bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the willingness of community pharmacists to test–treat–immunize during the COVID-19 pandemic in Puerto Rico
Authors: Silva-Suárez Georgina , Alvarado Reyes Yarelis , Colón-Pratts Frances M , Sanchez Jesus , Ortiz Blanca I , Rabionet Silvia E 
Published: February 2021

Abstract

Objective
The objective of this study was to assess community pharmacists’ willingness to test, treat and immunize for COVID-19 in Puerto Rico.

Methods
In this cross-sectional study, a 37-item survey was distributed via email and social media in May 2020 through REDCap online software. All licensed community pharmacists in Puerto Rico (N = 1200) were invited to complete the survey. Retired community pharmacists were excluded. Analysis of frequencies and chi-square tests were performed to evaluate the willingness to test, treat and immunize for COVID-19 and their associations with sociodemographic variables.

Key findings
The survey response rate was 26% (314/1200). Subjects’ mean age was 42 (±13), 86.1% were female, and most practiced in independent community or specialty pharmacy (62%). Among respondents, 44% reported willingness to test. Top concerns for testing were family (73.4%) and self (66.8%) exposure and ability to manage the workflow (53.3%). Most participants indicated their willingness to treat (88.4%) and to administer the COVID-19 vaccine (76.1%). Study participants who worked in retail pharmacies were more willing to test for COVID-19 (50.9%, P = 0.34) and to immunize (91.2%, P &lt; 0.001). Pharmacists ≤39 years (90.3%), those who graduate in 2000 or later (88.3%), and those with a Pharm.D. degree or higher (88.6%), were more willing to immunize (P &lt; 0.001).

Conclusions
Most community pharmacists were more willing to treat and immunize, than to perform COVID-19 testing. This underscores the need for training and workflow changes to facilitate the acquisition of this new role. Local pharmacists’ associations should advocate for a safe and manageable work environment. These efforts are vital to empower pharmacists to adopt new roles during a public health emergency.
Providing pharmaceutical care during the COVID-19 pandemic: attitudes and experiences of home-treated patients in Jordan
Authors: Mukattash Tareq L , Jarab Anan S , Al-Qerem Walid , Abu Farha Rana K , Itani Rania , Karout Samar , Mukattash Ibrahim L , Basheti Iman 
Published: February 2021

Abstract

Objectives
This study aims to explore home-treated COVID-19 patients’ experiences and perceptions of pharmaceutical care services offered during their sickness.

Methods
This is a cross-sectional online questionnaire study, where a 30-item questionnaire was texted via a link to COVID-19 patients who were tested positive previously. A list of anonymised numbers was obtained from different COVID-19 testing centres. The study received ethical approval from the Institutional Review Board at the King Abdulla University Hospital/Jordan University of Science and Technology.

Key findings
A total of 268 patients who were previously diagnosed with COVID-19 agreed to participate in this study. Only 22.9% of patients reported taking medications regularly. Almost one-third of respondents (28.7%) indicated that pharmacists were involved in prescribing medicine to patients. Almost half the respondents (49.6%) stated that they or their caregivers obtained information and advice about their medicine from the pharmacists. Only 54.9% of the respondents agreed/strongly agreed that pharmacists have enough scientific information to provide the necessary medical assistance to COVID-19 patients. Patients who work in the medical field, and who always get their medication from the same pharmacy, showed better perception towards pharmaceutical care services that might be provided to COVID-19 patients (P &lt; 0.01).

Conclusions
Pharmacists had an unsatisfactory contribution to the management of the disease in outpatient settings. Moreover, there was a poor perception of the pharmacists’ role including their knowledge, communication skills and counselling skills. Thus, it is essential to improve pharmacists’ knowledge and practices about infectious diseases.
Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS)
Authors: Shutov Evgeny , Sułowicz Władysław , Esposito Ciro , Tataradze Avtandil , Andric Branislav , Reusch Michael , Valluri Udaya , Dimkovic Nada 
Published: February 2021

Abstract

Background
Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of chronic kidney disease (CKD) anemia.

Methods
This Phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with Stages 3–5 CKD, not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52–104 weeks. This study examined two primary efficacy endpoints: European Union (European Medicines Agency)—hemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that increased from baseline (BL) by ≥1.0 g/dL in patients with Hb &gt;8.0 g/dL or ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; US Food and Drug Administration—change in Hb from BL to the average Hb level during Weeks 28–52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined.

Results
A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response [odds ratio = 34.74, 95% confidence interval (CI) 20.48–58.93] and change in Hb from BL [roxadustat – placebo: +1.692 (95% CI 1.52–1.86); both P &lt; 0.001]. Superiority of roxadustat was demonstrated for low-density lipoprotein cholesterol change from BL, and time to first use of rescue medication (both P &lt; 0.001). The incidences of treatment-emergent adverse events were comparable between groups (roxadustat: 87.7%, placebo: 86.7%).

Conclusions
Roxadustat demonstrated superior efficacy versus placebo in terms of both Hb response rate and change in Hb from BL. The safety profiles of roxadustat and placebo were comparable.
Predicting Spinal Surgery Candidacy From Imaging Data Using Machine Learning
Authors: Wilson Bayard , Gaonkar Bilwaj , Yoo Bryan , Salehi Banafsheh , Attiah Mark , Villaroman Diane , Ahn Christine , Edwards Matthew , Laiwalla Azim , Ratnaparkhi Anshul , Li Ien , Cook Kirstin , Beckett Joel , Macyszyn Luke 
Published: February 2021

Abstract

BACKGROUND
The referral process for consultation with a spine surgeon remains inefficient, given a substantial proportion of referrals to spine surgeons are nonoperative.

OBJECTIVE
To develop a machine-learning-based algorithm which accurately identifies patients as candidates for consultation with a spine surgeon, using only magnetic resonance imaging (MRI).

METHODS
We trained a deep U-Net machine learning model to delineate spinal canals on axial slices of 100 normal lumbar MRI scans which were previously delineated by expert radiologists and neurosurgeons. We then tested the model against lumbar MRI scans for 140 patients who had undergone lumbar spine MRI at our institution (60 of whom ultimately underwent surgery, and 80 of whom did not). The model generated automated segmentations of the lumbar spinal canals and calculated a maximum degree of spinal stenosis for each patient, which served as our biomarker for surgical pathology warranting expert consultation.

RESULTS
The machine learning model correctly predicted surgical candidacy (ie, whether patients ultimately underwent lumbar spinal decompression) with high accuracy (area under the curve = 0.88), using only imaging data from lumbar MRI scans.

CONCLUSION
Automated interpretation of lumbar MRI scans was sufficient to correctly determine surgical candidacy in nearly 90% of cases. Given that a significant proportion of referrals placed for spine surgery evaluation fail to meet criteria for surgical intervention, our model could serve as a valuable tool for patient triage and thereby address some of the inefficiencies within the outpatient surgical referral process.
Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era
Authors: Wood Shannon , Won Seung Hyun , Hsieh Hsing-Chuan , Lalani Tahaniyat , Kronmann Karl , Maves Ryan C , Utz Gregory , Schofield Christina , Colombo Rhonda E , Okulicz Jason F , Blaylock Jason , Agan Brian K , Ganesan Anuradha 
Published: February 2021

Abstract

Background
As morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era.

Methods
Participants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE.

Results
Of 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28–1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270–2.395), non–nucleoside reverse transcriptase inhibitor–based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378–3.616), being cART naïve (HR, 6.046; 95% CI, 3.686–9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651–16.164). African American race (HR, 0.669; 95% CI, 0.510–0.877) and integrase strand transfer inhibitor (INSTI)–based cART (HR, 0.222; 95% CI, 0.104–0.474) were protective.

Conclusions
Our findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.
Gene Targeting Facilitated by Engineered Sequence-Specific Nucleases: Potential Applications for Crop Improvement
Authors: Miki Daisuke , Wang Rui , Li Jing , Kong Dali , Zhang Lei , Zhu Jian-Kang 
Published: February 2021

Abstract
Humans are currently facing the problem of how to ensure that there is enough food to feed all of the world’s population. Ensuring that the food supply is sufficient will likely require the modification of crop genomes to improve their agronomic traits. The development of engineered sequence-specific nucleases (SSNs) paved the way for targeted gene editing in organisms, including plants. SSNs generate a double-strand break (DSB) at the target DNA site in a sequence-specific manner. These DSBs are predominantly repaired via error-prone non-homologous end joining and are only rarely repaired via error-free homology-directed repair if an appropriate donor template is provided. Gene targeting (GT), i.e. the integration or replacement of a particular sequence, can be achieved with combinations of SSNs and repair donor templates. Although its efficiency is extremely low, GT has been achieved in some higher plants. Here, we provide an overview of SSN-facilitated GT in higher plants and discuss the potential of GT as a powerful tool for generating crop plants with desirable features.
AtLURE1/PRK6-mediated signaling promotes conspecific micropylar pollen tube guidance
Authors: Liu Meiling , Wang Zhijuan , Hou Saiying , Wang Lele , Huang Qingpei , Gu Hongya , Dresselhaus Thomas , Zhong Sheng , Qu Li-Jia 
Published: February 2021

AbstractReproductive isolation is a prerequisite to form and maintain a new species. Multiple prezygotic and postzygotic reproductive isolation barriers have been reported in plants. In the model plant, Arabidopsis thaliana conspecific pollen tube precedence controlled by AtLURE1/PRK6-mediated signaling has been recently reported as a major prezygotic reproductive isolation barrier. By accelerating emergence of own pollen tubes from the transmitting tract, A. thaliana ovules promote self-fertilization and thus prevent fertilization by a different species. Taking advantage of a septuple atlure1null mutant, we now report on the role of AtLURE1/PRK6-mediated signaling for micropylar pollen tube guidance. Compared with wild-type (WT) ovules, atlure1null ovules displayed remarkably reduced micropylar pollen tube attraction efficiencies in modified semi-in vivo A. thaliana ovule targeting assays. However, when prk6 mutant pollen tubes were applied, atlure1null ovules showed micropylar attraction efficiencies comparable to that of WT ovules. These findings indicate that AtLURE1/PRK6-mediated signaling regulates micropylar pollen tube attraction in addition to promoting emergence of own pollen tubes from the transmitting tract. Moreover, semi-in vivo ovule targeting competition assays with the same amount of pollen grains from both A. thaliana and Arabidopsis lyrata showed that A. thaliana WT and xiuqiu mutant ovules are mainly targeted by own pollen tubes and that atlure1null mutant ovules are also entered to a large extent by A. lyrata pollen tubes. Taken together, we report that AtLURE1/PRK6-mediated signaling promotes conspecific micropylar pollen tube attraction representing an additional prezygotic isolation barrier.
First measurement using a nuclear emulsion detector of theνμcharged-current cross section on iron around the 1 GeV energy region
Authors: Oshima H , Matsuo T , Ali A , Aoki S , Berns L , Fukuda T , Hanaoka Y , Hayato Y , Hiramoto A , Ichikawa A K , Kawahara H , Kikawa T , Komatani R , Komatsu M , Kuretsubo K , Marushima T , Matsumoto H , Mikado S , Minamino A , Mizuno K , Morimoto Y , Morishima K , Naganawa N , Naiki M , Nakamura M , Nakamura Y , Nakano N , Nakano T , Nakaya T , Nishio A , Odagawa T , Ogawa S , Rokujo H , Sato O , Shibuya H , Sugimura K , Suzui L , Suzuki Y , Takagi H , Takahashi S , Takao T , Tanihara Y , Watanabe R , Yamada K , Yasutome K , Yokoyama M 
Published: February 2021

AbstractWe have carried out $\nu_{\mu}$ charged-current interaction measurement on iron using an emulsion detector exposed to the T2K neutrino beam in the J-PARC neutrino facility. The data samples correspond to $4.0 \times 10^{19}$ protons on target, and the neutrino mean energy is 1.49 GeV. The emulsion detector is suitable for precision measurements of charged particles produced in neutrino–iron interactions with a low momentum threshold thanks to a thin-layered structure and sub-$\mu$m spatial resolution. The charged particles are successfully detected, and their multiplicities are measured using the emulsion detector. The cross section was measured to be $\sigma^{\mathrm{Fe}}_{\mathrm{CC}} = (1.28 \pm 0.11({\mathrm{stat.}})^{+0.12}_{-0.11}({\mathrm{syst.}})) \times 10^{-38} \, {\mathrm{cm}}^{2}/{\mathrm{nucleon}}$. The cross section in a limited kinematic phase space of induced muons, $\theta_{\mu} &lt; 45^{\circ}$ and $p_{\mu} &gt; 400 \, {\rm MeV}/c$, on iron was $\sigma^{\mathrm{Fe}}_{\mathrm{CC \hspace{1mm} phase \hspace{0.5mm} space}} = (0.84 \pm 0.07({\mathrm{stat.}})^{+0.07}_{-0.06}({\mathrm{syst.}})) \times 10^{-38} \, {\mathrm{cm}}^{2}/{\mathrm{nucleon}}$. The cross-section results are consistent with previous values obtained via different techniques using the same beamline, and they are reproduced well by current neutrino interaction models. These results demonstrate the capability of the detector in the detailed measurement of neutrino–nucleus interactions around the 1 GeV energy region.
Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep indb/dbmice
Authors: Pho Huy , Berger Slava , Freire Carla , Kim Lenise J , Shin Mi-Kyung , Streeter Stone R , Hosamane Nishitha , Cabassa Meaghan E , Anokye-Danso Frederick , Dergacheva Olga , Amorim Mateus R , Fleury-Curado Thomaz , Jun Jonathan C , Schwartz Alan R , Ahima Rexford S , Mendelowitz David , Polotsky Vsevolod Y 
Published: February 2021

AbstractStudy ObjectivesObesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin-deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepRb-deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals.MethodsWe measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepRb or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO2 production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin.ResultsAwake db/db mice had elevated CO2 levels in the arterial blood. Ad-LepRb infection resulted in LepRb expression in the DMH neurons in a similar fashion to wildtype mice. In LepRb-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume, and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in these animals.ConclusionLeptin stimulates breathing and treats obesity hypoventilation acting on LepRb-positive neurons in the DMH.
COVID-19 vaccines for low- and middle-income countries
Authors: Choi Edward M 
Published: February 2021

AbstractThe COVID-19 pandemic is the biggest threat to public health in a century. Through hard work and ingenuity, scientists have developed a number of safe and effective vaccines against COVID-19 disease. However, demand far outstrips supply and countries around the world are competing for available vaccines. This review describes how low- and middle-income countries access COVID-19 vaccines, what is being done to distribute vaccines fairly, as well as the challenges ahead.
Deep neural network estimated electrocardiographic-age as a mortality predictor
Authors: Lima Emilly M , Ribeiro Antônio H , Paixão Gabriela MM , Ribeiro Manoel Horta , Filho Marcelo M Pinto , Gomes Paulo R , Oliveira Derick M , Sabino Ester C , Duncan Bruce B , Giatti Luana , Barreto Sandhi M , Meira Wagner , Schön Thomas B , Ribeiro Antonio Luiz P 
Published: February 2021

AbstractThe electrocardiogram (ECG) is the most commonly used exam for the screening and evaluation of cardiovascular diseases. Here we propose that the age predicted by artificial intelligence (AI) from the raw ECG tracing (ECG-age) can be a measure of cardiovascular health and provide prognostic information. A deep convolutional neural network was trained to predict a patient’s age from the 12-lead ECG using data from patients that underwent an ECG from 2010 to 2017 - the CODE study cohort (n=1,558,415 patients). On the 15% hold-out CODE test split, patients with ECG-age more than 8 years greater than chronological age had a higher mortality rate (hazard ratio (HR) 1.79, p<0.001) in a mean follow-up of 3.67 years, whereas those with ECG-age more than 8 years less than chronological age had a lower mortality rate (HR 0.78, p<0.001). Similar results were obtained in the external cohorts ELSA-Brasil (n=14,236) and SaMi-Trop (n=1,631). The ability to predict mortality from the ECG predicted age remains even when we adjust the model for cardiovascular risk factors. Moreover, even for apparent normal ECGs, having a predicted ECG-age 8 or more years greater than chronological age remained a statistically significant predictor of risk (HR 1.53, p<0.001 in CODE 15% test split). These results show that AI-enabled analysis of the ECG can add prognostic information to the interpretation of the 12-lead ECGs.
Diagnostic value in colorectal tumorous lesions of SDC2/TFPI2 methylation based on bowel subsite difference
Authors: Zhang Lianglu , Dong Lanlan , Lu Changming , Huang Wenxian , Yang Cuiping , Wang Qian , Wang Qian , Lei Ruixue , Sun Rui , Wan Kangkang , Li Tingting , Sun Fan , Gan Tian , Lin Jun , Yin Lei 
Published: February 2021

AbstractBackgroundSDC2 methylation is a potential biomarker for colorectal cancer detection with specificity over 90%, but its sensitivity is usually less than 90%. The study aims to improve the sensitivity and specificity by adding TFPI2 methylation as a complement.MethodsTFPI2 was identified using colorectal cancer samples from TCGA database with SDC2 methylation level lower than 0.2. SDC2/TFPI2 methylation specific PCR was performed using tissue samples (184 cancer and 54 healthy control) and stool samples (289 cancer, 190 adenoma and 217 healthy control). Detection sensitivity was calculated among tumors from different biopsy locations.Results88% of 50 TCGA specimens of colorectal cancer with SDC2 methylation level lower than 0.2 showed TFPI2 methylation level higher than 0.2. SDC2/TFPI2 combined detection in stool specimens showed AUC value of 0.98 with the specificity of 96.40% and sensitivity of 96.60% for cancer vs control, AUC value of 0.87 with the specificity of 95.70% and sensitivity of 80.00% for adenoma vs control. The sensitivities were much higher than those of SDC2, and the improvement was most significant in lesions from left colon and rectum.ConclusionsThis research indicated that the addition of TFPI2 can reduce the miss detection rate of colorectal cancer and adenomas while maintaining high specificity, probably by finding neoplasms in left colon.The method is non-invasive and has good compliance, also avoiding the pain of bowel preparation and risk of cross infection during endoscopy, so it will provide an easy and precise tool for colorectal cancer and its precancerous lesions screening.
Using mixed-effects modeling to estimate decay kinetics of response to SARS-CoV-2 infection
Authors: Bottino D. , Hather G. , Yuan L. , Stoddard M. , White L. , Chakravarty A. 
Published: February 2021

AbstractThe duration of natural immunity in response to SARS-CoV-2 is a matter of some debate in the literature at present. For example, in a recent publication characterizing SARS-CoV-2 immunity over time, the authors fit pooled longitudinal data, using fitted slopes to infer the duration of SARS-CoV-2 immunity. In fact, such approaches can lead to misleading conclusions as a result of statistical model-fitting artifacts. To exemplify this phenomenon, we reanalyzed one of the markers (pseudovirus neutralizing titer) in the publication, using mixed-effects modeling, a methodology better suited to longitudinal datasets like these. Our findings showed that the half-life was both longer and more variable than reported by the authors. The example selected by us here illustrates the utility of mixed-effects modeling in provide more accurate estimates of the duration and heterogeneity of half-lives of molecular and cellular biomarkers of SARS-CoV-2 immunity.