cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular mechanisms of head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide and the overall 50% five-year survival rate is among the lowest of the major cancers. Alterations in cellular molecules controlling DNA repair, proliferation, apoptosis, invasion and angiogenesis are known to contribute to the development of HNSCC. This review will focus on the molecular changes contributing to the pathogenesis of HNSCC and their clinical implications in designing new therapeutic strategies.
Bedside monitoring of the QT interval

Cardiac repolarization, represented on the ECG by the QT interval, is of particular clinical interest in critical care. Once it is measured and corrected for changes in heart rate, the QT interval is known as the QTc. Measurement of the QT interval is important because a prolonged QT interval is associated with ventricular tachycardia and sudden cardiac death. Despite the serious complications associated with a prolonged QT interval, the interval is not routinely measured because a standardized method for measuring it has not been established and the length of QT interval critical to the development of ventricular tachycardia has not been determined. Much has been written about the conditions associated with prolonged QT intervals and specific actions to take when complications appear. Guidelines to be used for QT analysis in the clinical area, based on currently available information, include (1) procedures for measuring QT interval and calculating QTc, (2) procedures for QT analysis, (3) warning signs that indicate increased risk of ventricular tachycardia associated with a prolonged QT interval, and (4) actions to consider once increased risk is determined.
Observations in wringer injuries. An experimental study.

An experimental study of the effect of a wringer injury to the hind limbs of immature rats has been presented. The findings in this study indicate that injuries produced by wringers extending over various periods of time (for example, sixty seconds versus 300 seconds) are similar histologically and vary only in degree. The histological preparations indicate that hemorrhage, edema, venous dilatation, leukocyte infiltration, and muscle necrosis may occur and that the injury is more severe near the bone. The changes first appear in from three to five hours and reach their maximum intensity in from sixteen to twenty-four hours. During this period the animals lose their ability to perform in a rat wheel. Necrosis of striated muscle has been observed as well as late replacement of the necrotic muscle fibers by fibrous tissue. Regeneration of muscle fibers may occur after a wringer injury although the evidence in the present material is inadequate for this conclusion to be reached. We have postulated that the factors giving rise to increased capillary pressure produce a condition of reduced oxygenation and ionic exchange at the fiber level and that these changes may produce muscle necrosis.
Best of Both Worlds: Conjugated Polymers Exhibiting Good Photovoltaic Behavior and High Tensile Elasticity

This paper examines a series of poly(3-alkylthiophene)s (P3ATs), a class of materials for which mechanical compliance and electronic performance have been observed to be in competition. P3ATs with longer alkyl side chains (n ≥ 8) have high elasticity and ductility, but poor electronic performance (as manifested in photovoltaic efficiency in blends with fullerenes); P3ATs with shorter chains (n ≤ 6) exhibit the opposite characteristics. A series of four polymer films in which the average length of the side chain is n = 7 is tested using mechanical, spectroscopic, microscopic, and photovoltaic device-based measurements to determine whether or not it is possible, in principle, to maximize both mechanical and electronic performance in a single organic semiconductor (the “best of both worlds”). The four polymer samples are (1) a physical blend of equal parts P3HT and P3OT (P3HT:P3OT, n = 6 and n = 8), (2) a block copolymer (P3HT-b-P3OT), (3) a random copolymer (P3HT-co-P3OT), and (4) poly(3-heptylthiophene) (P...
The effect of whole egg on DNA hypomethylation and disruption of one-carbon metabolism in insulin dependent diabetes mellitus

Diabetes mellitus is linked with a higher risk of cardiovascular disease and certain types of cancer [61-63]. A study of Type 1 and Type 2 diabetics in Australia showed multi-fold increases in the risk for several types of cancer. Diabetics are also two to four times more likely to have CVD than an adult without diabetes. The common thread among these three medical conditions is oxidative stress. To date, little work has been done on the impact of dietary intervention on the body’s ability to handle the increased oxidative stress caused by diabetes. In this study, male Sprague-Dawley rats were fed a high choline diet for 4 weeks (3 weeks acclimation and 1 week experimental). Diabetes was induced using STZ and after 1 week the rats were sacrificed and liver tissue was harvested for study. There was a significant decrease in GNMT abundance between the non-diabetic control and whole egg diet groups, but not between the diabetic control group and whole egg diet group. There was no attenuation of hepatic hypomethylation in the group fed the high choline diet in comparison to the diabetic control group (P = .121). No significant difference was seen in serum TG levels between groups (P = 0.462).
A 0.4 micron fully complementary BiCMOS technology for advanced logic and microprocessor applications

A modular process architecture has been adopted to develop a versatile yet manufacturable, single-poly, four-level metal, fully complementary BiCMOS technology for sub-0.5 mu m logic and microprocessor products. Both the poly-emitter vertical n-p-n and p-n-p bipolar transistors are integrated into a dual-poly (n/sup +//p/sup +/) gate CMOS process flow. Using a pedestal implant in the emitter window, the n-p-n performance has been enhanced to 26 GHz. Lateral p-n-p and TiSi/sub 2/ Schottky barrier diode devices formed during the titanium self-aligned silicide process are available for various circuit applications. Stacking of the tungsten-plug contacts and vias is allowed in the multilevel metallization module. A process window analysis has also been performed to derive the optimal device design targets. Compared with the CMOS counterpart, approximately 40% speed improvement (at 3.3 V V/sub cc/) in a 68030 critical path has been demonstrated using this logic BiCMOS technology. >
Intraseasonal Periodicity in the Southern Hemisphere Circulation on Regional Spatial Scales

AbstractWave activity in the Southern Hemisphere extratropical atmosphere exhibits robust periodicity on time scales of ~20–25 days. Previous studies have demonstrated the robustness of the periodicity in hemispheric averages of various eddy quantities. Here the authors explore the signature of the periodicity on regional spatial scales.Intraseasonal periodicity in the Southern Hemisphere circulation derives from out-of-phase anomalies in wave activity that form in association with extratropical wave packets as they propagate to the east. In the upper troposphere, the out-of-phase anomalies in wave activity form not along the path of extratropical wave packets, but in their wake. The out-of-phase anomalies in wave activity give rise to periodicity not only on hemispheric scales, but also on synoptic scales when the circulation is sampled along an eastward path between ~5 and 15 m s−1. It is argued that 1) periodicity in extratropical wave activity derives from two-way interactions between the heat fluxes ...
A New Class of Antiarrhythmics for Late ICA,L

Early Afterdepolarizations (EADs) of the cardiac action potential (AP) are membrane potential oscillations arising during phase 2-3 and well-recognized cellular triggers of lethal cardiac arrhythmias. The L-type Ca2+ current (ICa,L) is a major regenerative inward current during these phases of the AP, and is therefore highly relevant to EAD upstroke and propagation at the tissue level. We recently discovered that late ICa,L reduction produced by minimally altering specific ICa,L biophysical properties (smaller pedestal ICa,L or more depolarized steady-state activation), potently suppresses EAD occurrence in rabbit ventricular myocytes under dynamic clamp. Based on these findings, we hypothesize that drugs able to mimic these late ICa,L modifications could constitute a new Class of antiarrhythmics that do not compromise inotropy. We are studying the antiarrhythmic effects of two pilots drugs, roscovitine and pregabalin, that we found to reduce late ICa,L in rabbit ventricular myocytes via two distinct mechanisms. Specifically, roscovitine reduced the non-inactivating (pedestal) ICa,L while leaving peak ICa,L intact and pregabalin induced a depolarizing shift of the steady-state activation. In this study we assessed the antiarrhythmic potential of these pilot compounds that reduce late ICa,L. We tested the ability of these drugs to suppress EADs in ventricular myocytes induced by oxidative stress (H2O2). The perfusion of roscovitine (20µM) or pregabalin (1mM) dramatically suppressed EAD occurrence (roscovitine: from 81.37%±8.1% to 0% APs with EADs; pregabalin from 64.5±17.7% to 6.6±3.8%) and restored normal AP duration. Moreover, both drugs suppressed EAD-mediated VT/VF in isolated perfused aged rat hearts, restoring sinus rhythm (roscovitine: 5/6; pregabalin: 2/2 hearts). These studies set the basis for the development of a conceptually new Class of antiarrhythmics (L-type Ca2+ channel gating modifiers) that selectively reduce late ICa,L, avoiding the negative inotropy caused by traditional CaV channel blockers used as Class IV Antiarrhythmics.
17.10 A 318-to-370GHz standing-wave 2D phased array in 0.13µm BiCMOS

Fully integrated implementation of mm-wave/THz radiators and phased arrays presents new potentials for applications like spectroscopy, imaging, and high data-rate communication. These applications demand sufficient radiated power, wide frequency range, and variable phase shifting between sources to perform beam steering. Limited power generation capability of transistors close to the maximum oscillation frequency (f max ) of available silicon processes in addition to the poor quality factor of varactors makes realizing these requirements particularly challenging. Harmonic oscillators are often coupled together in arrays to boost the output power and steer the radiation beam [1–6]. The coupling elements along with varactors used for frequency tuning add loss and parasitics to the circuit and significantly reduce the output power, operation frequency, and tuning range at mm-wave/THz frequencies. In this work, we implemented a standing-wave (SW) structure that overcomes these challenges to achieve broadband frequency tuning, wide beam steering and high power radiation at the same time.
MUC1-C INTEGRATES PD-L1 INDUCTION WITH REPRESSION OF IMMUNE EFFECTORS IN NON-SMALL CELL LUNG CANCER

Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65→ZEB1 pathway and confers a poor prognosis. The present studies demonstrate that MUC1-C activates PD-L1 expression in NSCLC cells. We show that MUC1-C increases NF-κB p65 occupancy on the CD274/PD-L1 promoter and thereby drives CD274 transcription. Moreover, we demonstrate that MUC1-C-induced activation of NF-κB→ZEB1 signaling represses the TLR9 (toll-like receptor 9), IFNG, MCP-1 (monocyte chemoattractant protein-1) and GM-CSF genes, and that this signature is associated with decreases in overall survival. In concert with these results, targeting MUC1-C in NSCLC tumors suppresses PD-L1 and induces these effectors of innate and adaptive immunity. These findings support a previously unrecognized central role for MUC1-C in integrating PD-L1 activation with suppression of immune effectors and poor clinical outcome.
La inducción del periodo ovulatorio

Two powerful instruments -the human gonadotropin and clomiphene-- citrate are at our disposal for the induction of ovulation period in all patients who show an anovulatory period of central origin: psychogenic, neurogenic and pituitary. These drugs must not be used without a prior study of the etiology excluding not only the peripheral fault OVO rich but also the end-organ failure. They are not used in cases of amenorrhea due to intermediary causes as chronic diseases, metabolic diseases -tiroides, adrenol, pancreas and nutritional conditions factors. To avoid complications that are polycystic ovaries and multiple pregnancies, one has to use the minimum effective dose. This dose is, to some extent, based on a single criterion. If these precautions are taken properly, one can expect to improve the outcome of difficult cases such as amenorrhea caused by neurogenic factors and pituitary, hypothalamic amenorrhea and perhaps eradicate the surgical treatment of Stein-Leventhal syndrome.
Relationship between rising bilateral mastectomy rates and increased use of neoadjuvant chemotherapy (NAC) in California, 1998-2012.

1052Background: The benefits of NAC for breast cancer are multifaceted, providing insight into chemosensitivity, facilitating breast conservation, and providing prognostic information. However, lit...
Abstract 116: Slit-Robo Signaling Regulates Lipopolysaccharide-induced Endothelial Inflammation and Expression of Slit/Robo is Dysregulated During Endotoxemia

Abstract Introduction: Lipopolysaccharide (LPS) is one of the critical factors which induce endothelial inflammation during the pathogenesis of atherosclerosis, endocarditis and sepsis shock induced heart injury. The secretory Slit2 protein and its endothelial receptors Robo1 and Robo4 have been shown to regulate mobility and permeability of endothelial cells, which could be functional in regulating LPS induced endothelial inflammation. Hypothesis: We hypothesized that in addition to regulating permeability and migration of endothelial cells, Slit2-Robo1/4 signaling might regulate other LPS-induced endothelial inflammatory responses. Methods and Results: Using Human Umbilical Vein Endothelial Cells (HUVEC) culture, we observed that Slit2 treatment suppressed LPS-induced secretion of pro-inflammatory cytokines (including GM-CSF), cell adhesion molecule upregulation and monocyte (THP-1 cell) adhesion. With siRNA knock down techniques, we further confirmed that this anti-inflammatory effect is mediated by the interaction of Slit2 with its dominant receptor in endothelial cells, Robo4, though the much lesser expressed minor receptor Robo1 is pro-inflammatory. Our signaling studies showed that downstream of Robo4, Slit2 suppressed inflammatory gene expression by inhibiting the Pyk2 - NF-kB pathway following LPS-TLR4 interaction. In addition, Slit2 can induce a positive feedback to its expression and downregulate the pro-inflammatory Robo1 receptor via mediation of miR-218. Moreover, both in in vitro studies using HUVEC and in vivo mouse model studies indicated that LPS also causes endothelial inflammation by downregulating the anti-inflammatory Slit2 and Robo4 and upregulating the pro-inflammatory Robo1 during endotoxemia, especially in mouse arterial endothelial cells and whole heart. Conclusions: Slit2-Robo1/4 signaling is important in regulation of LPS induced endothelial inflammation, and LPS in turn causes inflammation by interfering with the expression of Slit2, Robo1 and Robo4. This implies that Slit2-Robo1/4 is a key regulator of endothelial inflammation and its dysregulation during endotoxemia is a novel mechanism for LPS induced cardiovascular pathogenesis.
Supporting Fault-Tolerance in Presence of In-Situ Analytics

In-situ analytics have recently emerged as a promising approach to reduce I/O, network, and storage congestion for scientific data analysis. At the same time, Mean Time To Failure (MTTF) has also continuously decreased for HPC clusters, making failures during the execution of a simulation more likely. It is difficult to apply Checkpointing and Restart (C/R) to a simulation executed with in-situ analytics, because we not only need to store analytic and simulation states, but also need to ensure consistency between them.To solve the above problem, we present a novel solution to apply C/R approach. The solution exploits a common property of analytics applications, which is that they fit the reduction-style processing pattern. Based on the observation that the global reduction result is correct if all local reduction objects have been processed, only global reduction objects and progress of the reduction procedure is checkpointed, together with an application-level checkpoint of the simulation. We also discuss the specific details for handling time-sharing and space sharing modes, which are suitable for multi-core and many-core environments, respectively.We have evaluated our approach in the context of Smart middleware for developing in-situ analytics, which provides a Map-Reduce like API. We demonstrate the low overheads of our approach with different scientific simulations and analytics tasks.
Arrow’s Impossibility Theorem

We have now looked at several ways to answer the question “When is one alternative socially preferred to another?” Each of the answers has been somehow disappointing. The Pareto criterion is incomplete; the Kaldor criterion is possibly inconsistent. The Scitovsky criterion reduces to a question of optimality vs. non-optimality. The Samuelson criterion might be completely devoid of content. The fairness and Rawls criteria might be inconsistent with the Pareto criterion. Majority voting might generate cycles, and the single-peakedness condition, which forces transitivity, is quite restrictive.
Guided Growth Treatment for Genu Valgum Secondary to Juxtaphyseal Recurrent Aneurysmal Bone Cyst of the Distal Femur

An 11 year 6 month old male with a history of recurrent aneurysmal bone cyst involving the distal metaphysis of the left femur presented with increasing asymmetric genu valgum affecting the left lower extremity. Plain radiographs and MRI scan confirmed the distal femoral valgus related to the recurrent juxtaphyseal lesion without any discrete bony bar. He underwent guided growth treatment with application of an extraperiosteal non-locking plate across the ipsilateral medial distal femoral physis as a same-day procedure. Over the next several months, progressive correction of his angular deformity was noted. After mild intentional overcorrection, the plate was removed 2 years postoperatively. At a 5-year follow-up, he was skeletally mature with equal leg lengths and symmetric physiologic alignment of his lower extremities. In a skeletally immature patient with a “sick” but viable physis, guided growth treatment using an extraperiosteal plate is a viable alternative to more invasive osteotomies. 1 Brief Clinical History An 11 year 6 month old male was seen as an outpatient with the chief concern of progressive leftsided genu valgum. His past history was pertinent for a diagnosis of recurrent aneurysmal bone cyst (ABC) involving the distal femoral metaphysis. He had previously undergone two surgeries on the left lower extremity. These procedures included an initial curettage and bone grafting of the lesion about 2 years earlier, followed by a repeat procedure 8 months prior to presentation due to recurrence of the lesion. There was no history of any postoperative infection or fracture. On physical exam, he had asymmetric genu valgum, left greater than right side. His leg lengths were equal within a centimeter. The range of motion of the left knee was 5–130 compared to 0–140 on the unaffected right side. Lateral maltracking of the left patella was noted. The torsional profile of the lower extremities was symmetric. 2 Preoperative Clinical Photos and Radiographs Preoperative clinical picture of the patient from the front (Fig. 1) and back (Fig. 2) demonstrating the left-sided genu valgum. A full-length standing radiograph of the lower extremities revealed a mechanical axis deviation (MAD) of 1.3 cm lateral on right and 6 cm lateral on left side (Fig. 3). *Email: sabharsa@njms.rutgers.edu Limb Lengthening and Reconstruction Surgery Case Atlas DOI 10.1007/978-3-319-02767-8_41-1 # Springer International Publishing Switzerland (outside the USA) 2014
Geometry of CMEs and ICMEs

In Chap. 4 we discussed the theory behind how CMEs and ICMEs are observed in visible white light. This is due to the Thomson scattering of the light from the electrons in the CME. However the means by which the light reaches us is not the only significant factor in determining the appearance of the CME. CME images are in fact sky plane projections and so additional data or careful analysis is required to extract their 3-D properties. In this chapter we review the importance of the geometry of the CME and how 3-D information may be extracted from white light images of them.
An upper arm A-V fistula for hemodialysis patients with distal access failures.

The technique of creating an upper arm side-to-side A-V fistula in patients with forearm vascular access failures has been described. The procedure has been used extensively in patients in Japan with a high degree of success. The limited U.S. experience has confirmed that the procedure results in trouble-free, reliable vascular access. It is proposed as an alternative approach for patients with forearm access failures.
Calcium and Light Adaptation in Invertebrate Photoreceptors

A light-induced increase in the concentration of intracellular calcium ions has been proposed to be a step in the cascade of reactions mediating light adaptation in invertebrate photoreceptors. The physiological and anatomical evidence consistent with that proposal is reviewed.
Glucoregulatory and Cardiometabolic Profiles of Almond vs. Cracker Snacking for 8 Weeks in Young Adults: A Randomized Controlled Trial

The transition to nutritional independence makes new college students vulnerable to alterations in eating patterns, which can increase the risk of cardiometabolic disorders. The aim of the study was to examine the potential benefits of almond vs. cracker snacking in improving glucoregulatory and cardiometabolic profiles in new college students. A randomized controlled, parallel-arm, 8-week intervention of 73 college students (BMI: 18–41 kg/m2) with no cardiometabolic disorders was conducted. Participants were randomized into either an almond snack group (56.7 g/day; 364 kcal; n = 38) or Graham cracker control group (77.5 g/day; 338 kcal/d; n = 35). Chronic, static changes were assessed from fasting serum/plasma samples at baseline, and after 4 and 8 weeks. Acute, dynamic effects were assessed during a 2-h oral glucose tolerance test (OGTT) at 8 weeks. Almond snacking resulted in a smaller decline in HDL cholesterol over 8 weeks (13.5% vs. 24.5%, p < 0.05), 13% lower 2-h glucose area under the curve (AUC), 34% lower insulin resistance index (IRI) and 82% higher Matsuda index (p < 0.05) during the OGTT, despite similar body mass gains over 8 weeks compared with the cracker group. In general, both almond and cracker snacking reduced fasting glucose, and LDL cholesterol. Conclusions: Incorporating a morning snack in the dietary regimen of predominantly breakfast-skipping, first-year college students had some beneficial effects on glucoregulatory and cardiometabolic health. Almond consumption has the potential to benefit postprandial glucoregulation in this cohort. These responses may be influenced by cardiometabolic risk factor status.
Prevalence and Characteristics of Moderate to Severe Pain among Hospitalized Older Adults.

Objectives To investigate the prevalence, characteristics, and management of pain in older hospitalized medical patients. Design Medical record aggregate review. Setting Tertiary care hospital. Participants Individuals aged 65 and older admitted to the medicine service between November 28, 2014, and May 28, 2015. Measurements Demographic characteristics, comorbidity burden, pain characteristics, and analgesics during index hospitalization were assessed in individuals with moderate to severe pain (≥4 on 0–10 Numeric Pain Rating Scale). Results Of 1,267 patients admitted to the medicine service, 248 (20%) had moderate to severe pain on admission (mean age 75 ± 8, 57% female, 50% white). During hospitalization, most participants received opioids (80%) and acetaminophen (74%), and few received nonsteroidal antiinflammatory drugs (9%). Participants with chronic pain had less reduction in pain intensity score from admission to discharge than those without a history of chronic pain (mean change score 3.7 vs 4.9, p=.002) and were more likely to receive opioids, adjuvant analgesics, and other analgesics (all p<.05). Conclusion Twenty percent of older adults admitted to a general medicine service had moderate to severe pain. Further research about optimal pain management in hospitalized older adults, particularly those with chronic pain, is necessary to improve care in this population.
A Study on Die Stresses in Flip Chip Package Subjected to Various Hygrothermal Exposures

Moisture has been one of the major concerns for package designers and reliability researchers. It is well-known that high humidity combined with high temperature can cause a number of failure modes to electronic devices, such as popcorn cracking, delamination, or electrochemical migration. While the fundamental knowledge of moisture effects on electronic packages has been extensively explored, there have been no published studies on the effects of underfill and substrate moisture absorption on the die stresses development and delamination growth in flip chip assemblies. In this study, on-chip piezoresistive sensors were used to measure moisture-induced device side die stresses in flip chip on laminate packages under three different moisture conditions. The die stresses were also monitored during the subsequent drying to evaluate the reversibility of the moisture effects. After the initial 10 days of moisture exposure, moisture was found to have significant effects on the package, generating tensile die normal stresses of up to 37 MPa under the harshest testing environment (95% RH, 95 °C). Also, it can be observed that more harsh condition produced larger stress level, but the stresses variation under all conditions showed the same behavior. Shear stresses however were found to be quite small relative to normal stresses. Upon the subsequent drying, it was seen that the moisture-induced stress changes were almost fully recordable. In addition to the measurements of the moisture-induced die stresses, a study on hygrothermal properties of polymer materials was conducted where diffusivity, saturated concentration and coefficient of moisture expansion (CME) of underfill and BT (Bismaleimide-Triazine) substrate were characterized under the moisture conditions used in the experiments. The obtained properties were later used for the finite element simulation of the moisture diffusion. The numerical predictions were finally correlated with the experimental results. They were found to be in good agreements.
Empirical analysis of intertemporal relations between downside risks and expected returns—Evidence from Asian markets

Abstract This paper tests the risk-return relations for Asian stock markets by employing conditional volatility, local downside risk, regional downside risk, and world/U.S. downside risk. We find positive and significant intertemporal relations between excess stock returns and various risks. The evidence supports the risk-return tradeoff not only from local risk but also from external risk. The model is robust as it pertains to the risk of small variations as well as big shocks. The evidence supports positive risk-return relations across 10 Asian markets after controlling for the lagged dividend yield, higher moments of stock returns, and exchange rate variations.
Treatment for severe combined immunodeficiency (SCID) in the era of newborn screening (NBS)

SCID is associated with excellent survival when treated with allogeneic hematopoietic cell transplantation (HCT), gene therapy (GT), or enzyme replacement therapy (ERT) within 3–4 months of birth or prior to infection. NBS for SCID results in the diagnosis by 2–3 weeks of age. This retrospective analysis describes therapy and immune reconstitution of 28 infants diagnosed by NBS in California since 2010 and treated at the University of California, San Francisco at a median of 56 (24–217) days of age. HCT with alkylating chemotherapy (N=6), serotherapy alone (N=6), or no conditioning (N=12) was used in 24 infants, and ERT followed by definitive GT at University of California, Los Angeles, was used in 4 ADA-deficient infants. Overall survival at >2 years was 93% with 1 death from HHV6 and 1 from CMV. The median time to CD4 T cell recovery (>200 T cells/uL) was 73 (10–96) days for ERT patients prior to GT, and 138 days (14–220) for HCT patients. Time from first appearance of donor chimerism to CD4 recovery was evaluable for 14 HCT survivors who lacked pre-HCT maternal chimerism or whose donors were not their mothers. After donor chimerism appeared in peripheral blood at a median of 21.5 (14–169) days, appearance of T cells took 32 (0–84) more days. Second transplant or stem cell boost was required for 10 of 24 patients at a median of 77 (35–382) days following first HCT; for patients eligible for analysis (N=15), need for 2 nd therapy was significantly higher in those without detectable donor chimerism by 28 days following therapy (0% vs 83%, p=0.04). NBS for SCID allowed rapid institution of anti-infective and definitive treatment to optimize outcomes, and early detection of donor chimerism was associated with successful T cell recovery.
Effect of Lidocaine on Viability and Gene Expression of Human Adipose-derived Mesenchymal Stem Cells: An in vitro Study.

OBJECTIVE To assess the biologic effects of lidocaine on the viability, proliferation, and function of human adipose tissue-derived mesenchymal stromal/stem cells (MSCs) in vitro. METHODS Adipose-derived MSCs from three donors were exposed to lidocaine at various dilutions (2 mg/mL to 8 mg/mL) and exposure times (0.5 to 4 hours). Cell number and viability, mitochondrial activity, and real-time reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) were analyzed at 0 (immediate effects) or 24 and 48 hours (recovery effects) after treatment with lidocaine. RESULTS Trypan blue staining showed that increasing concentrations of lidocaine decreased the number of observable viable cells. 3-[4,5,dimethylthiazol-2-yl]-5-[3-carboxymethoxy-phenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTS) assays revealed a concentration- and time- dependent decline of mitochondrial activity and proliferative ability. Gene expression analysis by RT-qPCR revealed that adipose-derived MSCs exposed to lidocaine express robust levels of stress response/cytoprotective genes. However, higher concentrations of lidocaine caused a significant downregulation of these genes. No significant differences were observed in expression of extracellular matrix (ECM) markers COL1A1 and DCN except for COL3A1 (P < .05). Levels of messenger RNA (mRNA) for proliferation markers (CCNB2, HIST2H4A, P < .001) and MKI67 (P < .001) increased at 24 and 48 hours. Expression levels of several transcription factors- including SP1, PRRX1, and ATF1-were modulated in the same manner. MSC surface markers CD44 and CD105 demonstrated decreased expression immediately after treatment, but at 24 and 48 hours postexposure, the MSC markers showed no significant difference among groups. CONCLUSION Lidocaine is toxic to MSCs in a dose- and time- dependent manner. MSC exposure to high (4-8 mg/mL) concentrations of lidocaine for prolonged periods can affect their biologic functions. Although the exposure time in vivo is short, it is essential to choose safe concentrations when applying lidocaine along with MSCs to avoid compromising the viability and potency of the stem cell therapy.
A 1-Year Cross-sectional Inflammatory Bowel Disease Surveillance Colonoscopy Cohort Comparing High-definition White Light Endoscopy and Chromoendoscopy

BACKGROUND We sought to compare the dysplasia detection rate of high-definition white light endoscopy (HDWLE) with that of chromoendoscopy in patients with long-standing inflammatory bowel disease (IBD). METHODS This is a retrospective observational cohort of patients with IBD who underwent surveillance colonoscopy between October 1, 2016 and September 30, 2017. We assessed the association between dysplasia detection and multiple variables. RESULTS A total of 808 unique colonoscopies were performed, of which 150 (18.6%) included chromoendoscopy. Primary sclerosing cholangitis was a comorbid diagnosis in 24.5% of patients. The performing endoscopist was an IBD specialist with 37.1% of patients and had >10 years' experience with 64.9% of patients. Prior dysplasia had been seen in 245 (30.3%) patients: 102 (68.0%) and 143 (22.0%) among patients who had chromoendoscopy and HDWLE, respectively. Dysplasia in polyps was found in 129 procedures (15.1%). Among patients who had chromoendoscopy and HDWLE, polypoid dysplasia was identified in 50 (33.0%) and 79 (12.0%) patients, respectively, P < 0.01. Dysplasia in random biopsies was found in 39 patients (4.8%): 15 (10%) who had chromoendoscopy and 24 (3.6%) who had HDWLE (P < 0.001). On multivariate analysis, patient and disease characteristics significantly associated with an increased odds for polypoid dysplasia included older age at diagnosis (odds ratio [OR] = 1.3 per 10 years; 95% confidence interval [CI], 1.07-1.60), having an IBD physician endoscopist (OR = 1.6; 95% CI, 1.01-2.67), having an endoscopist with less than 10 years' experience (OR = 1.8; 95% CI (1.16-2.89), and prior random dysplasia (OR = 4.2; 95% CI (1.93-9.17). Concomitant primary sclerosing cholangitis was significantly associated with random dysplasia (OR = 2.3; 95% CI, 1.02-5.07). After multivariate analysis adjusting for these variables, chromoendoscopy was no more likely to identify dysplasia than was HDWLE. CONCLUSIONS Chromoendoscopy and HDWLE had a similar diagnostic yield for dysplasia detection in patients with chronic IBD-colitis after adjusting for multiple known risk factors.
MRGPRX2 Activation Causes Increased Skin Reactivity in Patients with Chronic Spontaneous Urticaria.

We present heightened skin reactivity in vivo to two MRGPRX2 drug ligands in patients with chronic spontaneous urticaria. Selectivity for the MRGPRX2 pathway by drug ligands was demonstrated by the loss of drug activation in MRGPRX2-KO LAD2 cells.
Aging-related changes in cortical mechanisms supporting postural control during base of support and optic flow manipulations

Behavioral findings suggest that aging alters the involvement of cortical sensorimotor mechanisms in postural control. However, corresponding accounts of the underlying neural mechanisms remain sparse, especially the extent to which these mechanisms are affected during more demanding tasks. Here, we set out to elucidate cortical correlates of altered postural stability in younger and older adults. 3D body motion tracking and high-density electroencephalography (EEG) were measured while 14 young adults (mean age = 24 years, 43% women) and 14 older adults (mean age = 77 years, 50% women) performed a continuous balance task under four different conditions. Manipulations were applied to the base of support (either regular or tandem (heel-to-toe) stance) and visual input (either static visual field or dynamic optic flow). Standing in tandem, the more challenging position, resulted in increased sway for both age groups, but for the older adults, only this effect was exacerbated when combined with optic flow compared to the static visual display. These changes in stability were accompanied by neuro-oscillatory modulations localized to midfrontal and parietal regions. A cluster of electro-cortical sources localized to the supplementary motor area showed a large increase in theta spectral power (4-7 Hz) during tandem stance, and this modulation was much more pronounced for the younger group. Additionally, the older group displayed widespread mu (8-12 Hz) and beta (13-30 Hz) suppression as balance tasks placed more demands on postural control, especially during tandem stance. These findings may have substantial utility in identifying early cortical correlates of balance impairments in otherwise healthy older adults.
Evaluating Wellness Interventions for Resident Physicians: A Systematic Review.

Background Wellness initiatives implemented by graduate medical education programs can help mitigate burnout in resident physicians. Objective This systematic review seeks to identify factors that impact the effectiveness of resident wellness interventions and to provide a conceptual framework to guide future interventions. Methods Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 6 electronic databases were searched in November 2019 using variations of the keywords "resident physicians," "wellness," and "intervention." Peer-reviewed full-text English-language articles on controlled studies were considered for inclusion. The quality of the studies was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. Results The initial search disclosed 1196 articles, of which 18 studies enrolling 666 resident physicians met inclusion criteria for qualitative review. Interventions using peer support and individual meditation enhanced well-being. Effective wellness interventions also used educational theory to guide program development, surveyed participants to guide intervention design, incorporated programming into existing didactic curricula, and recruited voluntary participants. The quality of most of the included studies was poor (13 of 18, 72%) and could be improved by using standardized wellness assessments supported by validity evidence. Conclusions This systematic review suggests that future resident wellness initiatives should focus on grounding interventions in educational theory, forging consensus on wellness instruments with validity evidence, and examining the impact of initiatives on patient outcomes. A logic model can provide a framework for designing and implementing effective wellness interventions.
Missing Shapiro steps in topologically trivial Josephson junction on InAs quantum well

Josephson junctions hosting Majorana fermions have been predicted to exhibit a 4π periodic current phase relation. One experimental consequence of this periodicity is the disappearance of odd steps in Shapiro steps experiments. Experimentally, missing odd Shapiro steps have been observed in a number of materials systems with strong spin-orbit coupling and have been interpreted in the context of topological superconductivity. Here we report on missing odd steps in topologically trivial Josephson junctions fabricated on InAs quantum wells. We ascribe our observations to the high transparency of our junctions allowing Landau-Zener transitions. The probability of these processes is shown to be independent of the drive frequency. We analyze our results using a bi-modal transparency distribution which demonstrates that only few modes carrying 4π periodic current are sufficient to describe the disappearance of odd steps. Our findings highlight the elaborate circumstances that have to be considered in the investigation of the 4π Josephson junctions in relationship to topological superconductivity. Recent observations of missing odd Shapiro steps have been interpreted in the context of topological superconductivity. Here, the authors observe missing odd Shapiro steps in topologically trivial Josephson junctions due to high transparency of the junctions, calling for caution in relationship to topological superconductivity.
Recursive Stochastic Choice

We characterize two sorts of stochastic choice rules in which the agent makes current decisions using a forward-looking value function that takes future randomizations into account. Both sorts of rules generalize logistic choice, and are equivalent to it in static problems. The rules differ in how the agent views future choice sets and how he views his future randomizations. One rule is equivalent to the discounted logit used in applied work, and exhibits a “preference for flexibility;” the other is “error-averse” and penalizes the addition of undesirable choices to a menu.
Solitary fibrous tumor of thoracic cavity, extra-thoracic sites and central nervous system: Clinicopathologic features and association with local recurrence and metastasis.

Abstract Published risk stratification models of solitary fibrous tumor (SFT) have been associated with distant metastases outside the central nervous system (CNS), but have not been studied for tumors occurring in the CNS. In a retrospective review, we identified 72 cases of solitary fibrous tumor or hemangiopericytoma (HPC) diagnosed between January 2011 and December 2020 at our institution. The tumors involved the central nervous system (N = 17), thoracic cavity (N = 28), and extrathoracic sites (N = 27). The risk of local recurrence, distant metastasis, or death at 5 years was 57% (95% CI 23%, 76%) in the CNS, 24% (95% CI 2%, 41%) in the thoracic cavity, and 13% (95% CI 0%, 25%) in extrathoracic sites. By contrast, the risk of distant metastasis or death at 5 years was 13% (95% CI 0%, 29%) in CNS primaries, 5% (95% CI 0%, 14%) in thoracic primaries, and 14% (95% CI 0%, 27%) in extrathoracic primaries. Using the published 3- and 4-variable risk stratification models by Demicco et al., we retrospectively assessed our cases for risk of local recurrence, distant metastasis, and death. For tumors outside the CNS, we show that three- and four-variable risk stratification models were associated with recurrence-free survival in addition to the previously known association with distant metastasis (all P
The Medical Management of Gastroesophageal Reflux Disease: A Narrative Review.

Objective The medical management of gastroesophageal reflux disease (GERD) continues to evolve. Our aim was to systematically assess the literature to provide an updated review of the evidence on lifestyle modifications and pharmacological therapy for the management of GERD. Background The cornerstones of GERD medical management consist of lifestyle modifications and pharmacologic agents. Most recently, evidence has emerged linking anti-reflux pharmacologic therapy to adverse events, such as kidney injury, metabolic bone disease, myocardial infarction, and even dementia, among others. Methods A systematic search of the databases of PubMed/MEDLINE, Embase, and Cochrane Library was performed for articles on the medical management of GERD between inception and March 1, 2021. Conclusion Although pharmacological therapy has been associated with potential adverse events, further research is needed to determine if this association exists. For this reason, lifestyle modifications should be considered first-line, while pharmacologic therapy can be considered in patients in whom lifestyle modifications have proven to be ineffective in controlling their symptoms or cannot institute them. Naturally, extra-esophageal causes for GERD-like symptoms must be considered on suspected high-risk patients and excluded before considering treatment for GERD.
Medicaid Expansion and Medical Liability Costs

This paper examines the impact of health insurance expansion on medical liability costs using the case of the Affordable Care Act’s (ACA) Medicaid expansion. Medicaid expansion has increased the demand for medical services, but in doing so it may also have increased physicians’ liability in medical practices. By studying medical malpractice insurers’ performance in the U.S. for the period 2010–2018, we find insurers operating in states with Medicaid expansion experienced significantly higher medical liability costs than those in non-expansion states. While insurers in expansion states did increase premiums, the increase was not enough to fully offset rising costs. In addition, we do not find evidence that tort reforms mitigate ACA-induced malpractice liability costs. By exploring the frequency and severity of malpractice claims, we find Medicaid expansion increased malpractice costs mainly by increasing the claim frequency, while tort reforms generally focus on reducing claim severity.
A review of Children's Advocacy Centers' (CACs) response to cases of child maltreatment in the United States

Child maltreatment is a serious and prevalent problem in the United States. Children's Advocacy Centers (CACs) were established in 1985 to better respond to cases of child maltreatment and address problems associated with an uncoordinated community-wide response to child maltreatment. CACs are community-based, multidisciplinary organizations that seek to improve the response and prosecution of child maltreatment in the United States. The primary purpose of this manuscript is to present a review of the literature on CACs, including the CAC model (e.g., practices, services, and programs) and CACs' response to cases of child maltreatment. This review suggests that there is preliminary evidence supporting the efficacy of CACs in reducing the stress and trauma imposed on child victims during the criminal justice investigation process into the maltreatment. However, this review also identified important CAC polices, practices, and components that need further evaluation and improvement. In addition, due to the methodological limitations and gaps in the existing literature, research is needed on CACs that employ longitudinal designs and larger samples sizes and that evaluate a larger array of center-specific outcomes. Finally, this review suggests that CACs might benefit from incorporating ongoing research into the CAC model and accreditation standards and by recognizing the importance of integrating services for child and adult victims of interpersonal violence. Language: en
Multibeam Stimulated Raman Scattering in Inertial Confinement Fusion Conditions

Stimulated Raman scattering from multiple laser beams arranged in a cone sharing a common daughter wave is investigated for inertial confinement fusion (ICF) conditions in a inhomogeneous plasma. It is found that the shared electron plasma wave (EPW) process, where the lasers collectively drive the same EPW, can lead to an absolute instability when the electron density reaches a matching condition dependent on the cone angle of the laser beams. This mechanism could explain recent experimental observations of hot electrons at early times in ICF experiments, at densities well below quarter critical when two plasmon decay is not expected to occur.