bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the COVID-19 pandemic on family medicine residency training
Authors: Awadallah Nida S , Czaja Angela S , Fainstad Tyra , McNulty Monica C , Jaiswal Kshama R , Jones Teresa S , Rumack Carol M 
Published: February 2021

Abstract

Background
Family physicians have played a unique clinical role during the COVID-19 pandemic. We hypothesized that the pandemic would be associated with significant deleterious effects on clinical activity, educational training, personal safety and well-being.

Objective
We conducted a national survey to obtain preliminary data that would assist in future targeted data collection and subsequent evaluation of the impact of the pandemic on family medicine residents and teaching faculty.

Methods
An anonymous online survey of residents and faculty was distributed via the Association of Family Medicine Residency Directors list serve between 5/21/2020 and 6/18/2020. Survey questions focused on clinical and educational activities, safety and well-being.

Results
One hundred and fifty-three residents and 151 teaching faculty participated in the survey. Decreased clinical activity was noted by 81.5% of residents and 80.9% of faculty and the majority began conducting telehealth visits (97.9% of residents, 91.0% of faculty). Distance learning platforms were used by all residents (100%) and 39.6% noted an overall positive impact on their education. Higher levels of burnout did not significantly correlate with reassignment of clinical duties (residents P = 0.164; faculty P = 0.064). Residents who showed significantly higher burnout scores (P = 0.035) and a decline in levels of well-being (P = 0.031) were more likely to participate in institutional well-being support activities.

Conclusions
Our preliminary data indicate that family medicine residents and teaching faculty were profoundly affected by the COVID-19 pandemic. Future studies can be directed by current findings with focus on mitigation factors in addressing globally disruptive events such as COVID-19.
Climatic criteria for successful introduction ofQuercusspecies identified by use of Arboretum data
Authors: Madsen Corrie Lynne , Kjær Erik Dahl , Ræbild Anders 
Published: February 2021

AbstractClimate change is projected to have a major influence on forest tree populations and composition. Translocation of species outside their historic range has been suggested to maintain healthy forests and tree species. The introduction of exotic species into botanical gardens and arboretums worldwide demonstrates the ability of many trees to grow outside their natural habitat and may play an important part in avoiding climate driven extinction if grown in a matching climate. However, it remains to be determined which climatic factors are the most important predictors of climatic match. In this study we use information from the arboretum in Hørsholm, Denmark, to analyse differences in performance of translocated Oak (Quercus) and show how data from tree collections can be used to predict success of assisted migration. Our data included archive lists of georeferenced Northern hemisphere introductions of Quercus, and assessments of their survival and growth rates in nursery and the Hørsholm arboretum. Using logistic and linear regression we modelled the importance of different bioclimatic predictor variables for survival and growth rate. Several correlations were identified across the Quercus genus. Survival of Quercus species depended primarily on the temperatures at the origin, whereas growth on the other hand was more dependent on a match in precipitation. The negative correlations indicated that introductions were less successful from sites with higher temperatures and wetter conditions. The study demonstrates an approach to use historical data collected from arboreta and botanical gardens in climate change research. This new approach can provide useful information in relation to assisted migration for an array of poorly investigated species where this may be the only source of information.
Does geographic spending variation exacerbate healthcare benefit inequality? A benefit incidence analysis for Indonesia
Authors: Sambodo Novat Pugo , Van Doorslaer Eddy , Pradhan Menno , Sparrow Robert 
Published: February 2021

Abstract
The Indonesian government has made some ambitious steps to achieve Universal Health Coverage through the newly formed National Health Insurance [Jaminan Kesehatan Nasional (JKN)], establishing a single-payer insurance agency and prospective provider payment mechanism. This study aims to assess the benefit incidence of healthcare funding in the JKN era, and its distribution by socio-economic status considering regional variation in unit costs. We evaluate whether the benefit incidence of funding is skewed towards urban and wealthier households. We also investigate whether standard benefit incidence analysis using national unit costs underestimates regional disparities in healthcare funding. Lastly, we examine whether the design of the JKN provider payment system exacerbates regional inequalities in healthcare funding and treatment intensity. The analysis relies on Indonesia’s annual National Socio-economic Survey (Susenas) and administrative data on JKN provider payments from 2015 to 2017, combined at district level for 466 districts. We find that the benefit incidence of healthcare expenditure favours the wealthier groups. We also observe substantial variation in hospital unit costs across regions in Indonesia. As a result, standard benefit incidence analysis (using national average unit transfers) underestimates the inequality due to regional disparities in healthcare supply and intensity of treatment. The JKN provider payment seems to favour relatively wealthier regions that harbour more advanced healthcare services. Urban dwellers and people living in Java and Bali also enjoy greater healthcare benefit incidence compared to rural areas and the other islands.
Negotiating the Legacies of Intragroup Violence in Timor Leste
Authors: Igreja Victor 
Published: February 2021

Abstract
The end of the Cold War raised the profiles of international tribunals and truth commissions as official mechanisms for dealing with the legacies of political violence around the world. However, these mechanisms have the tendency to generate somewhat stark accounts of the past and present, and of guilt and heroism, and are thus an inadequate forum for grasping the complexities of protracted, multiple and fracturing intragroup violence. This article is based on fieldwork in Timor Leste. It analyzes the unresolved legacies of Timorese intragroup political violence through a focus on the interventions of political leaders in the Timorese national parliament over time, coupled with an analysis of some of their autobiographies. It reveals how the crisscrossing histories of violence and fluctuating group affiliations have shaped ongoing political struggles, from silence and denial to unsettling voices and deliberations, which constitute sources of enduring political negotiations, mistrust and tension among Timorese leaders.
Symmetric Decompositions and the Veronese Construction
Authors: Jochemko Katharina 
Published: February 2021

Abstract
We study rational generating functions of sequences $\{a_n\}_{n\geq 0}$ that agree with a polynomial and investigate symmetric decompositions of the numerator polynomial for subsequences $\{a_{rn}\}_{n\geq 0}$. We prove that if the numerator polynomial for $\{a_n\}_{n\geq 0}$ is of degree $s$ and its coefficients satisfy a set of natural linear inequalities, then the symmetric decomposition of the numerator for $\{a_{rn}\}_{n\geq 0}$ is real-rooted whenever $r\geq \max \{s,d+1-s\}$. Moreover, if the numerator polynomial for $\{a_n\}_{n\geq 0}$ is symmetric, then we show that the symmetric decomposition for $\{a_{rn}\}_{n\geq 0}$ is interlacing. We apply our results to Ehrhart series of lattice polytopes. In particular, we obtain that the $h^\ast $-polynomial of every dilation of a $d$-dimensional lattice polytope of degree $s$ has a real-rooted symmetric decomposition whenever the dilation factor $r$ satisfies $r\geq \max \{s,d+1-s\}$. Moreover, if the polytope is Gorenstein, then this decomposition is interlacing.
Strategic Spirituality: Positive Psychology, the Army, and the Ambiguities of “Spirituality Fitness”
Authors: Weitzman Steven 
Published: February 2021

AbstractIn the wake of increased mental health issues resulting from combat in Afghanistan and Iraq, psychologists affiliated with the field of positive psychology developed a resiliency training program for the US Army that included strengthening “spirituality fitness” as one of its goals. The initiative represents what may be the largest single effort to use spirituality to intervene in people’s mental health, but it also represents an intervention in the semantics of spirituality, an attempt to make it signify in new ways. This study treats this intervention as an exercise in “strategic ambiguity,” the use of unclear language to balance between contradictory goals, and draws from this approach some inferences about what it is that those working in the field of positive psychology import into the spirituality they have promoted within American military culture.
Impact of extracorporeal membrane oxygenation (ECMO) support on piperacillin exposure in septic patients: a case–control study
Authors: Fillâtre P , Lemaitre F , Nesseler N , Schmidt M , Besset S , Launey Y , Maamar A , Daufresne P , Flecher E , Le Tulzo Y , Tadie J M , Tattevin P 
Published: February 2021

Abstract

Objectives
To describe the impact of extracorporeal membrane oxygenation (ECMO) devices on piperacillin exposure in ICU patients.

Methods
This observational, prospective, multicentre, case–control study was performed in the ICUs of two tertiary care hospitals in France. ECMO patients with sepsis treated with piperacillin/tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin were described based on a population pharmacokinetic model, calculating the proportion of time the piperacillin plasma concentration was above 64 mg/L (i.e. 4× MIC breakpoint for Pseudomonas aeruginosa).

Results
Forty-two patients were included. Median (IQR) age was 60 years (49–66), SOFA score was 11 (9–14) and creatinine clearance was 47 mL/min (5–95). There was no significant difference in the proportion of time piperacillin concentrations were ≥64 mg/L in patients treated with ECMO and controls during the first administration (P = 0.184) or at steady state (P = 0.309). Following the first administration, 36/42 (86%) patients had trough piperacillin concentrations &lt;64 mg/L. Trough concentrations at steady state were similar in patients with ECMO and controls (P = 0.535). Creatinine clearance ≥40 mL/min was independently associated with piperacillin trough concentration &lt;64 mg/L at steady state [OR = 4.3 (95% CI 1.1–17.7), P = 0.043], while ECMO support was not [OR = 0.5 (95% CI 0.1–2.1), P = 0.378].

Conclusions
ECMO support has no impact on piperacillin exposure. ICU patients with sepsis are frequently underexposed to piperacillin, which suggests that therapeutic drug monitoring should be strongly recommended for severe infections.
Phase II study of cetuximab plus S-1/cisplatin therapy in Japanese patients with advanced gastric cancer
Authors: Yamaguchi Kensei , Fuse Nozomu , Komatsu Yoshito , Fujii Hirofumi , Hironaka Shuichi , Omuro Yasushi , Muro Kei , Yasui Hirofumi , Ueda Shinya , Nishina Tomohiro , Watanabe Morihiro , Ohtsu Atsushi 
Published: February 2021

Abstract

Objective
We evaluated the efficacy and safety of first-line S-1 plus cisplatin in combination with cetuximab for Japanese patients with advanced gastric cancer, including gastroesophageal junction adenocarcinoma.

Methods
This open-label, single arm, multicenter, phase 2 trial was conducted to assess first-line cetuximab plus S-1 plus cisplatin for advanced gastric cancer. A total of 40 patients from 10 centers were enrolled. Cetuximab was administered weekly, with the initial infusion at 400 mg/m2 and then 250 mg/m2 each subsequent week. S-1 plus cisplatin chemotherapy was concomitantly conducted in a 5-week cycle: S-1 (40–60 mg, adjusted for body surface area) was given twice daily for 3 consecutive weeks, followed by a 2-week rest period, and cisplatin (60 mg/m2) was given on day 8 of each cycle for a maximum of 8 cycles. Treatment continued until the occurrence of radiographically confirmed progressive disease, unacceptable toxicity or withdrawal of consent. The primary endpoint was the best overall response. Secondary endpoints included progression-free survival and safety.

Results
A total of 40 patients were evaluable. One patient (2.5%) had a complete response; 15 patients (37.5%) had a partial response. The observed overall response rate according to the independent review committee was 40.0% (95% confidence interval, 24.9–56.7; P = 0.7043 [one-sided null hypothesis: overall response rate ≤ 43%]); median PFS was 5.6 months (95% confidence intervals, 4.2–8.3). No adverse events leading to death were reported during the study, and no specific safety concerns were observed.

Conclusions
Overall, the addition of cetuximab to S-1 plus cisplatin was well tolerated in patients with advanced gastric cancer but provided no additional clinical benefit in this study.
ClinicalTrials.gov identifier: NCT01388790.
A review of the AJCC melanoma staging system in the TNM classification (eighth edition)
Authors: Ogata Dai , Namikawa Kenjiro , Takahashi Akira , Yamazaki Naoya 
Published: February 2021

Abstract
In the eighth edition of the American Joint Committee on Cancer Staging Manual, several modifications were made for melanoma. These modifications were aimed at improving the prognosis prediction accuracy of the staging system. The main modifications are as follows: the cutoff value of the T1 category has been changed, and there are new classifications of stage IIID and of M1d (metastasis of the central nervous system). These changes will allow for more accurate stratification of melanoma prognosis. However, it is necessary to validate the new modifications through future clinical research.
The Heterogeneous Landscape and Early Evolution of Pathogen-Associated CpG Dinucleotides in SARS-CoV-2
Authors: Di Gioacchino Andrea , Šulc Petr , Komarova Anastassia V , Greenbaum Benjamin D , Monasson Rémi , Cocco Simona 
Published: February 2021

AbstractCOVID-19 can lead to acute respiratory syndrome, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We characterize CpG content by a CpG force that accounts for statistical constraints acting on the genome at the nucleotidic and amino acid levels. The CpG force, as the CpG content, is overall low compared with other pathogenic betacoronaviruses; however, it widely fluctuates along the genome, with a particularly low value, comparable with the circulating seasonal HKU1, in the spike coding region and a greater value, comparable with SARS and MERS, in the highly expressed nucleocapside coding region (N ORF), whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3′UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic, finding a signature of CpG loss in regions with a greater CpG force. Sequence motifs preceding the CpG-loss-associated loci in the N ORF match recently identified binding patterns of the zinc finger antiviral protein. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven in the SARS-CoV-2 genome, and particularly in the N ORF, by the viral codon bias, the transition–transversion bias, and the pressure to lower CpG content.
Elucidating the role of long intergenic non-coding RNA 339 in human endometrium and endometriosis
Authors: Holdsworth-Carson Sarah J , Churchill Molly , Donoghue Jacqueline F , Mortlock Sally , Fung Jenny N , Sloggett Clare , Chung Jessica , Cann Leonie , Teh Wan Tinn , Campbell Katie-Rose , Luwor Rodney , Healey Martin , Montgomery Grant , Girling Jane E , Rogers Peter A W 
Published: February 2021

ABSTRACT
Endometriosis is a complex disease, influenced by genetic factors. Genetic markers associated with endometriosis exist at chromosome 1p36.12 and lead to altered expression of the long intergenic non-coding RNA 339 (LINC00339), however, the role of LINC00339 in endometriosis pathophysiology remains unknown. The aim of this work was to characterize the expression patterns of LINC00339 mRNA in endometrium and endometriotic lesions in situ and to determine the functional role of LINC00339 in human endometrium. We employed RNA-sequencing (RNA-seq), quantitative RT-PCR and in situ hybridization to investigate the abundance of LINC00339 transcripts in endometrium and endometrial cell lines and to describe the pattern and localization of LINC00339 expression in endometrium and endometriotic lesions. LINC00339 mRNA expression was manipulated (overexpressed and silenced) in endometrial stromal cell lines and RNA-seq data from overexpression models were analysed using online bioinformatics platforms (STRING and Ingenuity Pathway Analysis) to determine functional processes. We demonstrated the expression of LINC00339 in endometriotic lesions for the first time; we found LINC00339 expression was restricted to the lesion foci and absent in surrounding non-lesion tissue. Furthermore, manipulation of LINC00339 expression in endometrial stromal cell lines significantly impacted the expression of genes involved in immune defence pathways. These studies identify a novel mechanism for LINC00339 activity in endometrium and endometriosis, paving the way for future work, which is essential for understanding the pathogenesis of endometriosis.
Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences
Authors: Karasik Agnes , Jones Grant D , DePass Andrew V , Guydosh Nicholas R 
Published: February 2021

Abstract
Ribonuclease L (RNase L) is activated as part of the innate immune response and plays an important role in the clearance of viral infections. When activated, it endonucleolytically cleaves both viral and host RNAs, leading to a global reduction in protein synthesis. However, it remains unknown how widespread RNA decay, and consequent changes in the translatome, promote the elimination of viruses. To study how this altered transcriptome is translated, we assayed the global distribution of ribosomes in RNase L activated human cells with ribosome profiling. We found that RNase L activation leads to a substantial increase in the fraction of translating ribosomes in ORFs internal to coding sequences (iORFs) and ORFs within 5′ and 3′ UTRs (uORFs and dORFs). Translation of these alternative ORFs was dependent on RNase L’s cleavage activity, suggesting that mRNA decay fragments are translated to produce short peptides that may be important for antiviral activity.
Role of a local transcription factor in governing cellular carbon/nitrogen homeostasis inPseudomonas fluorescens
Authors: Naren Naran , Zhang Xue-Xian 
Published: February 2021

AbstractAutoactivation of two-component systems (TCSs) can increase the sensitivity to signals but inherently cause a delayed response. Here, we describe a unique negative feedback mechanism enabling the global NtrB/NtrC regulator to rapidly respond to nitrogen starvation over the course of histidine utilization (hut) in Pseudomonas fluorescens. NtrBC directly activates transcription of hut genes, but overexpression will produce excess ammonium leading to NtrBC inactivation. To prevent this from occurring, the histidine-responsive repressor HutC fine-tunes ntrBC autoactivation: HutC and NtrC bind to the same operator site in the ntrBC promoter. This newly discovered low-affinity binding site shows little sequence similarity with the consensus sequence that HutC recognizes for substrate-specific induction of hut operons. A combination of genetic and transcriptomic analysis indicated that both ntrBC and hut promoter activities cannot be stably maintained in the ΔhutC background when histidine fluctuates at high concentrations. Moreover, the global carbon regulator CbrA/CbrB is involved in directly activating hut transcription while de-repressing hut translation via the CbrAB-CrcYZ-Crc/Hfq regulatory cascade. Together, our data reveal that the local transcription factor HutC plays a crucial role in governing NtrBC to maintain carbon/nitrogen homeostasis through the complex interactions between two TCSs (NtrBC and CbrAB) at the hut promoter.
Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release
Authors: Ijäs Heini , Shen Boxuan , Heuer-Jungemann Amelie , Keller Adrian , Kostiainen Mauri A , Liedl Tim , Ihalainen Janne A , Linko Veikko 
Published: February 2021

AbstractDoxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA-carriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. These features have been largely ignored in experimenting with DNA nanostructures, but are probably the major sources of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA-carriers.