bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating Spatial Associations in Inpatient Deaths Between Organ Procurement Organizations
Authors: Adler Joel T. , Dey Tanujit 
Published: February 2021

Background.
To improve the measurement of organ procurement organization (OPO) performance, the Center for Medicare and Medicaid Services recently proposed using inpatient deaths defined as the eligible pool of organ donors within an OPO as patients 75 years or younger that died from any cause that would not preclude donation.

Methods.
To account for the geographic variation in OPO performance and organ availability across the United States, we utilized spatial analysis to appraise the newly proposed metric of inpatient deaths.

Results.
Using spatial clustering that accounts for geographic relationships between Organ Procurement Organizations, the top 5 causes of donation-eligible death, and inpatient deaths, we identified 4 unique OPO clusters. Each group had a distinct demographic composition, cause of death, and inpatient death pattern. In multivariate analysis accounting for these geographic relationships, the spatial clusters remained significantly associated with the outcome of inpatient deaths (P < 0.001) and were the best-fitting model compared with models without the spatial clusters; this suggests that further risk adjustment of inpatient deaths should include these geographic considerations.

Conclusions.
This approach provides not only a manner to assess donor potential by improving risk adjustment but also an opportunity to further explore geographic and spatial relationships in the practice of organ transplantation and OPO performance.
Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources’ Allocation
Authors: Giovinazzo Francesco , Avolio Alfonso W. , Galiandro Federica , Vitale Alessandro , Dalla Riva Giulio V. , Biancofiore Gianni , Sharma Shivani , Muiesan Paolo , Agnes Salvatore , Burra Patrizia 
Published: February 2021

Background.
Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases.

Methods.
SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources’ allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed.

Results.
There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate-multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to “urgent” cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19-related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question.

Conclusions.
In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed.
“A longitudinal study of healthcare workers’ surveillance during the ongoing COVID-19 Epidemics in Italy: is SARS-CoV-2 still a threat for the Health-care System?”
Authors: Barbaro F , Della Rocca F , Padoan A , Aita A , Cianci V , Basso D , Cattelan A , Donato D , Plebani M , Dall’Olmo L 
Published: February 2021

ABSTRACTObjectivesIn spring 2020, Northern Italy was the first area outside China to be involved in the SARS-CoV-2 pandemic. This observational study depicts SARS-CoV-2 prevalence and serological curves among first-line healthcare workers (HCWs) at Padua University Hospital (PdUH), North-East Italy.Method344 HCWs, working at the PdUH Emergency Department and Infectious Disease Unit, underwent a SARS-CoV-2 RNA nasopharyngeal swab with paired IgM and IgG antibody detection for 4 consecutive weeks. At every session, a questionnaire recorded symptoms, signs and recent contacts with SARS-CoV-2 patients. Positive cases were followed up for 5 months.ResultsTwenty-seven HCWs (7.84%) had positive serology (Abs) with 12 positive swabs during the study period. Two additional HCWs were positive by swab but without Abs. Fourteen cases (4%) had SARS-CoV-2 infection before the beginning of the study. An HCW with autoimmune disease showed false Ab results. 46% of individuals with Abs reported no symptoms, in accordance with previous population studies. Fever, nasal congestion, diarrhoea and contacts with SARS-CoV-2 individuals correlated to SARS-CoV-2 infection. 96% of Abs+ cases showed persistent positive antibodies 5 months later and none was re-infected.DiscussionCorrect use of PPEs and separate paths for positive/negative patients in the hospital can result in a low percentage of SARS-CoV-2 infections among HCWs, even in high risk settings. Frequent testing for SARS-CoV-2 with nasopharyngeal swabs is worthwhile, irrespective of HCWs’ symptoms, due to the lack of specificity together with the high percentage of asymptomatic cases. Further studies are needed to elucidate the neutralizing effect of SARS-CoV-2 antibodies.
Prior COVID-19 Infection and Antibody Response to Single Versus Double Dose mRNA SARS-CoV-2 Vaccination
Authors: Ebinger Joseph E. , Fert-Bober Justyna , Printsev Ignat , Wu Min , Sun Nancy , Figueiredo Jane C. , Eyk Jennifer E. Van , Braun Jonathan G. , Cheng Susan , Sobhani Kimia 
Published: February 2021

ABSTRACTThe double dose regimen for mRNA vaccines against SARS-CoV-2 presents both a hope and a challenge for global efforts to curb the COVID-19 pandemic. With supply chain logistics impacting the rollout of population-scale vaccination programs, increasing attention has turned to the potential efficacy of single versus double dose vaccine administration for select individuals. To this end, we examined response to Pfizer-BioNTech mRNA vaccine in a large cohort of healthcare workers including those with versus without prior COVID-19 infection. For all participants, we quantified circulating levels of SARS-CoV-2 anti-spike (S) protein IgG at baseline prior to vaccine, after vaccine dose 1, and after vaccine dose 2. We observed that the anti-S IgG antibody response following a single vaccine dose in persons who had recovered from confirmed prior COVID-19 infection was similar to the antibody response following two doses of vaccine in persons without prior infection (P≥0.58). Patterns were similar for the post-vaccine symptoms experienced by infection recovered persons following their first dose compared to the symptoms experienced by infection naïve persons following their second dose (P=0.66). These results support the premise that a single dose of mRNA vaccine could provoke in COVID-19 recovered individuals a level of immunity that is comparable to that seen in infection naïve persons following a double dose regimen. Additional studies are needed to validate our findings, which could allow for public health programs to expand the reach of population wide vaccination efforts.
Depression and anxiety before and during the COVID-19 lockdown: a longitudinal cohort study with university students
Authors: da Conceição Virgínia , Rothes Inês , Gusmão Ricardo , Barros Henrique 
Published: February 2021

AbstractBackgroundFor young people, just as in the general population, COVID-19 caused many changes in their lives, including an increased risk for mental illness symptoms. We aimed to study the impact of the COVID-19 pandemic in anxiety and depression symptoms in a cohort of university students.MethodsThis study is part of broader longitudinal research on university students’ mental health with data of the Portuguese version of The Patient Health Questionnaire (PHQ-9) and the Portuguese version of the Generalised Anxiety Disorder (GAD-7) with evaluations on January, May and October 2019 and June 2020, as well as socio-demographic information.Results341 university students (257 females and 84 males) were included, with a mean age of 19.91 (SD=1.58). In June 2020, the mean for perceived wellbeing loss was 60.47% (SD=26.56) and 59.54% (SD=28.95) for mental health loss. The proportion of students with scores equal to or above 15 in the PHQ-9 ranged between 22.6% and 25.5% in 2019 and 37.0% in June 2020. The proportion of GAD-7 scores above cut-off ten ranged between 46.0% and 47.8% in 2019 and 64.5% in 2020. Compared with preceding trends, PHQ-9 scores were 3.11 (CI=2.40-3.83) higher than expected, and GAD-7 scores were 3.56 (CI=2.75-5.37) higher.DiscussionCOVID-19 impacted negatively depressive and anxiety symptoms, confirming previous studies and young people’s vulnerability in such uncertain times.
Changes in lipids and inflammation in adults with super-refractory status epilepticus on a ketogenic diet
Authors: Dickens Alex M , Johnson Tory , Lamichhane Santosh , Kumar Anupama , Pardo Carlos A. , Gutierrez Erie G. , Haughey Norman , Cervenka Mackenzie C. 
Published: February 2021

AbstractObjectiveTo test the hypothesis that increased ketone body production with a ketogenic diet (KD) will correlate with reductions in pro-inflammatory cytokines, lipid subspecies, and improved clinical outcomes in adults treated with an adjunctive ketogenic diet for super-refractory status epilepticus (SRSE).MethodsAdults (18 years or older) were treated with a 4:1 (fat:carbohydrate and protein) ratio enteral KD as adjunctive therapy to pharmacologic seizure suppression for SRSE. Blood and urine samples and clinical measurements were collected at baseline (n=10), after 1 week (n=8), and after 2 weeks of KD (n=5). Urine acetoacetate, serum β-hydroxybutyrate, lipidomics, pro-inflammatory cytokines (IL-1β, IL-6), chemokines (CCL3, CCL4, CXCL13), and clinical measurements were obtained at these 3 time points. Univariate and multivariate data analyses were performed to determine the correlation between ketone body production and circulating lipids, inflammatory biomarkers, and clinical outcome.ResultsChanges in lipids included an increase in ceramides, mono-hexosyl ceramide, sphingomyelin, phosphocholine, and phosphoserines, and there was a significant reduction in pro-inflammatory mediators IL-6 and CXCL13 seen at 1 and 2 weeks of KD. Higher blood β-hydroxybutyrate levels at baseline correlated with better clinical outcome however, ketone body production did not correlate with other variables during treatment. Higher chemokine CCL3 levels following treatment correlated with greater length of intensive care unit stay, higher modified Rankin Scale score (worse neurologic disability) at discharge and 6-month follow up.ConclusionsAdults receiving an adjunctive enteral ketogenic diet for super-refractory status epilepticus have alterations in select pro-inflammatory cytokines and lipid species that may predict response to treatment.
Identification of promising oilseed rape genotypes for the tropical regions of Iran using multivariate analysis
Authors: Bakhshi Behnam , Oghan Hassan Amiri , Alizadeh Bahram , Rameeh Valiollah , Payghamzadeh Kamal , Kiani Davood , Rabiee Mohammad , Rezaizad Abbas , Shiresmaeili Gholamhossein , Dalili Alireza , Kia Shahriar 
Published: February 2021

Abstractproducing new adapted oilseed rape cultivars among the available resources of rapeseed would be a valuable method to increase the cultivar diversity in the tropical regions. Low adaptable and high yield cultivars resources of oilseed rapes are now available in the tropical regions of Iran. The current study aimed to identify new high yield and adaptable genotypes adaptable across various tropical regions. To this end, 20 new genotypes and a check variety (Dalgan) were cultivated in the tropical regions of Iran based on a randomized complete block design (RCBD) with three replications during the 2019 to 2020 cropping season. The experimental sites are composed of five locations, including Gorgan, Sari, Rasht, Borazjan and Zabol. During the growth season, several phenological and quantitative traits were recorded. Combined ANOVA revealed significant genotype by environment interaction for all studied quantitative traits. Days to start flowering and days to end flowering showed the highest heritability. Correlation analysis showed a significant positive relationship between yield and flowering period, the number of sub-branches and also the number of pods per plant, but a negative and significant correlation with the days to maturity. Path analysis showed that the days to maturity had the most negative direct effect on yield and the days to start flowering, while the number of sub-branches had the most positive direct effect on yield. Canonical correlation showed that yield is correlated positively with phenological traits. The principal component analysis showed that the two first components covered 68.07% of all data variations which 12 genotypes were correlated with these two components. Cluster analysis categorized evaluated genotypes into three main groups. Finally, eight genotypes (from class 2 of the cluster) were selected in the current study, which had high yield and adaptability in the tropical regions of Iran.
The Organelle in the Ointment: cryptic mitochondria account for many unknown sequences in cross-species microbiome comparisons
Authors: Sonett Dylan , Brown Tanya , Bengtsson-Palme Johan , Padilla-Gamiño Jacqueline L. , Zaneveld Jesse R. 
Published: February 2021

AbstractThe genomes of mitochondria and chloroplasts contain ribosomal RNA (rRNA) genes, reflecting their evolutionary ancestry as free-living bacteria prior to endosymbiosis. In microbiome studies of animals, plants, or other eukaryotic hosts, these organellar rRNAs are often amplified. If identified, they can be discarded, merely reducing sequencing depth. However, incorrectly annotated mitochondrial reads may compromise statistical analysis by distorting relative abundances of free-living microbes. We quantified this by reanalyzing 7,459 samples from seven 16S rRNA sequencing studies, including the microbiomes of 927 unique animal genera. We find that under-annotation of cryptic mitochondrial reads affects multiple of these large-scale cross-species microbiome comparisons, and can be severe in some samples. It also varies between host species, potentially biasing cross-species microbiome comparisons. We propose a straightforward solution: by supplementing existing taxonomies with diverse mitochondrial rRNA sequences, we resolve up to 97% of unique unclassified sequences in some entire studies as mitochondrial (14% averaged across all studies), without increasing false positive annotations in mitochondria-free mock communities. Overall, improved annotation decreases the proportion of unknown sequences by ≥10-fold in 2,262 of 7,459 samples (30%), including representatives from 5 of 7 studies examined. While standard DADA2 analyses are severely affected, the default positive filter in Deblur run through QIIME2 discards many divergent mitochondrial sequences, preventing bias in analysis, but also making analysis of these sequences more difficult. We recommend leveraging mitochondrial sequence diversity to better identify, remove and analyze mitochondrial rRNA gene sequences in microbiome studies.
Small-molecule inhibitors of the RNA m6A demethylase FTO potently support the survival of dopamine neurons
Authors: Selberg Simona , Yu Li-Ying , Bondarenko Olesja , Kankuri Esko , Seli Neinar , Kovaleva Vera , Herodes Koit , Saarma Mart , Karelson Mati 
Published: February 2021

AbstractThe fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, is an important regulator of central nervous system development, neuronal signalling and disease. We present here the target-tailored development and biological characterization of small-molecule inhibitors of FTO. The active compounds were identified using high-throughput molecular docking and molecular dynamics screening of the ZINC compound library. In FTO binding and activity-inhibition assays the two best inhibitors demonstrated Kd= 185 nM; IC50= 1.46 μM (compound2) and Kd= 337 nM; IC50= 28.9 μM (compound3). Importantly, the treatment of mouse midbrain dopamine neurons with the compounds promoted cellular survival and rescued them from growth factor deprivation induced apoptosis already at nanomolar concentrations. Moreover, these inhibitors demonstrated good blood-brain-barrier penetration in the model system, 31.7% and 30.8%, respectively. The compounds2and3protected dopamine neurons with greater potency than our recently developed alkylation repair homolog protein 5 (AlkBH5) m6A demethylase inhibitors. Inhibition of m6A RNA demethylation by small-molecule drugs, as presented here, has therapeutic potential and provides tools for the identification of disease-modifying m6A RNAs in neurogenesis and neuroregeneration. Further refinement of the lead compounds identified in this study, can also lead to unprecedented breakthroughs in the treatment of neurodegenerative diseases.
Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis
Authors: Casey Theresa , Suarez-Trujillo Aridany , Cummings Shelby , Huff Katelyn , Crodian Jennifer , Bhide Ketaki , Aduwari Clare , Teeple Kelsey , Shamay Avi , Mabjeesh Sameer J. , Miguel Phillip San , Thimmapuram Jyothi , Plaut Karen 
Published: February 2021

ABSTRACTThe role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line withBmal1gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). Q-PCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr),Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.
Effect of exogenously applied alpha-tocopherol on vital agronomic, physiological and biochemical attributes of Lentil (Lens culinarisMedik.) under induced drought stress
Authors: Shah Wadood , Ullah Sami , Ali Sajjad , Idrees Muhammad , Khan Muhammad Nauman , Ali Kasif , Khan Ajmal , Ali Muhammad , Younas Frhan 
Published: February 2021

AbstractWater being a vital part of cell protoplasm plays a significant role in sustaining life on earth; drastic changes in climatic condition leads to limit the availability of water and causing other environmental chaos. Alpha-tocopherol being a powerful antioxidant plays a vital role in scavenging the ill effects of oxidative stress. A pot experiment was conducted by exposing lentil cultivar (Punjab-2009) to varying levels of induced drought stress, sprinkled with α-tocopherol 100, 200 and 300 mg/L. Induced water deficit stress conditions caused a pronounced decline in growth parameters including absolute growth rate (AGR), leaf area index (LAI), leaf area ratio (LAR), root shoot ratio (RSR), relative growth rate (RGR), chlorophyll a, b, total chlorophyll content, carotenoids and soluble protein content (SPC) which were significantly enhanced by exogenously applied α-tocopherol. Moreover, a significant increase was reported in total proline content (TPC), soluble sugar content (SSC), glycine betaine (GB) content, endogenous tocopherol levels, ascorbate peroxidase (APX), catalase (CAT) peroxidase (POD) and superoxide dismutase (SOD) activities. On contrary, exogenously applied α-tocopherol significantly reduced the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2). In conclusion, it was confirmed that exogenously applied α-tocopherol under induced drought stress regimes ameliorated drought stress tolerance potential of lentil cultivar to a great extent; by enhancing growth, physiological and biochemical attributes.
Difference in hoof conformation between shod and barefoot-managed hooves
Authors: De Klerk J.N. 
Published: February 2021

AbstractReasons for performing the studyHoof conformation is linked to biomechanics of the hoof and injury occurrence. There is no scientific data if conformation differs between shod and barefoot-managed hooves.ObjectivesTo investigate if and how shod and barefoot hooves differ in conformation.Study designRetrospective cohort study.MethodsStandardised lateral, dorsopalmar/dorsoplantar and solar photographs of 98 shod and 69 barefoot-managed hooves were included. Thirty-six of the barefoot horses were farrier-managed, 33 were podiatrist-managed. Length and angular measurements produced nine conformation parameters; dorsopalmar/plantar balance, solar symmetry, toe angle, heel angle, heel/toe angle difference, heel width, splaying index, flaring index and frog size.ResultsBarefoot hooves showed significantly fewer underrun heels, steeper heel angles, wider heels, increased splaying, increased flaring and larger frog size compared to hooves of shod horses. Solar symmetry showed a significant difference in front hooves but not hind hooves (P=0.038, P=0.104) and toe angle was not significantly different (P=0.368, P=0.425). There was no significant difference in the conformation of barefoot farrier and podiatrist-managed front hooves, however there was a significant difference in the hind hooves: farrier-managed hooves had longer frogs and shorter toes, compared to podiatrist-managed hooves.ConclusionsThe significant differences in hoof conformation found should be considered when managing the individual horse, since hoof conformation affects loading of the internal structure of the hoof and hence influences aetiopathogenesis of hoof pathology.