bluuebunny/crossref_metadata_2025 huggingface dataset:
Authorized Generics and Biosimilars as Part of Drug Life Cycle Management
Authors: Kunst Manuel , Kaufmann Ulrike
Published: November 2020

Nowadays there is no longer a clear distinction between innovative pharmaceutical companies and generic and biosimilar manufacturers. The latter seek patent protection for new formulations or medical uses of known pharmaceuticals, and originators have responded by building their own generic divisions. Through them, innovative pharmaceutical companies are able to launch their own generics or biosimilars to cushion the loss of revenues after the expiry of blockbuster patents. In particular, in recent years so-called authorized generics and biosimilars have received increased attention as part of patent expiry strategies.
Water column structure defines vertical habitat of twelve pelagic predators in the South Atlantic
Authors: Madigan Daniel J , Richardson Andrew J , Carlisle Aaron B , Weber Sam B , Brown Judith , Hussey Nigel E
Published: November 2020

Quantifying vertical distributions of pelagic predators elucidates pelagic ecosystem structure and informs fisheries management. In the tropical South Atlantic Ocean, the recently designated large-scale marine protected area around Ascension Island hosts diverse pelagic predators for which basin-specific vertical habitat information is minimal or absent. We used pop-up satellite archival tags to analyse vertical habitat use in 12 species (bigeye tuna Thunnus obesus, blue marlin Makaira nigricans, blue shark Prionace glauca, dolphinfish Coryphaena hippurus, Galapagos shark Carcharhinus galapagensis, oceanic whitetip Carcharhinus longimanus, sailfish Istiophorus albicans, silky shark Carcharhinus falciformis, swordfish Xiphias gladius, tiger shark Galeocerdo cuvier, wahoo Acanthocybium solandri, and yellowfin tuna Thunnus albacares) and quantify parameters (temperature, dissolved oxygen, diel cycles, lunar phase) known to constrain vertical movements. Predator depth distributions varied widely, and classification trees grouped predators into four clades: (i) primarily epipelagic; (ii) partial thermocline use; (iii) oscillatory diving with thermocline/sub-thermocline use; and (iv) extensive use of sub-thermocline waters. Vertical habitat differences were linked to thermal physiology and foraging ecology, and species-specific physical constraints from other ocean basins were largely conserved in the South Atlantic. Water column features defined species-specific depth distributions, which can inform fisheries practices and bycatch risk assessments and population estimates.
On Transitive Action on Quiver Varieties
Authors: Chen Xiaojun , Eshmatov Farkhod , Eshmatov Alimjon , Tikaradze Akaki
Published: November 2020

Associated with each finite subgroup $\Gamma $ of ${\textrm {SL}}_2({\mathbb {C}})$ there is a family of noncommutative algebras $O_\tau (\Gamma )$ quantizing ${\mathbb {C}}^2/\!\!/\Gamma $. Let $G_\Gamma $ be the group of $\Gamma $-equivariant automorphisms of $O_\tau $. In [16], one of the authors defined and studied a natural action of $G_\Gamma $ on certain quiver varieties associated with $\Gamma $. He established a $G_\Gamma $-equivariant bijective correspondence between quiver varieties and the space of isomorphism classes of $O_\tau $-ideals. In this paper we prove that the action of $G_\Gamma $ on the quiver variety is transitive when $\Gamma $ is a cyclic group. This generalizes an earlier result due to Berest and Wilson who showed the transitivity of the automorphism group of the 1st Weyl algebra on the Calogero–Moser spaces. Our result has two important implications. First, it confirms the Bocklandt–Le Bruyn conjecture for cyclic quiver varieties. Second, it will be used to give a complete classification of algebras Morita equivalent to $O_\tau (\Gamma ),$ thus answering the question of Hodges. At the end of the introduction we explain why the result of this paper does not extend when $\Gamma $ is not cyclic.
Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With HigherPlasmodium falciparumParasite Prevalence
Authors: Digitale Jean C , Callaway Perri C , Martin Maureen , Nelson George , Viard Mathias , Rek John , Arinaitwe Emmanuel , Dorsey Grant , Kamya Moses , Carrington Mary , Rodriguez-Barraquer Isabel , Feeney Margaret E
Published: November 2020

Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands influence the outcome of many infectious diseases. We analyzed the relationship of compound KIR-HLA genotypes with risk of Plasmodium falciparum infection in a longitudinal cohort of 890 Ugandan individuals. We found that presence of HLA-C2 and HLA-Bw4, ligands for inhibitory KIR2DL1 and KIR3DL1, respectively, increased the likelihood of P. falciparum parasitemia in an additive manner. Individuals homozygous for HLA-C2, which mediates strong inhibition via KIR2DL1, had the highest odds of parasitemia, HLA-C1/C2 heterozygotes had intermediate odds, and individuals homozygous for HLA-C1, which mediates weaker inhibition through KIR2DL2/3, had the lowest odds of parasitemia. In addition, higher surface expression of HLA-C, the ligand for inhibitory KIR2DL1/2/3, was associated with a higher likelihood of parasitemia. Together these data indicate that stronger KIR-mediated inhibition confers a higher risk of P. falciparum parasitemia and suggest that KIR-expressing effector cells play a role in mediating antiparasite immunity.
Calling in the Heavyweights: Why the World Bank Established the Carbon Pricing Leadership Coalition, and What It Might Achieve
Authors: Wettestad Jørgen , Gulbrandsen Lars H , Andresen Steinar
Published: November 2020

The initial key international climate policy and carbon market hub was the United Nations Framework Convention on Climate Change. Over time several international organizations and networks have been added to the “international carbon market web,” such as several World Bank (WB) initiatives. As to the latter, the Carbon Pricing Leadership Coalition (CPLC) was launched in 2015. A key question then becomes: considering an increasingly dense international environment, why was the Coalition formed? Our analysis shows the importance of taking into account institutional pathways in the Bank itself and the character of previous WB-internal initiatives. However, it is particularly important to note interaction with a strong external pull, stemming both from more “systemic” developments such as the collapse of the Clean Development Mechanism system and the explicit request for new initiatives from key actors, such as UN General Secretary Ban-Ki Moon. We suggest seeing entrepreneurship from the bureaucracies of international organizations as conditional on member-state behavior or a conducive institutional environment (or both). We also discuss main prospects ahead, both for the Coalition and the more general organizational set-up in this issue-area. Here we draw attention to the role of the WB as an international “heavyweight” and CPLC and Bank meetings held back to back.
Efficacy of dual carbapenem treatment in a murine sepsis model of infection due to carbapenemase-producing Acinetobacter baumannii
Authors: Cebrero-Cangueiro T , Nordmann P , Carretero-Ledesma M , Pachón J , Pachón-Ibáñez M E
Published: November 2020

Objectives

To evaluate the in vivo efficacy of a dual carbapenem combination containing imipenem plus meropenem against carbapenem-resistant Acinetobacter baumannii producing carbapenemases OXA-23 or OXA-58.

Methods

An experimental model of peritonitis using C57BL/6J female mice was developed and the minimum lethal doses were calculated for infections due to OXA-23 or OXA-58 producers of A. baumannii clinical isolates. The efficacies of the carbapenems in monotherapy and in combination were tested.

Results

Meropenem was better than imipenem in mice infected with either of the carbapenem-resistant A. baumannii (CRAb) strains. The combination of meropenem plus imipenem significantly improved the clearance of CRAbs from spleen compared with non-treated groups. The carbapenem-containing combination was better than imipenem for treating mice infected with both carbapenemase producers. In blood, the carbapenem combination significantly decreased the bacterial load of the OXA-23 producers compared with imipenem or meropenem used in monotherapy.

Conclusions

These results suggest that dual carbapenem combination could be an option for the treatment of infections due to carbapenemase-producing A. baumannii such as OXA-23 and OXA-58 producers.
Hypermobility, age 40 years or older and BMI >30 kg m−2 increase the risk of complications following peri-acetabular osteotomy
Authors: Salih Saif , Groen Floris , Hossein Fahad , Witt Johan
Published: November 2020

The peri-acetabular osteotomy (PAO) is a powerful surgical procedure for correcting symptomatic acetabular dysplasia, but it carries the potential for significant surgical complications. This study aims to determine the complication profile of PAO in a series performed by an experienced single surgeon. This was as retrospective review of 223 hips in 200 patients (23 bilateral, 22 males and 201 females). Complication data were collected from notes and radiographic review and graded according to a modified Dindo–Clavien classification. Each hip could be recorded as having more than one complication. Mean age at surgery was 28.8 years (range 13-48), mean weight was 70.9 kg (range 45–115 kg). Diagnosis was dysplasia in 185 hips, retroversion in 25 and a combination in 13. Mean follow-up was 26 months. In all, 61.4% of hips (137) had no complications; 74.0% had no complications or a Grade I complication (one that did not change management); 52 hips (23%) required pharmaceutical interventions (Grade II complications). Six hips (2.7%) suffered a major complication (Grade III or IV) as a direct consequence of the PAO. There were no Grade V complications (death). Hypermobility (Beighton’s score of ≥6, Odds ratio (OR) 2.525 P = 0.041), age 40 years or older (OR 3.126 P = 0.012) and BMI >30 (OR 2.506 P = 0.031), but not Tonnis grade (P = 0.193) increased the risk of more severe complications following a PAO. This single surgeon series from a high volume centre demonstrates that age 40 years or older and BMI >30 kg m−2 and hypermobility increase the risk of more severe of complications.
Empirically Derived Profiles of Health-Related Quality of Life in Youth and Young Adults with Sickle Cell Disease
Authors: Keenan Mary E , Loew Megan , Berlin Kristoffer S , Hodges Jason , Alberts Nicole M , Hankins Jane S , Porter Jerlym S
Published: November 2020

Objective

Determining how the health-related quality of life (HRQOL) is impacted by living with Sickle Cell Disease (SCD) can inform psychosocial interventions. The purpose of the present study is to determine if demographic and treatment variables predict membership into empirically derived subgroups of HRQOL among youth and young adults with SCD.

Methods

Three hundred and seven youth and young adults with SCD (mean 17.63 years ± 3.74 years, 50.5% female) completed the Pediatric Quality of Life InventoryTM Sickle Cell Disease Module. Latent profile analysis examined subgroups/classes of HRQOL and relationships with demographic and treatment variables.

Results

Three distinct classes emerged: High HRQOL (34% of the sample), Moderate HRQOL (44% of the sample), and Low HRQOL (22% of the sample). Being female was associated with increased odds of being in the moderate or low groups. Living with more severe SCD (genotypes HbSS and HbSβ0 thalassemia) was associated with increased odds of being in the Low HRQOL group. Treatment with chronic red blood cell transfusion therapy was associated with increased odds of being in the High HRQOL group. Older age predicted a small increase in the odds of being in the Low versus High HRQOL group.

Conclusions

The present study adds to the literature on HRQOL in SCD by exploring person-centered, empirically derived groups of HRQOL. Identification of demographic and treatment factors that predict membership into those groups within a large sample assists in tailoring needed psychosocial interventions for youth with SCD.
MOBSTER – V. Discovery of a magnetic companion star to the magnetic β Cep pulsator HD 156424
Authors: Shultz M E , Rivinius Th , Wade G A , Kochukhov O , Alecian E , David-Uraz A , Sikora J
Published: November 2020

HD 156424 (B2 V) is a little-studied magnetic hot star in the Sco OB4 association, previously noted to display both high-frequency radial velocity (RV) variability and magnetospheric H α emission. We have analysed the Transiting Exoplanet Survery Satellite (TESS) light curve, and find that it is a β Cep pulsator with 11 detectable frequencies, 4 of which are independent p-modes. The strongest frequency is also detectable in RVs from ground-based high-resolution spectroscopy. RVs also show a long-term variation, suggestive of orbital motion with a period of ∼years; significant differences in the frequencies determined from TESS and RV data sets are consistent with a light-time effect from orbital motion. Close examination of the star’s spectrum reveals the presence of a spectroscopic companion, however, as its RV is not variable it cannot be responsible for the orbital motion and we therefore infer that the system is a hierarchical triple with a so-far undetected third star. Reanalysis of least-squares deconvolution profiles from ESPaDOnS and HARPSpol spectropolarimetry reveals the surprising presence of a strong magnetic field in the companion star, with 〈Bz〉 about +1.5 kG as compared to 〈Bz〉 ∼−0.8 kG for the primary. HD 156424 is thus the second hot binary with two magnetic stars. We are unable to identify a rotational period for HD 156424A. The magnetospheric H α emission appears to originate around HD 156424B. Using H α, as well as other variable spectral lines, we determine a period of about 0.52 d, making HD 156424B one of the most rapidly rotating magnetic hot stars.
Temperature inversions on hot super-Earths: the case of CN in nitrogen-rich atmospheres
Authors: Zilinskas Mantas , Miguel Yamila , Lyu Yipeng , Bax Morris
Published: November 2020

We show that in extremely irradiated atmospheres of hot super-Earths shortwave absorption of CN can cause strong temperature inversions. We base this study on previous observations of 55 Cancri e, which lead us to believe that ultrashort-period super-Earths can sustain volatile atmospheres, rich in nitrogen and/or carbon. We compute our model atmospheres in a radiative-convective equilibrium for a variety of nitrogen-rich cases and orbital parameters. We demonstrate the effects caused by thermal inversions on the chemistry and compute low-resolution synthetic emission spectra for a range of 0.5–28 $\rm{\mu m}$. Our results indicate that due to shortwave absorption of CN, atmospheres with temperatures above 2000 K and C/O ≥ 1.0 are prone to thermal inversions. CN is one of the few molecules that is extremely stable at large temperatures occurring on the dayside of short-period super-Earths. The emission spectrum of such atmospheres will differ substantially from non-inverted cases. In the case of inversions, absorption features become inverted, showing higher than expected flux. We propose that inversions in hot atmospheres should be the expected norm. Hot super-Earths are some of the most extreme natural laboratories for testing predictions of atmospheric chemistry and structure. They are frequently occurring, bright in emission and have short orbital periods. All these factors make them perfect candidates to be observed with JWST and ARIEL missions.
The kinematics and dark matter fractions of TNG50 galaxies at z = 2 from an observational perspective
Authors: Übler Hannah , Genel Shy , Sternberg Amiel , Genzel Reinhard , Price Sedona H , Förster Schreiber Natascha M , Shimizu Taro T , Pillepich Annalisa , Nelson Dylan , Burkert Andreas , Davies Ric , Hernquist Lars , Lang Philipp , Lutz Dieter , Pakmor Rüdiger , Tacconi Linda J
Published: November 2020

We contrast the gas kinematics and dark matter contents of z = 2 star-forming galaxies (SFGs) from state-of-the-art cosmological simulations within the ΛCDM framework to observations. To this end, we create realistic mock observations of massive SFGs ($M_*\gt 4\times 10^{10} \, \mathrm{M}_{\odot}$, SFR >50 M⊙ yr−1) from the TNG50 simulation of the IllustrisTNG suite, resembling near-infrared, adaptive-optics assisted integral-field observations from the ground. Using observational line fitting and modelling techniques, we analyse in detail the kinematics of seven TNG50 galaxies from five different projections per galaxy, and compare them to observations of twelve massive SFGs by Genzel et al. (2020). The simulated galaxies show clear signs of disc rotation but mostly exhibit more asymmetric rotation curves, partly due to large intrinsic radial and vertical velocity components. At identical inclination angle, their 1D velocity profiles can vary along different lines of sight by up to Δv = 200 km s−1. From dynamical modelling we infer rotation speeds and velocity dispersions that are broadly consistent with observational results. We find low central dark matter fractions compatible with observations ($f_{\rm DM}^v(\lt R_e)=v_{\rm DM}^2(R_e)/v_{\rm circ}^2(R_e)\sim 0.32\pm 0.10$), however for disc effective radii Re that are mostly too small: at fixed Re the TNG50 dark matter fractions are too high by a factor of ∼2. We speculate that the differences in gas kinematics and dark matter content compared to the observations may be due to physical processes that are not resolved in sufficient detail with the numerical resolution available in current cosmological simulations.
Cell-like-carbon-micro-spheres for robust potassium anode
Authors: Ding Hongbo , Zhou Jiang , Rao Apparao M , Lu Bingan
Published: November 2020

Large-scale low-cost synthesis methods for potassium ion battery (PIB) anodes with long cycle life and high capacity have remained challenging. Here, inspired by the structure of a biological cell, biomimetic carbon cells (BCCs) were synthesized and used as PIB anodes. The protruding carbon nanotubes across the BCC wall mimicked the ion-transporting channels present in the cell membrane, and enhanced the rate performance of PIBs. In addition, the robust carbon shell of the BCC could protect its overall structure, and the open space inside the BCC could accommodate the volume changes caused by K+ insertion, which greatly improved the stability of PIBs. For the first time, a stable solid electrolyte interphase layer is formed on the surface of amorphous carbon. Collectively, the unique structural characteristics of the BCCs resulted in PIBs that showed a high reversible capacity (302 mAh g−1 at 100 mA g−1 and 248 mAh g−1 at 500 mA g−1), excellent cycle stability (reversible capacity of 226 mAh g−1 after 2100 cycles and a continuous running time of more than 15 months at a current density of 100 mA g−1), and an excellent rate performance (160 mAh g−1 at 1 A g−1). This study represents a new strategy for boosting battery performance, and could pave the way for the next generation of battery-powered applications.
Shocks and labour cost adjustment: evidence from a survey of European firms*
Authors: Mathä Thomas Y. , Millard Stephen , Rõõm Tairi , Wintr Ladislav , Wyszyński Robert
Published: November 2020

We use firm-level survey data from 25 EU countries to analyse how firms adjusted their labour costs (employment, wages, and hours) in response to shocks in the years 2008–13. We find that the pattern of adjustment is not much affected by the type of the shock, but differs according to the direction of the shock (positive or negative), its size, and persistence. In 2010–13, firms responding to negative shocks were most likely to reduce employment, then hourly wages, and then hours worked. Results for the 2008–9 period indicate that the ranking might change during deep recessions as the likelihood of wage cuts increases. In response to positive shocks in 2010–13, firms were more likely to increase wages, followed by increases in employment, and then hours worked. Finally, we found that employment and hours cuts are less likely following negative shocks in countries with decentralized wage bargaining.
Rhabdomyolysis After the Use of Percussion Massage Gun: A Case Report
Authors: Chen Jian , Zhang Fan , Chen Haizhu , Pan Hui
Published: November 2020

Objective

Percussion massage guns are commonly used by professional athletes and nonathletes worldwide for warm-up and physical recovery; however, there are no published clinical or evidence-based reports on percussion guns regarding their benefits, indications, contraindications, and even side effects. The purpose of this case report is to describe the first case of rhabdomyolysis as a severe and potentially life-threatening illness following use of a percussion gun.

Methods

A young Chinese woman with untreated iron deficiency anemia presented with fatigue and pain in her thigh muscles for 3 days and tea-colored urine for 1 day, after cycling and subsequently receiving percussion gun treatment by her coach for the purpose of massage and relaxing tired muscles. Muscle tenderness and multiple hematomas were found on her thighs, and her urinalysis indicated hemoglobinuria. Her serum creatine kinase was reported as “undetectably high,” a hallmark of serious muscle damage leading to a diagnosis of severe rhabdomyolysis. Aggressive intravenous fluid resuscitation, urine alkalinization via intravenous alkaline solution, assessment of urine output, and maintenance of electrolyte balance were administered during hospitalization.

Results

The patient’s clinical presentation gradually improved with the decline of creatine kinase, and she recovered well during follow-up.

Conclusion

A case of severe rhabdomyolysis after percussion massage should alert caregivers, sports professionals, and the public to suspect and recognize the potentially serious adverse effects of percussion guns and to ensure that percussion massage guns be used appropriately and safely in rehabilitation therapy, especially in individuals with an underlying disease or condition. Research is needed to examine the benefits, indications, contraindications, and adverse reactions of percussion guns.
Application of an iris speculum for removing Soemmerring's ring during secondary intraocular lens implantation in congenital cataract patients with small pupils
Authors: Huang Liuhui , Jin Haiying , Zhao Peiquan
Published: November 2020

An application of the XpandNT iris speculum in eyes with small pupils during secondary intraocular lens (IOL) implantation in congenital cataract patients is described. The iris speculum was first positioned in the eye to expand the pupil. A 30-gauge needle was used to separate the adhesion of the iris tissue and the capsular rim. Vitrectomy was used to clean Soemmerring’s ring near the capsular rim. The iris expander was retracted with the Williamson XpandNT Manipulator. The IOL was then implanted. Fourteen aphakic eyes from 10 consecutive patients were studied retrospectively; pupil expansion was achieved in all 14 eyes intraoperatively without serious intraoperative or postoperative complications. The iris speculum was a safe and excellent tool for removing Soemmerring’s ring and solving small pupil problems during secondary IOL implantation in pediatric cataract surgery patients.
Modified big-bubble for deep anterior lamellar keratoplasty
Authors: Fogla Rajesh , Indumathy T.R. , Fontana Luigi
Published: November 2020

A new technique of air injection is described for big-bubble deep anterior lamellar keratoplasty (DALK) in eyes with keratoconus, along with a comparative analysis of the original technique. Fifty eyes were analyzed in each group. The mean steep keratometry and anterior chamber depth distribution were comparable between the 2 groups. The mean size of type 1 bubble achieved with single air injection (Group 1) was 7.8 ± 0.4 mm (range 6.5 to 8.5 mm), and with sequential air injection (Group 2) was 8.5 ± 0.3 (range 8 to 9 mm) (P < .001). Intraoperative complications of spontaneous bursting of bubble in 1 eye (2%) and peripheral microperforation in 3 eyes (6%) occurred only in Group 1. The modified technique of big-bubble DALK using sequential air injection aided by paracentesis to lower intraocular pressure allowed enlargement of a type 1 bubble in a safe and controlled manner with minimal risk for complications.
Single-piece S-plasty for small-incision IOL removal
Authors: Coassin Marco , Mori Tommaso , McLeod Stephen D.
Published: November 2020

A foldable acrylic intraocular lens (IOL) with a 6.0 mm optic was removed through a 2.2 mm corneal incision as a single piece with minimal wound trauma. By viscodissection, the IOL was freed from its position in the capsular bag and moved into the anterior chamber. Vannas scissors were introduced through a 2.2 mm corneal incision. A 4.5 mm straight slit was cut at each optic–haptic junction on opposite sides, perpendicular to each haptic shaft. This pair of parallel cuts generated 3 IOL segments in an S configuration that remained connected. The IOL was grasped by 1 haptic and removed as a single piece.
Piggyback miLOOP-assisted phacoemulsification combined with intraocular lens scaffold in hypermature cataracts
Authors: Vivekanandan Vellam Ramakrishnan , Nachiappan Sivagami , Odayappan Annamalai , Venkatesh Rengaraj , Chang David F.
Published: November 2020

Hypermature cataracts with liquified cortex pose a higher risk for capsular complications due to a distended capsular bag, floppy posterior capsule, and absence of any cushioning epinucleus. Disassembly of a brunescent nucleus is more difficult because of the thickened, leathery posterior plate. Relying on mechanical forces, miLOOP nucleotomy reduces ultrasound time and is assured of bisecting the posterior nuclear plate. However, using this instrument with brunescent nuclei might impart significant stress on the zonular fibers and posterior capsule, particularly if there is no epinuclear shell. Evacuating the liquefied cortex and prolapsing one nuclear pole through capsulorhexis with ophthalmic viscosurgical devices create enough space to implant an intraocular lens (IOL) into the capsular bag beneath the undivided nucleus. This IOL scaffold shields the floppy posterior capsule and stabilizes the nucleus and zonular fibers during miLOOP nucleotomy. Combining and piggybacking these 2 techniques successfully avoided capsular and corneal complications in a series of 32 cases.
Important decrease in invariant natural killer T, CD4+ regulatory T cells, CD8+ regulatory T cells, gamma–delta T cells, and CD4+ T lymphocytes in HIV-negative patients with hemophilia
Authors: Vela-Ojeda Jorge , Garcia-Chavez Jaime , Majluf-Cruz Abraham , Reyes-Maldonado Elba , Garcia-Ruiz Esparza Miriam A. , Montiel-Cervantes Laura A.
Published: November 2020

Hereditary hemophilias are X-linked inherited bleeding disorders defined as deficiencies of the coagulation factors VIII or IX. They are characterized by easy to provoke or spontaneous bleeding. HIV infection in hemophilic patients is a risk factor for the reduction of CD4+ T cells. There is no information regarding the cellular immune function in HIV-negative patients with hemophilia. To evaluate the number of lymphocyte subsets in adult patients with hemophilia A or B as compared with healthy donors. 39 Adult hemophilics and 27 healthy donors were included. Lymphocyte subsets [CD4 and CD8 T cells, natural killer cells, natural killer T (NKT) cells, invariant NKT (iNKT) cells, gamma–delta T (γδT) cells, type 1 and 2 dendritic cells, CD14 monocytes, CD4 and CD8 regulatory T cells (Tregs), and B cells], were analyzed by flow cytometry. A significant decrease of CD4+ T lymphocytes, γδT cells, iNKT cells, CD4+ and CD8+ Tregs was observed in patients with hemophilia. Those patients having factor VIII inhibitor had the lowest CD4+ Treg and CD8+ Treg counts. CD14 monocytes were increased, as well as iNKT and type 2 dendritic cells in obese–overweight hemophilics. CD4+ lymphocytes, iNKT, γδT cells, and Tregs (CD4+ and CD8+), are significantly decreased in patients with hemophilia. Depletion of Tregs is more important in patients with factor VIII inhibitor. Physicians caring for hemophilia patients should realize that, even when they are not suffering infections frequently, may have early evidence of cellular immunodeficiency.
The efficacy of baroreflex activation therapy for heart failure
Authors: Cai Guoqiang , Guo Kai , Zhang Dongyin , Qin Shu
Published: November 2020

Introduction:

The efficacy of baroreflex activation therapy for heart failure is elusive. This meta-analysis aims to evaluate the impact of baroreflex activation therapy on treatment efficacy of heart failure.

Methods:

Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been searched, and we include randomized controlled trials (RCTs) regarding the efficacy of baroreflex activation therapy for patients with heart failure.

Results:

This meta-analysis includes 4 RCTs. Baroreflex activation therapy shows significantly positive impact on the quality of life score (standard mean difference SMD = −4.61; 95% confidence interval CI = −6.24 to −2.98; P < .00001), 6-minute hall walk (6MHW) distance (SMD = 2.83; 95% CI = 1.44– 4.22; P < .0001), New York Heart Association (NYHA) Class (SMD = −3.23; 95% CI = −4.76 to −1.69; P < .0001), N-terminal pro-brain natriuretic peptide (NT-proBNP) (SMD = −1.24; 95% CI = −1.58 to −0.89; P < .00001) and the duration of hospitalization (SMD = −1.65; 95% CI = −2.90 to −0.39; P = .01) compared with control group for heart failure, but has no obvious effect on left ventricular ejection fraction (LVEF) (SMD = 1.43; 95% CI = −0.15–3.01; P = .08), or the number of hospitalization per year (SMD = −1.17; 95% CI = −2.56–0.22; P = .10).

Conclusions:

Baroreflex activation therapy can improve the treatment efficacy for heart failure.
Bioinformatics-based identification of miRNA-, lncRNA-, and mRNA-associated ceRNA networks and potential biomarkers for preeclampsia
Authors: Jiang Ruoan , Wang Ting , Zhou Feifei , Yao Yingsha , He Jing , Xu Dong
Published: November 2020

This study aimed to identify significantly altered long non-coding RNAs (lncRNAs), microRNAs (miRNAs), mRNAs, pathways in preeclampsia (PE), and to investigate their targeted relationships and biological functions.

GSE96985 from Gene Expression Omnibus database was extracted, involving 3 PE and 4 normal tissues. After the differential expression analysis of miRNAs, lncRNAs, and mRNAs using the limma package, protein-protein interaction (PPI) network and module analyses were performed for differentially expressed mRNAs (dif-mRNAs). Combined with the miRanda and miRWalk tools, a regulatory relationship between dif-miRNAs and dif-mRNAs/lncRNAs (dif-mRNAs/dif-lncRNAs) was predicted. Finally, mRNA-miRNA-lncRNA regulatory network construction was performed using Cytoscape software.

A total of 511 dif-mRNAs were screened in PE. The top 5 nodes in the PPI networks included up-regulated complement component 3 (C3), C-X-C motif chemokine ligand 8 (CXCL8), and fibronectin 1 (FN1). Three significant network modules were identified for dif-mRNAs. C3 and CXCL8 were identified in module A, and FN1 was identified in module C. A disintegrin and metalloproteinase with thrombospondin motifs 6 (ADAMTS6) was down-regulated by the miR-210-3p. Therefore, lnc-CTD-2383M3.1 functions as a competing endogenous RNA in ADAMTS6 expression regulation by competitively binding to miR-210-3p during the regulation process of PE.

C3, CXCL8, FN1, and ADAMTS6 might be involved in the development of PE. The lnc-CTD-2383M3.1-miR-210-3p-ADAMTS6 axis might be a potential regulatory mechanism in PE.
Sleep disturbance and delirium in patients with acromegaly in the early postoperative period after transsphenoidal pituitary surgery
Authors: Kim Seung Hyun , Kim Namo , Min Kyeong Tae , Kim Eui Hyun , Oh Hanseul , Choi Seung Ho
Published: November 2020

Sleep disturbance is a common comorbidity among patients with acromegaly [patients with growth hormone (GH)-secreting tumor] due to somatotropic axis change and sleep apnea. However, no previous studies exist concerning sleep disturbance and delirium in the early postoperative period in patients with acromegaly undergoing transsphenoidal tumor surgery. Herein, we aimed to compare the incidence of postoperative sleep disturbance and delirium in the early postoperative period between patients with GH-secreting and nonfunctioning pituitary tumors.

We retrospectively reviewed the medical records of 1286 patients (969 with nonfunctioning and 317 with GH-secreting tumors) without history of psychological disease and sedative or antipsychotic use. We examined the use of antipsychotics/sedatives and findings of psychology consultation within the first postoperative week. Only patients with sleep disturbance noted in medical records were considered to have postoperative sleep disturbance. Patients with an Intensive Care Delirium Screening Checklist score of 4 or more were considered to have postoperative delirium.

The incidence of postoperative sleep disturbance was higher in the GH-secreting group than in the nonfunctioning tumor group (2/969 [0.2%] vs 6/317 [1.9%]; P = .004; odds ratio = 9.328 [95% confidence interval, 1.873–46.452]). Univariable regression analysis showed that only diagnosis (GH-secreting tumor or nonfunctioning tumor) was a risk factor for sleep disturbance, and not sex, age, body mass index, American Society of Anesthesiologists physical status score, surgery duration, anesthesia duration, anesthesia type, tumor size, cavernous sinus invasion, or bleeding. The incidence of postoperative delirium was comparable between the 2 groups (6/969 [0.6%] vs 0/317 [0%]; P = .346).

Patients with acromegaly showed increased incidence of sleep disturbance than those with nonfunctioning tumors in the early postoperative period after transsphenoidal tumor surgery. A prospective study evaluating sleep quality in patients with GH-secreting tumors in the early postoperative period could be conducted based on our findings.
Moving FORWARD With Patient Experience and Employee Engagement
Authors: Dellosso Michael
Published: November 2020

The author shares his philosophy for patient experience and employee engagement, using the acronym FORWARD: Find a better way; Offer a helping hand; Respect for all; Working as one; Assume positive intent; Raise the bar; and Do the right thing. Suggestions for actions to take for each of the seven values in FORWARD are provided.
Addressing Home Healthcare Staffing Challenges Through Geo-Intelligent Scheduling
Authors: Schwartz Larry S.
Published: November 2020

Industries that face challenges in staffing and scheduling have successfully addressed these issues through the implementation of intraday staffing automation. Home healthcare, however, introduces an additional dimension: location—specifically, efficiently scheduling the appropriate healthcare worker based on their projected location at a given time with the location of a patient who needs care. Geo-Intelligent Scheduling has the potential to effectively address the unique staffing/scheduling challenges in home healthcare: the ability to get the right clinician to the right patient at the right location at the right time by taking into account the real-time location of the patient and clinician throughout the day. Geo-Intelligent Scheduling also has the potential to automatically create route-optimized intraday schedules for clinicians and increase effective staffing capacity by over 16% with no additional labor cost. Finally, Geo-Intelligent Scheduling can potentially improve appointment-time adherence, automate Electronic Visit Verification compliance, enhance patient/clinician communication, and improve employee retention through self-scheduling empowerment.
Program Evaluation of a Home Visiting Program
Authors: Gudger Kaitlin , Cartagena Diana , Lowe Kelsi
Published: November 2020

The purpose of this program evaluation was to determine if home visitors at the Child Development Resources (CDR) home visiting program perceived themselves to have adequate knowledge and resources to support the goals of the program. In addition, we aimed to determine what home visitors found to be facilitators and barriers to a successful program. The project was conducted with a convenience sample of 18 home visitors and included the following instruments: (a) demographics survey, (b) CDR Home Visiting Program Survey, and (c) Breastfeeding Knowledge Questionnaire. Results suggest (a) most of the home visitors believed they had adequate resources and knowledge necessary to support families and children, (b) some perceived barriers to carrying out goals of the home visiting program were financial limitations, lack of internet and mobile devices in many homes, and perception that programs were not designed for families with significant stressors such as poverty and mental health difficulties, (c) most of the home visitors believed their families benefit from their visiting programs, but many did not overwhelmingly feel new technology would greatly help families during home visits, and (d) most home visitors appeared to have adequate breastfeeding knowledge, however, some suggested that additional breastfeeding education would be beneficial. The information gathered from this project can be used to inform and improve home visiting programs seeking to enhance the quality of their programs which will ultimately contribute to better health outcomes for at-risk mothers and children.
Breaking the COVID-19 Barriers to Health Professional Team Training With Online Simulation
Authors: Malhotra Atul , Kumar Arunaz
Published: November 2020

Summary Statement

The COVID-19 pandemic led to disruption of most interprofessional simulation workshops in our center, including the obstetric and neonatal emergency simulation or ONE-Sim workshops for medical, nursing, midwifery students, and health professional staff in Australia and overseas.

We devised online versions of the workshop for students and staff. In this report, we describe the details of these innovative online workshops. This has enabled us to continue this vital simulation-based education during the pandemic, when strict lockdowns, physical distance requirements, and travel restrictions precluded the usual conduct of these workshops.

The online workshops were well received by students and staff in Australia and overseas. Some important lessons that were learned from the preliminary experience of these workshops are detailed in this report.
Defensive structures influence fighting outcomes
Authors: Emberts Zachary , Wiens John J.
Published: November 2020

In many animal species, individuals engage in fights with conspecifics over access to limited resources (e.g. mates, food, or shelter). Most theory about these intraspecific fights assumes that damage has an important role in determining the contest winner. Thus, defensive structures that reduce the amount of damage an individual accrues during intraspecific competition should provide a fighting advantage.

Examples of such damage-reducing structures include the dermal shields of goats, the dorsal osteoderms of crocodiles, and the armored telsons of mantis shrimps. Although numerous studies have identified these defensive structures, no study has investigated whether they influence the outcomes of intraspecific fights.

Here, we investigated whether inhibiting damage by enhancing an individual’s armor influenced fighting behavior and success in the giant mesquite bug,Thasus neocalifornicus(Insecta: Hemiptera: Coreidae).

We found that experimentally manipulated individuals (i.e. those provided with additional armor) were 1.6 times more likely to win a fight when compared to the control. These results demonstrate that damage, and damage-reducing structures, can influence fighting success.

The implications of these results are twofold. First, our results experimentally support a fundamental assumption of most theoretical fighting models: that damage is a fighting cost that can influence contest outcomes. Second, these results highlight the importance of an individual’s defensive capacity, and why defense should not be ignored.
Per capita COVID-19 Case Rates are Lower in U.S. Counties Voting more Heavily Democratic in the 2016 Presidential Election, except not in States with a Republican Governor and Legislature
Authors: Chambless Lloyd
Published: November 2020

In our recent paper Why do per capita COVID-19 Case Rates Differ Between U.S. States? we established that U.S. states with a Democratic governor and a Democratic legislature have lower COVID-19 per capita case rates than states with a Republican governor and a Republican legislature, and case rates of states with a mixed government fall between the two. This difference remained after accounting for differences between states in several demographic and socio-economic variables. In a recent working paper The Changing Political Geographies of COVID-19 in the U.S. it was found that that early in the pandemic U.S. counties at higher levels of percentage Democratic vote in the 2016 presidential election had higher weekly per capita COVID-19 rates, but that the situation was in the opposite direction by August 2020. We show here that counties with a higher percentage of Democratic vote in the 2016 presidential election have a lower mean cumulative per capita rate of COVID-19 cases and of COVID-19 deaths, adjusted for county demographic and socio-economic characteristics, but only for counties in states that currently have a Democratic governor and both chambers of the legislature Democratic or in states that have a mixed government, but not for states that currently have a Republican governor and both chambers in the legislature Republican. One possible contributor to this difference is that some state Republican governments have restricted local action to fight the spread of COVID-19.
Improved chromosome level genome assembly of the Glanville fritillary butterfly (Melitaea cinxia) based on SMRT Sequencing and linkage map
Authors: Blande Daniel , Smolander Olli-Pekka , Ahola Virpi , Rastas Pasi , Tanskanen Jaakko , Kammonen Juhana I. , Oostra Vicencio , Pellegrini Lorenzo , Ikonen Suvi , Dallas Tad , DiLeo Michelle F. , Duplouy Anne , Cem Duru Ilhan , Halimaa Pauliina , Kahilainen Aapo , Kuwar Suyog S. , Kärenlampi Sirpa O. , Lafuente Elvira , Luo Shiqi , Makkonen Jenny , Nair Abhilash , de la Paz Celorio-Mancera Maria , Pennanen Ville , Ruokolainen Annukka , Sundell Tarja , Tervahauta Arja I. , Twort Victoria , van Bergen Erik , Österman-Udd Janina , Paulin Lars , Frilander Mikko J. , Auvinen Petri , Saastamoinen Marjo
Published: November 2020

The Glanville fritillary (Melitaea cinxia) butterfly is a long-term model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome level assembly of the butterfly’s genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses. The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO, indicates that the genome contains 93 - 95% of the BUSCO genes in complete and single copies. We predicted 14,830 gene models using the MAKER pipeline and manually curated 1,232 of these gene models. The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome and genetics studies on this species.
Copy number-aware deconvolution of tumor-normal DNA methylation profiles
Authors: Cadieux Elizabeth Larose , Mensah Nana E. , Castignani Carla , Tanić Miljana , Wilson Gareth A. , Dietzen Michelle , Dhami Pawan , Vaikkinen Heli , Verfaillie Annelien , Martin Cristina Cotobal , Baker Toby , Watkins Thomas B. K. , Veeriah Selvaraju , Jamal-Hanjani Mariam , Kanu Nnennaya , McGranahan Nicholas , Feber Andrew ,   TRACERx Consortium, Swanton Charles , Beck Stephan , Demeulemeester Jonas , Van Loo Peter
Published: November 2020

Aberrant methylation is a hallmark of cancer, but bulk tumor data is confounded by admixed normal cells and copy number changes. Here, we introduce Copy number-Aware Methylation Deconvolution Analysis of Cancers (CAMDAC;https://github.com/VanLoo-lab/CAMDAC), which outputs tumor purity, allele-specific copy number and deconvolved methylation estimates. We apply CAMDAC to 122 multi-region samples from 38 TRACERx non-small cell lung cancers profiled by reduced representation bisulfite sequencing. CAMDAC copy number profiles parallel those derived from genome sequencing and highlight widespread chromosomal instability. Deconvolved polymorphism-independent methylation rates enable unbiased tumor-normal and tumor-tumor differential methylation calling. Read-phasing validates CAMDAC methylation rates and directly links genotype and epitype. We show increased epigenetic instability in adenocarcinomavs.squamous cell carcinoma, frequent hypermethylation at sites carrying somatic mutations, and parallel copy number losses and methylation changes at imprinted loci. Unlike bulk methylomes, CAMDAC profiles recapitulate tumor phylogenies and evidence distinct patterns of epigenetic heterogeneity in lung cancer.
Cross-species analysis between the maize smut fungiUstilago maydisandSporisorium reilianumhighlights the role of transcriptional plasticity of effector orthologs for virulence and disease
Authors: Zuo Weiliang , Depotter Jasper RL , Gupta Deepak K , Thines Marco , Doehlemann Gunther
Published: November 2020

The constitution and regulation of effector repertoires determines and shapes the outcome of the interaction with the host.Ustilago maydisandSporisorium reilianumare two closely related smut fungi, which both infect maize, but cause distinct disease symptoms. Understanding how effector orthologs are regulated in these two pathogens can therefore provide insights to pathogen evolution and host adaption.

We tracked the infection progress ofU. maydisandS. reilianumin maize leaves, characterized two distinct infection stages for cross species RNA-sequencing analysis and identified 207 out of 335 one-to-one effector orthologs being differentially regulated during host colonization, while transcriptional plasticity of the effector orthologs correlated with the distinct disease development strategies.

By using CRISPR-Cas9 mediated gene conversion, we identified two differentially expressed effector orthologs with conserved function between two pathogens. Thus, differential expression of functionally conserved genes contributes to species specific adaptation and symptom development. Interestingly, another differentially expressed orthogroup (UMAG_05318/Sr1007) showed diverged protein function during speciation, providing a possible case for neofunctionalization.

Collectively, we showed the diversification of effector genes in related pathogens can be caused both by plasticity on the transcriptional level, as well as through functional diversification of the encoded effector proteins.
Global and national trends in documenting and monitoring species distributions
Authors: Oliver Ruth Y. , Meyer Carsten , Ranipeta Ajay , Winner Kevin , Jetz Walter
Published: November 2020

Conserving and managing biodiversity in the face of ongoing global change requires sufficient evidence to assess status and trends of species distributions. Here we analyze national trajectories in closing spatiotemporal knowledge gaps for terrestrial vertebrates (1950-2019) based on novel indicators of data coverage and sampling effectiveness. Despite a rapid rise in data coverage, particularly in the last two decades, strong geographic and taxonomic biases persist. For some taxa and regions, a tremendous growth in records failed to directly translate into newfound knowledge due to a sharp decline in sampling effectiveness. But nation’s coverage is stronger for species they hold greater stewardship for. As countries under the post-2020 Global Biodiversity Framework renew their commitments to an improved, rigorous biodiversity knowledge base, our findings highlight opportunities for international collaboration to close critical information gaps.