bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contemporary debates
Authors: Pearsall Sarah M. S. 
Published: April 2022

Abstract
‘Contemporary debates’ opens with a government raid on the residents of the Arizona town of Short Creek in 1953. They were practicing polygamy as members of the Fundamentalist Church of Jesus Christ of Latter-day Saints, an organization that had separated from the Mormon Church over their continued devotion to polygamy. In many such situations, the revival of so-called traditional polygamy has been connected with religious fundamentalism and limits on women’s public participation, as is also the case among some Muslims in Saudi Arabia. Yet there have also been “campaigns for monogamy” among Muslims in places like Malaysia. At the same time, there has been pressure on monogamy from US left-wing critics, who question married monogamy as the correct or only path for domestic organization. There is a liberal, even libertarian, celebration of “poly,” especially polyamory, in Western liberal democracies.
Impact of Ergonomic Posture on the Chemical Exposure of Workers in the Petroleum and Chemical Industry
Authors: Whitehead Carson , Maier M Andrew , Rao Marepalli B , Eturki Mohamed , Snawder John E , Davis Kermit G 
Published: April 2022

Abstract

Objectives
Despite a rise in automation, workers in the petroleum refining and petrochemical manufacturing industry are potentially exposed to various chemicals through inhalation while performing routine job duties. Many factors contribute to the degree of exposure experienced in this setting. The study objective was to characterize the impact of workplace conditions, anthropometric variability, and task orientation on exposure for a simulated routine operations task.

Methods
A chemical exposure laboratory simulation study was designed to evaluate the dependent variable of chemical exposure level in the breathing zone for methane and sulfur hexafluoride. The independent variables were (i) posture of the worker, (ii) worker anthropometry, (iii) process configuration, and (iv) gas density.

Results
Pipe height was a significant predictor of gas concentration measured in the breathing zone when located in a position that encouraged the gas to enter the breathing zone of the worker. Worker anthropometry had a major impact; tall worker’s (male) chemical concentrations exceeded those of the short worker (female) for methane simulations but the opposite resulted for sulfur hexafluoride. Also, worker posture had a significant impact on gas exposure where nonneutral postures were found to have higher levels of chemical concentration.

Conclusions
The study findings indicate that the breathing zone location is altered by posture and worker height, which changes the exposures relative to the emission source depending on the gas density of the chemicals that are present. As a result, qualitative risk assessment cannot be performed accurately without accounting for these factors. Practically, controls may need to account for worker size differences and posture adaptations.
Oligoribonucleotide interference-PCR: principles and applications
Authors: Shimizu Takeshi , Fujita Toshitsugu , Fujii Hodaka 
Published: April 2022

Abstract
Polymerase chain reaction (PCR) amplification of multiple templates using common primers is used widely for molecular biological research and clinical diagnosis. However, amplifying a specific DNA sequence harboring a mutation that is present in a small number of mutant cells within a large population of normal cells (e.g., as in cancer) in a tissue is difficult using the original PCR protocol. Thus, some measures are necessary to suppress amplification of background signals. To achieve this, we developed the oligoribonucleotide (ORN) interference-PCR (ORNi-PCR) technology in which an ORN (short RNA) hybridizes with a complementary DNA sequence to inhibit PCR amplification across the specific target sequence. ORNs can be prepared inexpensively, and ORNi-PCR can be carried out easily by adding ORNs to the PCR reaction mixture. Suppressing amplification of target sequences by ORNi-PCR is useful for detecting target sequence mutations. We showed that ORNi-PCR can discriminate single-nucleotide mutations in cancer cells and indel mutations introduced by genome editing. We also showed that ORNi-PCR can identify the CpG methylation status of a target sequence within bisulfite-treated DNA, and can enrich DNA sequences of interest from a DNA mixture by suppressing amplification of unwanted sequences. Thus, ORNi-PCR has many potential applications in various fields, including medical diagnosis and molecular biology. In this review, we outline the principles of the ORNi-PCR method and its use to detect nucleotide mutations in a variety of specimens.
Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial
Authors: Holubar Marisa , Subramanian Aruna , Purington Natasha , Hedlin Haley , Bunning Bryan , Walter Katharine S , Bonilla Hector , Boumis Athanasia , Chen Michael , Clinton Kimberly , Dewhurst Liisa , Epstein Carol , Jagannathan Prasanna , Kaszynski Richard H , Panu Lori , Parsonnet Julie , Ponder Elizabeth L , Quintero Orlando , Sefton Elizabeth , Singh Upinder , Soberanis Luke , Truong Henry , Andrews Jason R , Desai Manisha , Khosla Chaitan , Maldonado Yvonne 
Published: April 2022

Abstract

Background
Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (COVID-19) in several countries.

Methods
We conducted a phase 2, double-blind, randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg BID days 2–10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir’s impact on mutagenesis.

Results
We randomized 149 participants with 116 included in the mITT cohort. The participants’ mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48–1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54–1.29]; sustained: HR, 0.87 [95% CI, .52–1.45]) and no difference in transition mutation accumulation in the viral genome during treatment.

Conclusions
Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19.

Clinical Trials Registration
NCT04346628.
Relationship between ischaemia, coronary artery calcium scores, and major adverse cardiovascular events
Authors: Miller Robert J H , Han Donghee , Singh Ananya , Pieszko Konrad , Slomka Piotr J , Gransar Heidi , Park Rebekah , Otaki Yuka , Friedman John D , Hayes Sean , Thomson Louise , Rozanski Alan , Berman Daniel S 
Published: April 2022

Abstract

Aims
Positron emission tomography (PET) myocardial perfusion imaging (MPI) is often combined with coronary artery calcium (CAC) scanning, allowing for a combined anatomic and functional assessment. We evaluated the independent prognostic value of quantitative assessment of myocardial perfusion and CAC scores in patients undergoing PET.

Methods and results
Consecutive patients who underwent Rb-82 PET with CAC scoring between 2010 and 2018, with follow-up for major adverse cardiovascular events (MACE), were identified. Perfusion was quantified automatically with total perfusion deficit (TPD). Our primary outcome was MACE including all-cause mortality, myocardial infarction (MI), admission for unstable angina, and late revascularization. Associations with MACE were assessed using multivariable Cox models adjusted for age, sex, medical history, and MPI findings including myocardial flow reserve.
In total, 2507 patients were included with median age 70. During median follow-up of 3.9 years (interquartile range 2.1–6.1), 594 patients experienced at least one MACE. Increasing CAC and ischaemic TPD were associated with increased MACE, with the highest risk associated with CAC &gt; 1000 [adjusted hazard ratio (HR) 1.67, 95% CI 1.24–2.26] and ischaemic TPD &gt; 10% (adjusted HR 1.80, 95% CI 1.40–2.32). Ischaemic TPD and CAC improved overall patient classification, but ischaemic TPD improved classification of patients who experienced MACE while CAC mostly improved classification of low-risk patients.

Conclusions
Ischaemic TPD and CAC were independently associated with MACE. Combining extent of atherosclerosis and functional measures improves the prediction of MACE risk, with CAC 0 identifying low-risk patients and regional ischaemia identifying high-risk patients in those with CAC &gt; 0.
The AAV-PCSK9 murine model of atherosclerosis and metabolic dysfunction
Authors: Keeter William Coles , Carter Nigeste M , Nadler Jerry L , Galkina Elena V 
Published: April 2022

AbstractAimsMouse models with genetic modifications are required to investigate atherogenesis and associated metabolic syndrome. Adeno-associated virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) induces hyperlipidaemia and promotes atherosclerosis in C57BL/6 mice. We aimed to assess whether AAV8-PCSK9-injected C57BL/6 mice fed high-fat diet with added cholesterol (HFD-C) would serve as a model of combined metabolic syndrome and atherosclerosis.Methods and resultsC57BL/6 mice received i.v. injection of AAV-PCSK9 and sex- and age-matched Ldlr−/− and C57BL/6 control mice were placed on HFD-C or chow diet for 20 weeks (B6-PCSK9-HFD-C, Ldlr−/− HFD-C, B6-HFD-C, and B6-Chow, respectively). High-fat diet with added cholesterol feeding led to insulin resistance and impaired glucose clearance in B6-PCSK9-HFD-C mice compared with B6-Chow controls. This decrease in metabolic health in B6-PCSK9-HFD-C mice as well as the development of atherosclerosis was similar to Ldlr−/− HFD-C mice. Importantly, HFD-C feeding induced pancreatic islet hyperplasia in B6-PCSK9-HFD-C and B6-HFD-C compared with B6-Chow controls. In line with alterations in the metabolic phenotype, there was an increase in the number of pro-inflammatory Ly6Chigh/med monocytes within the adipose tissues of B6-PCSK9-HFD-C and B6-HFD-C compared with B6-Chow controls.ConclusionHigh-fat diet with added cholesterol-fed AAV-PCSK9-injected C57BL/6 mice can serve as a useful model of integrated metabolic syndrome and atherosclerosis that does not require genetic manipulations.
Factors associated with excess female mortality in obstructive hypertrophic cardiomyopathy
Authors: Javidgonbadi Davood , Schaufelberger Maria , Östman-Smith Ingegerd 
Published: April 2022

Abstract

Background
Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown.

Aims
To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM).

Methods and results
Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P &lt; 0.001), but not different in outflow-gradients and median NYHA-class. However, septal hypertrophy was more advanced: 10.6 [IQR = 3.2] vs. 9.6 [2.5] mm/m2 BSA; P = 0.002. Females had higher disease-related mortality than males (P = &lt;0.001), with annual mortality 2.9% vs. 1.5% in age-matched groups (P = 0.010 log-rank). For each risk-category identified (NYHA-class ≥ III, outflow-gradient ≥50 mmHg), a higher proportion of females died (P = 0.0004; P = 0.001). Calcium-blocker therapy was a risk-factor (P = 0.005) and was used more frequently in females (P = 0.034). A beta-blocker dose above cohort-median reduced risk for disease-related death in both males (HR = 0.32; P = 0.0040) and in females (HR = 0.49; P = 0.020). Excess female deaths occurred in chronic heart-failure (P = 0.001) and acute myocardial infarctions (P = 0.015). Fewer females received beta-blocker therapy after diagnosis (64% vs. 78%, P = 0.018), in a smaller dose (P = 0.007), and less frequently combined with disopyramide (7% vs. 16%, P = 0.048).

Conclusion
Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.
Invasive candidiasis in Africa, what is the current picture?
Authors: Okoye Chinonyelum A , Nweze Emeka , Ibe Chibuike 
Published: April 2022

AbstractInvasive candidiasis is a serious, progressive, and potentially deadly infection that can affect the brain, heart, bones, eyes, and other parts of the body. It is associated with risk factors such as the use of indwelling medical devices, prolonged hospital stay, and broad-spectrum antibiotics use. It is especially seen in immunocompromised individuals such as patients with prolonged hospital stay, gastrointestinal surgery, haematological malignancies, and respiratory diseases. We have conducted a systematic search of literature using a select group of databases and appropriate search words and found that in Africa, there are 18 293 documented/reported cases of invasive candidiasis in the last few decades (1976–2021) and 16 636(91%) were cases of candidaemia. South Africa had the highest number of reported cases—15 002(82%), which may be due to underreporting of cases in other countries. HIV positive persons with invasive candidiasis in Africa accounted for 1 052(5.8%). Candida albicans was the most frequently isolated species 6 328(32.6%), followed by Candida parapsilosis 5 910(30.4%), and Candida auris 1 505(7.8%). Due to the affordability and availability of blood culture, it was used for diagnosis in most of the studies examined, while a few studies combined other techniques and just three studies from two countries used serological tests. Echinocandins are recommended as first-line therapy but are only available in 12 countries and are highly priced. The use of fluconazole, because of its availability and relatively inexpensive nature, has led to increased resistance of Candida species to the drug.
A Polynesian-specific copy number variant encompassing the MICA gene associates with gout
Authors: Wang Ke , Cadzow Murray , Bixley Matt , Leask Megan P , Merriman Marilyn E , Yang Qiangzhen , Li Zhiqiang , Takei Riku , Phipps-Green Amanda , Major Tanya J , Topless Ruth , Dalbeth Nicola , King Frances , Murphy Rinki , Stamp Lisa K , de Zoysa Janak , Wang Zhuo , Shi Yongyong , Merriman Tony R 
Published: April 2022

Abstract
Gout is of particularly high prevalence in the Māori and Pacific (Polynesian) populations of Aotearoa New Zealand (NZ). Here, we investigated the contribution of common population-specific copy number variation (CNV) to gout in the Aotearoa NZ Polynesian population. Microarray-generated genome-wide genotype data from Aotearoa NZ Polynesian individuals with (n = 1196) and without (n = 1249) gout were analyzed. Comparator population groups were 552 individuals of European ancestry and 1962 of Han Chinese ancestry. Levels of circulating major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) were measured by enzyme-linked immunosorbent assay. Fifty-four CNV regions (CNVRs) appearing in at least 10 individuals were detected, of which seven common (&gt;2%) CNVRs were specific to or amplified in Polynesian people. A burden test of these seven revealed associations of insertion/deletion with gout (odds ratio (OR) 95% confidence interval [CI] = 1.80 [1.01; 3.22], P = 0.046). Individually testing of the seven CNVRs for association with gout revealed nominal association of CNVR1 with gout in Western Polynesian (Chr6: 31.36–31.45 Mb, OR = 1.72 [1.03; 2.92], P = 0.04), CNVR6 in the meta-analyzed Polynesian sample sets (Chr1: 196.75–196.92 Mb, OR = 1.86 [1.16; 3.00], P = 0.01) and CNVR9 in Western Polynesian (Chr1: 189.35–189.54 Mb, OR = 2.75 [1.15; 7.13], P = 0.03). Analysis of European gout genetic association data demonstrated a signal of association at the CNVR1 locus that was an expression quantitative trait locus for MICA. The most common CNVR (CNVR1) includes deletion of the MICA gene, encoding an immunomodulatory protein. Expression of MICA was reduced in the serum of individuals with the deletion. In summary, we provide evidence for the association of CNVR1 containing MICA with gout in Polynesian people, implicating class I MHC-mediated antigen presentation in gout.
Real-world Short-term Effectiveness of Ustekinumab in Crohn’s Disease: Results from a Multicenter, Prospective Study in China
Authors: Cao Qian , Chen Chunxiao , Gao Xiang , Chen Yan , Hu Naizhong , Liang Jie , Wu Kaichun 
Published: April 2022

Lay Summary
Ustekinumab effectively induced a clinical response and clinical remission, with remission rates superior to those in the UNITI-1 study. Ustekinumab is more effective in biologic-naive patients with Crohn’s disease than those who were not responsive to anti–tumor necrosis factor treatment.
Network Clinical Collaboration to Improve Quality of Care of Patients With Inflammatory Bowel Disease in China
Authors: Mao Ren , Chien Ng Siew , Chen Minhu 
Published: April 2022

Lay SummaryThe burden of IBD management in China is increasing due to the mounting number of patients. We presented in the 2021 China IBD Special Issue a series of original articles, which will be important for encouraging and inspiring more network collaboration to improve quality of care of patients with IBD in China.
Guidelines for Discontinuation of Antipsychotics in Patients Who Recover From First-Episode Schizophrenia Spectrum Disorders: Derived From the Aggregated Opinions of Asian Network of Early Psychosis Experts and Literature Review
Authors:   Asian Network of Early Psychosis Writing Group, Hui Christy L M , Chen Eric Y H , Swapna Verma , Tagata Hiromi , Mizuno Masafumi , Liu Chen‑Chung , Takeuchi Hiroyoshi , Kim Sung-Wan , Chung Young-Chul 
Published: April 2022

Abstract

Objective
Antipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation to develop guidelines for antipsychotic discontinuation in such patients.

Methods
We reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results
Most studies had low to very low quality, and 2 had moderate quality. All studies, except 1, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19%–82% at 1-year follow-up) than the treatment maintenance group compared with the maintenance group. Based on expert opinion and Grading of Recommendations Assessment, Development, and Evaluation evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders.

Conclusions
Currently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed.
Antibiotic susceptibility patterns of viridans group streptococci isolates in the United States from 2010 to 2020
Authors: Singh Nidhi , Poggensee Linda , Huang Yanqin , Evans Charlesnika T. , Suda Katie J. , Bulman Zackery P. 
Published: April 2022

Abstract

Background
Viridans group streptococci (VGS) are typically part of the commensal flora but can also cause severe invasive diseases such as infective endocarditis. There are limited data available showing antibiotic susceptibility over time for VGS.

Objectives
To evaluate antibiotic susceptibility trends in VGS over time.

Methods
In vitro susceptibility patterns for 33 antibiotics were examined for Streptococcus mitis, Streptococcus oralis, and non-speciated VGS isolates from patients in Veterans Affairs (VA) Medical Centers in the United States between 2010 and 2020. Susceptibility determinations were made by the individual clinical microbiology laboratories and data were retrospectively collected from the VA Corporate Data Warehouse. Susceptibility trends were analysed using Poisson regression.

Results
A total of 14 981 VGS isolates were included of which 19.5%, 0.7% and 79.8% were S. mitis, S. oralis and non-speciated VGS isolates, respectively. Cumulative susceptibility rates across all years were similar between species for ceftriaxone (range: 96.0% to 100%), clindamycin (81.3% to 84.5%), and vancomycin (99.7% to 100%). For penicillin, susceptibility rates were 71.0%, 80.9% and 86.3% for S. mitis, S. oralis and non-speciated isolates, respectively. From 2010 to 2020, susceptibility of non-speciated VGS isolates decreased for erythromycin (P = 0.0674), penicillin (P = 0.0835), and tetracycline (P = 0.0994); though the decrease was only significant for clindamycin (P = 0.0033). For S. mitis, a significant susceptibility rate decrease was observed for erythromycin (P = 0.0112).

Conclusions
Susceptibility rates for some clinically relevant antibiotics declined between 2010 and 2020. This worrisome trend highlights the need to improve antimicrobial stewardship efforts to limit unnecessary antibiotic use and preserve empirical treatment options.
ICU Cockpit: a platform for collecting multimodal waveform data, AI-based computational disease modeling and real-time decision support in the intensive care unit
Authors: Boss Jens Michael , Narula Gagan , Straessle Christian , Willms Jan , Azzati Jan , Brodbeck Dominique , Luethy Rahel , Suter Susanne , Buehler Christof , Muroi Carl , Mack David Jule , Seric Marko , Baumann Daniel , Keller Emanuela 
Published: April 2022

Abstract
ICU Cockpit: a secure, fast, and scalable platform for collecting multimodal waveform data, online and historical data visualization, and online validation of algorithms in the intensive care unit. We present a network of software services that continuously stream waveforms from ICU beds to databases and a web-based user interface. Machine learning algorithms process the data streams and send outputs to the user interface. The architecture and capabilities of the platform are described. Since 2016, the platform has processed over 89 billion data points (N = 979 patients) from 200 signals (0.5–500 Hz) and laboratory analyses (once a day). We present an infrastructure-based framework for deploying and validating algorithms for critical care. The ICU Cockpit is a Big Data platform for critical care medicine, especially for multimodal waveform data. Uniquely, it allows algorithms to seamlessly integrate into the live data stream to produce clinical decision support and predictions in clinical practice.