bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Resection of the Outer Table of the Cranium in Locally Invasive Primary Squamous Cell Carcinoma of the Scalp
Authors: Leach Garrison A. , Pflibsen Lacey R. , Mathew Denzil P. , Sharma Ayushi D. , Reid Christopher M. , Holcombe Travis C. 
Published: July 2022

Introduction:
Nonmelanoma skin cancer is the most common malignancy of the scalp. Of these, squamous cell carcinoma (SCC) is the most troublesome. It poses a challenge to the surgeons caring for these patients as the anatomy of the scalp makes excision and reconstruction difficult. Although more superficial lesions are amenable to Mohs micrographic surgery, more invasive lesions require a different approach. This manuscript is a retrospective review of outer table resection for SCC of the scalp invading to the depth of the pericranium. We include a discussion of full thickness craniectomy for invasive SCC, regardless of depth of invasion, for completeness.

Methods:
IRB approval was obtained from St. Joseph’s Hospital and Medical Center in Phoenix, Arizona. One hundred four potential cases identified based on ICD codes. Ultimately, 23 cases met study criteria and were included in this analysis. Seventeen cases of outer table resection and 6 cases of full craniectomy were discussed. Additionally, the authors’ approach for resection and reconstruction is articulated.

Results:
Seventeen patients underwent outer table resection at an average age of 79.3 years. All had invasion of the pericranium with a mean surface area of 42.6 cm2. Eight patients had prior radiation treatment for SCC of the scalp and 12 patients had at least 1 prior surgery to attempt excision of their lesions. Two patients had local recurrence for a local control rate of 88.2% (15/17). One patient with metastasis prior to presentation, died 6 months after his initial surgery for disease-free survival rate of 94.1% (16/17) at a mean of 15.4months. Thirteen patients were able to achieve immediate reconstruction with local flaps with or without additional skin grafting (76.5%).

Discussion:
The data in this study supports that in instances of locally invasive primary SCC of the scalp that extends to the pericranium, excision down to the calvarium with complete circumferential and deep peripheral margin assessment, followed by resection of the outer table, is an excellent option. The low rate of local recurrence and high disease-free survival in this study support that this method allows for optimal oncologic outcome while mitigating the significant morbidity associated with the alternative option of a full thickness craniectomy.
Normal Values of Central, Peripheral, and Root Motor Conduction Times in a Healthy Korean Population
Authors: Park Dougho , Kim Byung Hee , Lee Sang-Eok , Cho Jae Man , Yang Joong Won , Yang Donghoon , Kim Mansu , Oh Gayeoul , Sophannara Yoeng , Kwon Heum Dai 
Published: July 2022

Purpose:
Central, peripheral, and root motor conduction times (CMCTs, PMCTs, and RMCTs, respectively) are valuable diagnostic tools for spinal cord and motor nerve root lesions. We investigated the normal values and the effects of age and height on each motor conduction time.

Methods:
This study included 190 healthy Korean subjects who underwent magnetic stimulation of the cortex and spinous processes at the C7 and L1 levels. Recording muscles were abductor pollicis brevis and abductor digiti minimi in the unilateral upper limb and extensor digitorum brevis and abductor hallucis in the contralateral lower limb. F-wave and compound motor nerve action potentials were also recorded. Central motor conduction time was evaluated as the difference between cortical motor evoked potential onset latency and PMCT using calculation and spinal stimulation methods. Root motor conduction time was computed as the difference between spinal stimulated and calculated CMCTs.

Results:
The average age and height of the participants were 41.21 ± 14.39 years and 164.64 ± 8.27 cm, respectively; 39.5% (75/190) patients were men. In the linear regression analyses, upper limb CMCTs showed a significant and weak positive relationship with height. Lower limb CMCTs demonstrated a significant and weak positive relationship with age and height. Peripheral motor conduction times were significantly and positively correlated with age and height. Root motor conduction times showed no significant relationship with age and height, except for abductor pollicis brevis-RMCT, which had a weak negative correlation with height.

Conclusions:
This study provides normal values of CMCTs, PMCTs, and RCMTs, which have potential clinical applications. When interpreting CMCTs, age and height should be considered.
Characterizing physiological high-frequency oscillations using deep learning
Authors: Zhang Yipeng , Chung Hoyoung , Ngo Jacquline P. , Monsoor Tonmoy , Hussain Shaun A. , Matsumoto Joyce H. , Walshaw Patricia D. , Fallah Aria , Sim Myung Shin , Asano Eishi , Sankar Raman , Staba Richard J. , Engel Jerome , Speier William , Roychowdhury Vwani , Nariai Hiroki 
Published: July 2022

ABSTRACTObjectiveIntracranially-recorded interictal high-frequency oscillations (HFOs) have been proposed as a promising spatial biomarker of the epileptogenic zone. However, HFOs can also be recorded in the healthy brain regions, which complicates the interpretation of HFOs. The present study aimed to characterize salient features of physiological HFOs using deep learning (DL).MethodsWe studied children with neocortical epilepsy who underwent intracranial strip/grid evaluation. Time-series EEG data were transformed into DL training inputs. The eloquent cortex (EC) was defined by functional cortical mapping and used as a DL label. Morphological characteristics of HFOs obtained from EC (ecHFOs) were distilled and interpreted through a novel weakly supervised DL model.ResultsA total of 63,379 interictal intracranially-recorded HFOs from 18 children were analyzed. The ecHFOs had lower amplitude throughout the 80-500 Hz frequency band around the HFO onset and also had a lower signal amplitude in the low frequency band throughout a one-second time window than non-ecHFOs, resembling a bell-shaped template in the time-frequency map. A minority of ecHFOs were HFOs with spikes (22.9%). Such morphological characteristics were confirmed to influence DL model prediction via perturbation analyses. Using the resection ratio (removed HFOs/detected HFOs) of non-ecHFOs, the prediction of postoperative seizure outcomes improved compared to using uncorrected HFOs (area under the ROC curve of 0.82, increased from 0.76).InterpretationWe characterized salient features of physiological HFOs using a DL algorithm. Our results suggested that this DL-based HFO classification, once trained, might help separate physiological from pathological HFOs, and efficiently guide surgical resection using HFOs.
Preoperative predictors of instrumental activities of daily living disability in older adults six months after knee arthroplasty
Authors: Nanjo Keigo , Ikeda Takashi , Nagashio Naoko , Sakai Tomoko , Jinno Tetsuya 
Published: July 2022

AbstractObjectiveTo investigate preoperative predictors of instrumental activities of daily living (IADL) disability in older adults six months after knee arthroplasty (KA).DesignProspective cohort studySettingGeneral hospital with an orthopedic surgery departmentParticipantsTwo hundred twenty (N = 220) patients 2: 65 years old with total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA)Interventions: Not applicableMain Outcome MeasureIADL status was evaluated for six activities. Participants chose “able,” “need help,” or “unable” according to their capacity of executing these IADL activities. If they chose “need help” or “unable” for one or more items, they were defined as “disabled.” Their usual gait speed (UGS), range of motion for the knee, isometric knee extension strength (IKES), pain status, depressive symptoms, pain catastrophizing, and self-efficacy were evaluated as predictors. Baseline and follow-up assessments were conducted one month before and six months after KA, respectively. Logistic regression analyses with IADL status as the dependent variable were performed at follow-up. All models were adjusted using age, sex, severity of the knee deformity, operation type (TKA or UKA), and preoperative IADL status as covariates.ResultsIn total, 166 patients completed the follow-up assessment, and 83 (50.0%) reported IADL disability six months after KA. Preoperative UGS, IKES on the non-operated side, and self-efficacy were statistically significantly different between those with a disability at follow-up and those who did not and were therefore included in logistic regression models as independent variables. UGS (odds ratio = 3.22, 95% confidence interval = 1.38–7.56,p= 0.007) was determined as a significant independent variable.ConclusionThe present study demonstrated the importance of evaluating preoperative gait speed to predict the presence of IADL disability in older adults six months after KA. Patients with poorer preoperative mobility should be provided careful postoperative care and treatment.
Interspecies normalization of dose response relationship for adeno-associated virus-mediated hemophilia gene therapy – application to first-in-human dose prediction
Authors: Zou Peng 
Published: July 2022

AbstractEstablishing dose response relationships in targeted patients is foundational in the development of therapeutic drugs including gene therapy products. Enlightened by interspecies normalization of plasma drug concentration-time curves using Dedrick plot, the author of this manuscript first demonstrated the feasibility of normalizing dose-response relationship of adeno-associated virus (AAV)-mediated hemophilia gene therapy products in multiple species to a species-invariant scale. Preclinical dose-response relationships of eight AAV vectors were normalized using an exponent of 0.25 and applied to first-in-human (FIH) dose prediction. The performance of this dose-response normalization approach for FIH dose prediction was compared to that of direct body weight-based dose conversion and allometric scaling approaches. The study results suggested that in addition to hemophilia dogs and non-human primates, inclusion of larger animal models (e.g., swine and cattle) in preclinical dose-finding studies of AAV vectors might improve the performance of interspecies dose-response normalization approach. Furthermore, it was found that AAV capsid-specific T cell responses in hemophilia patients might cause underprediction of FIH dose while novel bioengineered capsids with a high transduction efficiency specifically in human hepatocytes might cause overprediction of FIH dose. These factors should be considered when dose-response is extrapolated from preclinical species to patients.
Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods
Authors: Fulkerson Patricia C. , Lussier Stephanie J. , Bendixsen Casper G. , Castina Sharon M. , Gebretsadik Tebeb , Marlin Jessica S. , Russell Patty B. , Seibold Max A. , Everman Jamie L. , Moore Camille M. , Snyder Brittney M. , Thompson Kathy , Tregoning George S. , Wellford Stephanie , Arbes Samuel J. , Bacharier Leonard B. , Calatroni Agustin , Camargo Carlos A. , Dupont William D. , Furuta Glenn T. , Gruchalla Rebecca S. , Gupta Ruchi S. , Hershey Gurjit Khurana , Jackson Daniel J. , Johnson Christine C. , Kattan Meyer , Liu Andrew H. , Murrison Liza , O’Connor George T. , Phipatanakul Wanda , Rivera-Spoljaric Katherine , Rothenberg Marc E. , Seroogy Christine M. , Teach Stephen J. , Zoratti Edward M. , Togias Alkis , Hartert Tina V. 
Published: July 2022

AbstractThe Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.
Nutraceutical supplement targeting multiple molecular steps synergistically enhances muscle glucose uptake and improves in vivo oral glucose disposal
Authors: Saxena Uday , Meher Kranti , K Saranya , Reddy Arpitha , Kadiyala Gopi , Iyer Subramanian , Vangala Subrahmanyam , Chandran Satish 
Published: July 2022

ABSTRACTPre diabetes and type 2 diabetes are increasingly becoming rampant world wide. While there are medications to control blood glucose in type 2 diabetics, currently there are no interventions prescribed for pre diabetes. Alternate strategies to control blood glucose are needed either to act alone in pre diabetes or as supplement to the existing drugs for type 2 diabetes. We report here the targeting of critical molecular steps in muscle glucose uptake and metabolism to result in glucose lowering using a combination of safe vitamins. Our in vitro and in vivo data support the potential for using such vitamin combination for glucose control in pre diabetes and as a supplement in type 2 diabetics.
Improved Predictions of Phase Behaviour of Intrinsically Disordered Proteins by Tuning the Interaction Range
Authors: Tesei Giulio , Lindorff-Larsen Kresten 
Published: July 2022

AbstractThe formation and viscoelastic properties of condensates of intrinsically disordered proteins (IDPs) is dictated by amino acid sequence and solution conditions. Because of the involvement of biomolecular condensates in cell physiology and disease, furthering our understanding of the relationship between protein sequence and phase separation (PS) may have important implications in the formulation of new therapeutic hypotheses. Here, we present CALVADOS 2, a coarse-grained model of IDPs that accurately predicts conformational properties and propensity to undergo PS for diverse sequences and solution conditions. In particular, we systematically study the effect of varying the range of nonionic interactions and use our findings to improve the temperature scale of the model. We further optimize the residue-specific model parameters against experimental data on the conformational properties of 55 proteins, while also leveraging 70 hydrophobicity scales from the literature to avoid overfitting the training data. Extensive testing shows that the model accurately predicts chain compaction and PS propensity for sequences of diverse length and charge patterning, as well as at different temperatures and salt concentrations.
In-vivo fast non-linear microscopy reveals impairment of fast axonal transport induced by molecular motor imbalances in the brain of zebrafish larvae
Authors: Grimaud Baptiste , Frétaud Maxence , Terras Feriel , Bénassy Antoine , Duroure Karine , Bercier Valérie , Trippé-Allard Gaëlle , Mohammedi Rabei , Gacoin Thierry , Del Bene Filippo , Marquier François , Langevin Christelle , Treussart François 
Published: July 2022

AbstractCargo transport by molecular motors along microtubules is essential for the function of eucaryotic cells, in particular neurons in which axonal transport defects constitute the early pathological features of neurodegenerative diseases. Mainly studied in motor and sensory neurons, axonal transport is still difficult to characterize in neurons of the brain in absence of appropriatein vivotools. Here, we measured fast axonal transport by tracing the second harmonic generation (SHG) signal of potassium titanyl phosphate (KTP) nanocrystals endocytosed by brain neurons of zebrafish (Zf) larvae. Thanks to the optical translucency of Zf larvae and of the perfect photostability of nanoKTP SHG, we achieved a high scanning speed of 20 frames (of ≈ 90μm×60μm size) per second in Zf brain. We focused our study on endolysosomal vesicle transport in axons of known polarization, separately analyzing kinesin and dynein motor-driven displacements. To validate our assay, we used either loss-of-function mutations of dynein or kinesin 1 or the dynein inhibitor dynapyrazole, and quantified several transport parameters. We successfully demonstrated that dynapyrazole reduces nanoKTP mobile fraction and retrograde run length consistently, while the retrograde run length increased in kinesin 1 mutants. Taking advantage of nanoKTP SHG directional emission, we also quantified fluctuations of vesicle orientation. Thus, by combining endocytosis of nanocrystals having non-linear response, fast two-photon microscopy, and high-throughput analysis, we are able to finely monitor fast axonal transportin vivoin the brain of a vertebrate, and reveal subtle axonal transport alterations. The high spatiotemporal resolution achieved in our model may be relevant to precisely investigate axonal transport impairment associated to disease models.
Metabolic profiling of drought tolerance: revealing how citrus rootstocks modulate plant metabolism under varying water availability
Authors: Silva Simone F. , Miranda Marcela T. , Cunha Camila P. , Domingues-Jr Adilson P. , Aricetti Juliana A. , Caldana Camila , Machado Eduardo C. , Ribeiro Rafael V. 
Published: July 2022

AbstractWater stress is a major environmental factor affectingCitrusspp. and Rangpur lime is a drought-tolerant rootstock used to enhance orange yield in rainfed orchards. Here, we combined morpho-physiological analyses with metabolic profiling of roots and leaves of Valencia orange scions grafted onto Rangpur lime, Swingle citrumelo or Sunki mandarin rootstocks under water deficit. Our aim was to present a comprehensive spatio-temporal evaluation of citrus responses to drought and highlight the metabolic adjustments associated with drought tolerance induced by Rangpur lime. Plant responses were evaluated during the initial phase of reduction in water availability, when water deficit was maximum and also after rehydration. Fifty-eight primary metabolites were modulated by water deficit, mainly amino acids, organic acids and sugars. Metabolic changes indicated adjustments related to osmotic, energetic and redox processes under low water availability, which were dependent on rootstock and varied between roots and leaves and along the experimental period. Rangpur lime prioritized root growth in the initial phase of water deficit, which was linked to less sugar accumulation, changes in nucleotide metabolism, downregulation in Shikimic acid pathway and accumulation of arginine. After rehydration, the resume of shoot growth was associated with high accumulation of arginine and asparagine. The better performance of Rangpur lime seems to be associated with its high sensitivity of roots to changes in water availability and possible signaling compounds have been suggested.
CryoEM structure of QacA, an antibacterial efflux transporter from Staphylococcus aureus
Authors: Majumder Puja , Ahmed Shahbaz , Ahuja Pragya , Athreya Arunabh , Ranjan Rakesh , Penmatsa Aravind 
Published: July 2022

AbstractEfflux of antibacterial compounds is a major mechanism for developing antimicrobial resistance. In the Gram-positive pathogen Staphylococcus aureus, QacA, a 14 transmembrane (TM) helix containing major facilitator superfamily antiporter, mediates proton-coupled efflux of mono and divalent cationic antibacterial compounds. In this study, we report the cryoEM structure of QacA, with a single mutation D411N that improves homogeneity and retains efflux activity against divalent cationic compounds like dequalinium and chlorhexidine. The structure of substrate-free QacA, complexed to two single-domain camelid antibodies, was elucidated to a resolution of 3.6 Å. The structure displays an outward-open conformation with an extracellular hairpin loop, which is conserved in a subset of DHA2 transporters and its deletion causes a loss of function in the transporter. Modeling and simulations of QacA’s cytosol-facing and occluded conformations reveal asymmetry in the rocker-switch mode of QacA’s conformational shifts, providing new insights into the organization and structural dynamics of DHA2 members.
Altered visual evoked potentials associated with verbal and nonverbal skills in Fragile X syndrome
Authors: Saoud Elizabeth , Fitzgerald John , Hartney Megan , Wilkinson Carol L. 
Published: July 2022

AbstractBackgroundUnderstanding the neurobiology behind Fragile X syndrome (FXS) is critical in identifying effective therapeutics and improving care for affected individuals.Electroencephalography (EEG) provides an opportunity to investigate the biological foundations of this disorder. We aimed to characterize the visual evoked potential (VEP) in young children with FXS, and to understand how measures of the VEP are associated with verbal and nonverbal development within FXS.MethodsVEPs were collected in children between 2-7 years old with FXS (n = 9) as well as corresponding age-(n = 10) and cognitive-matched (n = 9) typically developing children. Additionally, the Mullen Scales of Early Learning and Preschool Language Scales were administered to collect measures of verbal and nonverbal development. Differences in component amplitudes and latencies of the VEP were assessed using ANCOVAs, and associations of VEP measures and verbal and nonverbal development were evaluated using linear regression with age as a covariate.ResultsNo differences between groups were observed in N1, P1, or N2 VEP components. However, a consistent and prominent P2 component (latency = 177ms ± 13.7), was observed in children with FXS. The P2 amplitude was significantly increased in FXS children compared to the cognitive-matched group (p = 0.004). For children with FXS, the amplitude of several VEP components were associated with verbal and nonverbal development; larger N1 amplitude and smaller P1 and P2 amplitudes were all associated with better receptive language (all p<0.05) and larger N1 amplitude was also associated with better fine motor skills (p<0.05).ConclusionsThe observed increase in P2 amplitude and its negative association with language development within the FXS group supports the P2 component as a potential biomarker for FXS as a disorder, as well as a pathophysiological marker of verbal impairment that could be used in clinical trials.