bluuebunny/crossref_metadata_2025 huggingface dataset:
TMOD-19. FROM PATIENT TO PETRI DISH: INCREASING PATIENT-DERIVED GLIOBLASTOMA CULTURE EFFICIENCIES TO 95%
Authors: Verheul Cassandra , Fabro Federica , Ntafoulis Ioannis , Beerens Cecile , Hoogstrate Youri , Kers Trisha , Van den Burg Judith , Van Stanley , French Pim , Chien Miao , Dirven Clemens , Leenstra Sieger , Lamfers* Martine ,   GLIOTRAIN Consortium Biobank
Published: November 2021

INTRODUCTION

The search for effective therapies for gliomas is progressively moving towards patient-specific medicine. In order to test patient-tailored therapies, it is vital to develop protocols for reliable establishment of patient-derived glioma cultures. We present a method for reliable culture establishment, with a 95% success rate in 114 consecutive high-grade samples.

METHODS

Cell cultures were established from either traditionally-resected tumor tissue or ultrasonic surgical aspirator (CUSA) derived tissue fragments, and expanded in serum-free culture, with selection of astrocytic populations if required. Cultures were started from single cells or small tumor fragments of 0.5-3mm (3D). Whole exome and RNA sequencing were carried out with the Illumina Novaseq and HiSeq platforms. Methylation profiling was performed with the Infinium MethylationEPIC array. Cultures and tumors were compared through analysis of single nucleotide polymorphisms and copy number profiles with the Infinium Global Screening Array. Intra-tumoral heterogeneity in cultures was investigated with single-cell transcriptomic sequencing (SORT-seq). We studied tumor-initiating potential by orthotopic injection of cultures in NOD-SCID mice.

RESULTS

Cultures started from single cells were established from CUSA material more efficiently (92%) than from traditional resection material (70%). 3D-derived cultures had a higher overall efficiency (95% for CUSA, 85% for traditional resection material). We confirmed high concordance in driver mutations, copy number and methylation profiles between tumors and derived cultures. Transcriptomics analysis, comparing tumors and derived cultures, revealed high consistency in gene expression distribution as demonstrated by correlation analysis (r=0.88). Singe-cell RNA-seq shows increased heterogeneity in CUSA derived-cultures, and decreased heterogeneity with passaging over time. Cultures faithfully produce tumors after orthotopic injection in NOD-SCID mice.

CONCLUSION

We present a highly successful method for the establishment of glioma cultures from patient material, with CUSA-derived cultures revealing greater heterogeneity. Cultures faithfully represent important molecular characteristics of parental tumors and can be used to test potential therapies in vitro.
TMOD-24. PATIENT-DERIVED ORGANOIDS TO MODEL AND CHARACTERIZE TUMORAL HETEROGENEITY OF PEDIATRIC BRAIN CANCERS
Authors: Lago Chiara , Ballabio Claudio , Miele Evelina , Tiberi Luca
Published: November 2021

Central nervous system (CNS) tumors are the most common solid tumors in the pediatric population and the main cause of death among childhood cancers. They present common features related to the development and produce symptoms based on their location, rate of tumor growth and age of the child. Tumors of embryonal origin, such as medulloblastoma or primitive neuroectodermal tumor, have a higher incidence in younger patients, whereas older ones tend to present tumors of glial origin. Most of CNS-embryonal tumors are highly malignant and consequently leading to poor prognoses. Despite the understanding of the underlying molecular landscape of these tumors that has helped in clinical advances to improve life expectancies of the patients, there is still an emerging need to minimize morbidity and manage the long-term therapy effects. Developing new models to better understand the heterogeneity of these tumors and to test personalized treatment strategies remains a clinical challenge. We are trying to answer to this medical need with Patient-Derived Organoids (PDOs) established through the direct in vitro culture of primary tumors and patient derived xenograft (PDX)-derived tumors. We have developed a method for generating PDOs from a variety of pediatric brain cancers that recapitulates the cellular heterogeneity, histological features and mutational profiles of the corresponding parental tumors. We have obtained promising results from the DNA methylation profile analysis, nowadays used for an accurate routine CNS tumors diagnosis. Through this new model, we confirmed the action of some clinically used drugs, obtaining a proof of concept of their possible application as a reliable tool for drug screening. Another interesting application derives from the enrichment of PDOs culture media for possible tumor-specific antigens: their identification could be of pivotal importance for the definition of tumor markers identifiable with diagnostic tests or as candidates for new therapies.
TMOD-28. MYC GENERATES AGGRESSIVE MEDULLOBLASTOMA BY HSP90 PATHWAY ACTIVATION AND ARF SILENCING
Authors: Mainwaring Oliver , Weishaupt Holger , Hutter Sonja , Zhao Miao , Borgenvik Anna , Rosén Gabriela , Breinschmid Laura , Verbaan Annemieke D , Sundström Anders , Annusver Karl , Kasper Maria , Swartling Fredrik
Published: November 2021

Medulloblastoma, the most common malignant pediatric brain tumor, often shows amplification or overexpression of the MYC transcription factor and arises in the presence of a functional p53 tumor suppressor protein. To elucidate the mechanism behind this inexplicable tumor development we generated an inducible, immunocompetent transgenic mouse model of MYC-expressing medulloblastoma. Aggressive tumors developed clonally in the presence of an unaltered p53 gene that molecularly resembled Group 3 medulloblastoma. Compared to MYCN-expressing medulloblastoma driven from the same promoter, we instead discovered pronounced and MIZ1-independent silencing of the ARF suppressor, which was also suppressed in MYC-amplified as compared to MYCN-amplified human medulloblastoma. While MYCN-driven tumor malignancy was more sensitive to ARF depletion, it dramatically increased metastatic spread of MYC-driven tumors. DNMT inhibition could restore ARF levels in MYC-expressing tumors but did not show any therapeutic advantage in tumors in vivo. Bioinformatics analysis further showed a strong correlation of the HSP90 pathway with MYC in human Group 3 MB and in the MYC-driven mouse model. The HSP90 inhibitor Onalespib showed significant selectivity for targeting MYC-driven as compared to MYCN-driven tumors. The drug promoted ARF restoration and increased the survival in our animal model which suggests that it could be potentially used in the treatment of MYC-driven ARF-silenced brain cancer patients.
TMOD-29. STANDARDIZED GENERATION OF TUMOR-ORGANOIDS AS NOVEL DRUG SCREENING MODEL IN MENINGIOMA
Authors: Jungwirth Gerhard , Yu Tao , Junguo Cao , Lotsch Catharina , Unterberg Andreas , Herold-Mende Christel
Published: November 2021

Tumor-organoids (TOs) are novel, complex three-dimensional ex vivo tissue cultures that under optimal conditions accurately reflect genotype and phenotype of the original tissue with preserved cellular heterogeneity and morphology. They may serve as a new and exciting model for studying cancer biology and directing personalized therapies. The aim of our study was to establish TOs from meningioma (MGM) and to test their usability for large-scale drug screenings. We were capable of forming several hundred TO equal in size by controlled reaggregation of freshly prepared single cell suspension of MGM tissue samples. In total, standardized TOs from 60 patients were formed, including eight grade II and three grade III MGMs. TOs reaggregated within 3 days resulting in a reducted diameter by 50%. Thereafter, TO size remained stable throughout a 14 days observation period. TOs consisted of largely viable cells, whereas dead cells were predominantly found outside of the organoid. H&E stainings confirmed the successful establishment of dense tissue-like structures. Next, we assessed the suitability and reliability of TOs for a robust large-scale drug testing by employing nine highly potent compounds, derived from a drug screening performed on several MGM cell lines. First, we tested if drug responses depend on TO size. Interestingly, drug responses to these drugs remained identical independent of their sizes. Based on a sufficient representation of low abundance cell types such as T-cells and macrophages an overall number of 25.000 cells/TO was selected for further experiments revealing FDA-approved HDAC inhibitors as highly effective drugs in most of the TOs with a mean z-AUC score of -1.33. Taken together, we developed a protocol to generate standardized TO from MGM containing low abundant cell types of the tumor microenvironment in a representative manner. Robust and reliable drug responses suggest patient-derived TOs as a novel drug testing model in meningioma research.
BRMP-04. AI-based biomarker of the peritumoral region using tissue microstructure
Authors: Samani Zahra Riahi , Parker Drew , Wolf Ronald , Brem Steven , Verma Ragini
Published: November 2021

PURPOSE

Glioblastomas, the most common malignant brain tumor [BS1], infiltrate into peritumoral brain structures, making clinical management challenging. An unmet need is to develop a biomarker that reliably characterize infiltration in the peritumoral region, where surgical biopsy or resection may be hazardous. Diffusion tensor imaging (DTI) with multicompartment modeling can characterize extracellular free water, providing unique information of the tissue microstructure that is able to capture this heterogeneity. We propose a novel biomarker based on peritumoral tissue microstructure, using deep-learning on DTI-based free water map.

METHOD

Peritumoral regions were automatically segmented for 136 patients with brain tumors (86 glioblastomas and 50 metastases, ages 23–87 years, 65 females). We trained a Convolutional Neural Network (CNN) on free-water maps using automatically defined patches in the peritumoral area from glioblastomas and metastases, labeled as low free-water and high free-water to extract a microstructural index for each voxel. To extract the biomarker, we grouped peritumoral voxels into connected components (CCs) where adjacent voxels have high (>0.9) microstructural index values. Two independent test sets related to two clinically significant problems were evaluated: i) metastases vs. glioblastomas; ii) glioma patients categorized into short and long survival groups and the number of CCs were statistically compared.

RESULT

Two-sample t-tests showed significant group difference in the number of CCs between metastases and glioblastomas (p< 0.05), and short and long-survivals (p<0.05) with higher number of CCs in metastases and long-survivals, which suggests smaller number of voxels in CCs.

CONCLUSION

The proposed biomarker based on CCs of microstructural index captures the differences in infiltration of the peritumoral region, showing larger CCs in glioblastomas and short-survivals corresponding to higher infiltration.

CLINICAL IMPORTANCE

The proposed biomarker provides a novel insight into the peritumoral microenvironment and can be derived from clinically feasible DTI data, providing new possibilities for the diagnosis and treatment of glioblastoma.
CNTM-06. Individual Cerebrocerebellar Functional Network Analysis for Decoding the Symptomatological Dynamics of Posterior Fossa Syndrome
Authors: Chen Ko-Ting , Huang Sheng-Yao
Published: November 2021

Posterior fossa syndrome (PFS) consists of three types of symptom (motoric, linguistic, and neurobehavioral) in patients with posterior fossa pathologies. The evolutional mechanism of this high cognitive syndromic complex from cerebellar origin remains unconfirmed. Previous studies analyzing PFS patients mostly focused on the association between structural abnormalities that occur during PFS, of which proximal efferent cerebellar pathway (pECP) injury appears to be the most common pathogenesis. However, structural imaging may not be sensitive enough to determine the dynamic course of PFS, since the symptomatology is primarily an output of cerebral operation. On the other hand, a network neuroscience approach using a mathematical model to extract information from functional imaging to generate interregional connectivity provides abundant evidence that the cerebellum is influential in modulating cerebral functions. This study applied a network approach to children with PFS. Scaling of each symptom domain was used to quantify the dynamics of the syndrome. An individual cerebrocerebellar functional network analysis was then performed to determine the network dynamics during PFS. Cross-validation of clinical neurophysiology and functional neuroscience suggested the critical role of the pECP within PFS from the network analysis. The employed approach was therefore useful in determining the complex clinical symptoms using individual functional network analysis, which bridges the gap between structural neuroimaging and clinical neurophysiology.
FLGS-04. Fluorescence lifetime imaging (FLIm) is a dye-free, high sensitivity approach for fluorescence guided surgery in high-grade and low-grade gliomas
Authors: Bloch Orin , Garcia Alba Alfonso , Anbunesan Silvia Noble , Frusciante Roberto , Bec Julien , Marcu Laura
Published: November 2021

INTRODUCTION

Fluorescence-guided surgery can improve tumor identification and extent of surgical resection. 5-ALA is the standard for GBM, but is limited by lack of quantitative fluorescence, a need to work in the dark, and a lack of sensitivity for low grade tumors. We have developed a novel instrument for dye-free tissue autofluorescence lifetime imaging (FLIm) to identify glioma tissue during resection. This approach utilizes time-resolved autofluorescence measurements in narrow-band channels to assess markers of tissue metabolism. Compared to intensity-based imaging of exogenous fluorophores, FLIm has greater sensitivity without dependence on background lighting. The advantages of FLIm include quantitative tissue analysis, the ability to work under full light conditions, sensitivity for high and low grade gliomas, and the potential ability to identify IDH mutational status. In this study, we validated the use of FLIm for identification of glioma tissue at tumor resection margins.

METHODS

FLIm was used to image tissue margins during glioma resections and compared to microbiopsies from imaged regions to correlate fluorescence with histopathology.

RESULTS

FLIm was applied intraoperatively to 11 GBM and 5 LGG patients (7 imaged biopsies per patient). In GBM, tumor infiltration of cortex was associated with significantly decreased fluorescence lifetime (FL) in channels 2 (470/28nm;p<0.05) and 3 (542/50nm;p<0.002). In subcortical margins, FL was inversely proportional to the density of tumor in channels 2,3 (p<0.05). When IDH wild-type GBMs were compared to IDH1-mutant tumors, FL was noted to be significantly longer in channel 1 (390/40nm;p<0.05), and trended towards longer FL in channel 2, shorter FL in channel 3. In LGG, FL was significantly correlated with tumor density in channel 2 (p<0.01).

CONCLUSIONS

FLIm is a dye-free, quantitative alternative to 5-ALA for fluorescence guided glioma resections with sensitivity to high and low-grade tumors, and the ability to predict IDH mutations in GBM. Further validation studies are on-going.
ITVT-02. Elucidating the pleiotropic effects of verteporfin photodynamic therapy in preclinical glioblastoma models
Authors: Price Gabrielle , Anastasiadou Maria , Sudhir Sweta , Bouras Alexandros , Tsankova Nadejda , Hadjipanayis Constantinos
Published: November 2021

Glioblastoma (GBM) ranks the highest in mortality rate, incidence, and aggressiveness of primary brain tumor types. The highly malignant nature of GBM makes it difficult for mainstay treatments to have an effect beyond stabilizing the disease. Deregulation of receptor tyrosine kinase (RTKs), such as EGFR and PI3K, have been implicated in GBM tumorigenesis. The expression of EGFR has been linked to hippo pathway transcriptional co-activators YAP and TAZ that bind to TEAD co-factors to drive the transcription of target genes. The convergence of EGFR signaling and the hippo pathway regulates stem cell programs, including proliferation, survival, and self-renewal. Verteporfin (VP), an FDA-approved macular degeneration therapy, has antitumor effects in in vitro and in vivo GBM preclinical models and phase I/II clinical trials for patients with EGFR mutated/amplified GBM by abrogating YAP/TAZ-TEAD interactions. As a porphyrin derivative, VP can exert therapeutic and photodynamic effects in the presence of 689 nm light; however, the efficacy of VP-PDT has not been explored in GBM. Our results indicate that VP-PDT reduces cell viability to a greater extent than solitary VP treatment (viability — 0.7 uM VP: 97%, 0.7 uM VP-PDT: 46%). The antitumor effects of VP-PDT are two pronged involving 1) inhibition of live cell dynamics, including migration and intravasation, by downregulating hippo pathway constituents YAP, TAZ and TEAD and transcriptional target EGFR and 2) induction of programmed cell death by reactive oxygen species. Our results suggest that VP-PDT can be a potential avenue for treating these incurable tumors.
ITVT-06. Application of artificial intelligence and radiomics for the analysis of intraoperative ultrasound images of brain tumors
Authors: Cepeda Santiago
Published: November 2021

BACKGROUND

Intraoperative ultrasound (ioUS) images of brain tumors contain information that has not yet been exploited. The present work aims to analyze images in both B-mode and strain-elastography using techniques based on artificial intelligence and radiomics. We pretend to assess the capacity for differentiating glioblastomas (GBM) from solitary brain metastases (SBM) and also to assess the ability to predict the overall survival (OS) in GBM.

METHODS

We performed a retrospective analysis of patients who underwent craniotomy between March 2018 to June 2020 with GBM and SBM diagnoses. Cases with an ioUS study were included. In the first group of patients, an analysis based on deep learning was performed. An existing neural network (Inception V3) was used to classify tumors into GBM and SBM. The models were evaluated using the area under the curve (AUC), classification accuracy, and precision. In the second group, radiomic features from the tumor region were extracted. Radiomic features associated with OS were selected employing univariate correlations. Then, a survival analysis was conducted using Cox regression.

RESULTS

For the classification task, a total of 36 patients were included. 26 GBM and 10 SBM. Models were built using a total of 812 ultrasound images. For B-mode, AUC and accuracy values ranged from 0.790 to 0.943 and from 72 to 89 % respectively. For elastography, AUC and accuracy values ranged from 0.847 to 0.985 and from 79 to 95 % respectively. Sixteen patients were available for the survival analysis. A total of 52 radiomic features were extracted. Two texture features from B-mode (Conventional mean and GLZLM_SZLGE) and one texture feature from strain-elastography (GLZLM_LZHGE) were significantly associated with OS.

CONCLUSIONS

Automated processing of ioUS images through deep learning can generate high-precision classification algorithms. Radiomic tumor region features in B-mode and elastography appear to be significantly associated with OS in GBM.
TWMP-01. RESECTION OF SUPPLEMENTARY MOTOR AREA GLIOMAS: REVISITING SUPPLEMENTARY MOTOR SYNDROME AND THE ROLE OF THE FRONTAL ASLANT TRACT
Authors: Young Jacob , Gogos Andrew , Aabedi Alex , Morshed Ramin , Pereira Matheus , Lashof-Regas Samuel , Mansoori Ziba , Luks Tracy , Hervey-Jumper Shawn , Villanueva-Meyer Javier , Berger Mitchel
Published: November 2021

INTRODUCTION

The supplemental motor area (SMA) is an eloquent region that is frequently a site for gliomas or the region is included in the resection trajectory to deeper lesions.

METHODS

Patient, tumor and outcome data were collected retrospectively from the UCSF tumor registry for patients who underwent surgical resection for newly diagnosed supratentorial diffuse glioma (WHO Grade II - IV) between 2010 and 2019 in the SMA region and the extent of SMA resection was determined by volumetric assessment. Tumors were registered to a standard brain atlas to create a frequency heat map of tumor volumes and resection cavities.

RESULTS

Although the volume of tumor within the SMA region did not correlate with the development of SMA syndrome, patients with SMA syndrome had larger resection cavities in the SMA region (25.4% SMA resection vs. 14.2% SMA resection, p = 0.039). The size of the resection cavity in the SMA region did not correlate with the severity of the SMA syndrome. Patients who developed SMA syndrome had cavities that were located more posteriorly in the SMA region and in the cingulate. When the frontal aslant tract (FAT) was preserved, 50% of patients developed SMA syndrome post-operatively; whereas 100% of patients who had disruption of the FAT during surgery developed SMA syndrome (p = 0.06). There was no difference in the overall survival for newly diagnosed glioblastoma patients with SMA syndrome compared to those without SMA syndrome (1.6 years vs. 3.0 years, p = 0.33).

CONCLUSION

For patients with SMA gliomas, larger resections and resections involving the posterior SMA region and posterior cingulate gyrus increased the likelihood of a post-operative SMA syndrome. Although SMA syndrome occurred in all cases where the FAT was resected, FAT preservation does not reliably avoid SMA syndrome post-operatively.
A phase II study of laser interstitial thermal therapy combined with doxorubicin in patients with recurrent glioblastoma
Authors: Butt Omar H , Zhou Alice Y , Huang Jiayi , Leidig William A , Silberstein Alice E , Chheda Milan G , Johanns Tanner M , Ansstas George , Liu Jingxia , Talcott Grayson , Nakiwala Ruth , Shimony Joshua S , Kim Albert H , Leuthardt Eric C , Tran David D , Campian Jian L
Published: November 2021

Background

The blood-brain barrier (BBB) is a major limiting factor for drug delivery in brain tumors. Laser interstitial thermal therapy (LITT) disrupts the peritumoral BBB. In this study, we examine survival in patients with recurrent glioblastoma (GBM) treated with LITT followed by low-dose doxorubicin, a potent anti-neoplastic drug with poor BBB permeability.

Methods

Forty-one patients with recurrent GBM were enrolled; thirty patients were evaluable. Participants underwent LITT followed by 6 weekly doxorubicin treatments starting within one week (Early Arm) or at 6–8 weeks (Late Arm) after LITT. The overall survival (OS), local progression-free survival (PFS), and any PFS were compared to historical controls treated with bevacizumab salvage therapy (n = 50) or LITT with standard BBB-permeable salvage therapy (n = 28). Cox proportional-hazards models examined the contribution of age, gender, MGMT promoter status, and IDH-mutation status on any PFS and OS. Adverse events were also cataloged.

Results

The Late Arm and all patients (Early Arm + Late Arm) demonstrated significant improvement in OS compared to historical controls treated with bevacizumab (p < 0.001) and LITT with standard salvage therapy (p < 0.05). No significant difference in any PFS was observed between either arm and historical controls. Low-dose doxorubicin was well tolerated with comparable adverse event rates between the arms.

Conclusions

Low-dose doxorubicin given after LITT is well tolerated and correlated with higher OS compared to historical controls treated with bevacizumab or LITT with standard salvage chemotherapy. A larger study is needed to further characterize survival and progression patterns.
Dichotomous roles of neutrophils in modulating pathogenic and repair processes of inflammatory bowel diseases
Authors: Chen Huimin , Wu Xiaohan , Xu Chunjin , Lin Jian , Liu Zhanju
Published: November 2021

Neutrophils are considered as complex innate immune cells and play a critical role in maintaining intestinal mucosal homeostasis. They exert robust pro-inflammatory effects and recruit other immune cells in the acute phase of pathogen infection and intestinal inflammation, but paradoxically, they also limit exogenous microbial invasion and facilitate mucosal restoration. Hyperactivation or dysfunction of neutrophils results in abnormal immune responses, leading to multiple autoimmune and inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel diseases (IBD). As a refractory intestinal inflammatory disease, the pathogenesis and progression of IBD are associated with complicated immune response processes in which neutrophils are profoundly involved. However, the consensus on potential roles of neutrophils in modulating pathogenic and repair processes of IBD remains not fully understood. Accumulated infiltrating neutrophils cross the epithelial barrier and contribute to microbial dysbiosis, aggravated intestinal architectural damage, compromised resolution of intestinal inflammation and increased risk of thrombosis during IBD. Paradoxically, activated neutrophils are also associated with effective elimination of invaded microbiota, promoted angiogenesis and tissue restoration of gut mucosa in IBD. Here, we discuss the beneficial and detrimental roles of neutrophils in the onset and resolution of intestinal mucosal inflammation, hoping to provide a precise overview of neutrophil functions in the pathogenesis of IBD.
Folk Theorem in Repeated Games with Private Monitoring
Authors: Sugaya Takuo
Published: November 2021

We show that the folk theorem holds generically for the repeated two-player game with private monitoring if the support of each player’s signal distribution is sufficiently large. Neither cheap talk communication nor public randomization is necessary.
Coordination and Continuous Stochastic Choice
Authors: Morris Stephen , Yang Ming
Published: November 2021

Players receive a return to investment that is increasing in the proportion of others who invest and the state and incur a small cost for acquiring information about the state. Their information is reflected in a stochastic choice rule, specifying the probability of a signal leading to investment. If discontinuous stochastic choice rules are infinitely costly, there is a unique equilibrium as costs become small, in which actions are a best response to a uniform (Laplacian) belief over the proportion of others investing. Infeasibility of discontinuous stochastic choice rules captures the idea that it is impossible to perfectly distinguish states that are arbitrarily close together and is both empirically documented and satisfied by many natural micro-founded cost functionals on information. Our results generalize global game selection results and establish that they do not depend on the specific additive noise information structure.
Musculoskeletal pain in psoriasis—relation to inflammation and additional value of ultrasound in psoriatic arthritis classification
Authors: Felbo Sara Kamp , Terslev Lene , Juul Sørensen Inge , Hendricks Oliver , Kuettel Dorota , Lederballe Pedersen Rasmus , Chrysidis Stavros , Duer Anne , Zachariae Claus  , Skov Lone , Østergaard Mikkel
Published: November 2021

Objective

To investigate and compare clinical features and US signs of inflammation in joints and entheses in patients with psoriasis with and without musculoskeletal pain, and the additional value of US in classification of PsA. Furthermore, to explore the association between such findings and patient-reported outcomes (PROs) and the performance of screening-questionnaires for identifying patients with PsA.

Methods

Patients with psoriasis (n = 126) recruited from a nationwide survey were evaluated at one of four rheumatology departments. The evaluation included clinical examination, laboratory tests, radiography, greyscale and colour Doppler US of 48 joints and 12 entheses, PROs, and four screening questionnaires for PsA. Patients were classified with Classification for PsA (CASPAR), US-modified CASPAR, and US-only criteria.

Results

When subgroups of self-reported pain (63%), no pain (29%) and diagnosed PsA (9%) were compared, patients with pain had higher tenderness-related clinical scores (tender joints, entheses and FM points) and US greyscale sum-scores, compared with ‘no pain’ patients. PROs were negligibly moderately correlated with pain-related clinical scores (Spearman’s rho = 0.11–0.59, all patients), and negligibly weakly with US sum-scores (rho = 0.01–0.34). More patients could be classified as PsA when US synovitis/enthesitis was included as an entry criterion (US-modified CASPAR, 66% of all patients) compared with conventional CASPAR (35%) or US-only criteria (52%). Sensitivities of screening questionnaires were low for fulfilment of CASPAR (0.23–0.66), US-modified CASPAR (0.17–0.57), and US-only (0.20–0.57) criteria.

Conclusion

Self-reported pain in psoriasis is related to US inflammation. US-modified CASPAR criteria identified almost twice as many patients as conventional CASPAR criteria. Screening questionnaires showed limited value.
Inter-brain synchronization is weakened by the introduction of external punishment
Authors: Li Jianbiao , Pan Jingjing , Zhu Chengkang , Wang Yiwen
Published: November 2021

Punishment is a popular institution to enforce social norms in human society. However, how the punishment institution impacts the inter-brain neural signatures of two-person social interactions is still an open question. By performing electroencephalography recording of brain activity in two interacting parties as they simultaneously played both the revised repeated ultimatum game (rrUG) and the revised repeated dictator game (rrDG), this study focused on exploring how the introduction of external punishment influences inter-brain synchronization between the two parties. The data showed a significant negative effect of external punishment on inter-brain synchronization, with greater inter-brain synchronization observed in the rrDG than in the rrUG. We proposed a possible mechanism underlying this result. In the rrDG, the similar moral motivation of both proposers and responders results in inter-brain synchronization between them. However, in the rrUG, the introduction of external punishment crowds out the intrinsic moral motivation of the proposers, thereby undermining the inter-brain synchronization. Moreover, we found a significant positive correlation between the rejection rate from responders for disadvantageous inequal offer and inter-brain synchronization in the rrDG. These findings contribute to understanding the negative effect of punishment institution and shed light on the inter-brain mechanism underlying social interaction.
Influence of beef genotypes on animal performance, carcass traits, meat quality, and sensory characteristics in grazing or feedlot-finished steers
Authors: Maciel Isabella C F , Schweihofer J P , Fenton J I , Hodbod J , McKendree M G S , Cassida K , Rowntree J E
Published: November 2021

A 2-yr study was conducted to evaluate the effects of beef genotypes and feeding systems on performance, carcass traits, meat quality, and sensory attributes. A 2×2 factorial experiment was used to randomly allocate 60 steers in year 1 (YR1) and 44 steers in year 2 (YR2). The two beef genotypes evaluated were Red Angus (RA), and RA x Akaushi (AK) crossbreed. The steers were allotted to two finishing feeding systems: grazing, a multi-species forage mixture (GRASS) and feedlot finishing, conventional total mixed ration (GRAIN). All steers were slaughtered on the same day, at 26 and 18 mo of age (GRASS and GRAIN, respectively), and carcass data were collected 48 h postmortem. Growth and slaughter characteristics were significantly impacted by the finishing system (P < 0.01), with the best results presented by GRAIN. Beef genotype affected dressing percent (P < 0.01), ribeye area (P = 0.04), and marbling score (P = 0.01). The AK steers had a tendency (P = 0.09) for lower total gain; however, carcass quality scores were greater compared to RA. There was a genotype by system interaction for USDA yield grade (P < 0.01), where it was lower in GRASS compared to GRAIN in both genotypes, and no difference was observed between the two genotypes for any GRASS or GRAIN systems. There was no difference in meat quality or sensory attributes (P > 0.10) between the two genotypes, except that steaks from AK tended to be juicier than RA (P = 0.06). Thawing loss and color variables were impacted by the finishing system (P < 0.01). L* (lightness) and hue angle presented greater values while a* (redness), b* (yellowness), and chroma presented lower values in GRAIN compared to GRASS. Sensory attributes were scored better in GRAIN than GRASS beef (P < 0.01). There was a genotype by system interaction for flavor (P = 0.02), where beef from RA had a lower flavor rating in GRASS than in GRAIN, and no difference was observed for AK. Within each system, no difference was observed for flavor between RA and AK. Beef from steers in GRASS had greater (P < 0.01) WBSF than those from GRAIN. These results indicate that steers from GRAIN had superior performance and carcass merit and that AK enhanced these traits to a greater degree compared to RA. Furthermore, the beef finishing system had a marked impact on the steaks’ sensory attributes and consumer acceptability. The favorable results for texture and juiciness in GRAIN, which likely impacted overall acceptability, may be related to high marbling.
Association of insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of three dual-purpose chicken breeds
Authors: Ogunpaimo Olaiwola J , Ojoawo Henry T , Wheto Mathew Y , Adebambo Ayotunde O , Adebambo Olufunmilayo A
Published: November 2021

The study was designed to investigate the association of Insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of FUNAAB-Alpha, Sasso, and Kuroiler dual-purpose chicken breeds. To achieve this, a total of 250 healthy hens were selected at 12 wk of age and were intensively managed in cages for 52 wk. Blood sample was taken from each chicken at the 34th week and genomic DNA was extracted using Qiagentm DNA extraction kit, PCR was used to amplify the DNA fragments, and the PCR products were electrophoresed. Amplicons obtained were digested with restriction enzyme hinf1, and were further electrophoresed on 1.5% agarose gel. Data obtained were analyzed using the General linear model of SAS (2002) version 9.0 to determine the effect of IGF1 gene polymorphism and the distribution of alleles within the breeds. Results show polymorphism of the IGF1 gene and the restriction analysis indicated two alleles; A 58% and C 42% with the identification of genotypes AA, AC, and CC, and genotypic frequency of 22%, 43%, and 35%, respectively. Significant associations were observed between the polymorphism of the IGF1 gene, age of the bird at first lay, and weight of the hen at first lay. Chickens with haplotype CC came earlier into lay compared to those with the other two haplotypes (AA and AC). Therefore, the study suggests that haplotype CC could be used as a genetic marker to select for an improved laying performance in chickens.
Effect of zinc source and implant strategy on performance, carcass characteristics, and trace mineral concentrations in finishing feedlot steers
Authors: Messersmith Elizabeth M , Hansen Stephanie L
Published: November 2021

Seventy-two Angus-crossbred steers (411 ± 16 kg) were assigned to a 2 × 3 factorial arrangement of treatments to examine the effects of blended Zn source supplementation on performance, carcass characteristics, and trace mineral parameters of steers administered no implant or a two-implant program. Factors included implant (IMP) strategies and Zn supplementation. During the 126-d study, steers were either not implanted (NoIMP) or implanted (IS/200; Elanco, Greenfield, IN) on days 0 (Component TE-IS; 80 mg trenbolone acetate + 16 mg estradiol) and 57 (Component TE-200; 200 mg trenbolone acetate + 20 mg estradiol). All steers were fed 70 mg Zn/kg on a dry matter (DM) basis from ZnSO4 + 30 mg Zn/kg DM from either basic ZnCl (Vistore Zn, Phibro Animal Health, Teaneck, NJ), Zn glycinate (Gemstone Zn, Phibro Animal Health), or ZnSO4 (ZnB, ZnG, or ZnS, respectively). Steers were blocked by weight into pens of 6 and fed a dry rolled corn-based diet via GrowSafe bunks (GrowSafe Systems Ltd.; Airdrie, AB, Canada). Data were analyzed using the Mixed Procedure of SAS, with fixed effects of Zn, IMP, and the interaction. Steer was the experimental unit (n = 12 steers/treatment). Liver and muscle collected on days −5, 14, 71, and 120 were analyzed for Zn concentration, and data were analyzed as repeated measures (repeated effect = Day). An IMP × Zn tendency (P = 0.07) was observed for day 126 body weight with no effects of Zn within NoIMP, whereas ZnS tended to be heavier than ZnB with ZnG intermediate within IS/200. Carcass-adjusted overall feed efficiency (G:F) was greatest for ZnS (Zn; P = 0.02). Implanted cattle had greater DM intake, G:F, and carcass-adjusted performance (P ≤ 0.01). Liver Zn concentrations were greater for IS/200 by day 120 (IMP × Day; P = 0.02). Within IS/200, ZnG tended to have greater muscle Zn than ZnS, whereas ZnB was intermediate (Zn × IMP; P = 0.09). No Zn or IMP × Zn (P ≥ 0.12) effects were observed for carcass data. However, IS/200 had greater hot carcass weight, dressing percentage, and ribeye area than NoIMP (P ≤ 0.001). These data suggest that implants improve growth and influence Zn metabolism. Future work should examine Zn sources and supplementation alongside implant strategies.
Screening of 6000 Compounds for Uncoupling Activity: A Comparison Between a Mechanistic Biophysical Model and the Structural Alert Profiler Mitotox
Authors: Ebert Andrea , Goss Kai-Uwe
Published: November 2021

Protonophoric uncoupling of phosphorylation is an important factor when assessing chemicals for their toxicity, and has recently moved into focus in pharmaceutical research with respect to the treatment of diseases such as cancer, diabetes, or obesity. Reliably identifying uncoupling activity is thus a valuable goal. To that end, we screened more than 6000 anionic compounds for in vitro uncoupling activity, using a biophysical model based on ab initio COSMO-RS input parameters with the molecular structure as the only external input. We combined these results with a model for baseline toxicity (narcosis). Our model identified more than 1250 possible uncouplers in the screening dataset, and identified possible new uncoupler classes such as thiophosphoric acids. When tested against 423 known uncouplers and 612 known inactive compounds in the dataset, the model reached a sensitivity of 83% and a specificity of 96%. In a direct comparison, it showed a similar specificity than the structural alert profiler Mitotox (97%), but much higher sensitivity than Mitotox (47%). The biophysical model thus allows for a more accurate screening for uncoupling activity than existing structural alert profilers. We propose to use our model as a complementary tool to screen large datasets for protonophoric uncoupling activity in drug development and toxicity assessment.
Finding Joy in the Dark
Authors: Kennedy Maureen Shawn
Published: November 2021

But it will be short lived if nurses aren't protected against increasing violence.
We Have No Choice but to Transform: The Future of Medical Education After the COVID-19 Pandemic
Authors: Lucey Catherine R. , Davis John A. , Green Marianne M.
Published: November 2021

Medical education exists to prepare the physician workforce that our nation needs, but the COVID-19 pandemic threatened to disrupt that mission. Likewise, the national increase in awareness of social justice gaps in our country pointed out significant gaps in health care, medicine, and our medical education ecosystem. Crises in all industries often present leaders with no choice but to transform—or to fail. In this perspective, the authors suggest that medical education is at such an inflection point and propose a transformational vision of the medical education ecosystem, followed by a 10-year, 10-point plan that focuses on building the workforce that will achieve that vision. Broad themes include adopting a national vision; enhancing medicine’s role in social justice through broadened curricula and a focus on communities; establishing equity in learning and processes related to learning, including wellness in learners, as a baseline; and realizing the promise of competency-based, time-variable training. Ultimately, 2020 can be viewed as a strategic inflection point in medical education if those who lead and regulate it analyze and apply lessons learned from the pandemic and its associated syndemics.
Supervision and Care Quality as Perceived by Redeployed Attendings, Fellows, and Residents During a COVID-19 Surge: Lessons for the Future
Authors: Young John Q. , Friedman Karen A. , Thakker Krima , Hennus Marije P. , Hennessy Martina , Patterson Aileen , Yacht Andrew , ten Cate Olle
Published: November 2021

Purpose

To better prepare for potential future large-scale redeployments, this study examines quality of supervision and care as perceived by redeployed residents, fellows, and attendings during a COVID-19 surge.

Method

During April and May 2020, attendings, fellows, and residents redeployed at 2 teaching hospitals were invited to participate in a survey, which included questions on respondents’ prior experience; redeployed role; amount of supervision needed and received; and perceptions of quality of supervision, patient care, and interprofessional collaboration. Frequencies, means, and P values were calculated to compare perceptions by experience and trainee status. Narrative responses to 2 open-ended questions were independently coded; themes were constructed.

Results

Overall, 152 of 297 (51.2%) individuals responded, including 64 of 142 attendings (45.1%), 40 of 79 fellows (50.6%), and 48 of 76 residents (63.2%). Fellows and attendings, regardless of prior experience, perceived supervision as adequate. In contrast, experienced residents reported receiving more supervision than needed, while inexperienced residents reported receiving less supervision than needed and rated overall supervision as poor. Attendings, fellows, and experienced residents rated the overall quality of care as acceptable to good, whereas inexperienced residents perceived overall quality of care as worse to much worse, particularly when compared with baseline.

Conclusions

Narrative themes indicated that the quality of supervision and care was buffered by strong camaraderie, a culture of informal consultation, team composition (mixing experienced with inexperienced), and clinical decision aids. The markedly negative view of inexperienced residents suggests a higher risk for disillusionment, perhaps even moral injury, during future redeployments. Implications for planning are explored.
Association of paraoxonase 1 activity and insulin resistance models in type 2 diabetes mellitus: Cross-sectional study
Authors: Adiga Usha , Banawalikar Nandit , Menambath Desy Thayyil
Published: November 2021

Background:

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Chronic hyperglycemia induces reactive oxygen species and increases oxidative stress. Human serum paraoxonase-1 (PON-1) is an enzyme synthesized in the liver, and it is an antioxidant enzyme with a beneficial role in fighting oxidative stress. The objective of the study was to compare PON-1 activity in type 2 diabetes mellitus (T2DM) and nondiabetics, as well as to find the association between PON-1 activity and different insulin resistance (IR) models in diabetics.

Methods:

The cross-sectional study recruited 100 diabetic and 100 age and gender-matched controls. Fasting blood glucose, insulin, and C-peptide, were assayed. PON-1 activity was measured by the spectrophotometric method. Various insulin resistance models based on insulin and C-peptide were constructed using appropriate formulae. Receiver operating characteristic was constructed to find if PON-1 can be a good marker for diabetes.

Results:

PON-1 activity was found to be significantly higher (p < 0.0001) in diabetics compared to controls. Highly significant hyperinsulinemia (p < 0.0001) was noted in diabetics. C-peptide levels were significantly lower in cases (p = 0.0215) as compared to controls. Homeostasis model assessment (HOMA)-IR C was insignificantly higher in cases. HOMA B cell, HOMA 1% B cell, and C-peptide–based IR (CIR) were significantly lower in cases (p < 0.0001 and p = 0.002), respectively, as compared to controls. An odds ratio of 3.15 was obtained, which suggests that the risk of T2DM is 3 times higher in subjects with elevated PON-1 levels. Chi-square showed a significant association (p = 0.0001) between DM and PON-1 levels; the chi-square statistic value (with Yates correction) was 14.49. Correlation data showed that PON-1 activity had a significant negative correlation with quantitative insulin sensitivity check index (r = −0.265, p = 0.019). A significant negative correlation (r = −0.22, p = 0.016) was also seen between PON-1 and CIR (HOMA-IR C). There was no significant correlation seen between PON-1 and other IR models.

Conclusion:

It can be concluded from our study that PON-1 activity is elevated in T2DM patients, which can be a beneficial marker.
Robotic Hepaticojejunostomy for Late Anastomotic Biliary Stricture After Liver Transplantation
Authors: Hawksworth Jason , Radkani Pejman , Nguyen Brian , Aguirre Oswaldo , Winslow Emily , Kroemer Alexander , Girlanda Raffaelle , Guerra Juan Francisco , Haddad Nadim , Fishbein Thomas
Published: November 2021

Biliary strictures after liver transplantation are common and when refractive to endoscopic and percutaneous intervention require surgical revision. Robotic technology facilitates minimally invasive biliary reconstruction and has not previously been described after liver transplantation. Robotic biliary revisions were retrospectively compared to all the historical open cases over a time period from May 2013 to October 2020. During the study period there were 3 robotic and 4 open surgical biliary revisions with a follow-up of at least 6months. All cases were hepaticojejunostomies for late choledocho-choledochostomy anastomotic strictures presenting > 4 weeks after transplant and refractive to at least 3 endoscopic and/or percutaneous interventions. Median (range) case time was longer in the robotic group, 373 minutes (286–373) compared to open group, 280 minutes (163–321). The median length of stay was shorter in the robotic group, 4 days (1–-4) compared to open group 7 days (4–10). Morbidity included 2 wound infections in the open group (grade II), 1 infected hematoma in the robotic group (grade Ilia), and 1 bile leak on the open group (grade Ilia). There was no biliary stricture recurrence or mortality in either group. Robotic biliary revision is a safe alternative to traditional open biliary revision for refractive biliary strictures after liver transplantation.