bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tofacitinib for Rescue Therapy in Acute Severe Ulcerative Colitis: A Real-world Experience
Authors: Kotwani Prashant , Terdiman Jonathan , Lewin Sara 
Published: February 2020

Abstract

Background
Acute severe ulcerative colitis is a high stakes event with significant numbers still requiring emergent colectomy, representing a need to establish alternative medical management options. We report a case series of tofacitinib as rescue therapy in biologic-experienced patients with acute severe ulcerative colitis.

Methods
Four patients were identified over a 1-year period at our institution who initiated tofacitinib for acute severe ulcerative colitis. All four had previously failed at least two biologics, including infliximab, and were failing high-dose oral prednisone therapy before admission. All patients had Mayo disease activity index of at least 10 at admission. After no significant improvement despite receiving a minimum of 3 days of intravenous methylprednisolone and based on elevated Ho and Travis indices at Day 3, patients were offered rescue tofacitinib for induction of remission, or colectomy. Standard induction of tofacitinib was used [10 mg twice daily], and one patient was escalated to 15 mg twice daily after inadequate response.

Results
All patients experienced improvement in objective symptoms and laboratory markers, and were discharged without colectomy on tofacitinib as maintenance therapy and prednisone taper; 30-day and 90-day colectomy rates on tofacitinib maintenance therapy were zero and 90-day readmission rate was also zero. Two of four patients achieved steroid-free remission on maintenance tofacitinib monotherapy based on clinical symptoms and follow-up endoscopy. No major adverse reaction was reported during induction or maintenance therapy.

Conclusions
Tofacitinib may be an acceptable rescue agent in biologic-experienced patients with acute severe ulcerative colitis. Tofacitinib may also be safely continued as maintenance therapy once remission has been achieved.
Assessing the supercooling of fresh-cut onions at −5°C using electrical impedance analysis
Authors: Koide Shoji , Yoneyama Ami , Orikasa Takahiro , Uemura Matsuo 
Published: February 2020

Abstract
We supercooled fresh-cut onion at −5°C for 12 h. After supercooling, the electric impedance properties of the samples were evaluated by electrical impedance spectroscopy over the frequency range of 42 Hz − 5 MHz. The time-temperature profiles of samples indicated that the freezing point and supercooling point were −2.3°C ± 0.7°C and −6.9°C ± 1.0°C, respectively. The results indicated that 34 of the 36 supercooled samples exhibited a definite circular arc in the Cole-Cole plot, which suggested that the cell membrane remained intact during supercooling. In the other two samples which did not exhibit a definite circular arc, the cell membrane had sustained serious damage during supercooling. Furthermore, there was large difference in drip loss percentage between supercooled samples exhibited a definite circular arc in the Cole-Cole plot and samples not exhibiting a definite circular arc. Our results suggest that fresh-cut onions can be supercooled at −5°C.
Evolution of cellular HIV DNA levels in virologically suppressed patients switching to dolutegravir/lamivudine versus maintaining a triple regimen: a prospective, longitudinal, matched, controlled study
Authors: Lombardi Francesca , Belmonti Simone , Borghetti Alberto , Fabbiani Massimiliano , Marchetti Simona , Tamburrini Enrica , Cauda Roberto , di Giambenedetto Simona 
Published: February 2020

Abstract

Objectives
To assess the impact of switching to dolutegravir plus lamivudine maintenance therapy on the HIV cellular reservoir size.

Patients and methods
This was a prospective, longitudinal, matched, controlled study. We enrolled virologically suppressed patients on stable three-drug ART who switched at baseline (BL) to dolutegravir/lamivudine (DT group) or maintained triple therapy (TT group); subjects in the TT group were matched 1:1 with those in the DT group according to age, gender, years since HIV diagnosis, years on ART and anchor drug. Total blood-associated HIV DNA levels were assessed by droplet digital PCR at BL and after 48 weeks (T48). Results were expressed as log10 HIV DNA copies/106 leucocytes.

Results
We enrolled 40 patients in the DT group and 40 in the TT group; the two groups were homogeneous for all main characteristics except nadir CD4 cell count. At BL, HIV DNA levels were comparable between the DT and TT groups: 2.27 (IQR 1.97–2.47) and 2.26 (IQR 2.05–2.61) log10 HIV DNA copies/106 leucocytes, respectively. Change in HIV DNA load from BL to T48 was −0.105 (IQR −0.384 to 0.121, P = 0.041) in the DT group and −0.132 (IQR −0.362 to 0.046, P = 0.005) in the TT group, with a comparable decline observed between the two groups (P = 0.821). A higher HIV DNA decline was associated with higher BL CD4/CD8 ratio.

Conclusions
Maintenance therapy with dolutegravir/lamivudine had the same impact as the triple regimen on HIV DNA levels after 48 weeks of treatment. These data seem to support the effectiveness of a dolutegravir/lamivudine dual regimen in controlling the magnitude of the cellular reservoir (www.clinicaltrials.gov, number NCT02836782).
Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy
Authors: Greene Dina N , Schmidt Robert L , Winston McPherson Gabrielle , Rongitsch Jessica , Imborek Katherine L , Dickerson Jane A , Drees Julia C , Humble Robert M , Nisly Nicole , Dole Nancy J , Dane Susan K , Frerichs Janice , Krasowski Matthew D 
Published: February 2020

Abstract

Background
Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy.

Methods
Healthy transgender individuals who had been prescribed estrogen (n = 93) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care. Total testosterone and estradiol were measured using immunoassay and mass spectrometry; LH, FSH, sex hormone binding globulin, prolactin, progesterone, anti-mullerian hormone (AMH), and dehydroepiandrosterone sulfate (DHEAS) were measured using immunoassay; free testosterone was calculated. Reference intervals (central 95%) were calculated according to Clinical Laboratory Standards Institute guidelines.

Results
The distribution of results for transgender women was different than what would be expected from cisgender men or women across all measurements. Use of spironolactone was associated with changes in the result distribution of AMH, FSH, LH, and progesterone. Compared to liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), immunoassay was sufficient for the majority of estradiol and total testosterone measurements; free testosterone added little clinical value beyond total testosterone.

Conclusion
Reference intervals specific to transgender women should be applied when evaluating reproductive endocrine analytes. Spironolactone is a significant variable for result interpretation of some tests.
Disc galaxies formed from major mergers in Illustris
Authors: Peschken Nicolas , Łokas Ewa L , Athanassoula E 
Published: February 2020

ABSTRACT
We show how wet major mergers can create disc galaxies in a cosmological context, using the Illustris simulation. We select a sample of 38 disc galaxies having experienced a major merger in their history with no subsequent significant minor merger, and study how they transform into discs after the merger. In agreement with what was previously found in controlled simulations of such mergers, we find that their disc is built gradually from young stars formed after the merger in the disc region, while the old stars born before the merger form an ellipsoidal component. Focusing on one fiducial case from our sample, we show how the gas was initially dispersed in the halo region right after the merger, but is then accreted on to a disc to form stars, and builds the disc component. We then select a sample of major mergers creating elliptical galaxies, to show that those cases correspond mainly to dry mergers, where the lack of star formation prevents the formation of a disc in the remnant galaxy. The amount of gas in the remnant galaxy after the merger is therefore essential to determine the final outcome of a major merger.
J. SAINSBURY PLC v FROMAGERIES BEL SA
Authors:   Intellectual Property Office
Published: February 2020

Abstract
H1 Trade marks – Invalidation proceedings – Shape mark with dimension and colour limitations – Assessment of essential characteristics – Effect of limitations - Whether mark consisting exclusively of a shape – Whether shape resulting from the nature of the goods or necessary to achieve a technical result – Whether shape giving substantial value to the goods – Colours – Graphical representation - Requirement of clarity and precision - Whether limitation to “red” sufficient
SYSTEM PRODUCTS UK LTD v TRUSCOTT TERRACE HOLDINGS LLC
Authors:   Appointed Person (Designs)
Published: February 2020

Abstract
H1 Registered designs – Validity – Bottle shapes – Novelty – Res judicata – Issue estoppel – Clarity of pleading – Whether ground now relied upon could and should have been raised in earlier proceedings – Whether sister companies were “privies” – Use of “Wayback Machine” evidence – Litigants without professional representation – Appeal to Appointed Person
Identification of Hidden Population Structure in Time-Scaled Phylogenies
Authors: Volz Erik M , Carsten Wiuf , Grad Yonatan H , Frost Simon D W , Dennis Ann M , Didelot Xavier 
Published: February 2020

Abstract
Population structure influences genealogical patterns, however, data pertaining to how populations are structured are often unavailable or not directly observable. Inference of population structure is highly important in molecular epidemiology where pathogen phylogenetics is increasingly used to infer transmission patterns and detect outbreaks. Discrepancies between observed and idealized genealogies, such as those generated by the coalescent process, can be quantified, and where significant differences occur, may reveal the action of natural selection, host population structure, or other demographic and epidemiological heterogeneities. We have developed a fast non-parametric statistical test for detection of cryptic population structure in time-scaled phylogenetic trees. The test is based on contrasting estimated phylogenies with the theoretically expected phylodynamic ordering of common ancestors in two clades within a coalescent framework. These statistical tests have also motivated the development of algorithms which can be used to quickly screen a phylogenetic tree for clades which are likely to share a distinct demographic or epidemiological history. Epidemiological applications include identification of outbreaks in vulnerable host populations or rapid expansion of genotypes with a fitness advantage. To demonstrate the utility of these methods for outbreak detection, we applied the new methods to large phylogenies reconstructed from thousands of HIV-1 partial pol sequences. This revealed the presence of clades which had grown rapidly in the recent past and was significantly concentrated in young men, suggesting recent and rapid transmission in that group. Furthermore, to demonstrate the utility of these methods for the study of antimicrobial resistance, we applied the new methods to a large phylogeny reconstructed from whole genome Neisseria gonorrhoeae sequences. We find that population structure detected using these methods closely overlaps with the appearance and expansion of mutations conferring antimicrobial resistance. [Antimicrobial resistance; coalescent; HIV; population structure.]
Effects of supplement amount, with or without calcium salts of fatty acids, on growth performance and intake behavior of grazing Bos indicus bulls
Authors: Cappellozza Bruno I , Velasco André C , Tongu Cintya , Moraes Gustavo , Dib Renato , Cervieri Rafael 
Published: February 2020

Abstract:
This study evaluated the effects of 2 supplement dry matter (DM) amounts, with or without calcium salts of fatty acids (CSFA), on growth performance, supplement and water intake behavior of grazing beef bulls. On day 0, 32 Nellore bulls were ranked by initial body weight (BW; 318 ± 11.2 kg), and then, randomly assigned to treatments (n = 8 bulls/treatment), in a 2 × 2 factorial design, which consisted of energy-based supplement DM amount of 0.3 (SP03) or 1.0 (SP1) % of BW with (+) or without (−) CSFA fortification (90 to 100 g/bull daily). During the experiment (98 d), all bulls were managed as single group and rotated between 2 Brachiaria pastures every 9 to 11 d. Each pasture contained an individual electronic data capture system with 2 feed bunks/treatment and 1 water through to determine individual supplement DM and water intake, as well number of visits, time spent at the feeder/waterer, and intake per visit (IPV). A supplement effect was detected (P = 0.02) for final BW. Bulls supplemented at 1.0% of BW, regardless of CSFA inclusion amount, were heavier at the end of the experiment vs. SP03 bulls. Overall average daily gain (ADG) was greater (P = 0.05) for SP03+ vs. SP03− bulls, and did not differ (P = 0.87) between SP1+ vs. SP1− bulls. No supplement amount, CSFA, or supplement amount × CSFA effects were observed (P ≥ 0.13) for supplement and water intake behavior, number of visits to the feeder or IPV. However, SP1 bulls spent (P = 0.05) more time at the feeder than SP1+ bulls, whereas bulls supplemented with CSFA tended (P = 0.10) to consume less water (as % of BW) than cohorts supplemented without CSFA. In summary, CSFA fortification into 0.3% of BW supplements increased ADG when compared with cohorts not offered CSFA. On the other hand, no benefits were observed when CSFA was included into 1.0% of BW supplements, primarily due to the lower than projected supplement, and consequently, CSFA intake. Moreover, CSFA fortification tended to reduced water intake, demonstrating a potential of this technology to increase performance of beef herds, while maintaining the utilization of natural resources.
Nucleos(t)ide analogue continuous therapy associated with reduced adverse outcomes of chronic hepatitis B
Authors: Su Chien-Wei , Wu Chun-Ying , Lin Jaw-Town , Ho Hsiu J. , Wu Jaw-Ching 
Published: February 2020

Background:
Nucleos(t)ide analogue (NA) therapy reduces the risk of disease progression in chronic hepatitis B virus-infected patients. However, the risk of liver decompensation, hepatic failure, and mortality after discontinuation of NA therapy remains unknown.

Methods:
Among 51,574 chronic hepatitis B patients who received NAs in the Taiwan National Health Insurance Research Database, we identified 8,631 patients who continued NA therapy (treatment cohort) and 8,631 propensity-score matched patients who stopped NA therapy after their initial 1.5 years treatment (off-therapy cohort) between October 1, 2003 and December 31, 2011. All study subjects were followed up from the index date, that is, the date 1.5 years after the first prescription of NA, until development of liver decompensation and hepatic failure, death or end of 18-month follow-up period.

Results:
Treatment cohort had significantly lower risks of liver decompensation (1.05%; 95% confidence interval [CI], 0.81%–1.30% vs 2.13%; 95% CI, 1.82%–2.45%; p < 0.001), hepatic failure (0.35%; 95% CI, 0.21%–0.49% vs 0.63%; 95% CI, 0.46%–0.80%; p = 0.008) and overall mortality (1.67%; 1.37%–1.98% vs 2.44%; 95% CI, 2.10%–2.77%; p < 0.001) during the 18-month follow-up period. After adjusting for potential confounders, NA continuous therapy was associated with reduced risks of liver decompensation (hazard ratio [HR]: 0.47; 95% CI, 0.36–0.62, p < 0.001), hepatic failure (HR: 0.53; 95% CI, 0.33–0.86, p = 0.01) and overall mortality (HR: 0.67; 95% CI, 0.53–0.84, p = 0.001). The number needed to reduce one less disease progression and mortality was 47. The protective effect of NA continuous therapy was found in nearly all subgroups.

Conclusion:
NA continuous therapy is associated with reduced risks of liver decompensation, hepatic failure, and overall mortality.
Infant anaphylaxis: Diagnostic and treatment challenges
Authors: Shroba Jodi A. 
Published: February 2020

ABSTRACT
Immediate administration of intramuscular epinephrine to a patient experiencing anaphylaxis is the first-line therapy for this life-threatening allergic reaction. Alhough anaphylaxis is generally a rare occurrence, it has dire consequences if left untreated. In infants, anaphylaxis is typically triggered by exposure to egg, cow's milk, or peanuts. The rapid onset of symptoms in multiple organ systems makes an accurate diagnosis in infants difficult because there are numerous ways in which anaphylaxis may present. The symptoms of infant anaphylaxis are often underrecognized or misdiagnosed for less serious illnesses or even normal findings, including drooling, loose stools, and irritability. Because infants are mostly nonverbal—and most pediatric emergency department visits for anaphylaxis cases are the first diagnosis—ascertaining potential exposure to common allergens is difficult; this further complicates diagnosis in these youngest patients for whom the clinical presentation of anaphylaxis varies widely. A key factor in diagnosing anaphylaxis is the temporal profile of symptom development following allergen exposure; however, some children with anaphylaxis develop symptoms that reoccur hours or days after an initial anaphylactic reaction, making diagnosis challenging. Advanced practice nurses are often the first health care provider to encounter a patient who may be experiencing anaphylaxis. Although diagnostic criteria exist for anaphylaxis, specific criteria for the diagnosis of anaphylaxis in infants have not been developed. As such, it is important to understand and recognize the variable presentation of anaphylaxis in infants and to rapidly diagnose and treat with epinephrine.
Small Cell Lung Cancer Neuroendocrine Subtypes are Associated with Different Immune Microenvironment and Checkpoint Molecule Distribution
Authors: Dora David , Rivard Christopher , Yu Hui , Bunn Paul , Suda Kenichi , Ren Shengxiang , Pickard Shivaun Lueke , Laszlo Viktoria , Harko Tunde , Megyesfalvi Zsolt , Moldvay Judit , Hirsch Fred R. , Dome Balazs , Lohinai Zoltan 
Published: February 2020

ABSTRACTSmall cell lung cancer (SCLC) has recently been sub-categorized into neuroendocrine (NE)- high and NE-low subtypes showing ‘immune desert’ and ‘immune oasis’ phenotypes, respectively. We aimed to characterize the immune cell localization and the microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes. Immunohistochemistry (IHC) was performed on FFPE TMAs with antibodies against CD45, CD3, CD8 and immune checkpoints including poliovirus receptor (PVR) and Indoleamine 2,3-dioxygenase (IDO).According to our results, the stroma was significantly more infiltrated by immune cells both in primary tumors and LN metastases (vs tumor cell nests). Immune (CD45+) cell density was significantly higher in tumor nests (110.6 ± 24.95 vs 42.74 ± 10.30, cell/mm2, p= 0.0048), with increased CD8+ effector T cell infiltration (21.81 ± 5.458 vs 3.16 ± 1.36 cell/mm2, p < 0.001) in NE-low vs NE-high tumors. Furthermore, the expression of IDO was confirmed on stromal and endothelial cells, and it positively correlated (r= 0.755, p<0.01) with higher immune cell density both in primary tumors and LN metastases, regardless of the NE pattern. Expression of IDO in tumor nests was significantly higher in NE-low (vs NE-high) primary tumors. PVR expression was significantly higher in NE-low (vs NE-high) patients both in primary tumors) and LN metastases.To our knowledge, this is the first human study that demonstrates in situ that NE-low tumors are associated with increased immune cell infiltration compared to NE-high tumors. PVR and IDO are potential new targets in SCLC, with increased expression in the NE-low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies.
Giant African snail genomes provide insights into molluscan whole-genome duplication and aquatic-terrestrial transition
Authors: Liu Conghui , Ren Yuwei , Li Zaiyuan , Hu Qi , Yin Lijuan , Qiao Xi , Zhang Yan , Xing Longsheng , Xi Yu , Jiang Fan , Wang Sen , Huang Cong , Liu Bo , Wang Hengchao , Liu Hangwei , Wan Fanghao , Qian Wanqiang , Fan Wei 
Published: February 2020

AbstractWhole-genome duplication (WGD) has been observed across a wide variety of eukaryotic groups, contributing to evolutionary diversity and environmental adaptability. Mollusks are the second largest group of animals, and are among the organisms that have successfully adapted to the nonmarine realm through aquatic-terrestrial (A-T) transition, and no comprehensive research on WGD has been reported in this group. To explore WGD and the A-T transition in Mollusca, we assembled a chromosome-level reference genome for the giant African snailAchatina immaculata, a global invasive species, and compared the genomes of two giant African snails (A. immaculataandAchatina fulica) to the other available mollusk genomes. The chromosome-level macrosynteny, colinearity blocks, Ks peak and Hox gene clusters collectively suggested the occurrence of a WGD event shared byA. immaculataandA. fulica. The estimated timing of this WGD event (∼70 MYA) was close to the speciation age of the Sigmurethra-Orthurethra (within Stylommatophora) lineage and the Cretaceous-Tertiary (K-T) mass extinction, indicating that the WGD reported herein may have been a common event shared by all Sigmurethra-Orthurethra species and could have conferred ecological adaptability and genomic plasticity allowing the survival of the K-T extinction. Based on macrosynteny, we deduced an ancestral karyotype containing 8 conserved clusters for the Gastropoda-Bivalvia lineage. To reveal the mechanism of WGD in shaping adaptability to terrestrial ecosystems, we investigated gene families related to the respiration, aestivation and immune defense of giant African snails. Several mucus-related gene families expanded early in the Stylommatophora lineage, functioning in water retention, immune defense and wound healing. The hemocyanins, PCK and FBP families were doubled and retained after WGD, enhancing the capacity for gas exchange and glucose homeostasis in aestivation. After the WGD, zinc metalloproteinase genes were highly tandemly duplicated to protect tissue against ROS damage. This evidence collectively suggests that although the WGD may not have been the direct driver of the A-T transition, it provided an important legacy for the terrestrial adaptation of the giant African snail.