospective comparative case series.

Methods:

Patients who had bilateral implantation of a diffractive extended depth-of-focus (EDoF), trifocal, or panfocal mIOL were assessed. Outcome parameters were SQV, symptom intensity of optical phenomena under 3 lighting conditions, quality of everyday lifestyle activities, spectacle independence (SI), and contrast sensitivity (CS).

Results:

The study comprised 108 eyes. The 3 lenses provided good total SQV under all lighting conditions. EDoF patients reported a slightly better total SQV (EDoF: 9.8 ± 6.67, trifocal: 22.2 ± 7.09, panfocal: 19.6 ± 16.25 visual analog scale, P = .041). A similar percentage of patients reported the presence of optical phenomena with no difference between mIOLs (P > .05). EDoF, trifocal, and panfocal patients rated symptom intensity of optical phenomena mild to moderate under all lighting conditions; however, EDoF patients reported a lower symptom intensity of halos (P < .05). Reported quality of everyday lifestyle activities and CS were comparable (P < .05). All panfocal and trifocal patients (100%) achieved complete SI, whereas almost half (44%) of the EDoF patients used reading spectacles.

Conclusions:

Diffractive EDoF, trifocal, and panfocal mIOLs provided good total SQV with mild to moderate intensity of optical phenomena under all lighting conditions. EDoF patients experienced the same percentage of optical phenomena but reported a weaker symptom intensity of halos and better night-driving ability. EDoF patients would all choose the same IOL, although a significant number of them needed reading spectacles, indicating that SI is not the main factor that determines patient selection of IOLs.
Assessment of the July Effect on Bronchoscopies in Teaching Hospitals Across the United States
Authors: Pescatore Jay , Asemota Iriagbonse , Davis William , Pinzon Viviana R. , Khamooshi Parnia , Rivera Mavi , Liao Hung-I
Published: November 2021

Background:

The July effect is the perceived notion that at the start of each academic year there is an increase in medical complications as the novice physician begins their new respective roles. Our study evaluated complication rates in the beginning versus end of the academic year with regards to bronchoscopy.

Methods:

This is a retrospective cohort study using the 2016 and 2017 Nationwide Inpatient Sample. Patients in the database that underwent bronchoscopy at teaching hospitals were determined using ICD-10 procedure codes. Our outcomes included length of hospital stay and several bronchoscope complications. We compared our outcomes in the first quarter of the academic year (July, August, and September) to the last quarter (April, May, and June). Multivariable logistic and linear regression analysis were used accordingly to adjust for confounders.

Results:

There was a total of 189,720 admission for bronchoscopy. Of these hospitalization 89,020 bronchoscopies were done in first academic Quarter (Q1) while 100,700 bronchoscopies were done in fourth academic Quarter (Q4) in 2016 to 2017 academic year. After adjusting for confounders, there was no difference in any postprocedural complications between Q1 and Q4 or length of stay.

Conclusion:

Within the limitation of the national data set provided, there appears to be similar procedural complication rates for patients admitted Q1 compared with Q4 of the academic year in respect to bronchoscopy, signaling the possibility of lack of the July effect. Prospective studies with improved data granularity is needed to further verify the absence or presence of the July effect regarding bronchoscopy.
Week 2 Adalimumab Levels Predict Short-term Clinical Remission in Patients With Inflammatory Bowel Disease
Authors: Buffone Elisa , Gupta Shaan , Al Ibrahim Bashaar , Marshall John K. , Halder Smita , Tse Frances , Albashir Siwar , Morgan David , Lumb Barry , Armstrong David , Narula Neeraj
Published: November 2021

Background and Goals:

The role of early proactive therapeutic drug level monitoring for anti–tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes.

Materials and Methods:

This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR.

Results:

Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P=0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P=0.11).

Conclusions:

Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.
Screening tool for identification of hip fractures in the prehospital setting
Authors: Gillette Danielle M. , Cheng Olivia , Wilson Alghin , Mantero Rogerio , Chisholm Douglas , Feldman Michael
Published: November 2021

Objectives:

This study aims to develop a screening tool that will help first responders identify patients with proximal femur fractures, commonly referred to as hip fractures, on site and direct these patients to hospitals with orthopaedic surgery services.

Study Design:

Prospective survey.

Methods:

Literature and expert opinion defined parameters for the Collingwood Hip Fracture Rule (CHFR) which predict a patient's likelihood of hip fracture. The study population included adults presenting to Collingwood General and Marine Hospital with lower extremity injuries between December 1, 2019 and March 10, 2020. Excluded patients had previous hip replacement, previous hip fracture on the side of the injury, or a high energy mechanism of injury. Patients were assessed with the CHFR before receiving x-ray imaging. The parameters were scored based on their predictive powers and analyzed by a receiver operating characteristic curve.

Results:

The study included 101 patients (mean age 66.3 years), and 25.7% had a hip fracture confirmed on imaging. The sensitivity, specificity, positive predictive value, and negative predictive value helped score each parameter. Factors receiving 1 point are: age 65 to 79 years, female, mechanical fall, unable to weight-bear, knee pain. Factors receiving 2 points are: bruising at greater trochanter, age >80 years. Factors receiving 3 points are: pain with hip rotation, leg shortened and externally rotated. Score is the summation of all the factors’ points. The receiver operating characteristic curve (0.953; P value < .0001) demonstrated scores of 7 had sensitivity:specificity of 84.6%:94.7%.

Conclusion:

The CHFR screening tool score of 7 can be used by first responders in the prehospital setting to identify patients who sustain a hip fracture and make appropriate triage decisions. This will improve patient outcomes and decrease institutional costs.
Diagnosis of Hypersensitivity Pneumonitis
Authors: Yang Soo-Ryum , Beasley Mary B. , Churg Andrew , Colby Thomas V. , Fernández Pérez Evans R. , Lynch David , Müller Nestor L. , Travis William D.
Published: November 2021

Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the pathologic features as outlined in the CHEST guidelines. The histologic criteria are divided into 4 diagnostic categories: (1) Typical nonfibrotic HP or fibrotic HP; (2) Compatible with nonfibrotic HP or fibrotic HP; (3) Indeterminate for nonfibrotic or fibrotic HP; and (4) Alternative Diagnosis. It is important to emphasize that patterns 1 to 3 do not represent discrete histologic entities or pathologic diagnoses. Rather, these categories are meant to serve as a practical guide for organizing a complex set of overlapping histologic patterns into an integrated diagnostic framework for facilitating multidisciplinary discussion. High-resolution computed tomography features are also summarized, emphasizing how the correlation of lung biopsies with computed tomography findings can help to favor the diagnosis, particularly in cases where biopsies are not typical for HP. This review highlights details of the histologic spectrum of HP as well as the utility of different types of biopsies and bronchoalveolar lavage. We also emphasize the importance of multidisciplinary discussion and the complex differential diagnosis.
A Peer-Led, Artificial Intelligence–Augmented Social Network Intervention to Prevent HIV Among Youth Experiencing Homelessness
Authors: Rice Eric , Wilder Bryan , Onasch-Vera Laura , DiGuiseppi Graham , Petering Robin , Hill Chyna , Yadav Amulya , Lee Sung-Jae , Tambe Milind
Published: November 2021

Background:

Youth experiencing homelessness (YEH) are at elevated risk of HIV/AIDS and disproportionately identify as racial, ethnic, sexual, and gender minorities. We developed a new peer change agent (PCA) HIV prevention intervention with 3 arms: (1) an arm using an artificial intelligence (AI) planning algorithm to select PCAs; (2) a popularity arm, the standard PCA approach, operationalized as highest degree centrality (DC); and (3) an observation-only comparison group.

Setting:

A total of 713 YEH were recruited from 3 drop-in centers in Los Angeles, CA.

Methods:

Youth consented and completed a baseline survey that collected self-reported data on HIV knowledge, condom use, and social network information. A quasi-experimental pretest/posttest design was used; 472 youth (66.5% retention at 1 month postbaseline) and 415 youth (58.5% retention at 3 months postbaseline) completed follow-up. In each intervention arm (AI and DC), 20% of youth was selected as PCAs and attended a 4-hour initial training, followed by 7 weeks of half-hour follow-up sessions. Youth disseminated messages promoting HIV knowledge and condom use.

Results:

Using generalized estimating equation models, there was a significant reduction over time (P < 0.001) and a significant time by AI arm interaction (P < 0.001) for condomless anal sex act. There was a significant increase in HIV knowledge over time among PCAs in DC and AI arms.

Conclusions:

PCA models that promote HIV knowledge and condom use are efficacious for YEH. Youth are able to serve as a bridge between interventionists and their community. Interventionists should consider working with computer scientists to solve implementation problems.
Expanding the Pie–Differentiated PrEP Delivery Models to Improve PrEP Uptake in the San Francisco Bay Area
Authors: Wilson Erin C. , Turner Caitlin M. , Sanz-Rodriguez Christina , Arayasirikul Sean , Gagliano Jayne , Woods Tiffany , Palafox Erika , Halfin Janet , Martinez Lorena , Makoni Bessa , Eskman Zebediah , Lin Royce , Rodriguez Esteban , Rapues Jenna , Pardo Seth , Liu Albert
Published: November 2021

Background:

Pre-exposure prophylaxis (PrEP) uptake among trans people to date has been low. Recommendations implemented in San Francisco to offer PrEP with feminizing hormones have not led to improvement of PrEP uptake in trans communities. New delivery models may be needed. The aim of this study was to examine whether a PrEP-only clinic was more likely to serve trans people at highest risk of HIV than trans-affirming primary care clinics.

Methods:

Participants were recruited between 2017 and 2019 as part of a PrEP demonstration project in the San Francisco Bay Area. Survey data including sociodemographics, HIV-related risk behavior, barriers to PrEP, and self-reported PrEP adherence were collected at baseline, 3 months, and 6 months for all participants. Bivariable Poisson regression models were used to examine differences between participants in the primary care clinics and PrEP-only clinic delivered to participants.

Results:

Baseline survey data were collected from 153 participants. Those with a higher number of sexual partners were significantly more likely to use the PrEP-only clinic rather than the primary care clinics. Participants with higher perceived HIV risk and those who engaged in sex work were also more likely to use the PrEP-only clinic compared with the primary care clinic. Medical mistrust was higher at baseline among participants of the PrEP-only clinic. PrEP adherence was not significantly different by delivery model. Few participants identified PrEP barriers, such as interactions with feminizing hormones, to be determinants of PrEP uptake.

Conclusions:

A PrEP-only delivery model could improve PrEP uptake and may better meet the needs of trans people who could most benefit from PrEP.
Growth variability, dimensional scaling, and the interpretation of osteohistological growth data
Authors: Cullen Thomas M. , Brown Caleb M. , Chiba Kentaro , Brink Kirstin S. , Makovicky Peter J. , Evans David C.
Published: November 2021

Osteohistological data are commonly used to study the life history of extant and extinct tetrapods. While recent advances have permitted detailed reconstructions of growth patterns, physiology and other features using these data, they are most commonly used in assessments of ontogenetic stage and relative growth in extinct animals. These methods have seen widespread adoption in recent years, rapidly becoming a common component of the taxonomic description of new fossil taxa, but are often applied without close consideration of the sources of variation present or the dimensional scaling relationships that exist among different osteohistological measurements. Here, we use a combination of theoretical models and empirical data from a range of extant and extinct tetrapods to review sources of variability in common osteohistological measurements, their dimensional scaling relationships and the resulting interpretations that can be made from those data. In particular, we provide recommendations on the usage and interpretation of growth mark spacing/zonal thickness data, when these are likely to be unreliable, and under what conditions they can provide useful inferences for studies of growth and life history.
Responsiveness to inhibitory signals changes as a function of colony size in honeybees (
Apis mellifera
)
Authors: Bell Heather C. , Hsiung Kevin , Pasberg Patrick , Broccard Frédéric D. , Nieh James C.
Published: November 2021

Biological collectives, like honeybee colonies, can make intelligent decisions and robustly adapt to changing conditions via intricate systems of excitatory and inhibitory signals. In this study, we explore the role of behavioural plasticity and its relationship to network size by manipulating honeybee colony exposure to an artificial inhibitory signal. As predicted, inhibition was strongest in large colonies and weakest in small colonies. This is ecologically relevant for honeybees, for which reduced inhibitory effects may increase robustness in small colonies that must maintain a minimum level of foraging and food stores. We discuss evidence for size-dependent plasticity in other types of biological networks.
Local and collective transitions in sparsely-interacting ecological communities
Authors: Marcus Stav , Turner Ari M. , Bunin Guy
Published: November 2021

Interactions in natural communities can be highly heterogeneous, with any given species interacting appreciably with only some of the others, a situation commonly represented by sparse interaction networks. We study the consequences of sparse competitive interactions, in a theoretical model of a community assembled from a species pool. We find that communities can be in a number of different regimes, depending on the interaction strength. When interactions are strong, the network of coexisting species breaks up into small subgraphs, while for weaker interactions these graphs are larger and more complex, eventually encompassing all species. This process is driven by emergence of new allowed subgraphs as interaction strength decreases, leading to sharp changes in diversity and other community properties, and at weaker interactions to two distinct collective transitions: a percolation transition, and a transition between having a unique equilibrium and having multiple alternative equilibria. Understanding community structure is thus made up of two parts: first, finding which subgraphs are allowed at a given interaction strength, and secondly, a discrete problem of matching these structures over the entire community. In a shift from the focus of many previous theories, these different regimes can be traversed by modifying the interaction strength alone, without need for heterogeneity in either interaction strengths or the number of competitors per species.
Gray Matter Differentiation Between Two Subordinate Personality Traits of Extraversion: Enthusiasm and Assertiveness
Authors: Frisk Magnus , Kastrati Gránit , Rosén Jörgen , Månsson Kristoffer N. T. , Åhs Fredrik
Published: November 2021

Enthusiasm and assertiveness are two subordinate personality traits of extraversion. These traits reflect different aspects of extroversion and have distinct implications on mental health. Whereas enthusiasm predicts satisfaction in life and positive relationships, assertiveness predicts psychological distress and reduced social support. The neural basis of these subordinate traits is not well understood. To investigate brain regions where enthusiasm and assertiveness have diverging relationship with morphology, enthusiasm and assertiveness were regressed to gray matter volume (GMV) across the whole brain in a sample of 301 healthy individuals. A significant interaction was found between enthusiasm and assertiveness in the left angular gyrus (t(296) = 4.18, family wise error corrected, FWE p = .001 (cluster-level); Cluster size = 880 voxels). Larger GMV in this area was associated with more enthusiasm and less assertiveness. Our study emphasizes the value of separating extraversion into its subordinate traits when investigating associations to neuroanatomy.
State-dependent modulation of activity in distinct layer 6 corticothalamic neurons in barrel cortex of awake mice
Authors: Dash Suryadeep , Autio Dawn M. , Crandall Shane R.
Published: November 2021

Layer 6 corticothalamic (L6 CT) neurons are in a strategic position to control sensory input to the neocortex, yet we understand very little about their functions. Apart from studying their anatomical, physiological and synaptic properties, most recent efforts have focused on the activity-dependent influences CT cells can exert on thalamic and cortical neurons through causal optogenetic manipulations. However, few studies have attempted to study them during behavior. To address this gap, we performed juxtacellular recordings from optogenetically identified CT neurons in whisker-related primary somatosensory cortex (wS1) of awake, head-fixed mice (either sex) free to rest quietly or self-initiate bouts of whisking and locomotion. We found a rich diversity of response profiles exhibited by CT cells. Their spiking patterns were either modulated by whisking-related behavior (∼28%) or not (∼72%). Whisking-responsive neurons exhibited either increases, activated-type, or decreases in firing rates, suppressed-type, that aligned with whisking onset better than locomotion. We also encountered responsive neurons with preceding modulations in firing rate before whisking onset. Overall, whisking better explained these changes in rates than overall changes in arousal. Whisking-unresponsive CT cells were generally quiet, with many having low spontaneous firing rates, sparse-type, and others being completely silent. Remarkably, the sparse firing CT population preferentially spiked at the state transition point when pupil diameter constricted and the mouse entered quiet wakefulness. Thus, our results demonstrate that L6 CT cells in wS1 show diverse spiking patterns, perhaps subserving distinct functional roles related to precisely timed responses during complex behaviors and transitions between discrete waking states.

SIGNIFICANCE STATEMENT

Layer 6 corticothalamic neurons provide a massive input to the sensory thalamus and local connectivity within cortex, but their role in thalamocortical processing remains unclear due to difficulty accessing and isolating their activity. Although several recent optogenetic studies reveal that the net influence of corticothalamic actions, suppression versus enhancement, depends critically on the rate these neurons fire, the factors that influence their spiking are poorly understood, particularly during wakefulness. Using the well-established Ntsr1-Cre line to target this elusive population in the whisker somatosensory cortex of awake mice, we found that corticothalamic neurons show diverse state-related responses and modulations in firing rate. These results suggest separate corticothalamic populations can differentially influence thalamocortical excitability during rapid state transitions in awake, behaving animals.
A self-amplifying mRNA COVID-19 vaccine drives potent and broad immune responses at low doses that protects non-human primates against SARS-CoV-2
Authors: Rappaport Amy R. , Hong Sue-Jean , Scallan Ciaran D. , Gitlin Leonid , Akoopie Arvin , Boucher Gregory R. , Egorova Milana , Espinosa J. Aaron , Fidanza Mario , Kachura Melissa A. , Shen Annie , Sivko Gloria , Van Abbema Anne , Veres Robert L. , Jooss Karin
Published: November 2021

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate potent cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 μg induced potent neutralizing antibody titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 μg dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera. Spike-specific T cell responses were observed at all dose levels. SAM vaccination provided protective efficacy against SARS-CoV-2 challenge as both a homologous prime-boost and as a single boost following ChAd prime, demonstrating reduction of viral replication in both the upper and lower airways. Protection was most effective with a SAM prime-boost vaccination regimen at 10 and 30 μg and with a ChAd/SAM heterologous prime-boost regimen. The SAM vaccine is currently being evaluated in clinical trials as both a homologous prime-boost regimen at low doses and as a boost following heterologous prime.
RB1 loss overrides PARP inhibitor sensitivity driven by RNASEH2B loss in prostate cancer
Authors: Miao Chenkui , Tsujino Takuya , Takai Tomoaki , Gui Fu , Tsutsumi Takeshi , Sztupinszki Zsofia , Szallasi Zoltan , Mouw Kent W. , Zou Lee , Kibel Adam S. , Jia Li
Published: November 2021

Current targeted cancer therapies are largely guided by mutations of a single gene, which overlooks concurrent genomic alterations. Here, we show that RNASEH2B, RB1, and BRCA2, three closely located genes on chromosome 13q, are frequently deleted in prostate cancer individually or jointly. Loss of RNASEH2B confers cancer cells sensitivity to poly(ADP–ribose) polymerase (PARP) inhibition due to impaired ribonucleotide excision repair and PARP trapping. When co-deleted with RB1, however, cells lose their sensitivity, in part, through E2F1-induced BRCA2 expression, thereby enhancing homologous recombination repair capacity. Nevertheless, loss of BRCA2 re-sensitizes RNASEH2B/RB1 co-deleted cells to PARP inhibition. Our results may explain some of the disparate clinical results from PARP inhibition due to interaction between multiple genomic alterations and support a comprehensive genomic testing to determine who may benefit from PARP inhibition. Finally, we show that ATR inhibition can disrupt E2F1-induced BRCA2 expression and overcome PARP inhibitor resistance caused by RB1 loss.
Minimal in-school SARS-CoV-2 transmission with strict mitigation protocols at two independent schools in Nashville, TN
Authors: Peetluk Lauren S. , Rebeiro Peter F. , Edwards Kathryn M. , Banerjee Ritu , Mallal Simon A. , Aronoff David M. , Lipworth Loren , Katz Sophie E.
Published: November 2021

BACKGROUND

The COVID-19 pandemic has greatly impacted school operations. To better understand the role of schools in COVID-19 transmission, we evaluated infections at two independent schools in Nashville, TN during the 2020-2021 school year.

METHODS

The cumulative incidence of COVID-19 within each school, age group, and exposure setting were estimated and compared to local incidence. Primary attack rates were estimated among students quarantined for in-school close contact.

RESULTS

Among 1401 students who attended school during the study period, 98 cases of COVID-19 were reported, corresponding to cumulative incidence of 7.0% (95% confidence interval (CI): 5.7-8.5). Most cases were linked to household (58%) or community (31%) transmission, with few linked to in-school transmission (11%). Overall, 619 students were quarantined, corresponding to >5000 person-days of missed school, among whom only 5 tested positive for SARS-CoV-2 during quarantine (primary attack rate: 0.8%, 95% CI: 0.3, 1.9). Weekly case rates at school were not correlated with community transmission.

CONCLUSION

These results suggest that transmission of COVID-19 in schools is minimal when strict mitigation measures are used, even during periods of extensive community transmission. Strict quarantine of contacts may lead to unnecessary missed school days with minimal benefit to in-school transmission.
TIR domains of plant immune receptors are 2′,3′-cAMP/cGMP synthetases mediating cell death
Authors: Yu Dongli , Song Wen , Tan Eddie Yong Jun , Liu Li , Cao Yu , Jirschitzka Jan , Li Ertong , Logemann Elke , Xu Chenrui , Huang Shijia , Jia Aolin , Chang Xiaoyu , Han Zhifu , Wu Bin , Schulze-Lefert Paul , Chai Jijie
Published: November 2021

2′,3′-cAMP is a positional isomer of the well-established second messenger 3′,5′-cAMP, but little is known on the biology of this noncanonical cyclic nucleotide monophosphate (cNMP). Toll/interleukin-1 receptor (TIR) domains of nucleotide-binding leucine-rich repeat (NLR) immune receptors have NADase function necessary but insufficient to activate plant immune responses. Here we show that plant TIR proteins, besides being NADases, act as 2′,3′-cAMP/cGMP synthetases by hydrolyzing RNA/DNA. Structural data shows that a TIR domain adopts distinct oligomers with dual and exclusive enzymatic activity. Mutations specifically disrupting the synthetase activity abrogate TIR-mediated cell death inNicotiana benthamiana, supporting an important role for these cNMPs in TIR signaling. Furthermore, theArabidopsisnegative regulator of TIR-NLR signaling, NUDT7 displays 2′,3′-cAMP/cGMP but not 3′,5′-cAMP/cGMP phosphodiesterase activity and suppresses cell death activity of TIRs inN. benthamiana. Our study identifies a novel family of 2′,3′-cAMP/cGMP synthetase and establishes a role for the noncanonical cNMPs in plant immune responses.
Long wavelength light that improves aged mitochondrial function selectively increases cytokine expression in serum and the retina
Authors: Shinhmar Harpreet , Hogg Chris , Jeffery Glen
Published: November 2021

Aged mitochondrial function can be improved with long wavelength light exposure. This reduces cellular markers of inflammation and can improve system function from fly though to human. Here, we ask what impact 670nm light has on cytokine expression using a 40 cytokine array in blood serum and retina in C57Bl6 mice. There was a relatively uniform increase in cytokine expression between 3 and 12 months of age in serum and retina.

670nm exposure was delivered daily for a week in 12 month old mice. This shifted patterns of cytokine expression in both serum and retina inducing a selective increase with some in serum increasing >5 fold. Changes in retina were smaller. In serum there were major increases in IL-7, 6, 13, 16 and 23, also in TNF-α and CXCL 9 and 10. In retina the increases were found mainly in some IL (interleukins) and CXCL’s (chemokines). A few cytokines were reduced by light exposure.

Changes in serum cytokines implies that long wavelengths impacts systemically even to unexposed tissues deep in the body. In the context of wider literature, increased cytokine expression may be protective. However, their upregulation by light merits further analysis as cytokines upregulation can also be negative.
Fatigue damage in bending of reinforced concrete frames using non-destructive tests for dynamic strength of the cylinder
Authors: Milašinović Dragan D. , Landović Aleksandar , Goleš Danica
Published: November 2021

Purpose

The purpose of this paper is to contribute to the solution of the fatigue damage problem of reinforced concrete frames in bending.

Design/methodology/approach

The problem of fatigue damage is formulated based on the rheological–dynamical analogy, including a scalar damage variable to address the reduction of stiffness in strain softening. The modal analysis is used by the finite element method for the determination of modal parameters and resonance stability of the selected frame cross-section. The objectivity of the presented method is verified by numerical examples, predicting the ductility in bending of the frame whose basic mechanical properties were obtained by non-destructive testing systems.

Findings

The modal analysis in the frame of the finite element method is suitable for the determination of modal parameters and resonance stability of the selected frame cross-section. It is recommended that the modulus of elasticity be determined by non-destructive methods, e.g. from the acoustic response.

Originality/value

The paper presents a novel method of solving the ductility in bending taking into account both the creep coefficient and the aging coefficient. The rheological-dynamical analogy (RDA) method uses the resonant method to find material properties. The characterization of the structural damping via the damping ratio is original and effective.
Pricing strategies of low-carbon enterprises in the Yellow River Basin considering demand information and traceability services
Authors: Liu Pan , Cui Xiaoyan , Zhang Ziran , Zhou Wenwen , Long Yue
Published: November 2021

Purpose

The purpose of this paper is to solve new pricing issues faced by low-carbon companies in the Yellow River Basin, which is caused by the change of key pricing factors in the mixed appliance background of Big Data and blockchain, such as product quality and carbon-emission reduction CER level (hereafter, CER level).

Design/methodology/approach

We choose a low-carbon supply chain with a low-carbon manufacturer and a retailer as our research object. Then, we propose that using the ineffective effect of the CER level and the quality and safety level to reflect the relationships among the CER level, the quality and safety level and the market demand is more suitable in the new environment. Based on these, we revise the demand equation. Afterwards, by using Stackelberg game, four cost-sharing situations and their pricing rules are analyzed.

Findings

Results indicated that in the four cost-sharing situations, the change trends and the magnitudes of the best retail prices were not affected by the changes of the inputs of the demand information and the traceability services costs (hereafter, DITS costs), the proportion about retailer's DITS costs undertaken by the manufacturer, the ineffective effect coefficient of the CER level and the quality and safety level and the cost optimization coefficient. However, the cost-sharing situations could affect the change magnitudes of the best revenues.

Originality/value

This paper has two main contributions. First, this paper proposes a demand function that is more suitable for the mixed appliance background of Big Data and blockchain. Secondly, this paper improves the cost-sharing model and finds that demand information sharing and traceability service sharing have different impacts on key pricing factors of low-carbon product. In addition, this research provides a theoretical reference for low-carbon supply chain members to formulate pricing strategies in the new background.
High‐speed terrestrial substrate transitions: How a fleeing cursorial day gecko copes with compliance changes that are experienced in nature
Authors: Naylor Emily R. , Higham Timothy E.
Published: November 2021

Animal movement is often largely determined by abiotic conditions of the environment, including substrate properties. While a large body of work has improved our understanding of how different substrate properties can impact locomotor performance and behaviour, few of these studies have investigated this relationship during transitions within a single locomotor event.

In nature, terrestrial animals frequently encounter substrate transitions, or changes in substrate level, incline, texture and/or compliance during a single bout of movement, which can be sudden for high‐speed animals. These animals often adjust their posture and kinematics during transitions, and in some cases lose forward velocity.

We examined the occurrence and effect of non‐elastic compliance transitions in Rhoptropus afer, a cursorial day gecko known for its ability to sprint rapidly for several metres at a time. We recorded substrate use during provoked escapes in the field and conducted locomotor trials on a trackway that mimicked natural structural habitat conditions with transitions from a rigid surface into sand and from sand back to a rigid surface.

During escapes, R. afer used substrates of different compliance (i.e. rock, gravel and sand) and transitioned to and from the more compliant surfaces with even frequency, which matched substrate and compliance availability estimates. In laboratory experiments, sprint speed was not significantly affected by acute changes in compliance, which was likely facilitated by an increased body angle and duty factor upon entering the sand, and potentially a high yield strength of the sand relative to applied forces.

We speculate that this species' ability to maintain speed during compliance transitions underlies their apparent indiscriminate substrate use during escapes, and that this behaviour may offer a selective advantage for evading larger terrestrial predators. Using field data to inform and contextualize laboratory experiments thus yields important insights as to how animals accommodate acute changes in substrate conditions encountered during critical locomotor events.

A free Plain Language Summary can be found within the Supporting Information of this article.
Economies of scale shape energetics of solitary and group‐living spiders and their webs
Authors: Straus Samantha , González Angélica L. , Matthews Philip , Avilés Leticia
Published: November 2021

Metabolic scaling, whereby larger individuals use less energy per unit mass than smaller ones, may apply to the combined metabolic rate of group‐living organisms as group size increases. Spiders that form groups in high disturbance environments can serve to test the hypothesis that economies of scale benefit social groups.

Using solitary and group‐living spiders, we tested the hypothesis that spiders exhibit negative allometry between body or colony mass and the standing mass of their webs and whether, and how, such a relationship may contribute to group‐living benefits in a cooperative spider.

Given the diverse architecture of spider webs—orb, tangle and sheet‐and‐tangle, and associated differences in silk content, we first assessed how standing web mass scales with spider mass as a function of web architecture and whether investment in silk differs among web types. As group‐living spiders are predominantly found in clades that build the presumably costlier sheet‐and‐tangle webs, we then asked whether cost‐sharing through cooperative web maintenance contributes to a positive energy budget in a social species.

We found that larger spiders had a relatively smaller investment in silk per unit mass than smaller ones, but more complex sheet‐and‐tangle webs contained orders of magnitude more silk than simpler orb or tangle ones. In the group‐living species, standing web mass per unit spider mass continued to decline as colony size increased with a similar slope as for unitary spiders. When web maintenance activities were considered, colonies also experienced reduced mass‐specific energy expenditure with increasing colony size. Activity savings contributed to a net positive energy balance for medium and large colonies after inputs from the cooperative capture of large prey were accounted for.

Economies of scale have been previously demonstrated in animal societies characterized by reproductive and worker castes, but not in relatively egalitarian societies as those of social spiders. Our findings illustrate the universality of scaling laws and how economies of scale may transcend hunting strategies and levels of organization.
Psychosocial resilience among left‐behind adolescents in rural Thailand: A qualitative exploration
Authors: Rose‐Clarke Kelly , Nambutr Waewdaw , Kongkamud Achara , Lertgrai Wachiraya , Prost Audrey , Benyakorn Songpoom , Albakri Muslihah , Devries Karen , Salisbury Tatiana , Jampaklay Aree
Published: November 2021

When parents migrate, they often leave children behind with relatives. Despite being at higher risk of socio‐emotional problems, many left‐behind children have good health and social outcomes, suggesting their resilience. We sought to understand how adolescents with internal and international migrant parents build resilience in Thailand. We conducted qualitative interviews with 24 adolescents aged 10–19, and six caregivers, parents and community leaders. Interviews were transcribed, translated and analysed, drawing on techniques from grounded theory. We found that resilience was built in a context where for many families, migration was a financial necessity and the parent–child relationship was mainly phone‐based. Adolescents built resilience using three key ‘resources’: warmth (love and understanding), financial support and guidance. Adolescents with insecure parent or caregiver relationships, or with caring responsibilities for relatives, were less likely to have access to these resources. These adolescents sought emotional and financial independence, prioritised friendships and identified role models to obtain key resources and build resilience. The findings indicate practical and psychosocial barriers to building resilience among left‐behind adolescents in Thailand. Further work could explore pathways to mental illness in this population, interventions that build peer networks and caregiver–child relationships and the use of technology to support remote parenting.