bluuebunny/crossref_metadata_2025_split huggingface dataset:
RARE-36. BORTEZOMIB WOKE UP A PATIENT WITH ANTI-NMDA RECEPTOR ENCEPHALITIS REFRACTORY TO STANDARD THERAPY AND LONG TERM FOLLOW-UP
Authors: Xiao-Tang Kong , Groysman Leonid , Dastur Cyrus , Fu Beverly , Bota Daniela 
Published: November 2019

Abstract

OBJECTIVE
To report a case with refractory NMDA encephalitis in comatose for 18 months, who was treated successfully with bortezomib.

BACKGROUND
Anti-NMDA encephalitis is a rare autoimmune encephalitis. Standard therapy include corticosteroid, IVIG or plasma exchange, cyclophosphamide, rituximab, and tumor removal. Refractory cases are very severe and often stay in ICU on ventilation for several months to years. Bortezomib for the treatment of refractory anti-NMDA receptor encephalitis was reported. We have applied the treatment to our refractory case and successfully woke up the patient. And we have followed up the patient for 3 years.

METHODS
Case report.

RESULTS
A 40 yo male was diagnosed as anti-NMDA encephalitis. Standard therapy was applied. After stabilization, the patient was eventually discharged to ICU at a long term care subacute hospital. The patient was brought back for more Rituxan or steroid or IVIG therapy. The condition had not improved at all. Eighteen months in comatose, the patient had worsening NMDA titer in CSF to 1:640. Decision was made to start bortezumib as reported with modification: 1.3 mg/m2 bortezomib were administered on days 1, 8, 11 and 14 and allowed two weeks off therapy. After first cycle, the patent started to talk first word “hurt.” After 6 cycles, the patient sat up and started riding bicycles for physical therapy. The NMDA titer in CSF was reduced to 1:40 at the end of 6 cycles. One year later, the patent stood up and ambulated with a walker. One and half year later, the patient walks without assistance and his speech and cognition have significantly improved with good communication with family members and staff.

CONCLUSIONS
Proteasome inhibitor bortezomib might be considered to be the third line therapy as early as possible if the first line and second line are ineffective to treat anti-NMDA receptor encephalitis.
STEM-20. RADIO-SENSITIZING GLIOBLASTOMA CANCER STEM CELLS BY INHIBITION OF FACT
Authors: Montgomery Miranda , Zalenski Abigail , Deighen Amanda , Mortach Sherry , Grubb Treg , Venere Monica 
Published: November 2019

Abstract
Glioblastoma (GBM) has a particularly high rate of recurrence with a 5-year overall survival rate of approximately 5%. This is in part due to a sub-population of cancer stem cells (CSC), which are both radioresistant and chemotherapeutically resistant to conventional treatments. Here we investigated CBL0137, a small molecule form of curaxin, in combination with radiotherapy as a means to radiosensitize CSCs. CBL0137 sequesters FACT (facilitates chromatin transcription) complex to chromatin, which leads to activation of p53 and inhibition of NF-κB. This sequestering of FACT results in cytotoxicity especially within tumor cells and prevents FACT from performing its primary role as a histone chaperone, as well as inhibits its part in the DNA damage response pathway. We show that when combined with radiotherapy, CBL0137 administration limited the ability of CSCs to identify and repair damaged DNA. CSCs treated in vitro with CBL0137 and irradiation showed an increased inhibition of cancer cell growth and decreased viability compared to irradiation or drug alone. Combination therapy also showed more DNA damage in the CSCs than with either agent alone. Based on our in vitro evidence for the efficacy of combination therapy to target CSCs, we moved forward to test the treatment in vivo. Using a subcutaneous model, we show that the amount of CD133+ cells (a marker for GMB CSCs) was reduced in irradiation plus CBL0137 compared to either treatment alone. Survival studies demonstrated that irradiation plus CBL0137 compared to irradiation alone or CBL0137 alone increase lifespan. Here we show the ability of CBL0137, in combination with irradiation, to target patient GBM CSCs both in vitro and in vivo. This work establishes a new treatment paradigm for GBM that inclusively targets CSCs and may ultimately reduce tumor recurrence.
Disruptive Behavior in Siblings Discordant for Exposure to Maternal Smoking During Pregnancy: A Multi-rater Approach
Authors: Ekblad Mikael O , Rolan Emily , Marceau Kristine , Palmer Rohan , Todorov Alexandre , Heath Andrew C , Knopik Valerie S 
Published: November 2019

Abstract

Introduction
Maternal smoking during pregnancy (SDP) is associated with disruptive behavior. However, there is debate whether the SDP-disruptive behavior association is a potentially causal pathway or rather a spurious effect confounded by shared genetic and environmental factors.

Aims and Methods
The Missouri Mothers and Their Children Study is a sibling comparison study that includes families (n = 173) selected for sibling pairs (aged 7–16 years) discordant for SDP. Critically, the sibling comparison design is used to disentangle the effects of SDP from familial confounds on disruptive behavior. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount of SDP). Multiple informants (parents and teachers) reported on disruptive behavior (i.e., DSM-IV semi-structured interview, the Child Behavior Checklist, and Teacher Report Form).

Results
The variability in disruptive behavior was primarily a function of within-family differences (66%–100%). Consistent with prior genetically informed approaches, the SDP–disruptive behavior association was primarily explained by familial confounds (genetic and environmental). However, when using a multi-rater approach (parents and teachers), results suggest a potentially causal effect of SDP on disruptive behavior (b = 0.09, SE = 0.04, p = 0.03). The potentially causal effect of SDP remained significant in sensitivity analyses.

Discussion
These findings suggest that familial confounding likely plays a complex role in the SDP–disruptive behavior association when examining both parent and teacher reports of behavior. Importantly, the current study highlights the importance of multiple raters, reflecting a more comprehensive measure of complex behaviors (e.g., disruptive behavior) to examine the teratogenic effects of SDP.

Implications
Our study provides additional evidence that controlling for genetic and family factors is essential when examining the effect of SDP on later behavioral problems, as it explains a portion of the association between SDP and later behavioral problems. However, we found a significant association between SDP and disruptive behavior when using a multi-rater approach that capitalizes on both parent and teacher report, suggesting that parent and teacher ratings capture a unique perspective that is important to consider when examining SDP–behavior associations.
Exploring Patients’ Experiences of Internet-Based Self-Management Support for Low Back Pain in Primary Care
Authors: Geraghty Adam W A , Roberts Lisa C , Stanford Rosie , Hill Jonathan C , Yoganantham Dinesh , Little Paul , Foster Nadine E , Hay Elaine M , Yardley Lucy 
Published: November 2019

Abstract

Objective
We explored patients’ experiences of using Internet-based self-management support for low back pain (LBP) in primary care, with and without physiotherapist telephone guidance.

Design
Exploratory descriptive qualitative study using thematic analysis, nested within a randomized feasibility trial.

Methods
Patients with LBP who participated in a feasibility trial of the SupportBack Internet intervention (ISRCTN: 31034004) were invited to take part in semistructured telephone interviews after the three-month intervention period (a convenience sample from within the trial population). Fifteen participants took part (age range = 36–87 years, 66.7% female, characteristics representative of the trial population). Data were analyzed thematically.

Results
Analysis resulted in the development of six themes (subthemes in parentheses): Perceptions of SupportBack’s design (Clarity and ease of use, Variety and range of information provided, Need for specificity and flexibility), Engaging with the SupportBack intervention, Promoting positive thought processes (Reassurance, Awareness of self-management), Managing behavior with SupportBack (Motivation and goal setting, Using activity as a pain management strategy, Preferences for walking or gentle back exercises), Feeling supported by telephone physiotherapists (Provision of reassurances and clarity, Physiotherapists are motivating), Severity and comorbidity as barriers (Preexisting condition or severity acting as a barrier, Less useful for mild low back pain).

Conclusions
The Internet intervention SupportBack appeared to feasibly support self-management of LBP. Reassurance and ongoing support to implement behavioral changes were central to reported benefits. The addition of physiotherapist telephone support further enhanced the patient experience and the potential utility of the intervention.
Renormalon structure in compactified spacetime
Authors: Ishikawa Kosuke , Morikawa Okuto , Shibata Kazuya , Suzuki Hiroshi , Takaura Hiromasa 
Published: November 2019

Abstract
We point out that the location of renormalon singularities in theory on a circle-compactified spacetime $\mathbb{R}^{d-1} \times S^1$ (with a small radius $R \Lambda \ll 1$) can differ from that on the non-compactified spacetime $\mathbb{R}^d$. We argue this under the following assumptions, which are often realized in large-$N$ theories with twisted boundary conditions: (i) a loop integrand of a renormalon diagram is volume independent, i.e. it is not modified by the compactification, and (ii) the loop momentum variable along the $S^1$ direction is not associated with the twisted boundary conditions and takes the values $n/R$ with integer $n$. We find that the Borel singularity is generally shifted by $-1/2$ in the Borel $u$-plane, where the renormalon ambiguity of $\mathcal{O}(\Lambda^k)$ is changed to $\mathcal{O}(\Lambda^{k-1}/R)$ due to the circle compactification $\mathbb{R}^d \to \mathbb{R}^{d-1} \times S^1$. The result is general for any dimension $d$ and is independent of details of the quantities under consideration. As an example, we study the $\mathbb{C} P^{N-1}$ model on $\mathbb{R} \times S^1$ with $\mathbb{Z}_N$ twisted boundary conditions in the large-$N$ limit.
Utilizing Telepresence Robots for Multiple Patient Scenarios in an Online Nurse Practitioner Program
Authors: Mudd Shawna S. , McIltrot Kimberly S. , Brown Kristen M. 
Published: November 2019

Abstract
Simulation has been utilized widely in nurse practitioner programs for competency development and training. With the growing number of online educational programs, innovative solutions need to be developed to assess student competency for a variety of clinical situations and scenarios. An innovative method is the implementation of telepresence robots for multiple patient scenarios in a simulated environment. This article demonstrates the use of multiple patient scenarios using telepresence robots in an online post master’s acute care pediatric nurse practitioner program.
Information Integration and Mesoscopic Cortical Connectivity during Propofol Anesthesia
Authors: Liang Zhenhu , Cheng Lei , Shao Shuai , Jin Xing , Yu Tao , Sleigh Jamie W. , Li Xiaoli 
Published: November 2019

Abstract

Background
The neurophysiologic mechanisms of propofol-induced loss of consciousness have been studied in detail at the macro (scalp electroencephalogram) and micro (spiking or local field potential) scales. However, the changes in information integration and cortical connectivity during propofol anesthesia at the mesoscopic level (the cortical scale) are less clear.

Methods
The authors analyzed electrocorticogram data recorded from surgical patients during propofol-induced unconsciousness (n = 9). A new information measure, genuine permutation cross mutual information, was used to analyze how electrocorticogram cross-electrode coupling changed with electrode-distances in different brain areas (within the frontal, parietal, and temporal regions, as well as between the temporal and parietal regions). The changes in cortical networks during anesthesia—at nodal and global levels—were investigated using clustering coefficient, path length, and nodal efficiency measures.

Results
In all cortical regions, and in both wakeful and unconscious states (early and late), the genuine permutation cross mutual information and the percentage of genuine connections decreased with increasing distance, especially up to about 3 cm. The nodal cortical network metrics (the nodal clustering coefficients and nodal efficiency) decreased from wakefulness to unconscious state in the cortical regions we analyzed. In contrast, the global cortical network metrics slightly increased in the early unconscious state (the time span from loss of consciousness to 200 s after loss of consciousness), as compared with wakefulness (normalized average clustering coefficient: 1.05 ± 0.01 vs. 1.06 ± 0.03, P = 0.037; normalized average path length: 1.02 ± 0.01 vs. 1.04 ± 0.01, P = 0.021).

Conclusions
The genuine permutation cross mutual information reflected propofol-induced coupling changes measured at a cortical scale. Loss of consciousness was associated with a redistribution of the pattern of information integration; losing efficient global information transmission capacity but increasing local functional segregation in the cortical network.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Effect of Home-Based Cardiac Rehabilitation in a Lower-Middle Income Country
Authors: Uddin Jamal , Joshi Vicky L. , Moniruzzaman Mohammad , Karim Rezaul , Uddin Jalal , Siraj Masoom , Rashid Mohammad Abdur , Rossau Henriette Knold , Taylor Rod S. , Zwisler Ann-Dorthe 
Published: November 2019

Purpose:
Cardiovascular disease is the leading cause of mortality and morbidity in lower-middle income countries (LMICs), including Bangladesh. Cardiac rehabilitation (CR) as part of secondary prevention of cardiovascular disease has been shown to reduce mortality and morbidity and improve quality of life and exercise capacity. However, to date, very few controlled trials of CR have been conducted in LMICs.

Methods:
A quasi-randomized controlled trial comparing home-based CR plus usual care with usual care alone was undertaken with patients following coronary artery bypass graft surgery. Participants in the CR group received an in-hospital CR class and were introduced to a locally developed educational booklet with details of a home-based exercise program and then received monthly telephone calls for 12 mo. Primary outcomes were coronary heart disease (CHD) risk factors, health-related quality of life (HRQOL), and mental well-being. Maximal oxygen uptake as a measure of exercise capacity was a secondary outcome.

Results:
In total, 142 of 148 eligible participants took part in the trial (96%); 71 in each group. At 12-mo follow-up, 61 patients (86%) in the CR group and 40 (56%) in the usual care group provided complete outcome data. Greater reductions in CHD risk factors and improvements in HRQOL, mental well-being, and exercise capacity were seen for the CR group compared with the usual care group.

Conclusions:
In the context of a single-center LMIC setting, this study demonstrated the feasibility of home-based CR programs and offers a model of service delivery that could be replicated on a larger scale.
Acquisition and Development of the Extremely Preterm Infant Microbiota Across Multiple Anatomical Sites
Authors: Young Gregory R. , van der Gast Christopher J. , Smith Darren L. , Berrington Janet E. , Embleton Nicholas D. , Lanyon Clare 
Published: November 2019

ABSTRACTObjectives:Microbial communities influencing health and disease are being increasingly studied in preterm neonates. There exists little data, however, detailing longitudinal microbial acquisition, especially in the most extremely preterm (<26 weeks’ gestation). This study aims to characterize the development of the microbiota in this previously under‐represented cohort.Methods:Seven extremely preterm infant‐mother dyads (mean gestation 23.6 weeks) were recruited from a single neonatal intensive care unit. Oral and endotracheal secretions, stool, and breast milk (n = 157 total), were collected over the first 60 days of life. Targeted 16S rRNA gene sequencing identified bacterial communities present.Results:Microbiota of all body sites were most similar immediately following birth and diverged longitudinally. Throughout the sampling period Escherichia, Enterococcus, Staphylococcus, and an Enterobacteriaceae were dominant and well dispersed across all sites. Temporal divergence of the stool from other microbiota was driven by decreasing diversity and significantly greater proportional abundance of Bifidobacteriaceae compared to other sites.Conclusions:Four taxa dominated all anatomical sampling sites. Rare taxa promoted dissimilarity. Cross‐seeding between upstream communities and the stool was demonstrated, possibly relating to buccal colostrum/breast milk exposure and indwelling tubes. Given the importance of dysbiosis in health and disease of extremely preterm infants, better understanding of microbial acquisition within this context may be of clinical benefit.
Reduced Time to Suppression Among Neonates With HIV Initiating Antiretroviral Therapy Within 7 Days After Birth
Authors: Domínguez-Rodríguez Sara , Tagarro Alfredo , Palma Paolo , Foster Caroline , Puthanakit Thanyawee , Jupimai Thidarat , Cotugno Nicola , Ananworanich Jintanat , Zangari Paola , Nastouli Eleni , Muñoz-Fernández María Ángeles , Navarro María Luisa , Giaquinto Carlo , Rossi Paolo , Kuhn Louise , Rojo Pablo ,   on behalf of the EPIICAL Consortium
Published: November 2019

Abstract:
There are limited data on infants with HIV starting antiretroviral therapy (ART) in the neonatal period. We investigated the association between the timing of ART initiation and time-to-suppression among infants who tested HIV-positive and initiated ART within the first 28 days of life. The effect was estimated using cumulative probability flexible parametric spline models and a multivariable generalized additive mixed model was performed to test nonlinear associations. Forty-four neonates were included. Nineteen (43.2%) initiated ART within 7 days of life and 25 (56.8%) from 8 to 28 days. Infants treated within 7 days were 4-fold more likely to suppress earlier than those treated after 7 days [Hazard ratio (HR) 4.01 (1.7–9.5)]. For each week the ART initiation was delayed, the probability of suppression decreased by 35% (HR 0.65 [0.46–0.92]). Age at ART start was linearly associated with time-to-suppression. However, a linear association with normally distributed residuals was not found between baseline viral load and time-to-suppression, with no association found when baseline viral loads were ≤5 log(10) copies/mL, but with exponential increase in time-to-suppression with > log5 copies/mL at baseline. Starting ART within 7 days of life led to 4-fold faster time to viral suppression, in comparison to initiation from 8 to 28 days.
Heterogeneous 68Ga–Prostate-Specific Membrane Antigen Uptake in the Left Upper Abdomen
Authors: Arçay Ayça , Aydin Funda , Kutlu Ömer , Ocak Güzide Ayşe , Güngör Firat 
Published: November 2019

Abstract
A 50-year-old man with recently diagnosed prostate adenocarcinoma was referred for whole-body 68Ga–prostate-specific membrane antigen (PSMA) PET/CT scan for staging. Apart from some nonspecific findings, 68Ga-PSMA PET/CT revealed large soft tissue mass in the left upper abdomen showing heterogeneous tracer uptake. Histological examination of the mass was interpreted as gastrointestinal/extragastrointestinal stromal tumor by pathologists. Prostate-specific membrane antigen is considered specific for prostate cancer cells, although PSMA activity has been described in many other benign or malign conditions. That is why PSMA uptake in uncommon locations for prostate cancer metastasis must be considered for second malignancies or other benign conditions.
A Quick and Reliable Method to Decellularize a Gracilis Flap
Authors: Sabbagh M. Diya , Roh Si-Gyun , Liu Junting , Morsy Mohamed , Abu-Ghname Amjed , Zhao Chunfeng , Carlsen Brian T. 
Published: November 2019

Introduction
Tissue loss as a consequence of congenital anomalies, trauma, malignancy, or gangrene represents a major health care problem in the United States. Because younger individuals are disproportionately affected, the costs are magnified over time and the resultant individual and societal effects are tremendous. The currently available options to restore soft tissue defects are associated with donor site morbidities. Vascularized composite allotransplantation may provide form, function, and esthetics without a donor site; however, it comes with the significant risk associated with toxic immunosuppression (Biomaterials. 2015;61:246-256, Ann Plast Surg. 2015;75(1):112-116, Transplantation. 2009;88(2):203-210). Engineered tissues offer promise in finding viable alternatives to allograft and autologous tissues. In this study, we present our simple and quick method to decellularize a muscle without disrupting the vascular network integrity or the extracellular matrix. Optimizing the decellularization process is a crucial step toward creating an “off-the-shelf” flap that can be used for soft tissue reconstruction.

Methods
The superficial gracilis muscle of 20 rats were harvested on their circulation and decellularized using perfusion with Krebs-Henseleit buffer and sodium dodecyl sulfate for 6 hours. These flaps were evaluated by gross morphology, histology, DNA quantification, integrity of the vascular network, scanning electron microscopy, and transmission electron microscopy.

Results
All samples were decellularized successfully as determined by DNA content and histological analysis for cellular content. The vascular network was preserved in all samples.

Conclusions
We present a quick, simple, and affordable method to decellularize a muscle flap through the vascular network. Our proposed method is efficient and can be completed in a significantly shorter time when compared with other methods. It is also safe and does not affect integrity of tissue, and this is essential for a reliable recellularization.
Total Nasal Reconstruction With Prefabricated and Prelaminated Free Flap
Authors: Cavadas Pedro C. , Torres Asia 
Published: November 2019

Abstract
Nasal reconstruction is a complex staged procedure. When optimal donor areas are unavailable, flap prefabrication and prelamination techniques can be used for total nasal reconstruction. A technique of total nasal reconstruction using neovascularization of the supraclavicular skin from a skin free flap used for internal lining, along with prelamination of the cartilage framework and surgical delays, is described in 2 patients with adverse anatomical conditions.
Monopole–antimonopole: interaction, scattering and creation
Authors: Saurabh Ayush , Vachaspati Tanmay 
Published: November 2019

The interaction of a magnetic monopole–antimonopole pair depends on their separation as well as on a second ‘twist’ degree of freedom. This novel interaction leads to a non-trivial bound state solution known as a sphaleron and to scattering in which the monopole–antimonopoles bounce off each other and do not annihilate. The twist degree of freedom also plays a role in numerical experiments in which gauge waves collide and create monopole–antimonopole pairs. Similar gauge wavepacket scatterings in the Abelian–Higgs model lead to the production of string loops that may be relevant to superconductors. Ongoing numerical experiments to study the production of electroweak sphalerons that result in changes in the Chern–Simons number, and hence baryon number, are also described but have not yet met with success.
This article is part of a discussion meeting issue ‘Topological avatars of new physics’.