cssi/SciSciGPT-SciSciNet huggingface dataset:
Early perception of medication benefit predicts subsequent antipsychotic response in schizophrenia: "the consumer has a point" revisited.

Background: An easy-to-administer tool for predicting response to antipsychotic treatment could improve the acute management of patients with schizophrenia. We assessed whether a patient’s perception of medication benefit early in treatment could predict subsequent response or nonresponse to continued use of the same treatment. Method: This post hoc analysis used data from a randomized, open-label trial of antipsychotics for treatment of schizophrenia in which attitudes about medication adherence were assessed after two weeks of antipsychotic treatment using the Rating of Medication Influences (ROMI) scale. The analysis included 439 patients who had Positive and Negative Syndrome Scale (PANSS) and ROMI scale data at Weeks 2 and 8. Scores on the ROMI subscale Perceived Medication Benefit factor were used to predict subsequent antipsychotic response at Week 8, defined as a ≥20% reduction from baseline on the PANSS. Logistic regression was used to identify a cut-off score for the Perceived Medication Benefit factor that could accurately identify antipsychotic responders vs. nonresponders at Week 8. Results: A score of ≥2.75 (equal to a mean subscale score of ≥11.00) on the ROMI scale Perceived Medication Benefit factor at Week 2 predicted response at Week 8 with high specificity (72%) and negative predictive value (70%), moderate sensitivity (44%) and positive pre dictive value (47%), and with a 38% misclassification rate. Conclusions: A brief assessment of the patient’s perception of medication benefit at two weeks into treatment appears to be a good predictor of subsequent response and nonre sponse after eight weeks of treatment with the same antipsychotic.
Pneumococcus and sickle cell disease: the beginning of the end?

anemia and, prior to the initiation of penicillin prophylaxis, was a major contributor to morbidity and the leading cause of death in children, adolescents, and young adults with sickle cell anemia [1]. More than 20 years ago, in a randomized, controlled clinical trial, Gaston et al. [2] showed that, when children with sickle cell disease received penicillin prophylactically, they experienced an 84% reduction in the rate of pneumococcal infection. The results of this landmark study led to a rapid medical response that improved the care of children with sickle cell disease. Neo-
Human Cardiovascular Adjustments to Rapid Changes in Skin Temperature during Exercise

In 11 normal men, central circulatory responses were measured while skin temperature was changed in a square-wave pattern during uninterrupted exercise (26% to 64% maximal oxygen consumption). Skin temperature was changed at 30-minute intervals, beginning at 32°C. On raising it to 38.2°C at low oxygen consumption (V·o2), cardiac output increased 2.5 liters/min, and central blood volume, aortic mean pressure, and stroke volume fell (7%, 7%, and 11%, respectively). Right atrial mean pressure fell 2.2 and 2.3 mm Hg during control and heating periods, respectively. All variables returned to control levels when skin temperature was reduced toward 26.9°C. Raising it to 40°C reproduced these changes with a more clear-cut drop in right atrial mean pressure. Results indicated reduced peripheral venous tone and cutaneous pooling of blood during heating and rapid reversal on cooling. On raising skin temperature to 38.7°C at high V·o2, cardiac output increased 19% (3.1 liters/min), stroke volume decreased 14%, and central blood volume rose slightly. Aortic mean pressure fell during the control period and was maintained or rose during heating periods. On cooling, central blood volume and stroke volume rose, cardiac output remained elevated, and aortic mean pressure fell. Increases in cardiac output during heating were related to skin temperature and not to V·o2 or body temperature. At high V·o2, circulatory adjustments favor metabolic rather than thermoregulatory demands.
A Self-Structuring Patch Antenna: Simulation and Prototype

A self-structuring patch antenna (patch SSA) is proposed. It combines the operating principles of the original self-structuring antenna with the desirable properties of a classic microstrip patch antenna. The patch self-structuring antenna has several computer-controlled shorting pins inserted between the patch and the ground plane. By opening and closing these pins, the antenna may be configured to operate at any arbitrary frequency within a very large bandwidth. Additionally, the patch self-structuring antenna may be configured to operate at several simultaneous frequencies that when placed near each other can be used to dramatically expand the instantaneous bandwidth of the antenna. A proof-of-principle study is undertaken both in simulation and by performing measurements on a prototype antenna.
Sexual dysfunction in women with epilepsy

Sexual dysfunction in women with epilepsy (WWE) is an important comorbidity. A significant minority of WWE have markedly decreased sexual interest and it appears that orgasmic dysfunction occurs more frequently in WWE than in control women. Enzyme-inducing antiepileptic drugs can adversely affect sexual functioning by decreasing bioactive testosterone levels. Temporal lobe epilepsy of right-sided versus left-sided origin may also be a risk factor for sexual dysfunction. In addition to these factors, emerging evidence suggests that the serotonin transporter protein is related to temporal lobe epilepsy and it is postulated that this transporter may play a role in altered sexual functioning in epilepsy, perhaps through the serotonergic effects of antiepileptic drugs (AEDs). Strategies for modifying the contributors to sexual dysfunction in WWE will be discussed as well as the role of the neurologist in initiating management of this challenging comorbidity.
Top-Down K-Best A* Parsing

We propose a top-down algorithm for extracting k-best lists from a parser. Our algorithm, TKA* is a variant of the k-best A* (KA*) algorithm of Pauls and Klein (2009). In contrast to KA*, which performs an inside and outside pass before performing k-best extraction bottom up, TKA* performs only the inside pass before extracting k-best lists top down. TKA* maintains the same optimality and efficiency guarantees of KA*, but is simpler to both specify and implement.
Controlling output gain uniformity by spatial variation of the X-ray preionization in a large-aperture discharge-pumped KrF amplifier

A technique for improving the output uniformity in fast-discharge large-aperture lasers is described. Spatial variation of the X-ray preionization flux is used to compensate for the discharge-plasma skin depth and nonuniformity in the initial electric-field distribution. The technique was demonstrated using a 4.25/spl times/4.25 cm clear-aperture KrF laser that produces 2.7 J in a 15 ns FWHM pulse. >
Bone mineral in the radius and vertebral osteoporosis in an insured population. A correlative study using 125-I photon absorption and miniature roentgenography.

Using miniature roentgenograms of the abdomen to estimate vertebral osteoporosis and the photon absorption (125I) method applied to the distal end of the radius to estimate bone mineral in a normal working population including four ethnicities, it was found that age, sex, and skin color in decreasing order had the greatest effect on bone mineral; that mineral content peaked at thirty-five in both men and women and fell abruptly after forty-five in women and after sixty-five years in men; and that 33.3 per cent of the women and 11.9 per cent of the men had slight osteoporosis. Although there was in general an inverse relationship between bone mineral and osteoporosis, it was concluded that the photon absorption method as applied in this study is not a useful technique for the early detection of osteoporosis.
Deterring Innovation: NY v. Actavis and the Duty to Subsidize Competitors’ Market Entry

This Article examines a relatively new business strategy in the pharmaceutical market — “product hopping” or “product replacement” — in which brand pharmaceutical companies shift their marketing efforts from a drug nearing the end of its patent period to a new, substitute drug with a longer patent life. In July 2015, the Second Circuit issued an opinion in the first appellate case addressing pharmaceutical product replacement, NY v. Actavis. This Article explains that product replacement is the predictable business response to the incentives created by patent law and state substitution laws, and withdrawing an obsolete product from market when there is a new and improved version is clearly within the patent rights of a patent holder. However, in NY v. Actavis, the Second Circuit ruled that such product replacement activities are exclusionary and produce anticompetitive effects. The Court’s decision creates a duty for brand drug companies to continue selling obsolete drugs after patent expiry in order to allow generic competitors to take advantage of automatic substitution laws. Although the court intended this new duty to benefit consumers, the actual effects of the ruling are likely to be the opposite. Requiring pharmaceutical companies to continue marketing obsolete drugs will reduce incentives for innovation and will likely increase health care spending in the long run.
Review of the Ongoing Story of Appetite Suppressants, Serotonin Pathway, and Pulmonary Vascular Disease.

Obesity is pandemic in the Western Hemisphere, especially in the United States (US) and is associated with morbidity and mortality. Recent data show that a large proportion of the US population is at least overweight and almost 2 in 5 Americans are obese. This ongoing trend of increasing obesity rates has led to a thriving market for anorexigens. Despite the health benefits of weight loss, several anorexigens had devastating side effects including pulmonary vascular disease which manifests as the clinical syndrome of pulmonary arterial hypertension (PAH). PAH is an incurable and fatal disease and is characterized by vascular constriction, hypertrophy, and proliferation that over time lead to right-sided cardiac failure. Over the past few decades, several weight loss medications have been associated with the development of PAH, possibly caused by an increase in systemic serotonin levels, resulting in vasoconstriction of the pulmonary arteries and initiating a cascade of pathologic vascular remodeling leading to vascular fibrosis. Once sufficient evidence for the association of these drugs with PAH or other related pathologies was found, many were removed from the market. However, there are other appetite suppressants still currently on the market (whether Food and Drug Administration–approved or “dietary supplements”) that have to some extent similar mechanisms of action to those associated with PAH but lack robust enough data to prove or disprove an association. The serotonin pathway seems to be repeatedly implicated. In conclusion, given that PAH is a progressive and debilitating disease, it is important to highlight possible risk factors that could be avoided.
Nanocomposites with functionalized carbon nanotubes

The main issues related with preparation of nanocomposites are dispersion, alignment and adhesion between carbon nanotubes and matrix. We are designing an approach where these issues are fully addressed. We combined a functionalization approach with in-situ technique of nanocomposites preparation. A good dispersion and intercalation of carbon nanotubes were observed in the prepared nanocomposites. A presence of strong interfacial region was also noted. It is also found that orientation of carbon nanotubes inside matrix can be done by mechanically stretching of nanocomposites. DSC analysis shows that inclusion of carbon nanotubes affects crystallization behavior of nylon 6 significantly and it is found that CNTs acts as nucleating agents.
Sequential auctions with budget constraints: evidence from fantasy basketball auction drafts.

Abstract We study bidding behavior in sequential auctions in a unique dataset drawn from a natural field experiment: fantasy basketball auction drafts. As auctions, they are novel in that they feature publicly “recommended” but non-binding bid prices and bidders with identical budget constraints. Recommended prices prove to be reasonable forecasts of player value and bidding on average tends to follow those recommendations. Individual bidding behavior, however, follows a distinct pattern of overbidding followed by underbidding (relative to recommended value). Participants tend to overbid early, paying more than the recommended value for the first two or three players they win, irrespective of who those players are. Underbidding for the next few picks then follows, with some overbidding occurring for the last pick. This behavior suggests a new variety of declining price phenomenon which we believe is reflective of the auction environment.
High-yield cultivation Technology of Fruit cucumber in Greenhouse in Spring

According to the working practice, this paper started from the seed selection, the cultivation of sound seedling, planting, management after planting, harvesting and otherwise analyzed of high yield cultivation techniques of greenhouse fruit cucumber in greenhouse, hoping to provide reference for high yield cultivation of fruit cucumber.
Characterizing the effect of multiple Fc glycan attributes on the effector functions and FcγRIIIa receptor binding activity of an IgG1 antibody

N-linked Fc glycosylation of IgG1 monoclonal antibody therapeutics can directly influence their mechanism of action by impacting IgG effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Therefore, identification and detailed characterization of Fc glycan critical quality attributes (CQAs) provides important information for process design and control. A two-step approach was used to identify and characterize the Fc glycan CQAs for an IgG1 Mab with effector function. First, single factor experiments were performed to identify glycan critical quality attributes that influence ADCC and CDC activities. Next, a full-factorial design of experiment (DOE) to characterize the possible interactions and relative effect of these three glycan species on ADCC, CDC, and FcγRIIIa binding was employed. Additionally, the DOE data were used to develop models to predict ADCC, CDC, and FcγRIIIa binding of a given configuration of the three glycan species for this IgG1 molecule. The results demonstrate that for ADCC, afuco mono/bi has the largest effect, followed by HM and β-gal, while FcγRIIIa binding is affected by afuco mono/bi and β-gal. CDC, in contrast, is affected by β-gal only. This type of glycan characterization and modeling can provide valuable information for development, manufacturing support and process improvements for IgG products that require effector function for efficacy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1181-1192, 2016.
The Medieval Spains: Iberia and the dār-al-Islam, 711–1009

No feature of the history of the eighth century is so remarkable as the genesis and explosive growth of the world of Islam. There was literally no precedent for it in antiquity and no reason why a reasonable, contemporary observer should have expected it. In scarcely two decades from the death of Muhammad in 632 a newly united Arab world had swept away the Persian Empire of the Sassanids and was probing the valley of the Indus in the east. The same period had seen it tear the provinces of Syria, Palestine, and Egypt, from the Byzantine Empire and for more than a century yet the ultimate survival of the Eastern Roman Empire was open to serious doubt. That the initial energies of Islam were far from spent meant that expansion to the west in Africa after the fall of Egypt in 642 was in the natural order of things. That northern coast had long been an important part of the Roman world, the Byzantine enemy was still entrenched there, and the climate and geography were congenial to the Arab. After a series of exploratory thrusts and counterthrusts, the great Byzantine capital and base at Carthage fell definitively in 698. The major problem to Arab rule in the African northwest now became the resistance of the native Berber peoples of the region. But in fairly short order there, Islam was to demonstrate its remarkable absorptive power for unsophisticated peoples.
EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations

Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (P<0.001), p53 positive by immunohistochemistry (P<0.001), CD30 negative (P<0.01), and of germinal center immunophenotype (P=0.01) compared with EBV-positive cases. No statistically significant difference in overall survival was identified based on EBV, TP53 mutation status, germinal center vs non-germinal center immunophenotype, or other immunohistochemical parameters evaluated. Patients who died of post-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (P<0.05). Our study demonstrates that diffuse large B-cell lymphoma-related immunohistochemical prognostic markers have limited relevance in the post-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.
Current irritability associated with hastened depressive recurrence and delayed depressive recovery in bipolar disorder

Current irritability is associated with greater retrospective and current bipolar disorder (BD) illness severity; less is known about prospective longitudinal implications of current irritability. We examined relationships between current irritability and depressive recurrence and recovery in BD. Outpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form during follow-up during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of any current irritability in depressed and recovered (euthymic ≥8 weeks) BD patients were assessed. Kaplan–Meier analyses (Log-Rank tests) assessed relationships between current irritability and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators. Recovered BD outpatients with vs. without current irritability had significantly higher rates of 13/19 (68.4 %) other baseline unfavorable illness characteristics/current mood symptoms and hastened depressive recurrence (Log-Rank p = 0.020), driven by lifetime history of anxiety disorder and prior year rapid cycling, and attenuated by history of psychosis. Depressed BD outpatients with vs. without current irritability had significantly higher rates of 7/19 (36.8 %) other unfavorable illness characteristics/current mood symptoms and delayed depressive recovery (Log-Rank p = 0.034), NOT mediated by any assessed parameter. Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample. Current irritability was associated with hastened depressive recurrence and delayed depressive recovery in BD. Treatment studies targeting irritability may yield strategies to mitigate increased longitudinal depressive burden.
The role of glycemia in insulin resistance in youth with type 1 and type 2 diabetes.

Background Hyperglycemia has traditionally been considered a major contributor to insulin resistance (IR) in type 1 diabetes (T1D), yet studies examining the relationship between HbA1c and IR are conflicting. Glucose measures captured by continuous glucose monitoring (CGM) (eg, peak glucose, standard deviation, hypoglycemia) in youth have not been explored as predictors of insulin sensitivity (IS). Objective Assess the relationship between IS and glycemia in youth with T1D and type 2 diabetes (T2D). Methods Sedentary 12-19 year olds with diabetes had peripheral IS measured by hyperinsulinemic-euglycemic clamp. HbA1c and 3 days of CGM data were also collected. Spearman correlation coefficients were calculated to examine the association between variables. Results Participants included 100 youth with T1D [46% male, median body mass index (BMI) 74 percentile, HbA1c 8.5%] and 42 with T2D (26% male, BMI 99 percentile, HbA1c 6.9%). Nineteen with T1D and 13 with T2D also wore CGM. In T2D youth, higher HbA1c, average sensor glucose, area under the CGM curve, and metabolic syndrome characteristics correlated with lower IS. In T1D youth, higher BMI percentile, waist circumference, triglycerides, and LDL cholesterol, but not HbA1c, correlated with lower IS. Moreover, higher CGM overnight means glucose correlated with greater IS, and CGM hypoglycemia correlated with lower IS. Conclusions Markers of metabolic syndrome and hyperglycemia predicted decreased IS in T2D youth. Paradoxically, hypoglycemia predicted decreased IS in T1D youth and hyperglycemia, particularly overnight, predicted improved IS. These preliminary results imply different mechanisms underlying IR in T1D vs T2D and suggest a role for non-insulin therapies in T1D to improve IR.
Detection and prevalence of variant sciatic nerve anatomy in relation to the piriformis muscle on MRI

To determine whether known variant anatomical relationships between the sciatic nerve and piriformis muscle can be identified on routine MRI studies of the hip and to establish their imaging prevalence. Hip MRI studies acquired over a period of 4 years at two medical centers underwent retrospective interpretation. Anatomical relationship between the sciatic nerve and the piriformis muscle was categorized according to the Beaton and Anson classification system. The presence of a split sciatic nerve at the level of the ischial tuberosity was also recorded. A total of 755 consecutive scans were reviewed. Conventional anatomy (type I), in which an undivided sciatic nerve passes below the piriformis muscle, was identified in 87% of cases. The remaining 13% of cases demonstrated a type II pattern in which one division of the sciatic nerve passes through the piriformis whereas the second passes below. Only two other instances of variant anatomy were identified (both type III). Most variant cases were associated with a split sciatic nerve at the level of the ischial tuberosity (73 out of 111, 65.8%). By contrast, only 6% of cases demonstrated a split sciatic nerve at this level in the context of otherwise conventional anatomy. Anatomical variations of the sciatic nerve course in relation to the piriformis muscle are frequently identified on routine MRI of the hips, occurring in 12–20% of scans reviewed. Almost all variants identified were type II. The ability to recognize variant sciatic nerve courses on MRI may prove useful in optimal treatment planning.
Associations of Partner Age Gap at Sexual Debut with Teenage Parenthood and Lifetime Number of Partners

CONTEXT Age at sexual debut and age gap between partners at debut are modifiable characteristics that may be related to risky sexual behaviors. Understanding any such relationships is a necessary first step toward strengthening risk interventions. METHODS Age at sexual debut and partner age gap were examined for 3,154 female and 2,713 male respondents to the 2011–2013 National Survey of Family Growth who first had intercourse before age 18. Multivariable logistic regression was used to assess associations between these measures and teenage parenthood and reporting a high lifetime number of partners (i.e., a number above the sample median). RESULTS Females’ odds of teenage parenthood were elevated if sexual debut occurred at ages 15–17 and involved a partner age gap of 3–4 years (odds ratio, 1.8) or more (2.0); they were reduced if debut occurred before age 15 and the gap was 3–4 years (0.8). Females’ likelihood of reporting a high lifetime number of partners was negatively associated with age gap (0.4–0.7, depending on age at debut and length of age gap). Males’ likelihood of reporting a large number of partners was positively associated with age gap if sexual debut was before age 15 and the gap was five or more years (1.7) or if debut was at ages 15–17 and involved a 3–4-year gap (2.0). CONCLUSION Identifying the mechanisms underlying these associations could inform program design and implementation.
Assessing total retinal blood flow in diabetic retinopathy using multiplane en face Doppler optical coherence tomography.

Aim To assess total retinal blood flow (TRBF) in diabetic retinopathy (DR) using multiplane en face Doppler optical coherence tomography (OCT). Methods A 70 kHz spectral-domain OCT system scanned a 2×2 mm area centred at the optic disc of the eyes with DR and healthy participants. The multiplane en face Doppler OCT algorithm generated a three-dimensional volumetric data set consisting of 195 en face planes. The TRBF was calculated from the maximum flow values of each branching retinal vein at an optimised en face plane. DR severity was graded according to the international clinical classification system. The generalised linear model method was used to compare flow values between DR groups and the control group. Results A total of 71 eyes from 71 participants were included. Ten eyes were excluded due to poor image quality. The within-visit repeatability of scans was 4.1% (coefficient of variation). There was no significant difference in the TRBF between the healthy (46.7±10.2 µL/min) and mild/moderate non-proliferative DR (44.9±12.6 µL/min) groups. The TRBF in severe non-proliferative DR (39.1±12.6 µL/min) and proliferative DR (28.9±8.85 µL/min) groups were significantly lower ( p =0.04 and p p Conclusion The novel multiplane en face Doppler OCT method provided reliable measurements of TRBF in DR eyes. This may be a useful tool in understanding the pathophysiology of DR.
Uptake and Utilization of Selenium from Selenoprotein P.

Selenoprotein P (SELENOP) is a serum glycoprotein that is required for proper selenium distribution in mammals, particularly in supplying selenium to the brain and testes. As the sole mechanism for providing essential selenium to developing spermatozoa, SELENOP metabolism is central to male fertility in all mammals. In addition, this process is important for proper brain function, especially under conditions of limited dietary selenium. Several specific and nonspecific mechanisms for SELENOP uptake in target tissues have been described, but the utilization of SELENOP as a source of selenium for intracellular selenoprotein production has not been systematically characterized. In this report, we examine the process of SELENOP uptake using a robust selenium uptake assay that measures selenium utilization in cells fed 75Se-SELENOP. Using a series of inhibitors and modulators we have identified specific regulators of the process and found that SELENOP must be in an oxidized state for uptake. This assay also demonstrates that SELENOP uptake is not highly sequence specific as the zebrafish protein is recognized and processed by mammalian cells.
Potential Role of Metabolic Intervention in the Management of Advanced Differentiated Thyroid Cancer.

Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98 percent. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC) die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions including the use of metformin, ketogenic diet and high dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies. The role of vitamin C has been of interest again after a pre-clinical mice study showed that high dose vitamin C is selectively lethal to KRAS and BRAF mutant colorectal cancer cells by targeting the glutathione pathway. This raises the possibility of utilizing high doses of vitamin C in the treatment of aDTC where KRAS and BRAF mutations are common. Similarly, alteration of cellular metabolism by low carbohydrate ketogenic diets can be an important therapeutic strategy to selectively kill cancer cells that mainly survive on glycolysis. Among the potential adjuvant therapies proposed in this manuscript, metformin is the only agent that has shown benefit in human model of aDTC, the others have shown benefit but in pre-clinical/animal studies only and need to be further evaluated in large clinical trials. In conclusion, in addition to concurrent chemotherapy options, these metabolic interventions may have a great potential as co-adjuvant therapy in the management of aDTC.
The Business of Healthcare and the Economics of Healthcare: Shall Ever the Twain Meet?

This note discusses the differing viewpoints of economic analysis and business leader perceptions of the causes and possible remedies for rising medical care spending that has persisted for many ye...
Deep-Coverage MPS Analysis of Heteroplasmic Variants within the mtGenome Allows for Frequent Differentiation of Maternal Relatives

Distinguishing between maternal relatives through mitochondrial (mt) DNA sequence analysis has been a longstanding desire of the forensic community. Using a deep-coverage, massively parallel sequencing (DCMPS) approach, we studied the pattern of mtDNA heteroplasmy across the mtgenomes of 39 mother-child pairs of European decent; haplogroups H, J, K, R, T, U, and X. Both shared and differentiating heteroplasmy were observed on a frequent basis in these closely related maternal relatives, with the minor variant often presented as 2–10% of the sequencing reads. A total of 17 pairs exhibited differentiating heteroplasmy (44%), with the majority of sites (76%, 16 of 21) occurring in the coding region, further illustrating the value of conducting sequence analysis on the entire mtgenome. A number of the sites of differentiating heteroplasmy resulted in non-synonymous changes in protein sequence (5 of 21), and to changes in transfer or ribosomal RNA sequences (5 of 21), highlighting the potentially deleterious nature of these heteroplasmic states. Shared heteroplasmy was observed in 12 of the 39 mother-child pairs (31%), with no duplicate sites of either differentiating or shared heteroplasmy observed; a single nucleotide position (16093) was duplicated between the data sets. Finally, rates of heteroplasmy in blood and buccal cells were compared, as it is known that rates can vary across tissue types, with similar observations in the current study. Our data support the view that differentiating heteroplasmy across the mtgenome can be used to frequently distinguish maternal relatives, and could be of interest to both the medical genetics and forensic communities.
Appearance Potentials of Ions Produced by Electron-Impact Induced Dissociative Ionization of SF6, SF4, SF5Cl, S2F10, SO2, SO2F2, SOF2, and SOF4

The identification of S2F10, a highly toxic compound,1 in SF6 that has been subjected to electrical discharges, including negative corona discharges,2,3 sparks,4 and arcs,5 has raised issues of safety and proper handling of SF6 removed from electrical equipment, and motivates the need for trace detection of S2F10 in SF6. 6 A reliable measurement protocol for trace detection of S2F10 may be applied to: 1) develop safe handling procedures for SF6 gas removed from operating machinery, 2) ensure compliance with regulatory agencies, 3) monitor the purity of SF6 supplied both by manufacture and reprocessing, and 4) replace animal toxicity tests of commercial SF6.
Development in Use of Cultured Endothelium in Corneal Transplantation

In cases of endothelial dystrophy it is at present necessary to perform a full thickness keratoplasty. There would be evident advantages in replacing only the affected layer with endothelial cells grown in tissue culture. These are as follows: 1. Cells of known origin and from younger donors could be available. 2. Fewer donor cells and of mixed genetic origin would be used, thus reducing the immunological challenge. 3. Donor material could be available at all times. 4. It may be possible to use the patient’s own stromal button for the graft, which would lessen the danger of poor apposition of graft and host.
Pap1+ confers microtubule damage resistance to mut2a, an extragenic suppressor of the rad26:4A allele in S. pombe.

The DNA structure checkpoint protein Rad26ATRIP is also required for an interphase microtubule damage response. This checkpoint delays spindle pole body separation and entry into mitosis following treatment of cells with microtubule poisons. This checkpoint requires cytoplasmic Rad26ATRIP, which is compromised by the rad26:4A allele that inhibits cytoplasmic accumulation of Rad26ATRIP following microtubule damage. The rad26::4a allele also disrupts minichromosome stability and cellular morphology, suggesting that the interphase microtubule damage checkpoint pathway operates in an effort to maintain chromosome stability and proper cell shape. To identify other proteins of the Rad26-dependent interphase microtubule damage response, we used ultra violet (UV) radiation to identify extragenic interaction suppressors of the rad26::4A growth defect on microtubule poisons. One suppressor mutation, which we named mut2a, permitted growth of rad26:4A cells on MBC media and conferred sensitivity to a microtubulin poison upon genetic outcross. In an attempt to clone this interaction suppressor using a genomic library complementation strategy, we instead isolated pap1+as an extracopy suppressor of the mut2a growth defect. We discuss the mechanism by which pap1+ overexpression may allow growth of mut2a cells in conditions that destabilize microtubules.
Risk analysis of electronic intraoperative radiation therapy for breast cancer

Abstract Purpose To evaluate the process and improve safety of intraoperative radiation therapy (IORT) for early-stage breast cancers treated with electronic brachytherapy. Methods and Materials A multidisciplinary team conducted a failure mode and effects analysis (FMEA) for IORT breast cancer treatments by first developing a process map. This map was then used to identify failure modes for all steps in the treatment workflow. Risk priority numbers (RPNs) were assigned to each failure mode and were calculated as the product of the failure mode's probability of occurrence (O), severity (S), and lack of detectability (D). Corrective steps were implemented to address failure modes with the highest risk, and a revised process was generated. Results The steps with the highest risk failure modes were related to source calibration, use of correct plan and dwell times, and the correct site and intent. The introduction of a physician calibration check and an extended time-out checklist reduced the risk of these failure modes. The highest risk steps in the Xoft breast IORT treatment process are associated with source calibration and manual entry of dwell positions for each balloon size and volume combination. High-risk failure modes that could be mitigated with improved hardware and software interlocks were identified. Conclusion High-risk failure modes are identified with FMEA and addressed with corrective steps. This application of FMEA can be used in principle for clinical processes throughout breast cancer care. This analysis demonstrates the importance of well-designed QC policies, procedures, and oversight in a Xoft electronic brachytherapy program for breast cancer IORT.
Localising the Humanitarian Toolkit: Lessons from Recent Philippines Disasters

Over the past decade, the political and legal landscape for managing disaster risk in Asia has undergone significant shifts. Almost all Asian countries have legal and institutional frameworks for managing disasters, regional bodies have assumed an increasingly prominent role, and national governments are asserting their capacity to manage their own disasters. But increased national capacities have not always kept pace with increased disaster risk, and international actors still have an important—albeit complementary—role to play. This shift in dynamics poses challenges for the international humanitarian system, which for the most part has been set up on the assumption that international actors will take the lead.
Deletion of a 19-Amino-Acid Region in Clostridioides difficile TcdB2 Results in Spontaneous Autoprocessing and Reduced Cell Binding and Provides a Nontoxic Immunogen for Vaccination

ABSTRACT Clostridioides difficile toxin B (TcdB) is an intracellular toxin responsible for many of the pathologies of C. difficile infection. The two variant forms of TcdB (TcdB1 and TcdB2) share 92% sequence identity but have reported differences in rates of cell entry, autoprocessing, and overall toxicity. This 2,366-amino-acid, multidomain bacterial toxin glucosylates and inactivates small GTPases in the cytosol of target cells, ultimately leading to cell death. Successful cell entry and intoxication by TcdB are known to involve various conformational changes in the protein, including a proteolytic autoprocessing event. Previous studies found that amino acids 1753 to 1852 influence the conformational states of the proximal carboxy-terminal domain of TcdB and could contribute to differences between TcdB1 and TcdB2. In the current study, a combination of approaches was used to identify sequences within the region from amino acids 1753 to 1852 that influence the conformational integrity and cytotoxicity of TcdB2. Four deletion mutants with reduced cytotoxicity were identified, while one mutant, TcdB2Δ1769–1787, exhibited no detectable cytotoxicity. TcdB2Δ1769–1787 underwent spontaneous autoprocessing and was unable to interact with CHO-K1 or HeLa cells, suggesting a potential change in the conformation of the mutant protein. Despite the putative alteration in structural stability, vaccination with TcdB2Δ1769–1787 induced a TcdB2-neutralizing antibody response and protected against C. difficile disease in a mouse model. These findings indicate that the 19-amino-acid region spanning residues 1769 to 1787 in TcdB2 is crucial to cytotoxicity and the structural regulation of autoprocessing and that TcdB2Δ1769–1787 is a promising candidate for vaccination.
2,2′,4,4′,5‐Pentabromodiphenyl ether induces lipid accumulation throughout differentiation in 3T3‐L1 and human preadipocytes in vitro

Flame retardants, specifically polybrominated diphenyl ethers (PBDEs), are chemical compounds widely used for industrial purposes and household materials. NHANES data indicate that nearly all Americans have trace amounts of PBDEs in serum, with even higher levels associated with occupational exposure. PBDEs are known to bioaccumulate in the environment due to their lipophilicity and stability, and more importantly, they have been detected in human adipose tissue. The present study examined whether the PBDE congener, BDE-99 (2,2',4,4',5-pentabromodiphenyl ether; 0.2-20 μM), enhances the adipogenesis of mouse and human preadipocyte cell models in vitro via induced lipid accumulation. 3T3-L1 mouse preadipocytes and human visceral preadipocytes demonstrated enhanced hormone-induced lipid accumulation upon BDE-99 treatment. In addition, BDE-99 (20 μM) induced preadipocyte differentiation and lipid development in nondifferentiated human preadipocytes. BDE-99, the second most abundant congener in human adipose tissue, increased total lipids in differentiating adipocytes and therefore showed a potential role in the regulation of adipogenesis. This warrants more research to further understand the impact of lipophilic persistent pollutants on adipose tissue homeostasis.
A Time-Space Stream of DACA Benefits and Barriers Gleaned From the American Community Survey:

This study investigates the educational and economic attainment of Mexican Dreamers over the 4 years since DACA was implemented (2012–2016). A time-space stream of benefits and barriers is evaluate...
The impact of genetic background and gender on the increase in mitotic index in response to mating of Drosophila melanogaster

The replenishment of specialized cells depends on the activity of stem cells. Recent advances in stem cell research have shown that the germline stem cells (GSCs) in Drosophila melanogaster can increase their mitotic activity in response to mating. Here, we show that this ability to respond to mating is eliminated if the males are mutant for the ABC transporter, White, the genetic background for a plethora of fly lines. Furthermore, we were not able to reproduce previous findings that female flies increase their GSC numbers and mitotic activity upon mating. Our findings underline the importance of careful experimental design and control specimen.
Boron Nitride Nanotubes for Optical Fiber Chemical Sensing Applications

Boron nitride nanotubes (BNNTs) are 1-D hollow fibrous nanomaterials. They are thermally stable up to 800 °C in open air and up to 1000 °C in a pure chlorine atmosphere, are electrically insulating, and possess superlative mechanical properties. Since the BNNT assembly is highly porous and easily penetrated by liquids and gases, BNNT thin film coated on optical fiber can be used as a novel sensing medium with enhanced sensitivity and selectivity. In this letter, uniform BNNT films have been successfully coated on optical fibers and tapered optical fibers (TOFs). A BNNT-coated TOF sensor has been developed for various liquids and gases sensing applications. We demonstrated experimentally that the BNNT-coated TOF can be used as a level sensor for liquids, even for those with refractive indices smaller than that of silica such as the organic solvents like acetone, hexane, tetrahydrofuran, ethyl ether, and dimethylformamide. As to gas sensing, HCl was selectively detected with enhanced sensitivity due to its high polarity and good affinity to the OH/NH2 functionalized BNNTs. The BNNT-coated optical fiber sensors can be potentially used at high temperatures and in some harsh environments.
On the feasibility of simultaneous identification of a material property of a Timoshenko beam and a moving vibration source

Abstract This paper presents a computational study for investigating the feasibility of simultaneous identification of a material property of a Timoshenko continuous beam and a moving vibration source on the beam by using the data of measured vibrations on it. This work employs the finite element method to solve the wave equations of a Timoshenko beam subject to a moving vibrational source. It uses the Genetic Algorithm (GA) as an inversion solver to identify the values of targeted control parameters that characterize a material property of the beam and a moving vibration source on it. The numerical results show that, first, the presented inversion method can detect the characteristics of a moving wave source as well as the spatial variation of the elastic modulus of a Timoshenko-beam continuous bridge model, which is set to be piece wisely homogeneous in this work. Second, the GA-based joint inversion is effective even when the moving vibrational source’s moving velocity is not constant over time. Third, the detrimental effect of noise in measurement data on the accuracy of the inversion becomes more significant as the number of control parameters increases. By using the presented method, engineers can take advantage of vehicle-induced ambient vibrations on bridges measured by modern sensors for the sake of passive wave source-based structural health monitoring (SHM).
The design and analysis of non-randomized studies: a case study of off-label use of hydroxychloroquine in the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted researchers to conduct non-randomized studies in an effort to find an off-label drug that can effectively combat the virus and its effects. While these studies can expedite the drug approval process, researchers must carefully design and analyze such studies in order to perform rigorous science that is reproducible and credible. This article focuses on several key design and analysis considerations that can improve the scientific rigor of non-randomized studies of off-label drugs. Areas covered: The aim of this article is to provide an overview of best approaches that should be considered for non-randomized studies on off-label drugs. We discuss these approaches in detail and use a non-randomized study by Rivera et al. in Cancer Discovery as an example of methods that have been undertaken for COVID-19. Expert opinion: While non-randomized studies are inherently biased, they may be unavoidable in situations such as the COVID-19 pandemic, where researchers need to find an effective treatment quickly. We believe that a well-formed experimental design, high-quality data collection, and a well-thought-out statistical and data analysis plan are sufficient to produce rigorous and credible results for making an optimal decision.
Correction to: Tropical varieties for exponential sums

A correction to this paper has been published: https ://doi.org/10.1007/s00208-019-01808-5 A subsidiary result (Theorem 1.1, on the undecidability of determining membership in the amoeba of $$1-x-y$$ ) from our original article had an erroneous proof. We give a correct proof. The statement of Theorem 1.1 remains correct. We thank Alexander Rashkovskii for pointing out the error in our original proof. We also correct a small typo in our main theorem on univariate exponential sums (Theorem 1.5).