bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature dependence studies of tissue-mimicking phantoms for ultra-wideband microwave breast tumor detection
Authors: Slanina T , Nguyen D H , Moll J , Krozer V
Published: July 2022

Microwave imaging (MWI) systems are being investigated for breast cancer diagnostics as an alternative to conventional x-ray mammography and breast ultrasound. This work aims at a next generation of tissue-mimicking phantoms modelling the temperature-dependent dielectric properties of breast tissue over a large frequency bandwidth. Such phantoms can be used to develop a novel kind of MWI systems that exploit the temperature-dependent permittivity of tissue as a natural contrast agent. Due to the higher water content in tumor tissue, a temperature increase leads to a different change in the complex permittivity compared to surrounding tissue. This will generate a tumor dominated scattering response when the overall tissue temperature increases by a few degrees, e.g. through the use of microwave hyperthermia systems. In that case a differential diagnostic image can be calculated between microwave measurements at reference (around 37 °C) and elevated temperature conditions. This work proposes the design and characterization of agar-oil-glycerin phantoms for fatty, glandular, skin and tumor tissue. The characterization includes measurements with an open-ended coaxial probe and a network analyzer for the frequency range from 50 MHz to 20 GHz in a temperature-controlled environment covering the temperature range from 25 °C to 46 °C. The phantoms show an unique temperature response over the considered frequency bandwidth leading to significant changes in the real and imaginary part of the complex permittivity. Comparative studies with porcine skin and fat tissue show a qualitative agreement.
A-01 Changes in Fixational Eye Movements (FEMs) Following Concussion
Authors: Albrecht T J , Mehmel B M , Eagle S R , Leonard B T , Marchetti G F , Zhang M , Reecher H M , Snyder V , Holland C L , Rossi E A , Collins M W , Kontos A P
Published: July 2022

Purpose: Identify changes in fixational eye movement (FEMs) outcomes following concussion and assess the association of FEMs outcomes with clinical outcomes including symptoms, neurocognitive, and vestibular/ocular motor. Methods: Participants included thirty-three individuals (13–27 years old; 54.5% female) diagnosed with concussion within the past 21 days. Concussion diagnosis was determined using current consensus guidelines. A tracking scanning laser ophthalmoscope (TSLO) was used to measure FEMS. Participants completed ImPACT, PCSS, and VOMS. Within-subjects changes in FEMS outcomes were calculated using paired-samples t-tests. A backwards stepwise linear regression to predict days to clearance was utilized with all FEMS outcomes as predictors. Results: MeanDriftH (slope of cumulative drift regression calculated horizontally; mean difference = 0.04; p = 0.03; Cohen’s d = 0.43) and drift proportion significantly changed over time (mean difference = 0.03; p = 0.03, d = 0.44). Average peak velocity of microsaccade (MsPkVel) predicted days to recovery (R = 0.26; p = 0.045; n = 24). MsPkVel and average duration of blink correlated with select reports of nausea on VOMS. Microsaccade frequency (r = −0.36; p = 0.04) correlated with NPC fogginess. Drift amplitude (DriftAmp) correlated with NPC distance (r = −0.41; p = 0.02) and VMS headache (r = 0.35; p = 0.04). MeanDriftH was negatively correlated with verbal memory (r = −0.44; p = 0.01), whereas DriftAmp was positively correlated (r = 0.50; p = 0.003). Bivariate contour ellipse area was correlated (r = 0.43; p = 0.01) with slower reaction time on ImPACT. Conclusions: FEMs outcomes demonstrated significant change and were useful in predicting recovery time following concussion. FEMs measurements may provide brief, objective data to augment current clinical assessment and inform prognosis for recovery. Future researchers should examine FEMS outcomes from pre- to post-concussion and explore age and sex differences.
A-24 Neurorehabilitation Improves Neuropsychological Symptoms in Active and Retired NFL Players
Authors: Kornfeld S , Kalambaheti E
Published: July 2022

Purpose: The prevalence of concussions in the NFL have decreased since 2017, however, they still occur frequently with about 177 concussions occurring per season. Neuropsychological symptoms continue to persist long after these players are cleared to return to play. This could be because the underlying cause of these symptoms may have not fully been addressed through neurorehabilitation. Methods: A neurorehabilitation clinic treated 4 active or retired NFL players with symptoms relating to head injury obtained during participation in their sport. A 5-day, multi-modal neurorehabilitation program was administered in 10 one-hour treatment sessions. Each session consisted of a combination of photobiomodulation, repetitive peripheral somatosensory stimulation, neuromuscular reeducation, vestibular rehabilitation, orthoptic exercises, cognitive exercises, and/or off-vertical axis rotation utilizing a multi-axis rotational chair. Results: On intake, a SCAT5 graded symptom checklist was performed with symptoms falling into four domains: somatic, emotional, cognitive, and sleep. The average overall symptom severity score was 57.75, and the average severity of emotional domain symptoms (Nervousness/Anxiety, Irritability, Sadness, More Emotional) was 14.5. On average, emotional domain symptom severity score decreased by 82.76% compared to the 72.73% decrease in total symptom severity. Conclusions: This neurorehabilitation program has shown to be beneficial at decreasing the severity in both overall symptoms and emotional domain symptoms in NFL players with persistent post-concussion symptoms. The authors suggest further research be performed over larger player populations and in other contact sports.
A-30 Preliminary Evidence for the Vestibular/Ocular Motor Screening-Child (VOMS-C) for Patients with Concussion (ages 5–9)
Authors: Mehmel B M , Trbovich A M , Mucha A , Eagle S , Kegel N , Fazio-Sumrok V , Collins M W , Kontos A P
Published: July 2022

Purpose: To establish preliminary evidence (i.e., predictive validity) for the new Vestibular/Ocular Motor Screening Child Version (VOMS-C) in a sample of concussed patients and controls aged 5–9 years. A secondary purpose was to identify risk factors for false positives in healthy controls. Methods: This study included 80 patients ages 5–9 (7.40+/−1.09, 41% female) years with a concussion during the past 30 days recruited from a concussion clinic, and 40 age- and sex-matched controls (7.10+/−1.26 years, 45% female). Participants completed a clinical interview, and the VOMS-C. Groups were compared with independent samples t-tests and chi-square analyses. Backwards stepwise logistic regression (LR) was used to discriminate groups and inform a receiver operating characteristic (ROC) curve analysis with area under the curve (AUC) values. Chi-square analyses with odds ratios (OR) were conducted to examine false positives in controls. Results: VOMS-C item provocation ranged from 2.5–20% in the control group and 13.2–30.3% for the concussed group. Results from the LR discriminated concussed from controls (R2 = 0.39; p < 0.001) with smooth pursuits (p = 0.047), family depression history (p = 0.02), and near-point of convergence distance (p = 0.01), as significant predictors. ROC curve analysis including these three predictors supported an AUC = 0.81 (95% CI: 0.73–0.89; p < 0.001) for differentiating concussed from controls. False positives among controls were only related to family history of anxiety (OR 13.37, CI 1.45–122.88, p = 0.007). Conclusions: The findings provide preliminary support for the VOMS-C to identify concussed patients aged 5–9 years.
A-35 Utility of the Child SCAT-5 for Identifying Concussion In Children Aged 5–9 Years
Authors: Preszler J , Trbovich A , Shaffer M , Fazio-Sumrok V , Kegel N , Collins M W , Kontos A P
Published: July 2022

Purpose: The Sport Concussion Assessment Tool-5 Child (Child SCAT-5) is designed to assess concussion in children aged 5 to 12 years and includes child- and parent-reported symptoms, as well as brief cognitive and balance screening. However, researchers have yet to examine the utility of the Child SCAT-5 for identifying concussion in young (5–9 years) children. Methods: 139 total participants aged 5–9 years (M = 7.31 ± 1.15, 43.9% female) consisted of 96 participants presenting within 30 days of concussion (M = 8.90 ± 5.78 days; 38.5% sport-related) and 43 healthy age- and gender-matched controls. Participants and parents completed a clinical interview and Child SCAT-5 at their first visit. Receiver operating characteristic (ROC) curves were estimated on the Child SCAT-5 balance and cognitive screening components, parent and child total and symptom severity reports, as well as each individual parent- and child-rated symptom’s severity. Results: Area under the curve (AUC) values fell between 0.32 and 0.64 for cognitive, balance, and symptom rating components. Variables with highest AUC values included parent-rated symptoms worsening after physical activity (0.73) and cognitive activity (0.72). Individual symptom severity items with highest AUC values included headaches (parent = 0.89; child = 0.81), tired a lot (parent = 0.75), and tired easily (parent = 0.72; child = 0.72). Conclusions: Results suggest the Child SCAT-5’s individual symptoms were useful in identifying concussion, but cognitive/balance domains were not. Parent-rated symptom worsening after cognitive/physical activity fell in the acceptable range. Results support use of the Child SCAT-5 symptom components as part of a multifaceted concussion evaluation.
A-39 Baseline And Initial Post-Injury Presentation Of Athletes With Self-Reported Neurodevelopmental Disorders As Measured By ImPACT
Authors: Rubinstein J B , McGrath N , Jackson A
Published: July 2022

Purpose: To compare neurocognitive profiles of high school athletes with self-reported LD and/or ADHD neurodevelopmental disorders (ND) to controls at baseline (BL) and during initial post-injury (PI) testing with ImPACT. Methods: A sample of 155 (112 males, 43 females) high school athletes who completed BL and PI testing with ImPACT from 2019 to present was analyzed. Students who self-reported ND (n = 36) were compared to those who did not. ImPACT composites Verbal Memory (VM), Visual Memory (VisM), Visual Motor Speed (VMS), Reaction Time (RT), Impulse Control (IC), and Total Symptom Score (TSS) were measured as dependent variables. Data was analyzed using multiple one-way ANOVA’s accounting for gender and presence of ND as fixed factors. Results: One-way ANOVA (CI = 95%) revealed a five-point difference on BL-VMS between NDs and controls (p < 0.001). ND students’ performance declined more after injury on VMS (p = 0.042). Analysis also showed ND PI-IC score about two points higher than controls (p = 0.014). With respect to gender, females reported greater symptoms on PI and more symptom increase than their male counterparts (p < 0.001, p = 0.01; respectively). Lastly, ND males performed eight points lower on BL-VM than ND females (p = 0.031). Conclusions: The present study confirms that performance differences on ImPACT VMS may be expected between student-athletes with self-reported ND and their counterparts. Gender appears to contribute to performance on some measures of ImPACT; females endorse more symptoms than males PI, and ND males perform worse on BL-VM than ND females.
Where is WAIR (and other wing-assisted behaviours)? Essentially everywhere: a response to Kuznetsov and Panyutina (2022)
Authors: Heers Ashley M , Tobalske Bret W , Jackson Brandon E , Dial Kenneth P
Published: July 2022

Kuznetsov and Panyutina (2022) offer a reanalysis of the kinematic and force plate data previously published by Bundle and Dial (2003). Their intention is to describe instantaneous wing forces during wing-assisted incline running (WAIR), focusing particularly on the upstroke phase. Based on their interpretation of wing forces and muscle function, the authors conclude that ‘WAIR is a very specialized mode of locomotion that is employed by a few specialized birds as an adaptation to a very specific environment and involving highly developed flying features of the locomotor apparatus’, and thus not relevant to the evolution of avian flight. Herein, we respond to the authors’ interpretations, offering an alternative perspective on WAIR and, more generally, on studies exploring the evolution of avian flight.
Johann Gottfried Herder, Enlightenment Anthropology, and the Jew as a ‘Parasitic Plant’
Authors: Niekerk Carl
Published: July 2022

Buffon’s ‘Histoire naturelle de l’homme’, published in volumes two and three of the Histoire naturelle (1749), was key to the development of a new material history of humankind with scientific ambitions that wanted to understand humans as part of natural history and eventually would be called ‘anthropology’. Buffon understands humanity as consisting of one species, to which the same natural laws apply as for any other species. He understands human diversity as the product of space and time; because of geographical and climatological factors, humans develop differently in different parts of the world. Among German intellectuals, Johann Gottfried Herder (1744–1803) is a key figure in promoting Buffon’s thinking, in particular by assigning a central role to the concept of ‘culture’. The following essay focuses on the role the image of Jews plays in the emerging intertwined discourses of natural history and anthropology during the second half of the eighteenth century as it manifests itself in Herder’s writings. Herder’s views of Jews are highly contradictory. While he is respectful of their history and culture, he also refers to them in derogatory terms, calling them twice in the Ideen zur Philosophie der Geschichte der Menschheit a ‘parasitic plant’. To understand Herder’s ambiguity, his views of Jews are traced back to the premises underlying his thinking in natural history and anthropology.
Prognostic risk stratification of gliomas using deep learning in digital pathology images
Authors: Chunduru Pranathi , Phillips Joanna J , Molinaro Annette M
Published: July 2022

Background

Evaluation of tumor-tissue images stained with hematoxylin and eosin (H&E) is pivotal in diagnosis, yet only a fraction of the rich phenotypic information is considered for clinical care. Here, we propose a survival deep learning (SDL) framework to extract this information to predict glioma survival.

Methods

Digitized whole slide images were downloaded from The Cancer Genome Atlas (TCGA) for 766 diffuse glioma patients, including isocitrate dehydrogenase (IDH)-mutant/1p19q-codeleted oligodendroglioma, IDH-mutant/1p19q-intact astrocytoma, and IDH-wildtype astrocytoma/glioblastoma. Our SDL framework employs a residual convolutional neural network with a survival model to predict patient risk from H&E-stained whole-slide images. We used statistical sampling techniques and randomized the transformation of images to address challenges in learning from histology images. The SDL risk score was evaluated in traditional and recursive partitioning (RPA) survival models.

Results

The SDL risk score demonstrated substantial univariate prognostic power (median concordance index of 0.79 [se: 0.01]). After adjusting for age and World Health Organization 2016 subtype, the SDL risk score was significantly associated with overall survival (OS; hazard ratio = 2.45; 95% CI: 2.01 to 3.00). Four distinct survival risk groups were characterized by RPA based on SDL risk score, IDH status, and age with markedly different median OS ranging from 1.03 years to 14.14 years.

Conclusions

The present study highlights the independent prognostic power of the SDL risk score for objective and accurate prediction of glioma outcomes. Further, we show that the RPA delineation of patient-specific risk scores and clinical prognostic factors can successfully demarcate the OS of glioma patients.
Impact of the COVID-19 Pandemic on Pediatric Elbow Fractures: Marked Change in Management and Resource Utilization, Without a Change in Incidence
Authors: Schultz Jacob D. , Windmueller Rachel , Rees Andrew B. , Wollenman Lucas C. , Lempert Nathaniel L. , Schoenecker Jonathan G. , Moore-Lotridge Stephanie N.
Published: July 2022

Background:

Elbow fractures are the most common pediatric fractures requiring operative treatment. Although recent reports have suggested that the COVID-19 pandemic has markedly reduced the incidence of pediatric fractures, no study has specifically evaluated the impact on pediatric elbow fractures. This study aimed to evaluate changes in the incidence, severity, and resource utilization for managing pediatric elbow fractures during the COVID-19 pandemic, compared with prepandemic years.

Methods:

A prepandemic (2007 to 2017) cohort and a COVID-19 pandemic period (March 2020 to March 2021) cohort of pediatric elbow injuries from a single tertiary hospital were retrospectively examined and compared. Exclusion criteria included outside treatment or lack of diagnosis by an orthopedist. Presentation information, injury patterns, transport, and treatment requirements were collected.

Results:

Although the incidence of pediatric elbow fractures and rate of neurovascular injury were comparable, seasonal patterns were not sustained and the rate of fracture displacement was found to be significantly elevated in the COVID-19 period compared with nonpandemic years. Likewise, marked changes to where patients first presented (emergency department vs. Clinic), how the patients were transported, and the distance traveled for care were observed. Specifically, patients were more likely to present to the clinic, were more likely to self-transport instead of using emergency medical service transportation, and traveled a greater distance for care, on average. Aligning with these changes, the resources utilized for the treatment of pediatric elbow fracture markedly changed during the COVID-19 period. This study found that there was an increase in the overall number of surgeries performed, the total operative time required to treat elbow fractures, and the number of patients requiring admission during the COVID-19 period.

Conclusions:

These data provide a contrasting viewpoint to prior reports, illustrating that the incidence of elbow fractures remained consistent during the COVID-19 period, whereas the operative volume and need for hospital admission increased compared with years prior. Furthermore, this study demonstrated how the COVID-19 pandemic altered the interface between pediatric patients with elbow fractures and our institution regarding the location of presentation and transportation.

Level of Evidence:

Level III—retrospective cohort study.
Pediatric-Type Indolent B-Cell Lymphomas With Overlapping Clinical, Pathologic, and Genetic Features
Authors: Lim Sojung , Lim Ka Young , Koh Jiwon , Bae Jeong Mo , Yun Hongseok , Lee Cheol , Kim Young A. , Paik Jin Ho , Jeon Yoon Kyung
Published: July 2022

Pediatric-type follicular lymphoma (PTFL) and pediatric nodal marginal zone lymphoma (PNMZL) are rare pediatric-type indolent B-cell lymphomas (PedIBCL) that differ clinicopathologically from their adult counterparts. Accurate diagnosis is important to avoid overtreatment but is often challenging. The mutational landscape of PTFL is known and may aid diagnosis, but the genetic features of PNMZL are not well understood. We analyzed 21 cases of PedIBCL according to their clinicopathologic findings and classified them into PTFL (n=11), PNMZL (n=2), and “mixed type” tumors (n=8) showing ambiguous histology. We also analyzed 2 cases of adult B-cell lymphomas showing features of PedIBCL. Targeted sequencing of 121 lymphoma-related genes was performed. The median age of PedIBCL patients was 16 years (range: 3 to 47), and all but 1 PTFL patient were male. All patients presented with limited-stage disease, and only 1 relapsed. There were no significant differences in clinical features among the 3 PedIBCL groups. The most frequently mutated genes were MAP2K1, TNFRSF14, KMT2C, IRF8, and NOTCH2. The genetic features of all groups were similar to the established mutational landscape of PTFL. The 2 adult B-cell lymphomas cases also had MAP2K1, TNFRSF14, and IRF8 mutations, but the clinical features were not typical of PedIBCL. In summary, this study demonstrated that PTFL and PNMZL are similar diseases with overlapping clinical, pathologic, and genetic features; mixed type tumors can also occur. Atypical adult cases with similar histologic features were also observed. Therefore, the disease spectrum of PedIBCL may be much broader than is currently believed.
Comparison of patient-reported and functional outcomes after transition from traditional upper limb prosthetics to multiarticulating hands in the user with a unilateral transradial amputation
Authors: MacEachen Vincent B. , Davie-Smith Fiona , Carse Bruce
Published: July 2022

Background:

Multiarticulating hands (MAHs) have been commercially available for over 15 years. Despite this, their cost remains significantly higher than traditional electric hands, and they are not routinely available in many countries. The Scottish Specialist Prosthetic Service within the National Health Service has been prescribing MAHs since 2014. However, the benefits of MAHs provided in clinical settings are not well known.

Objectives:

This study aimed to compare patient-reported and functional measures in unilateral transradial prosthetic users transitioning from a body-powered or traditional myoelectric prosthesis to a MAH.

Study design:

This was a retrospective cohort analysis of individuals with a unilateral transradial amputation provided with a MAH.

Methods:

Of 38 users provided with MAHs, 20 had complete data sets of patient-reported and functional measures before and 6 months after provision. These included Disabilities of the Arm, Shoulder, and Hand; Southampton Hand Assessment Procedure Index of Function; health-related quality of life (EQ-5D-5L Health Index); Trinity Amputation and Prosthesis Experience Scales satisfaction; and Box and Block Test.

Results:

The mean age was 44 years (SD 16) (n = 20), and 75% were male. There were an 8-unit mean reduction in the Disabilities of the Arm, Shoulder, and Hand (P = .01) and a 9.5-unit improvement in the Southampton Hand Assessment Procedure IOF (P = .007) at 6 months after provision. Health-related quality of life did not change (P = .581). Users reported a four-point improvement in their Trinity Amputation and Prosthesis Experience Scales (P = .004) and transferred 3.3 blocks more completing the Box and Block Test (P = .001).

Conclusions:

The evidence clearly supports continued provision of MAHs to this group of moderate users: the more function the user achieves, the less of a disability they perceive to have.
Solitary Central Nervous System Relapse of Posttransplant Lymphoproliferative Disorder on 18F-FDG PET/CT
Authors: Feng Lijuan , Yang Xu , Lu Xia , Wang Wei , Yang Jigang
Published: July 2022

A 41-year-old woman received stem cell transplant due to acute myeloid leukemia. Six months after the stem cell transplant, the patient experienced monomorphic PTLD (posttransplant lymphoproliferative disorder) and underwent chemotherapy. Postchemotherapy PET/CT did not show any abnormal 18F-FDG accumulation in the scanned body, including brain. Four months later, she presented with nausea and vomiting. Brain MRI showed a lesion in the right temporal lobe. In addition to the abnormal 18F-FDG accumulation in the brain, no other abnormal foci were noted in the torso PET/CT. Biopsy pathology confirmed the diagnosis of monomorphic PTLD.
Rhodococcus yananensis sp. nov., a novel denitrification actinobacterium isolated from microbial fermentation bed material from a pig farm
Authors: Jiang Yingying , Zheng Chaochao , Yu Tianfei , Li Jing , Ai Jiamin , Li Maiping , Liu Xiaodong , Deng Zhenshan
Published: July 2022

An opaque, pink-coloured, gram-positive, aerobic bacteria (designated as FBM22-1T), was isolated from microbial fermentation bed material from a pig farm in northwestern China. Optimal growth occurred at 30–37 °C, pH 7.0 and with 0.5 % NaCl (w/v). The strain had nitrification and denitrification functions. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the novel isolate belonged to the genus

Rhodococcus

. Strain FBM22-1T was closely related to

Rhodococcus zopfii

NBRC 100606T and

Rhodococcus rhodochrous

NBRC 16069T, with 16S rRNA gene sequence similarities of 97.9 and 97.7 %, respectively. The predominant menaquinone in strain FBM22-1T was MK-8(H2). The cellular fatty acids consisted primarily of C16 : 1ω7c and/or C16 : 1 ω6c, C16 : 0 and 10-methyl C18 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and glycolipid. The G+C content of strain FBM22-1T was 68.64 mol%. Based on the phenotypic, phylogenetic and chemotaxonomic characterization results, in combination with low values of digital DNA–DNA hybridization between strain FBM22-1T and its closest neighbours, FBM22-1T represents a novel species of the genus

Rhodococcus

, for which the name Rhodococcus yananensis sp. nov. is proposed; the type strain is FBM22-1T (=KCTC 49502T=CCTCC AB2020275T).
Mice immunized with trimethyl chitosan nanoparticles containing DENV-2 envelope domain III elicit neutralizing antibodies with undetectable antibody-dependent enhancement activity
Authors: Seesen Mathurin , Jearanaiwitayakul Tuksin , Limthongkul Jitra , Sunintaboon Panya , Ubol Sukathida
Published: July 2022

Dengue is a disease that poses a significant global public health concern. Although a tetravalent live-attenuated dengue vaccine has been licensed, its efficacy is still debated due to evidence of vaccine breakthrough infection. To avoid this issue, dengue vaccines should stimulate a high degree of serotype-specific response. Thus, envelope domain III (EDIII), which contains serotype-specific neutralizing epitopes, is an attractive target for dengue vaccine development. In this study, we investigated how EDIII encapsidated in N, N, N-trimethyl chitosan chloride nanoparticles (TMC NPs) stimulates a serotype-specific response and whether this response exerts a potential in vitro breakthrough infection. The immune response to DENV-2 elicited by EDIII TMC NP-immunized mice was monitored. We demonstrated that immunization with EDIII TMC NPs resulted in a high level of anti-EDIII antibody production. These antibodies included IgG, IgG1, and IgG2a subtypes. Importantly, antibodies from the immunized mice exerted efficient neutralizing activity with undetectable antibody dependent enhancement (ADE) activity. We also found that EDIII TMC NPs activated functional EDIII-specific CD4+ and CD8+ T cell responses. In conclusion, EDIII TMC NPs stimulated humoral immunity with a strong neutralizing antibody response, as well as a cellular immune response against DENV-2.
How tactile afferents in the human fingerpad encode tangential torques associated with manipulation: are we better than monkeys?
Authors: Loutit Alastair J. , Wheat Heather E. , Khamis Heba , Vickery Richard M. , Macefield Vaughan G. , Birznieks Ingvars
Published: July 2022

Dexterous object manipulation depends critically on information about forces normal and tangential to the fingerpads, and also on torque associated with object orientation at grip surfaces. In this study we investigated how torque information is encoded by human tactile afferents, including slowly adapting type-II (SA-II) afferents, in the fingerpads. SA-II afferent properties seemed perfectly suited for torque encoding but could not be previously investigated as they are absent in the glabrous skin of monkeys. Torques of different magnitudes (3.5-7.5 mNm) were applied in clockwise and anticlockwise directions to a standard central site on the fingerpads of 34 participants. Torques were superimposed on a 2 N, 3 N, or 4 N background normal force. Unitary microneurography recordings were made from fast adapting type-I (FA-I, n=39), slowly adapting type-I (SA-I, n=31), and type-II (SA-II, n=13) afferents supplying the fingerpads. All three afferent types encoded torque magnitude and direction, with SA-II afferents showing excitatory and inhibitory modulation depending on torque direction. Most afferents of all three types had higher torque sensitivity with smaller normal force. FA-I afferents showed the best torque magnitude and worst directional discrimination abilities in both species. Human SA-I afferent response to static torque was inferior to dynamic stimuli, while in monkeys the opposite was true. In humans this might be compensated by the addition of a sustained SA-II afferent input. In comparison to monkeys the performance of each afferent type was inferior in humans, likely due to differences in fingertip tissue compliance and skin friction. [currently 246 words; 250 words max]

Significance Statement

We investigate how individual human tactile nerve fibres encode rotational forces (torques) and compare them to their monkey counterparts. Human hands, but not monkey hands, are innervated by a tactile neuron type (SA-II afferents) specialised to encode directional skin strain, yet so far, torque encoding has only been studied in monkeys. We find that human SA- I afferents were generally less sensitive and less able to discriminate torque magnitude and direction than their monkey counterparts, especially during the static phase of torque loading. However, this shortfall in humans could be compensated by the addition of SA-II afferent input. This indicates that variation in afferent types might compliment their specialisation for stimulus features, by slight differences between encoding in the two species.
KDM6A loss sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition
Authors: Boila Liberalis Debraj , Ghosh Subhadeep , Bandyopadhyay Subham K. , Jin Liqing , Murison Alex , Zeng Andy G. X. , Shaikh Wasim , Bhowmik Satyaki , Muddineni Siva Sai Naga Anurag , Biswas Mayukh , Sinha Sayantani , Chatterjee Shankha Subhra , Mbong Nathan , Gan Olga I. , Bose Anwesha , Chakraborty Sayan , Arruda Andrea , Kennedy James A. , Mitchell Amanda , Lechman Eric R. , Banerjee Debasis , Milyavsky Michael , Minden Mark D. , Dick John E. , Sengupta Amitava
Published: July 2022

Acute myeloid leukemia (AML) is a heterogeneous, aggressive malignancy with dismal prognosis and with limited availability of targeted therapies. AML exhibits epigenetic deregulation and transcriptional plasticity that contributes to pathogenesis. KDM6 proteins are histone-3 lysine-27 demethylases that play major context dependent roles in AML evolution and therapy resistance. Here, we demonstrate that KDM6 demethylase function critically regulates DNA damage repair (DDR) gene expression programs in AML. Mechanistically, KDM6 family protein expression is regulated by genotoxic stress, with deficiency of KDM6A (UTX) and KDM6B (JMJD3) impairing DDR transcriptional activation and compromising repair potential. Acquired KDM6A loss-of-function mutations have been implicated in chemoresistance, although a significant percentage of relapsed AML have upregulated KDM6A. Based on these mechanistic findings, olaparib treatment significantly reduced engraftment of patient-derived xenografts. Thus KDM6A-mutant human primary AML samples have increased susceptibility to Poly-(ADP-ribose)-polymerase (PARP) inhibition in vivo. Crucially, a higher KDM6A expression is correlated with venetoclax tolerance. Loss of KDM6A increased mitochondrial activity, BCL2 expression, and sensitized AML cells to venetoclax. Additionally, KDM6A loss was accompanied with a downregulated BCL2A1, which is commonly associated with venetoclax resistance. Corroborating these results, dual targeting of PARP and BCL2 was superior to PARP or BCL2 inhibitor monotherapy in inducing AML apoptosis, and primary AML cells carrying acquired KDM6A-domain mutations were even more sensitive to the combination. Together, our study illustrates a mechanistic rationale in support for a novel combination targeted therapy for human AML based on subtype heterogeneity, and establishes KDM6A as an important molecular regulator for determining therapeutic efficacy.
The Effects of N-linked Glycosylation on SLC6 Transporters
Authors: Chan Matthew C. , Shukla Diwakar
Published: July 2022

Membrane transporters of the solute carrier 6 (SLC6) family mediate various physiological processes by facilitating the translocation of amino acids, neurotransmitters, and other metabolites. In the human body, these transporters are tightly controlled through various post-translational modifications with implications on protein expression, stability, membrane trafficking, and dynamics. While N-linked glycosylation is a universal regulatory mechanism among eukaryotes, the exact molecular mechanism of how glycosylation affects the SLC6 transporter family. It is generally believed that glycans influence transporter stability and membrane trafficking, however, the role of glycosylation on transporter dynamics remains inconsistent, with differing conclusions among individual transporters across the SLC6 family. In this study, we collected over 1 millisecond of aggregated all-atom molecular dynamics (MD) simulation data to identify the impact of N-glycans of four human SLC6 transporters: the serotonin transporter, dopamine transporter, glycine transporter, and neutral amino acid transporter B0AT1. We designed our computational study by first simulating all possible combination of a glycan attached to each glycosylation sites followed by investigating the effect of larger, oligo-N-linked glycans to each transporter. Our simulations reveal that glycosylation does not significantly affect transporter structure, but alters the dynamics of the glycosylated extracellular loop. The structural consequences of glycosylation on the loop dynamics are further emphasized in the presence of larger glycan molecules. However, no apparent trend in ligand stability or movement of gating helices was observed. In all, the simulations suggest that glycosylation does not consistently affect transporter structure and dynamics among the collective SLC6 family and should be characterized at a per-transporter level to further elucidate the underlining mechanisms of in vivo regulation.
Density-dependent habitat selection alters drivers of population distribution in northern Yellowstone elk
Authors: Smith Brian J. , MacNulty Daniel R. , Stahler Daniel R. , Smith Douglas W. , Avgar Tal
Published: July 2022

Although it is well established that density dependence drives changes in organismal abundance over time, relatively little is known about how density dependence affects variation in abundance over space. We tested the hypothesis that spatial tradeoffs between food and safety can change the drivers of population distribution, caused by opposing patterns of density-dependent habitat selection (DDHS) that are predicted by the multidimensional ideal free distribution. We addressed this using winter aerial survey data of northern Yellowstone elk (Cervus canadensis) spanning four decades. Supporting our hypothesis, we found positive DDHS for food (herbaceous biomass) and negative DDHS for safety (openness and roughness), such that the primary driver of habitat selection switched from food to safety as elk density decreased from 9.3 to 2.0 elk/km2. Our results demonstrate how population density can drive landscape-level shifts in population distribution, confounding habitat selection inference and prediction, and potentially affecting community-level interactions.
“Leap before you look”: Conditions that promote implicit visuomotor adaptation without explicit learning
Authors: Savalia Tejas , Cowell Rosemary A. , Huber David E.
Published: July 2022

When learning a novel visuomotor mapping (e.g., mirror writing), accuracy can improve quickly through explicit learning (e.g., move left to go right) but after considerable practice, implicit learning takes over, producing fast, natural movements. This implicit learning occurs automatically, but it has been unknown whether explicit learning is similarly obligatory. Using a reaching task with a 90-degree rotation between screen position and movement direction, we found that explicit learning could be “turned off” by introducing the rotation gradually (increments of 10-degrees) and instructing participants to move quickly. These specific conditions were crucial, because both explicit and implicit learning occurred if the rotation occurred suddenly, if participants were told to emphasize accuracy, or if visual feedback during movement was removed. We reached these conclusions by examining the time course of learning (e.g., whether there was fast improvement followed by a long tail of additional improvement), by examining the aftereffects of learning when the rotation was abruptly removed, and by using formal model comparison between a dual-state (explicit and implicit) versus a single-state learning model as applied to the data.

Author summary

In some situations, the relationship between motion direction and what we see is different than normal. For instance, try using a computer mouse that is held sideways (a 90-degree rotation). When first encountering this situation, people move carefully, using explicit strategies (e.g., move right to go up). However, after many learning trials, motion becomes automatic (implicit) and natural. Prior results found that implicit visuomotor learning always occurs with enough experience. In our study, we found that this is not true of explicit visuomotor learning; in some situations, explicit learning can be turned off. More specifically, we found that this occurs when the novel visuomotor situation is: 1) introduced gradually (e.g., a gradual introduction of 90-degree rotation in steps of 10 degrees); 2) when there is pressure to move quickly; and 3) with real-time onscreen views of the motion path. If any of these three components are missing, then people use explicit learning. These conclusions were reached by examining the time course of learning (e.g., whether there was both fast and slow learning as assessed with mathematical models) and by examining the tendency to automatically move in the opposite direction from the rotation when the rotation is abruptly removed after learning.
Studying Pathogens Degrades BLAST-based Pathogen Identification
Authors: Beal Jacob , Clore Adam , Manthey Jeff
Published: July 2022

As synthetic biology becomes increasingly capable and accessible, it is likewise increasingly critical to be able to make accurate biosecurity determinations regarding the pathogenicity or toxicity of particular nucleic acid or amino acid sequences. At present, this is typically done using the BLAST algorithm to determine the best match with sequences in the NCBI databases. Neither BLAST nor the NCBI databases, however, are actually designed for biosafety determination. Critically, taxonomic errors or ambiguities in the NCBI databases can also cause errors in BLAST-based taxonomic categorization. With heavily studied taxa and frequently used biotechnology tools, even low frequency taxonomic categorization issues can lead to high rates of errors in biosecurity decision-making. Here we focus on the implications for false positives, finding that NCBI BLAST will now incorrectly categorize a number of commonly used biotechnology tool sequences as the pathogens or toxins with which they have been used. Paradoxically, this implies that problems are expected to be most acute for the pathogens and toxins of highest interest and the most widely used biotechnology tools. We thus conclude that biosecurity tools should shift away from BLAST against NCBI and towards new methods that are specifically tailored for biosafety purposes.
The spatial distribution and temporal trends of livestock damages caused by wolves in Europe
Authors: Singer Liam , Wietlisbach Xenia , Hickisch Raffael , Schoell Eva Maria , Leuenberger Christoph , Van den Broek Angela , Désalme Manon , Driesen Koen , Lyly Mari , Marucco Francesca , Kutal Miroslav , Pagon Nives , Papp Cristian Remus , Milioni Paraskevi , Uzdras Remigijus , Zihmanis Ilgvars , Zimmermann Fridolin , Marsden Katrina , Hackländer Klaus , López-Bao José Vicente , Klenzendorf Sybille , Wegmann Daniel
Published: July 2022

Wolf populations are recovering and expanding across Europe, causing conflicts with livestock owners. To mitigate these conflicts and reduce livestock damages, authorities spend considerable resources to compensate damages, support damage prevention measures, and manage wolf populations. However, the effectiveness of these measures remains largely unknown, especially at larger geographic scales. Here we compiled incident-based livestock damage data across 21 countries for the years 2018, 2019 and 2020, during which 39,262 wolf-caused incidents were reported from 470 administrative regions. We found substantial regional variation in all aspects of the data, including the primary target species, the density of damages, their seasonal distribution, and their temporal trend. More than half of the variation in damage densities across regions is explained by the area of extensively cultivated habitats occupied by wolves and namely natural grasslands and broad-leaved forests. Regional variation in husbandry practices and damage prevention, while difficult to quantify at a continental scale, appear important factors to further modulate these incidents. As illustrated with detailed data from Germany, for instance, the relationship between the number of wolf units and damages is diminishing over time, suggesting some adaptation of livestock owners and local authorities to their presence, for example by increasing prevention efforts. As we argue, temporal trends of damage incidents, which are robust to variation in data collection across regions, are thus informative about the local intensity of the wolf-human conflict. We estimated increasing trends for the majority of regions, reflecting the current expansion of wolves across the continent. Nonetheless, many of these increases were moderate and for more than one third of all regions, trends were negative despite growing wolf populations, thus indicating that wolf-livestock conflicts can be successfully mitigated with proper management.
Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
Authors: Collins Lindsay , Francis John , Emanuel Brett , McCormick David
Published: July 2022

Fluctuations in brain and behavioral state are supported by broadly projecting neuromodulatory systems. In this study, we use mesoscale two-photon calcium imaging to examine spontaneous activity of cholinergic and noradrenergic axons in awake mice in order to determine the interaction between arousal/movement state transitions and neuromodulatory activity across the dorsal cortex at distances separated by up to 4 mm. We confirm that GCaMP6s activity within axonal projections of both basal forebrain cholinergic and locus coeruleus noradrenergic neurons track arousal, indexed as pupil diameter, and changes in behavioral engagement, as reflected by bouts of whisker movement and/or locomotion. The broad coordination in activity between even distant axonal segments indicates that both of these systems can communicate, in part, through a global signal, especially in relation to changes in behavioral state. In addition to this broadly coordinated activity, we also find evidence that a subpopulation of both cholinergic and noradrenergic axons may exhibit heterogeneity in activity that appears to be independent of our measures of behavioral state. By monitoring the activity of cholinergic interneurons in the cortex we found that a subpopulation of these cells also exhibit state-dependent (arousal/movement) activity. These results demonstrate that cholinergic and noradrenergic systems provide a prominent and broadly synchronized signal related to behavioral state, and therefore may contribute to state-dependent cortical activity and excitability.
High-throughput Identification of Novel Heat Tolerance Genes via Genome-wide Pooled Mutant Screens in the Model Green AlgaChlamydomonas reinhardtii
Authors: Mattoon Erin M. , McHargue William , Bailey Catherine E. , Zhang Ningning , Chen Chen , Eckhardt James , Daum Chris G. , Zane Matt , Pennacchio Christa , Schmutz Jeremy , O’Malley Ronan C. , Cheng Jianlin , Zhang Ru
Published: July 2022

Different high temperatures adversely affect crop and algal yields with various responses in photosynthetic cells. The list of genes required for thermotolerance remains elusive. Additionally, it is unclear how carbon source availability affects heat responses in plants and algae. We utilized the insertional, indexed, genome-saturating mutant library of the unicellular, eukaryotic green algaChlamydomonas reinhardtiito perform genome-wide, quantitative, pooled screens under moderate (35°C) or acute (40°C) high temperatures with or without organic carbon sources. We identified heat-sensitive mutants based on quantitative growth rates and identified putative heat tolerance genes (HTGs). By triangulating HTGs with heat-induced transcripts or proteins in wildtype cultures and MapMan functional annotations, we present a high/medium-confidence list of 933Chlamydomonasgenes with putative roles in heat tolerance. Triangulated HTGs include those with known thermotolerance roles and novel genes with little or no functional annotation. About 50% of these high-confidence HTGs in Chlamydomonas have orthologs in green lineage organisms, including crop species.Arabidopsis thalianamutants deficient in the ortholog of a high-confidenceChlamydomonasHTG were also heat sensitive. This work expands our knowledge of heat responses in photosynthetic cells and provides engineering targets to improve thermotolerance in algae and crops.
Recent transposable element bursts triggered by insertions near genes in a fungal pathogen
Authors: Oggenfuss Ursula , Croll Daniel
Published: July 2022

The activity of transposable elements (TEs) contributes significantly to genome evolution. TEs often destabilize genome integrity but may also confer adaptive variation in phenotypic traits. De-repression of epigenetically silenced TEs often initiates bursts of transposition activity that may be counteracted by purifying selection and genome defenses. However, how these forces interact to determine the expansion routes of TEs within a species remains largely unknown. Here, we analyzed a set of 19 telomere-to-telomere genomes of the fungal wheat pathogenZymoseptoria tritici. Phylogenetic reconstruction and ancestral state estimates of individual TE families revealed that TEs have undergone distinct activation and repression periods resulting in highly uneven copy numbers between genomes of the same species. Most TEs are clustered in gene poor niches, indicating strong purifying selection against insertions near coding sequences. TE families with high copy numbers have low sequence divergence and strong signatures of defense mechanisms (i.e., RIP). In contrast, small non-autonomous TEs (i.e., MITEs) are less impacted by defense mechanisms and are often located in close proximity to genes. Individual TE families have experienced multiple distinct burst events that generated many nearly identical copies. We found that aCopiaelement burst was initiated from recent copies inserted substantially closer to genes compared to older insertions. Overall, TE bursts tended to initiate from copies in GC-rich niches that escaped inactivation by genomic defenses. Our work shows how specific genomic environments features provide triggers for TE proliferation.