bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired Genomic Alterations on First-Line Chemotherapy With Cetuximab in Advanced Colorectal Cancer: Circulating Tumor DNA Analysis of the CALGB/SWOG-80405 Trial (Alliance)
Authors: Raghav Kanwal , Ou Fang-Shu , Venook Alan P. , Innocenti Federico , Sun Ryan , Lenz Heinz-Josef , Kopetz Scott 
Published: September 2022

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Acquired genomic alterations (Acq-GAs), specifically RAS, BRAF, and EGFR-ectodomain mutations and ERBB2 and MET amplifications, are recognized as major mechanisms of resistance to later-line anti–EGFR-antibody therapy in metastatic colorectal cancer (mCRC). However, data regarding emergence of these Acq-GAs under the selective pressure of first-line anti–EGFR-chemotherapy are lacking. We performed next-generation sequencing (Guardant360) on circulating tumor DNA obtained from paired plasma samples (pretreatment and postprogression) from the CALGB/SWOG-80405 trial, which randomly assigned patients with mCRC between first-line chemotherapy with cetuximab (anti–EGFR-chemotherapy) or bevacizumab (anti–VEGF-chemotherapy). The primary objective was to determine the prevalence of Acq-GAs on anti–EGFR-chemotherapy and compare this to the prevalence with anti–VEGF-chemotherapy on trial and pooled estimates (N = 292) seen with later-line anti–EGFR-antibody therapy as reported in the literature. Among the 61 patients on anti–EGFR-chemotherapy, only four (6.6%) developed ≥ 1 Acq-GAs of interest compared with 10.1% (7) on anti–VEGF-chemotherapy (odds ratio, 0.62; 95% CI, 0.20 to 2.11) and 62.0% on anti–EGFR-antibody therapy in later lines (odds ratio, 0.09; 95% CI, 0.03 to 0.23). Acq-GAs, classically associated with anti–EGFR-antibody resistance in later lines ( RAS, BRAF, and EGFR-ectodomain mutations; ERBB2 and MET amplifications), were rare with up-front use of anti–EGFR-chemotherapy indicating divergent resistance mechanisms. These findings have critical translational relevance to timing and value of circulating tumor DNA–guided anti-EGFR rechallenge in patients with mCRC, especially those treated with anti-EGFR therapy upfront.
Consensus Recommendations for the Use of Automated Insulin Delivery Technologies in Clinical Practice
Authors: Phillip Moshe , Nimri Revital , Bergenstal Richard M , Barnard-Kelly Katharine , Danne Thomas , Hovorka Roman , Kovatchev Boris P , Messer Laurel H , Parkin Christopher G , Ambler-Osborn Louise , Amiel Stephanie A , Bally Lia , Beck Roy W , Biester Sarah , Biester Torben , Blanchette Julia E , Bosi Emanuele , Boughton Charlotte K , Breton Marc D , Brown Sue A , Buckingham Bruce A , Cai Albert , Carlson Anders L , Castle Jessica R , Choudhary Pratik , Close Kelly L , Cobelli Claudio , Criego Amy B , Davis Elizabeth , de Beaufort Carine , de Bock Martin I , DeSalvo Daniel J , DeVries J Hans , Dovc Klemen , Doyle Francis J , Ekhlaspour Laya , Shvalb Naama Fisch , Forlenza Gregory P , Gallen Geraldine , Garg Satish K , Gershenoff Dana C , Gonder-Frederick Linda A , Haidar Ahmad , Hartnell Sara , Heinemann Lutz , Heller Simon , Hirsch Irl B , Hood Korey K , Isaacs Diana , Klonoff David C , Kordonouri Olga , Kowalski Aaron , Laffel Lori , Lawton Julia , Lal Rayhan A , Leelarathna Lalantha , Maahs David M , Murphy Helen R , Nørgaard Kirsten , O’Neal David , Oser Sean , Oser Tamara , Renard Eric , Riddell Michael C , Rodbard David , Russell Steven J , Schatz Desmond A , Shah Viral N , Sherr Jennifer L , Simonson Gregg D , Wadwa R Paul , Ward Candice , Weinzimer Stuart A , Wilmot Emma G , Battelino Tadej 
Published: September 2022

AbstractThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.
Design and experimental study of a fiber Bragg grating strain sensor with enhanced sensitivity
Authors: Pan Jianjun , Hou Wei , Wang Liangying , Zou Zisong , Xiao Fan 
Published: September 2022

A novel high-sensitivity fiber Bragg grating (FBG) strain sensor is reported, to the best of our knowledge. The sensitivity of the sensor is improved by fixing the FBG on an elastic substrate with a sensitization function. The sensitization principle of the designed sensor is introduced, and the mathematical model of the sensor is established. In the static and dynamic experiments of the sensor, the effect of adhesive between the sensor and the measured structure on the sensitivity of the FBG strain sensor is experimentally investigated. The experimental results show that the adhesive with high shear strength is beneficial to the realization of a high-sensitivity sensor. The sensor fixed with planting bar glue can achieve a sensitivity of 9.42 pm/µ

ε

, a repeatability error of 4.79%, and a hysteresis error of 3.36%, which is consistent with theoretical and simulation results. The designed high-sensitivity strain sensor has a simple structure, small size, and convenient installation, so it has a good application prospect in micro-strain monitoring.
Urban rats as carriers of invasive Salmonella Typhimurium sequence type 313, Kisangani, Democratic Republic of Congo
Authors: Falay Dadi , Hardy Liselotte , Tanzito Jacques , Lunguya Octavie , Bonebe Edmonde , Peeters Marjan , Mattheus Wesley , Van Geet Chris , Verheyen Erik , Akaibe Dudu , Katuala Pionus , Ngbonda Dauly , Weill François-Xavier , Pardos de la Gandara Maria , Jacobs Jan 
Published: September 2022

Background
Invasive non-typhoidal Salmonella (iNTS–mainly serotypes Enteritidis and Typhimurium) are major causes of bloodstream infections in children in sub-Saharan Africa, but their reservoir remains unknown. We assessed iNTS carriage in rats in an urban setting endemic for iNTS carriage and compared genetic profiles of iNTS from rats with those isolated from humans.

Methodology/Principal findings
From April 2016 to December 2018, rats were trapped in five marketplaces and a slaughterhouse in Kisangani, Democratic Republic of the Congo. After euthanasia, blood, liver, spleen, and rectal content were cultured for Salmonella. Genetic relatedness between iNTS from rats and humans—obtained from blood cultures at Kisangani University Hospital—was assessed with multilocus variable-number tandem repeat (VNTR) analysis (MLVA), multilocus sequence typing (MLST) and core-genome MLST (cgMLST). 1650 live-capture traps yielded 566 (34.3%) rats (95.6% Rattus norvegicus, 4.4% Rattus rattus); 46 (8.1%) of them carried Salmonella, of which 13 had more than one serotype. The most common serotypes were II.42:r:- (n = 18 rats), Kapemba (n = 12), Weltevreden and Typhimurium (n = 10, each), and Dublin (n = 8). Salmonella Typhimurium belonged to MLST ST19 (n = 7 rats) and the invasive ST313 (n = 3, isolated from deep organs but not from rectal content). Sixteen human S. Typhimurium isolates (all ST313) were available for comparison: MLVA and cgMLST revealed two distinct rat-human clusters involving both six human isolates, respectively, i.e. in total 12/16 human ST313 isolates. All ST313 Typhimurium isolates from rats and humans clustered with the ST313 Lineage 2 isolates and most were multidrug resistant; the remaining isolates from rats including S. Typhimurium ST19 were pan-susceptible.

Conclusion
The present study provides evidence of urban rats as potential reservoirs of S. Typhimurium ST313 in an iNTS endemic area in sub-Saharan Africa.
Laboratory evaluation of RealStar Yellow Fever Virus RT-PCR kit 1.0 for potential use in the global yellow fever laboratory network
Authors: Basile Alison J. , Niedrig Matthias , Lambert Amy J. , Meurant Robyn , Brault Aaron C. , Domingo Cristina , Goodman Christin H. , Johnson Barbara W. , Mossel Eric C. , Mulders Mick N. , Velez Jason O. , Hughes Holly R. 
Published: September 2022

Background
Early detection of human yellow fever (YF) infection in YF-endemic regions is critical to timely outbreak mitigation. African National Laboratories chiefly rely on serological assays that require confirmation at Regional Reference Laboratories, thus delaying results, which themselves are not always definitive often due to antibody cross-reactivity. A positive molecular test result is confirmatory for YF; therefore, a standardized YF molecular assay would facilitate immediate confirmation at National Laboratories. The WHO-coordinated global Eliminate Yellow Fever Epidemics Laboratory Technical Working Group sought to independently evaluate the quality and performance of commercial YF molecular assays relevant to use in countries with endemic YF, in the absence of stringent premarket assessments. This report details a limited laboratory WHO-coordinated evaluation of the altona Diagnostics RealStar Yellow Fever Virus RT-PCR kit 1.0.

Methodology and principal findings
Specific objectives were to assess the assay’s ability to detect YF virus strains in human serum from YF-endemic regions, determine the potential for interference and cross-reactions, verify the performance claims as stated by the manufacturer, and assess usability. RNA extracted from normal human serum spiked with YF virus showed the assay to be precise with minimal lot-to-lot variation. The 95% limit of detection calculated was approximately 1,245 RNA copies/ml [95% confidence interval 497 to 1,640 copies/ml]. Positive results were obtained with spatially and temporally diverse YF strains. The assay was specific for YF virus, was not subject to endogenous or exogenous interferents, and was clinically sensitive and specific. A review of operational characteristics revealed that a positivity cutoff was not defined in the instructions for use, but otherwise the assay was user-friendly.

Conclusions and significance
The RealStar Yellow Fever Virus RT-PCR kit 1.0 has performance characteristics consistent with the manufacturer’s claims and is suitable for use in YF-endemic regions. Its use is expected to decrease YF outbreak detection times and be instrumental in saving lives.
COMPASS II—Coordination of Medical Professions Aiming at Sustainable Support Protocol for a feasibility study of cooperation between general practitioner practices and community care points
Authors: Peter Lisa , Stumm Judith , Wäscher Cornelia , Kümpel Lisa , Heintze Christoph , Döpfmer Susanne 
Published: September 2022

Introduction
General practitioners (GP) increasingly face the challenge of meeting the complex care needs of multi-morbid patients. Previous studies show that GP practices would like support from other institutions in advising on social aspects of care for multi-morbid patients. Already existing counselling services, like community care points, are not sufficiently known by both GPs and patients. The aim of COMPASS II is to investigate the feasibility of cooperation between GP practices and community care points.

Methods and analysis
During the intervention, GPs send eligible multi-morbid patients with social care needs to a community care point. The community care points report the consultation results back to the GPs. In preparation for the intervention, in a moderated process, GP practices meet with the community care points to agree on information exchange. The primary outcome is the feasibility of the cooperation: Questionnaires will be sent to GPs, medical practice assistances and community care point personnel (focus: practicality, acceptability). Data will be collected on frequency and reasons for GP-initiated consultations at community care points (focus: demand). Qualitative interviews will be conducted with all participating groups (focus: acceptability, satisfaction). The secondary outcome is the assessment of changes in health-related quality of life, social support and satisfaction with care: participating patients complete a questionnaire before and three to six months after their counselling. The results of the study will be incorporated into a manual in which the experiences of the cooperation will be made available to other GP practices and community care points.

Discussion
In COMPASS II, GP practices establish cooperation with community care points. The latter are already existing institutions that provide independent and free advice on social matters. By using an existing institution, the established cooperation and experiences from the study can be used beyond the end of the study.

Trial registration
The trial is registered with DRKS-ID: DRKS00023798, Coordination of Medical Professions Aiming at Sustainable Support II.
Sex differences in saliva-based DNA methylation changes and environmental stressor in young African American adults
Authors: Saadatmand Forough , Abbas Muneer , Apprey Victor , Tailor Krishma , Kwabi-Addo Bernard 
Published: September 2022

Background
Low socioeconomic status neighborhood exposure to stress and violence may be sources of negative stimuli that poses significant health risks for children, adolescents and throughout the life course of an individual. The study aims to investigate if aberrant epigenetic DNA methylation changes may be a potential mechanism for regulating neighborhood exposures and health outcomes.

Methods
Exposure to environmental stressors identified in 98 young African American (AA) adults aged 18–25 years old from the Washington D.C., area were used in the study. We correlated the association between stress markers; cortisol, CRP, IgG, IGA, IgM, and self-reported exposure to violence and stress, with quantitative DNA methylation changes in a panel of gene-specific loci using saliva DNA.

Results
In all participants studied, the exposure to violence was significant and negatively correlated with DNA methylation of MST1R loci (p = 0.032; r = -0.971) and nominally significant with NR3C1 loci (p = 0.053; r = -0.948). In addition, we observed significant and negative correlation of DNA methylation changes of LINE1 (p = 0.044; r = -0.248); NR3C1 (p = 0.017; r = -0.186); MSTR1 (p = 0.022; r = -0.192); and DRD2 (p = 0.056; r = -0.184; albeit nominal significant correlation) with IgA expression. On the other hand, we observed a significant and position correlation of DNA methylation changes in DRD2 (p = 0.037; r = 0.184) with IgG expression. When participants were stratified by sex, we observed in AA young male adults, significant DNA methylation changes of MST1R (p< 0.05) and association with exposure to violence and IgG level. We also observed significant DNA methylation levels of DRD2 (p< 0.05) and association with IgA, IgG, and cortisol level. Furthermore, we observed significant DNA methylation changes of NR3C1 (p< 0.05) with stress, IgA, and IgG in the male participants only. On the other hand, we only observed significant and a positive association of IgG with DNA methylation levels of ESR1 (p = 0.041) in the young AA female participants.

Conclusion
Our preliminary observation of significant DNA methylation changes in neuronal and immune genes in saliva samples supports our recently published genome-wide DNA methylations changes in blood samples from young AA male adults indicating that saliva offers a non-invasive means for DNA methylation prediction of exposure to environmental stressors in a gender-specific manner.
Overlap between dengue, Zika and chikungunya hotspots in the city of Rio de Janeiro
Authors: Queiroz Eny Regina da Silva , Medronho Roberto de Andrade 
Published: September 2022

Background
Arboviruses represent a threat to global public health. In the Americas, the dengue fever is endemic. This situation worsens with the introduction of emerging, Zika fever and chikungunya fever, causing epidemics in several countries within the last decade. Hotspot analysis contributes to understanding the spatial and temporal dynamics in the context of co-circulation of these three arboviral diseases, which have the same vector: Aedes aegypti.

Objective
To analyze the spatial distribution and agreement between the hotspots of the historical series of reported dengue cases from 2000 to 2014 and the Zika, chikungunya and dengue cases hotspots from 2015 to 2019 in the city of Rio de Janeiro.

Methods
To identify hotspots, Gi* statistics were calculated for the annual incidence rates of reported cases of dengue, Zika, and chikungunya by neighborhood. Kendall’s W statistic was used to analyze the agreement between diseases hotspots.

Results
There was no agreement between the hotspots of the dengue fever historical series (2000–2014) and those of the emerging Zika fever and chikungunya fever (2015–2019). However, there was agreement between hotspots of the three arboviral diseases between 2015 and 2019.

Conclusion
The results of this study show the existence of persistent hotspots that need to be prioritized in public policies for the prevention and control of these diseases. The techniques used with data from epidemiological surveillance services can help in better understanding of the dynamics of these diseases wherever they circulate in the world.
Predictors of knowledge and adherence to COVID-19 safety protocols among nurses at health facilities in Tamale Metropolis of Northern Ghana
Authors: Kanligi David Abatanie , Boah Michael , Adokiya Martin Nyaaba 
Published: September 2022

Background
Corona Virus Disease of 2019 (COVID-19) emerged in 2019 and caused widespread disruption to many facets of life, including healthcare. Healthcare workers, particularly nurses, became the front-line fighters against the pandemic, making it imperative to comply with recommended safety protocols. However, many nurses were infected by the virus in the Tamale Metropolis, raising concerns regarding their level of adherence to the safety protocols. This study assessed the predictors of knowledge and adherence to COVID-19 safety protocols among nurses at selected health facilities in the Tamale Metropolis of northern Ghana.

Methods
A facility based cross-sectional study design was adopted and 339 nurses from six (6) public health facilities in the Tamale Metropolis were recruited for the study using questionnaires. The questionnaires were transformed into Google Forms for respondents to answer online via WhatsApp or email. The data were exported from the Google spreadsheet into SPSS and analyzed using descriptive and inferential statistics.

Results
Of the 339 participants, 60.2% were classified as having adequate knowledge while only 9.1% demonstrated high adherence to COVID-19 safety protocols. Knowledge of COVID-19 was predicted by source of information, and marital status, whereas health facility types predicted level of adherence. The odds of having adequate knowledge were higher among unmarried nurses (AOR = 1.94; 95% CI: 1.16–3.25; p = 0.012) and nurses using social media (AOR = 1.80; 95%CI 1.02–3.18; p = 0.042) compared to their counterparts. Meanwhile, primary health care nurses (AOR = 0.24; 95% CI = 0.12–0.50; p<0.001) and secondary health care nurses (AOR = 0.52; 95% CI = 0.31–0.88; P = 0.016) had reduced odds of exhibiting higher adherence compared to nurses from tertiary-level facility.

Conclusion
In this study, we found that knowledge was high but adherence to COVID-19 safety protocols was low. We suggest that facility managers should enforce compliance of their staff to the safety protocols to prevent spread of the virus within healthcare settings.
NMR-based metabolomic analysis identifies RON-DEK-β-catenin dependent metabolic pathways and a gene signature that stratifies breast cancer patient survival
Authors: Vicente-Muñoz Sara , Hunt Brian G. , Lange Taylor E. , Wells Susanne I. , Waltz Susan E. 
Published: September 2022

Background
Advances in detection techniques and treatment have increased the diagnosis of breast cancer at early stages; however, recurrence occurs in all breast cancer subtypes, and both recurrent and de novo metastasis are typically treatment resistant. A growing body of evidence supports the notion that metabolic plasticity drives cancer recurrence. RON and DEK are proteins that promote cancer metastasis and synergize mechanistically to activate β-catenin, but the metabolic consequences are unknown.

Methods
To ascertain RON-DEK-β-catenin dependent metabolic pathways, we utilized an NMR-based metabolomics approach to determine steady state levels of metabolites. We also interrogated altered metabolic pathway gene expression for prognostic capacity in breast cancer patient relapse-free and distant metastasis-free survival and discover a metabolic signature that is likely associated with recurrence.

Results
RON-DEK-β-catenin loss showed a consistent metabolite regulation of succinate and phosphocreatine. Consistent metabolite alterations between RON and DEK loss (but not β-catenin) were found in media glucose consumption, lactate secretion, acetate secretion, and intracellular glutamine and glutathione levels. Consistent metabolite alterations between RON and β-catenin loss (and not DEK) were found only in intracellular lactate levels. Further pathway hits include β-catenin include glycolysis, glycosylation, TCA cycle/anaplerosis, NAD+ production, and creatine dynamics. Genes in these pathways epistatic to RON-DEK-β-catenin were used to define a gene signature that prognosticates breast cancer patient survival and response to chemotherapy.

Conclusions
The RON-DEK-β-catenin axis regulates the numerous metabolic pathways with significant associations to breast cancer patient outcomes.
PERSEPSI PUBLIK TERHADAP PENULARAN PANDEMI KORONA DI INDONESIA KLUSTER GOWA
Authors: Kusno Ali 
Published: September 2022

ABSTRAKPenelitian ini bertujuan untuk mengidentifikasi persepsi publik yang berkembang terhadap eks peserta Ijtima Ulama di Gowa yang dianggap sebagai salah satu kluster persebaran pandemi korona di Indonesia. Pendekatan penelitian menggunakan analisis wacana kritis Model Fairclough. Pendekatan itu memungkinkan penggunaan bahasa dalam wacana ditempatkan sebagai praktik sosial; wacana atau penggunaan bahasa dihasilkan dalam sebuah peristiwa diskursif tertentu; dan wacana yang dihasilkan berbentuk sebuah genre tertentu. Data penelitian berupa wacana tanggapan para pengguna Facebook terhadap pemberitaan tentang pandemi korona kluster Gowa. Teknik analisis data menggunakan model interaktif. Hasil penelitian menunjukkan bahwa setelah kegiatan Ijtima Ulama di Gowa, para eks peserta kegiatan tersebut mendapat beragam stigma negatif. sebagian besar warganet beranggapan bahwa eks kegiatan Gowa sebagai salah satu penyebar wabah korona di Indonesia. Meskipun para eks peserta kegiatan Gowa sudah menjalani proses karantina dan pengobatan, tetap mendapatkan perlakuan yang tidak mengenakkan dari masyarakat sekitar, terkesan eks kegiatan Gowa dan keluarga dikucilkan meskipun sebenarnya masyarakat lebih menarik diri. Pemahaman agama yang trerkesan membabi buta akan sangat berbahaya bagi kehidupan umat Islam. Penanganan lebih tegas terhadap kejadian serupa agar masyarakat agar lebih patuh terhadap kebijakan pemerintah.