bluuebunny/crossref_metadata_2025 huggingface dataset:
Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy
Authors: Yamamoto Kazuhito , Shinagawa Atsushi , DiNardo Courtney D , Pratz Keith W , Ishizawa Kenichi , Miyamoto Toshihiro , Komatsu Norio , Nakashima Yasuhiro , Yoshida Chikashi , Fukuhara Noriko , Usuki Kensuke , Yamauchi Takahiro , Asada Noboru , Asou Norio , Choi Ilseung , Miyazaki Yasushi , Honda Hideyuki , Okubo Sumiko , Kurokawa Misaki , Zhou Ying , Zha Jiuhong , Potluri Jalaja , Matsumura Itaru
Published: October 2021

Background

The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

Methods

Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1–7 of each 28-day cycle.

Results

Median follow-up was 16.3 months (range, 1.0–20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation.

Conclusions

This Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.
Predictors of Pain Reduction in Trials of Interventions for Aromatase Inhibitor–Associated Musculoskeletal Symptoms
Authors: Henry N Lynn , Unger Joseph M , Till Cathee , Crew Katherine D , Fisch Michael J , Hershman Dawn L
Published: October 2021

Background

Almost one-half of aromatase inhibitor (AI)–treated breast cancer patients experience AI-associated musculoskeletal symptoms (AIMSS); 20%-30% discontinue treatment because of severe symptoms. We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from previously conducted trials.

Methods

We pooled patient-level data from 3 randomized trials testing interventions (omega-3 fatty acids, acupuncture, and duloxetine) for AIMSS that had similar eligibility criteria and the same patient-reported outcome measures. Only patients with a baseline Brief Pain Inventory average pain score of at least 4 of 10 were included. The primary outcome examined was 2-point reduction in average pain from baseline to week 12. Variable cut-point selection and logistic regression were used. Risk models were built by summing the number of factors statistically significantly associated with pain reduction. Analyses were stratified by study and adjusted for treatment arm.

Results

For the 583 analyzed patients, the 4 factors statistically significantly associated with pain reduction were Functional Assessment of Cancer Therapy Functional Well-Being greater than 24 and Physical Well-Being greater than 14 (higher scores reflect better function), and Western Ontario and McMaster Universities Osteoarthritis Index less than 50 and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands less than 33 (lower scores reflect less pain). Patients with all 4 factors were greater than 6 times more likely to experience at least a 2-point pain reduction (odds ratio = 6.37, 95% confidence interval = 2.31 to 17.53, 2-sided P < .001); similar results were found for secondary 30% and 50% pain reduction endpoints.

Conclusions

Patients with AIMSS who have lower symptom and functional distress at study entry on AIMSS intervention trials are more likely to experience meaningful pain reduction. Baseline symptom and functional status should be considered as stratification factors in future interventional trials.
Immunoenhancement and antioxidative damage effects of Polygonum Cillinerve polysaccharide on RAW264.7 cells
Authors: Lv Yizhou , Liu Zhenxiu , Duan Xueqin , Cui Jing , Zhang Weimin , Ma Wuren , Liu Yingqiu , Song Xiaoping , Fan Yunpeng
Published: October 2021

Objectives

The effects of Polygonum Cillinerve polysaccharide (PCP) on the immune and antioxidant activity were studied.

Methods

The effects of PCP on cell proliferation, phagocytic activity, cell uptake, the secretion of NO, iNOS, IL-6, IL-12, CAT and POD, intracellular ROS, cell apoptosis and antioxidative mechanism were measured by MTT, ELISA, fluorescence staining, flow cytometry and western blot.

Key findings

The results showed that PCP had no toxic effect at 31.25–1.95 µg/ml, could improve the uptake of neutral red and fluorescein isothiocyanate-labelled ovalbumin and promote the release of nitric oxide and nitric oxide synthase. Moreover, PCP also could promote the secretion of IL-6 and IL-12. The damage of RAW264.7 cells induced by hydrogen peroxide was significantly alleviated by PCP at 15.63–0.975 µg/ml. The mechanism of antioxidative damage might be that PCP inhibited the upstream p38 and the phosphorylation of JNK and ERK proteins, and down-regulated caspase 3 and up-regulated the protein expressions of cytochrome C and Bcl-2, finally PCP improved the antioxidative capacity and protected the oxidative damage of cells.

Conclusions

These results indicated that PCP had the better immunopotentiation and antioxidative damage activity.
Loiasis and diurnal microfilaremia: searching at the right moment
Authors: Musumeci Stefano , Ramu Léa , Chappuis François , Eperon Gilles
Published: October 2021

A healthy young woman from Cameroon was addressed to the tropical medicine consultation of the University Hospitals of Geneva to investigate an asymptomatic eosinophilia of 1.22 G/l and a history of ‘eye worms’ during childhood. Direct microscopic observation found viable microfilariae, and the stained blood smear confirmed Loa loa species.
Cosmographic approach to Running Vacuum dark energy models: New constraints using BAOs and Hubble diagrams at higher redshifts
Authors: Rezaei Mehdi , Peracaula Joan Solá , Malekjani Mohammad
Published: October 2021

In this work we study different types of dark energy (DE) models in the framework of the cosmographic approach, with emphasis on the Running Vacuum models (RVMs). We assess their viability using different information criteria and compare them with the so-called Ghost DE models (GDEs) as well as with the concordance ΛCDM model. We use the Hubble diagrams for Pantheon SnIa, quasars (QSOs), gamma-ray bursts (GRBs) as well as the data on baryonic acoustic oscillations (BAOs) in four different combinations. Upon minimizing the χ2 function of the distance modulus in the context of the Markov Chain Monte Carlo method (MCMC), we put constraints on the current values of the standard cosmographic parameters in a model-independent way. It turns out that, in the absence of BAOs data, the various DE models generally exhibit cosmographic tensions with the observations at the highest redshifts (namely with the QSOs and GRBs data). However, if we include the robust observations from BAOs to our cosmographic sample, the ΛCDM and RVMs are clearly favored against the GDEs. Finally, judging from the perspective of the deviance information criterion (DIC), which enables us to compare models making use of the Markov chains of the MCMC method, we conclude that the RVMs are the preferred kind of DE models. We find it remarkable that these models, which had been previously shown to be capable of alleviating the σ8 and H0 tensions, appear now also as the most successful ones at the level of the cosmographic analysis.
Lensing of gravitational waves as a probe of compact dark matter
Authors: Urrutia Juan , Vaskonen Ville
Published: October 2021

We study gravitational lensing of gravitational waves from compact object binaries as a probe of compact dark matter (DM) objects such as primordial black holes. Assuming a point mass lens, we perform parameter estimation of lensed gravitational wave signals from compact object binaries to determine the detectability of the lens with ground based laser interferometers. Then, considering binary populations that LIGO-Virgo has been probing, we derive a constraint on the abundance of compact DM from non-observation of lensed events. We find that the LIGO-Virgo observations imply that compact objects heavier than $M_l = 200\, {\rm M}_{\odot }$ cannot constitute all DM and less than $40{{\ \rm per\ cent}}$ of DM can be in compact objects heavier than $M_l = 400\, {\rm M}_{\odot }$. We also show that the DM fraction in compact objects can be probed by LIGO in its final sensitivity for $M_l \gt 40\, {\rm M}_{\odot }$ reaching $2{{\ \rm per\ cent}}$ of the DM abundance at $M_l \gt 200\, {\rm M}_{\odot }$, and by ET for $M_l \gt 1\, {\rm M}_{\odot }$ reaching DM fraction as low as 7 × 10−5 at $M_l \gt 40\, {\rm M}_{\odot }$.
The photosphere emission spectrum of hybrid relativistic outflow for gamma-ray bursts
Authors: Meng Yan-Zhi , Geng Jin-Jun , Wu Xue-Feng
Published: October 2021

The photospheric emission in the prompt phase is the natural prediction of the original fireball model for gamma-ray burst (GRB) due to the large optical depth (τ > 1) at the base of the outflow, which is supported by the quasi-thermal components detected in several Fermi GRBs. However, which radiation mechanism (photosphere or synchrotron) dominates in most GRB spectra is still under hot debate. The shape of the observed photosphere spectrum from a pure hot fireball or a pure Poynting-flux-dominated outflow has been investigated before. In this work, we further study the photosphere spectrum from a hybrid outflow containing both a thermal component and a magnetic component with moderate magnetization (σ0 = LP/LTh ∼ 1 − 10), by invoking the probability photosphere model. The high-energy spectrum from such a hybrid outflow is a power law rather than an exponential cutoff, which is compatible with the observed Band function in a great amount of GRBs. Also, the distribution of the low-energy indices (corresponding to the peak-flux spectra) is found to be quite consistent with the statistical result for the peak-flux spectra of GRBs best-fitted by the Band function, with similar angular profiles of structured jet in our previous works. Finally, the observed distribution of the high-energy indices can be well understood after considering the different magnetic acceleration (due to magnetic reconnection and kink instability) and the angular profiles of dimensionless entropy with the narrower core.
Spectropolarimetry of the Type Ia SN 2019ein rules out significant global asphericity of the ejecta
Authors: Patra Kishore C , Yang (杨轶) Yi , Brink Thomas G , Höflich Peter , Wang Lifan , Filippenko Alexei V , Kasen Daniel , Baade Dietrich , Foley Ryan J , Maund Justyn R , Zheng WeiKang , Hung Tiara , Cikota Aleksandar , Wheeler J Craig , Bulla Mattia
Published: October 2021

Detailed spectropolarimetric studies may hold the key to probing the explosion mechanisms and the progenitor scenarios of Type Ia supernovae (SNe Ia). We present multi-epoch spectropolarimetry and imaging polarimetry of SN 2019ein, an SN Ia showing high expansion velocities at early phases. The spectropolarimetry sequence spans from ∼−11 to +10 d relative to peak brightness in the B band. We find that the level of the continuum polarization of SN 2019ein, after subtracting estimated interstellar polarization, is in the range 0.0–0.3 per cent, typical for SNe Ia. The polarization position angle remains roughly constant before and after the SN light-curve peak, implying that the inner regions share the same axisymmetry as the outer layers. We observe high polarization (∼1 per cent) across both the Si ii λ6355 and Ca ii near-infrared triplet features. These two lines also display complex polarization modulations. The spectropolarimetric properties of SN 2019ein rule out a significant departure from spherical symmetry of the ejecta for up to a month after the explosion. These observations disfavour merger-induced and double-detonation models for SN 2019ein. The imaging polarimetry shows weak evidence for a modest increase in polarization after ∼20 d since the B-band maximum. If this rise is real and is observed in other SNe Ia at similar phases, we may have seen, for the first time, an aspherical interior similar to what has been previously observed for SNe IIP. Future polarization observations of SNe Ia extending to post-peak epochs will help to examine the inner structure of the explosion.
C ii*/C ii ratio in high-redshift DLAs: ISM phase separation drives the observed bimodality of [C ii] cooling rates
Authors: Balashev S A , Telikova K N , Noterdaeme P
Published: October 2021

We discuss observations of C ii*/C ii ratios and cooling rates due to [C ii] 158μm emission in high-redshift intervening damped Lyman-α (DLA) systems towards quasars. We show that the observed bimodality in the C ii cooling rates actually reflects a bimodality in the C ii*/C ii−metallicity plane that can be naturally explained by phase segregation of the neutral medium, without invoking differences in star-formation scenarios. Assuming realistic distributions of the physical parameters to calculate the phase diagrams, we also reproduce qualitatively the metallicity dependence of this bimodality. We emphasize that high-z DLAs mostly probe low-metallicity gas ($Z\lesssim 0.1 \, \mathrm{Z}_{\odot }$), where heating is dominated by cosmic rays (and/or turbulence), and not by photoelectric heating. Therefore, even if the gas of DLA is predominantly cold (where the cooling is dominated by [C ii]), the excitation of C ii can be used to derive the cosmic ray ionization rate (and/or turbulent heating), but not the UV field, as was previously considered. Alternatively, if the gas in DLA is predominantly warm, C ii*/C ii can be used to constrain its number density. Finally, we also discuss the importance of the ionized medium, which, if also present along the line of sight, can significantly increase the average C ii*/C ii ratio.
FuzDB: a new phase in understanding fuzzy interactions
Authors: Hatos Andras , Monzon Alexander Miguel , Tosatto Silvio C E , Piovesan Damiano , Fuxreiter Monika
Published: October 2021

Fuzzy interactions are specific, variable contacts between proteins and other biomolecules (proteins, DNA, RNA, small molecules) formed in accord to the cellular context. Fuzzy interactions have recently been demonstrated to regulate biomolecular condensates generated by liquid-liquid phase separation. The FuzDB v4.0 database (https://fuzdb.org) assembles experimentally identified examples of fuzzy interactions, where disordered regions mediate functionally important, context-dependent contacts between the partners in stoichiometric and higher-order assemblies. The new version of FuzDB establishes cross-links with databases on structure (PDB, BMRB, PED), function (ELM, UniProt) and biomolecular condensates (PhaSepDB, PhaSePro, LLPSDB). FuzDB v4.0 is a source to decipher molecular basis of complex cellular interaction behaviors, including those in protein droplets.
Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs
Authors: Pfafenrot Christina , Schneider Tim , Müller Christin , Hung Lee-Hsueh , Schreiner Silke , Ziebuhr John , Bindereif Albrecht
Published: October 2021

Circular RNAs (circRNAs) are noncoding RNAs that exist in all eukaryotes investigated and are derived from back-splicing of certain pre-mRNA exons. Here, we report the application of artificial circRNAs designed to act as antisense-RNAs. We systematically tested a series of antisense-circRNAs targeted to the SARS-CoV-2 genome RNA, in particular its structurally conserved 5′-untranslated region. Functional assays with both reporter transfections as well as with SARS-CoV-2 infections revealed that specific segments of the SARS-CoV-2 5′-untranslated region can be efficiently accessed by specific antisense-circRNAs, resulting in up to 90% reduction of virus proliferation in cell culture, and with a durability of at least 48 h. Presenting the antisense sequence within a circRNA clearly proved more efficient than in the corresponding linear configuration and is superior to modified antisense oligonucleotides. The activity of the antisense-circRNA is surprisingly robust towards point mutations in the target sequence. This strategy opens up novel applications for designer circRNAs and promising therapeutic strategies in molecular medicine.
Dual expression and anatomy lines allow simultaneous visualization of gene expression and anatomy
Authors: Kümpers Britta M C , Han Jingyi , Vaughan-Hirsch John , Redman Nicholas , Ware Alexander , Atkinson Jonathan A , Leftley Nicola , Janes George , Castiglione Giuseppe , Tarr Paul T , Pyke Kevin , Voß Ute , Wells Darren M , Bishopp Anthony
Published: October 2021

Studying the developmental genetics of plant organs requires following gene expression in specific tissues. To facilitate this, we have developed dual expression anatomy lines, which incorporate a red plasma membrane marker alongside a fluorescent reporter for a gene of interest in the same vector. Here, we adapted the GreenGate cloning vectors to create two destination vectors showing strong marking of cell membranes in either the whole root or specifically in the lateral roots. This system can also be used in both embryos and whole seedlings. As proof of concept, we follow both gene expression and anatomy in Arabidopsis (Arabidopsis thaliana) during lateral root organogenesis for a period of over 24 h. Coupled with the development of a flow cell and perfusion system, we follow changes in activity of the DII auxin sensor following application of auxin.
New-onset versus relapsing giant cell arteritis treated with tocilizumab: 3-year results from a randomized controlled trial and extension
Authors: Stone John H , Spotswood Helen , Unizony Sebastian H , Aringer Martin , Blockmans Daniel  , Brouwer Elisabeth , Cid Maria C , Dasgupta Bhaskar , Rech Juergen , Salvarani Carlo , Spiera Robert , Bao Min
Published: October 2021

Objective

Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with GCA. However, its long-term benefits in new-onset vs relapsing disease are uncertain, and the value of weekly vs every-other-week dosing has not been evaluated.

Methods

In Giant-Cell Arteritis Actemra (GiACTA) part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W) or placebo for 52 weeks, with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments, and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status.

Results

Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, the median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; the median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo.

Conclusion

TCZ QW delayed the time to flare and reduced the cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT01791153.
Impact of the COVID-19 pandemic on juvenile idiopathic arthritis presentation and research recruitment: results from the CAPRI registry
Authors: Dushnicky Molly J , Campbell Catherine , Beattie Karen A , Berard Roberta , Cellucci Tania , Chan Mercedes , Gerschman Tommy , Johnson Nicole , Lim Lillian , Luca Nadia , Miettunen Paivi , Morishita Kimberly A , Proulx-Gauthier Jean-Philippe , Rumsey Dax G , Schmeling Heinrike , Scuccimarri Rosie , Tam Herman , Guzman Jaime , Batthish Michelle ,   for the CAPRI Registry Investigators, Cabral David , Chédeville Gaëlle , Duffy Ciarán , Gerhold Kerstin , Guzman Jaime , Hiraki Linda , Huber Adam , Schmeling Heinrike , Shiff Natalie , Tucker Lori
Published: October 2021

Objective

The COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada.

Methods

Data collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021). Outcomes included time from symptom onset to first assessment, disease severity at presentation and registry recruitment. Proportions and medians were used to describe categorical and continuous variables, respectively.

Results

The median time from symptom onset to first assessment was 138 (IQR 64–365) days pre-pandemic vs 146 (IQR 83–359) days during the pandemic. The JIA category frequencies remained overall stable (44% oligoarticular JIA pre-pandemic, 46.8% pandemic), except for systemic JIA (12 cases pre-pandemic, 1 pandemic). Clinical features, disease activity (cJADAS10), disability (CHAQ) and quality of life (JAQQ) scores were similar between the two cohorts. Pre-pandemic, 225 patients were enrolled, compared with 111 in the pandemic year, with the greatest decrease from March to June 2020.

Conclusions

We did not observe the anticipated delay in time to presentation or increased severity at presentation, suggesting that, within Canada, care adapted well to provide support to new patient consults without negative impacts. The COVID-19 pandemic was associated with an initial 50% decrease in registry enrolment but has since improved.
Getting under the Skin: The Impact of Terrorist Attacks on Native and Immigrant Sentiment
Authors: Frey Arun
Published: October 2021

There is growing academic interest in examining how terrorist attacks shape the majority’s attitudes towards minority groups. Yet, little is known of how these minority groups react to the backlash such events provoke. This paper leverages the exogenous occurrence of a series of terrorist attacks during the fieldwork period of two surveys to estimate how such events affect the sentiment of both citizens and asylum seekers in Germany. Results of the natural experiment reveal that the 2016 terror attacks in Nice, Würzburg, and Ansbach substantially increased anti-refugee sentiment among German respondents. In line with this increase in hostility, refugees experienced more discrimination, felt less welcome in Germany, and suffered clinically relevant declines in mental health in the aftermath of the attacks. These results provide a more holistic understanding of how terrorism corrodes intergroup relations and how it affects those that are blamed for the events and thus suffer the brunt of the backlash following their occurrence.
Weather Conditions Conducive for the Early-Season Production and Dispersal ofCercospora beticolaSpores in the Great Lakes Region of North America
Authors: Bublitz Daniel M. , Hanson Linda E. , McGrath J. Mitchell
Published: October 2021

In many parts of the world including the Great Lakes region of North America, Cercospora leaf spot (CLS), caused by the fungal pathogen Cercospora beticola, is a major foliar disease of sugar beet (Beta vulgaris). Management of CLS involves an integrated approach which includes the application of fungicides. To guide fungicide application timings, disease prediction models are widely used by sugar beet growers in North America. While these models have generally worked well, they have not included information about pathogen presence. Thus, incorporating spore production and dispersal could make them more effective. The current study used sentinel beets to assess the presence of C. beticola spores in the environment early in the 2017 and 2018 growing seasons. Weather variables including air temperature, relative humidity, rainfall, leaf wetness, wind speed, and solar radiation were collected. These data were used to identify environmental variables that correlated with spore levels during a time when CLS is not generally observed in commercial fields. C. beticola spores were detected during mid-April both years, which is much earlier than previously reported. A correlation was found between spore data and all the weather variables examined during at least one of the two years, except for air temperature. In both years, spore presence was significantly correlated with rainfall (P < 0.0001) as well as relative humidity (P < 0.0090). Rainfall was particularly intriguing, with an adjusted R2of 0.3135 in 2017 and 0.1652 in 2018. Efforts are ongoing to investigate information on spore presence to improve prediction models and CLS management.
Joint-Venture Ambulatory Surgery Centers: The Perfect Partnership
Authors: Tanna Neil , Gibstein Alexander R. , Boll Adam , Coppa Gene F. , Kasabian Armen K. , Bello Stephen , Solazzo Mark
Published: October 2021

Background:

Ambulatory surgery growth has increased in the last few decades as ambulatory surgery centers have been shown to succeed in cost efficiencies through their smaller size and breadth, specialization of care, and ability to quickly participate in perioperative process improvement and education.

Methods:

A 5-year retrospective fiscal review was performed for all Northwell Health–physician ambulatory surgery center joint ventures. The outcome measures studied included model of ownership, specialty types, and gross revenue. Additional facility characteristics were studied, including growth trajectory, facility size, and cost to build a de novo facility.

Results:

Eleven free-standing ambulatory surgery centers were identified at Northwell Health during the 5-year study period. The total gross revenue for all Northwell clinical joint ventures for 2019 alone was $102,854,000. Northwell Health is a majority stakeholder in eight of their joint venture ambulatory surgery centers, with an average Northwell ownership of 53 percent and an average number of physician owners per facility of 11. The number of hospital-physician joint-venture ambulatory surgery centers grew from two to 11 facilities during the study period (450 percent). Surgical volume followed a similar trajectory, increasing 295 percent over the same time period.

Conclusions:

The ambulatory surgery center setting provides a vast number of possibilities for key stakeholders, including patients themselves, to benefit from financial and clinical efficiencies. Ambulatory surgery centers have been popular, as they meet patient expectations for convenience of elective surgery, reduce payer and clinical pressures to minimize length of stay in hospitals, and achieve similar or higher quality care with less intense resources.
The Relationship of Psychiatric Comorbidities and Their Impact on Trigger Site Deactivation Surgery for Headaches
Authors: Amador Ricardo O. , Gfrerer Lisa , Hansdorfer Marek A. , Colona Mia R. , Tsui Jane M. , Austen William G.
Published: October 2021

Background:

Patients seeking trigger site deactivation surgery for headaches often have debilitating symptoms that can affect their functional and mental health. Although prior studies have shown a strong correlation between psychiatric variables and chronic headaches, their associations in patients undergoing surgery have not been fully elucidated. This study aims to analyze psychiatric comorbidities and their impact on patients undergoing trigger site deactivation surgery for headaches.

Methods:

One hundred forty-two patients were prospectively enrolled. Patients were asked to complete the Patient Health Questionnaire-2 and Migraine Headache Index surveys preoperatively and at 12 months postoperatively. Data on psychiatric comorbidities were collected by means of both survey and retrospective chart review.

Results:

Preoperatively, 38 percent of patients self-reported a diagnosis of depression, and 45 percent of patients met Patient Health Questionnaire-2 criteria for likely major depressive disorder (Patient Health Questionnaire-2 score of ≥3). Twenty-seven percent of patients reported a diagnosis of generalized anxiety disorder. Patients with depression and anxiety reported more severe headache symptoms at baseline. At 1 year postoperatively, patients with these conditions had successful surgical outcomes comparable to those of patients without these conditions. Patients also reported a significant decrease in their Patient Health Questionnaire-2 score, with 22 percent of patients meeting criteria suggestive of depression, compared to 45 percent preoperatively.

Conclusions:

There is a high prevalence of depression and anxiety in patients undergoing trigger site deactivation surgery. Patients with these comorbid conditions achieve successful surgical outcomes comparable to those of the general surgical headache population. Furthermore, trigger site deactivation surgery is associated with a significant decrease in depressive symptoms.
A Novel Alaska Pollock Gelatin Sealant Shows Higher Bonding Strength and Nerve Regeneration Comparable to That of Fibrin Sealant in a Cadaveric Model and a Rat Model
Authors: Masuda Shusuke , Suzuki Taku , Shibata Shinsuke , Moritoki Nobuko , Abe Yoshifumi , Chen Xi , Mizuno Yosuke , Nishiguchi Akihiro , Kimura Hiroo , Matsumura Noboru , Iwamoto Takuji , Taguchi Tetsushi , Matsumoto Morio , Nakamura Masaya
Published: October 2021

Background:

A novel biocompatible sealant composed of Alaska pollock–derived gelatin (ApGltn) has recently shown good burst strength and biocompatibility in a porcine aorta. The purpose of this study was to investigate the bonding strength and biocompatibility of the ApGltn sealant in transected digital nerves of fresh frozen cadavers and in the sciatic nerves of a rat model.

Methods:

Eighty human digital nerves of fresh frozen cadavers were transected for biomechanical traction testing. They were treated with four surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; and (4) fibrin sealant. Forty-three sciatic nerves of male Wistar rats were used for functional and histopathologic evaluation. They were treated with six surgical interventions: (1) suture plus ApGltn sealant; (2) suture; (3) ApGltn sealant; (4) fibrin sealant; (5) resection with a 5-mm gap (10 rats per group); and (6) sham operation (three rats). Macroscopic confirmation, muscle weight measurement, and histopathologic findings including G-ratio were examined 8 weeks after the procedure.

Results:

The maximum failure load of the ApGltn sealant was significantly higher than that of a fibrin sealant (0.22 ± 0.05 N versus 0.06 ± 0.04 N). The maximum failure load of the ApGltn sealant was significantly lower that of suture plus ApGltn sealant (1.37 N) and suture (1.27 N). Functional evaluation and histologic examination showed that sciatic nerves repaired with ApGltn sealant showed similar nerve recovery compared to repair with the suture and fibrin sealant.

Conclusion:

The ApGltn sealant showed higher bonding strength and equal effect of nerve regeneration when compared with the fibrin sealant.
RNA virome diversity and Wolbachia infection in individual Drosophila simulans flies
Authors: Ortiz-Baez Ayda Susana , Shi Mang , Hoffmann Ary A. , Holmes Edward C.
Published: October 2021

The endosymbiont bacteria of the genus

Wolbachia

are associated with multiple mutualistic effects on insect biology, including nutritional and antiviral properties. Members of the genus

Wolbachia

naturally occur in fly species of the genus Drosophila, providing an operational model host for studying how virome composition may be affected by its presence. Drosophila simulans populations can carry a variety of strains of members of the genus

Wolbachia

, with the wAu strain associated with strong antiviral protection under experimental conditions. We used D. simulans sampled from the Perth Hills, Western Australia, to investigate the potential virus protective effect of the wAu strain of

Wolbachia

on individual wild-caught flies. Our data revealed no appreciable variation in virus composition and abundance between individuals infected or uninfected with

Wolbachia

associated with the presence or absence of wAu. However, it remains unclear whether wAu might affect viral infection and host survival by increasing tolerance rather than inducing complete resistance. These data also provide new insights into the natural virome diversity of D. simulans. Despite the small number of individuals sampled, we identified a repertoire of RNA viruses, including nora virus, galbut virus, thika virus and La Jolla virus, that have been identified in other species of the genus Drosophila. Chaq virus-like sequences associated with galbut virus were also detected. In addition, we identified five novel viruses from the families Reoviridae, Tombusviridae, Mitoviridae and Bunyaviridae. Overall, this study highlights the complex interaction between

Wolbachia

and RNA virus infections and provides a baseline description of the natural virome of D. simulans.
ICTV Virus Taxonomy Profile: Herpesviridae 2021
Authors: Gatherer Derek , Depledge Daniel P. , Hartley Carol A. , Szpara Moriah L. , Vaz Paola K. , Benkő Mária , Brandt Curtis R. , Bryant Neil A. , Dastjerdi Akbar , Doszpoly Andor , Gompels Ursula A. , Inoue Naoki , Jarosinski Keith W. , Kaul Rajeev , Lacoste Vincent , Norberg Peter , Origgi Francesco C. , Orton Richard J. , Pellett Philip E. , Schmid D. Scott , Spatz Stephen J. , Stewart James P. , Trimpert Jakob , Waltzek Thomas B. , Davison Andrew J.
Published: October 2021

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.
Genome-wide association study of liver fat, iron, and extracellular fluid fraction in the UK Biobank
Authors: O’Dushlaine Colm , Germino Mary , Verweij Niek , Nielsen Jonas B. , Yadav Ashish , Benner Christian , Backman Joshua D. , Lin Nan , R. Abecasis Gonçalo , Baras Aris , Ferreira Manuel A. , Lotta Luca A. , Walls Johnathon R. , Parasoglou Prodromos , Marchini Jonathan L.
Published: October 2021

Abdominal magnetic resonance imaging (MRI) represents a non-invasive approach allowing the extraction of clinically informative phenotypes. We developed an automated pipeline to segment liver pixels from abdominal MRI images and apply published models to approximate fat fraction, extracellular fluid fraction and iron content in 40,058 MRIs from the UK Biobank. We then conducted a genome-wide association of these traits using imputed variants (N=37,250 individuals, 11,914,698 variants) and exome sequence data (N=35,274 individuals, 8,287,315 variants). For liver fat we identified 8 novel loci in or near genes MARC1, GCKR, ADH1B, MTTP, TRIB1, GPAM, PNPLA2 and APOH. For liver iron we identified 1 novel locus between the genes ASNSD1 and SLC40A1, an iron transporter involved in hemochromatosis. For extracellular fluid fraction we identified 6 novel loci in or near genes AGMAT, NAT2, MRPL4-S1PR2, FADS1, ABO and HFE, with almost all having prior associations to obesity, liver, iron, or lipid traits.
Limited impact of Delta variant’s mutations in the effectiveness of neutralization conferred by natural infection or COVID-19 vaccines in a Latino population
Authors: Sariol Carlos A. , Serrano-Collazo Crisanta , Ortiz Edwin J. , Pantoja Petraleigh , Cruz Lorna , Arana Teresa , Atehortua Dianne , Pabon-Carrero Christina , Espino Ana M.
Published: October 2021

The SARS-CoV-2 pandemic has impacted public health systems all over the world. The Delta variant seems to possess enhanced transmissibility, but no clear evidence suggests it has increased virulence. Our data shows that pre-exposed individuals had similar neutralizing activity against the authentic COVID-19 strain and the Delta and Epsilon variants. After one vaccine dose, the neutralization capacity expands to all tested variants. Healthy vaccinated individuals showed a limited breadth of neutralization. One vaccine dose induced similar neutralizing antibodies against the Delta compared to the authentic strain. However, even after two doses, this capacity only expanded to the Epsilon variant.
A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination
Authors: Colwill Karen , Galipeau Yannick , Stuible Matthew , Gervais Christian , Arnold Corey , Rathod Bhavisha , Abe Kento T , Wang Jenny H , Pasculescu Adrian , Maltseva Mariam , Rocheleau Lynda , Pelchat Martin , Fazel-Zarandi Mahya , Iskilova Mariam , Barrios-Rodiles Miriam , Bennett Linda , Yau Kevin , Cholette François , Mesa Christine , Li Angel X , Paterson Aimee , Hladunewich Michelle A , Goodwin Pamela J , Wrana Jeffrey L , Drews Steven J , Mubareka Samira , McGeer Allison J , Kim John , Langlois Marc-André , Gingras Anne-Claude , Durocher Yves
Published: October 2021

OBJECTIVES

Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction.

METHODS

We developed methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD), and nucleocapsid (N). We automated a surrogate neutralization (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard.

RESULTS

Our single-point IgG-based ELISAs accurately distinguished non-infected and infected individuals. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability.

CONCLUSIONS

Measuring antibodies to three viral antigens and identify neutralizing antibodies capable of disrupting spike-ACE2 interactions in high-throughput enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The reagents are available to enable scaling up of standardized serological assays, permitting inter-laboratory data comparison and aggregation.
Open chromatin analysis inTrypanosoma cruzilife forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci
Authors: Lima Alex Ranieri Jerônimo , Poubel Saloe Bispo , Rosón Juliana Nunes , de Lima Loyze Paola Oliveira , Costa-Silva Héllida Marina , de Sousa Silva Herbert Guimarães , Gonçalves Camila Silva , Galante Pedro A. F. , Holetz Fabiola , Motta Maria Cristina Machado M. , Silber Ariel M. , Elias M. Carolina , da Cunha Julia Pinheiro Chagas
Published: October 2021

Background

Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood.

Results

Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasiteTrypanosoma cruziand its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences inT. cruzigenome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels.

Conclusion

Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.
Anatomic development of the upper airway during the first five years of life: A three-dimensional imaging study
Authors: Chuang Ying Ji , Hwang Seong Jae , Buhr Kevin A. , Miller Courtney A. , Avey Gregory D. , Story Brad H. , Vorperian Houri K.
Published: October 2021

Purpose

Normative data on the growth and development of the upper airway across the sexes is needed for the diagnosis and treatment of congenital and acquired respiratory anomalies and to gain insight on developmental changes in speech acoustics and disorders with craniofacial anomalies.

Methods

The growth of the upper airway in children ages birth-to-five years, as compared to adults, was quantified using an imaging database with computed tomography studies from typically developing individuals. Methodological criteria for scan inclusion and airway measurements included: head position, histogram-based airway segmentation, anatomic landmark placement, and development of a semi-automatic centerline for data extraction. A comprehensive set of 2D and 3D supra- and sub-glottal measurements from the choanae to tracheal opening were obtained including: naso-oro-laryngo-pharynx subregion volume and length, each subregion’s superior and inferior cross-sectional-area, and antero-posterior and transverse/width distances.

Results

Growth of the upper airway during the first five years of life was more pronounced in the vertical and transverse/lateral dimensions than in the antero-posterior dimension. By age five years, females have larger pharyngeal measurement than males. Prepubertal sex-differences were identified in the subglottal region.

Conclusions

Our findings demonstrate the importance of studying the growth of the upper airway in 3D. As the lumen length increases, its shape changes, becoming increasingly elliptical during the first five years of life. This study also emphasizes the importance of methodological considerations for both image acquisition and data extraction, as well as the use of consistent anatomic structures in defining pharyngeal regions.
A cadmium(II) coordination polymer with a fivefold interpenetrating diamondoid three-dimensional framework: synthesis, crystal structure, luminescence and photocatalytic properties
Authors: Chen Hui-Ru
Published: October 2021

A novel three-dimensional (3D) CdII coordination polymer, namely, poly[[μ2-4,4′-bis(2-methylimidazol-1-yl)-[1,1′-biphenyl]](μ2-5-methylisophthalato)cadmium(II)], [Cd(C9H6O4)(C20H18N4)]
n
or [Cd(MIP)(4,4′-BMIBP)]
n
, (I), was synthesized by the hydrothermal method using 5-methylisophthalic acid (H2MIP), 4,4′-bis(2-methylimidazol-1-yl)-[1,1′-biphenyl] (4,4′-BMIBP) and Cd(NO3)2·6H2O, and characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy and thermogravimetric analysis. Compound (I) exhibits a novel fivefold interpenetrating 3D diamondoid framework. Additionally, it shows fluorescence emission in the solid state and promising photocatalytic activities for the degradation of methylene blue (MB) in water at room temperature.
Value creation through omnichannel practices for multi-actor customers: an evolutionary view
Authors: Costa Climent Ricardo , Haftor Darek M. , Chowdhury Soumitra
Published: October 2021

Purpose

The purpose of this paper is to investigate the omnichannel practices to porpose a conceptual overview to offer guidance on how to handle their inherent complexities.

Design/methodology/approach

This study is based on a literature review of more than 100 academics papers about the multichannel practices and omnichannel practices in the global market.

Findings

To this end, this paper identifies and addresses three limitations of the contemporary omnichannel literature: the failure to articulate the sources of value creation generated by omnichannel practices, the conception of omnichannel as targeting a single customer actor only and the static conception of omnichannel practices. In response to these limitations, this study offers the following: four sources of value creation based on the business model concept, a multi-actor customer conception, where several actors partake in the overall purchase decision and an evolutionary notion of omnichannel practices in terms of their constitution and use as part of the overall evolution of a marketplace

Originality/value

The framework presented in this paper provides a map to take new research beyond its current boundaries and an audit tool to help managers identify their firm’s current omnichannel situation, including limitations and opportunities for further development.