bluuebunny/crossref_metadata_2025 huggingface dataset:
Timeliness of Point-of-Care Viral Load Results Improves Human Immunodeficiency Virus Monitoring in Nigeria
Authors: Chaplin Beth , Agbaji Oche , Reyes Nieva Harry , Olatunde Bola , Chang Charlotte , Mitruka Kiren , Sule Halima , Dajel Titus , Zee Aaron , Ahmed Mukhtar L , Ahmed Isah , Okonkwo Prosper , Rawizza Holly , Kanki Phyllis
Published: July 2022

Background

Human immunodeficiency virus (HIV) viral load (VL) monitoring is critical for antiretroviral therapy (ART) management. Point-of-care (POC) VL testing has been reported to be feasible and preferred over standard-of-care (SOC) testing in many low- and middle-income country settings where rapid results could improve patient outcomes.

Methods

The timeliness of receipt of VL results was evaluated in an open-label, randomized, controlled trial among patients newly initiating ART. Clinical outcomes with POC VL monitoring using Cepheid Xpert vs SOC VL at Jos University Teaching Hospital and Comprehensive Health Centre Zamko in Nigeria were assessed. We determined time between specimen collection and recording of VL in patient charts, receipt of results, and ART switch for those who met virologic failure criteria.

Results

Between April 2018 and October 2019, we screened 696 ART-naive individuals; 273 were randomized to POC and 268 to SOC HIV-1 VL testing. Participants in the POC arm received VL results significantly faster than those in the SOC arm (0.1 median days, interquartile range [IQR], 0.1–0.2 vs 143.1 days, IQR, 56.0–177.1, respectively; P < .0001). Participants in the POC arm with confirmed virologic failure vs those in the SOC arm were switched more rapidly to a second-line regimen (0 median days, IQR, 0–28 vs 66 days, IQR, 63–123, respectively; P = .03).

Conclusions

POC VL testing resulted in significant improvement in the timeliness of VL result receipt by patients and use for effective HIV clinical management. In patients experiencing VL failure, POC monitoring enabled prompt switching to second-line ART regimens.

Clinical Trials Registration

NCT03533868.
Extracellular volume fraction improves risk-stratification for ventricular arrhythmias and sudden death in non-ischaemic cardiomyopathy
Authors: Di Marco Andrea , Brown Pamela F , Bradley Joshua , Nucifora Gaetano , Anguera Ignasi , Miller Christopher A , Schmitt Matthias
Published: July 2022

Aims

To evaluate whether cardiac magnetic resonance (CMR)-based parametric mapping and strain analysis can improve the risk-stratification for ventricular arrhythmias (VA) and sudden death (SD) in non-ischaemic cardiomyopathy (NICM).

Methods and results

Secondary analysis of a prospective single-centre-registry (NCT02326324), including 703 consecutive NICM patients, 618 with extracellular volume (ECV) available. The combined primary endpoint included appropriate implantable cardioverter defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest and SD. During a median follow-up of 21 months, 14 patients (2%) experienced the primary endpoint. Native T1 was not associated with the primary endpoint. Left ventricular global longitudinal strain lost its significant association after adjustment for left ventricular ejection fraction (LVEF). Among patients with ECV available, 11 (2%) reached the primary endpoint. Mean ECV was significantly associated with the primary endpoint and the best cut-off was 30%. ECV ≥ 30% was the strongest independent predictor of the primary endpoint (hazard ratio 14.1, P = 0.01) after adjustment for late gadolinium enhancement (LGE) and LVEF. ECV ≥ 30% discriminated the arrhythmic risk among LGE+ cases and among those with LVEF ≤ 35%. A simple clinical risk-stratification model, based on LGE, LVEF ≤ 35% and ECV ≥ 30%, achieved an excellent predictive ability (Harrell’s C 0.82) and reclassified the risk of 32% of the study population as compared to LVEF ≤ 35% alone.

Conclusions

Comprehensive CMR evaluation in NICM showed that ECV was the only parameter with an independent and strong predictive value for VA/SD, on top of LGE and LVEF. A risk-stratification model based on LGE, LVEF ≤ 35% and ECV ≥ 30% achieved an excellent predictive ability for VA/SD.

Clinical Trial Registration

UHSM CMR study (NCT02326324) https://clinicaltrials.gov/ct2/show/NCT02326324.
Non-steroidal anti-inflammatory drugs and risk of myocardial infarction adjusting for use of proton pump-inhibitors in patients with no major risk factors: a nested case-control study in the UK Clinical Practice Research Datalink
Authors: Baak Brenda N , Jick Susan S
Published: July 2022

Aims

Studies have found an increased risk of myocardial infarction (MI) in association with some non-steroidal anti-inflammatory drugs (NSAIDs). We evaluated this association in patients without major cardiovascular risk factors and assessed potential reverse causality bias.

Methods and results

In this nested case-control study of patients aged 40–79 in Clinical Practice Research Datalink GOLD who received at least one NSAID prescription between 2006 and 2019, we found 8639 MI cases and 34 556 matched controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for MI comparing NSAID users to non-exposed according to the number and timing of NSAID prescriptions and proton-pump inhibitor (PPI) use. Current diclofenac use was associated with a two-fold increased risk of MI regardless of duration of use (adjusted OR, 2.08; 95% CI, 1.82–2.38). ORs ranged from 3 to 5 among current and recent diclofenac users newly exposed to PPIs. There was no spike in risk in new current diclofenac users not exposed to PPIs, but ORs rose with increasing prescriptions. The risk of MI in ibuprofen users was concentrated in new PPI users. There was no material increased risk in naproxen users, nor in past users of most NSAIDs in the absence of PPIs.

Conclusion

The risk of MI was elevated in current diclofenac users, particularly in new concomitant PPI users. ORs increased in new users of ibuprofen and PPIs but declined with extended use and were lower in non-PPI users. This suggests that some of the findings may be explained by reverse causality bias.
Impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention: an analysis from the e-Ultimaster registry
Authors: Kobo Ofer , Saada Majdi , von Birgelen Clemens , Tonino Pim A L , Íñiguez-Romo Andres , Fröbert Ole , Halabi Majdi , Oemrawsingh Rohit M , Polad Jawed , IJsselmuiden Alexander J J , Roffi Marco , Aminian Adel , Mamas Mamas A , Roguin Ariel
Published: July 2022

Background

Multisite artery disease is considered a ‘malignant’ type of atherosclerotic disease associated with an increased cardiovascular risk, but the impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention (PCI) is unknown.

Methods

Patients enrolled in the large, prospective e-Ultimaster study were grouped into (1) those without known prior vascular disease, (2) those with known single-territory vascular disease, and (3) those with known two to three territories (i.e coronary, cerebrovascular, or peripheral) vascular disease (multisite artery disease). The primary outcome was coronary target lesion failure (TLF), defined as the composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 1-year. Inverse propensity score weighted (IPSW) analysis was performed to address differences in baseline patient and lesion characteristics.

Results

Of the 37 198 patients included in the study, 62.3% had no prior known vascular disease, 32.6% had single-territory vascular disease, and 5.1% had multisite artery disease. Patients with known vascular disease were older and were more likely to be men and to have more co-morbidities. After IPSW, the TLF rate incrementally increased with the number of diseased vascular beds (3.16%, 4.44%, and 6.42% for no, single, and multisite artery disease, respectively, P < 0.01 for all comparisons). This was also true for all-cause death (2.22%, 3.28%, and 5.29%, P < 0.01 for all comparisons) and cardiac mortality (1.26%, 1.91%, and 3.62%, P ≤ 0.01 for all comparisons).

Conclusions

Patients with previously known vascular disease experienced an increased risk of adverse cardiovascular events and mortality post-PCI. This risk is highest among patients with multisite artery disease.

Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02188355.
Gap distribution mapping to visualize regions associated with type 1 endoleak in a fenestrated thoracic stent graft
Authors: Shukuzawa Kota , Fujii Tomoya , Sumi Makoto , Kozaki Junya , Umezu Mitsuo , Ohki Takao , Iwasaki Kiyotaka
Published: July 2022

OBJECTIVES

Our goal was to analyse the relationships between aortic surface irregularity and a type 1 endoleak (T1EL) after a thoracic endovascular repair using the Najuta fenestrated stent graft.

METHODS

The patients who were treated using the Najuta stent graft for an intact aortic arch aneurysm at the Saitama Cardiovascular and Respiratory Center between June 2013 and June 2017 were analysed retrospectively. The primary end point was the occurrence of a T1EL. The gap between a virtual aorta and the patient's aortic wall at the stent graft fixation was calculated over the whole circumference at 1 mm intervals, and gap distribution mapping was performed. The rate of freedom from a T1EL was estimated using the Kaplan–Meier method and compared between the patients with or without a continuously malapposed region of >1 mm from the branches to the aneurysm.

RESULTS

Twenty-one patients were analysed. During the mean follow-up period of 21.7 months, 4 patients were confirmed to have T1ELs. Three of the T1Els were detected during the perioperative period and occurred through a fenestration. The remaining patient had a T1EL 2 years postoperatively. The gap distribution mapping confirmed the presence of a continuously malapposed region of >1 mm from the cervical branch to the aneurysm postoperatively in 4 patients with T1ELs. Patients who had a continuously malapposed region of >1 mm showed a statistically lower T1EL rate than those without (p < 0.001). Malapposed regions defined using the gap distribution mapping were consistent with flow channels through T1EL fenestrations detected using the perioperative computed tomography data.

CONCLUSIONS

The gap distribution mapping could be useful to predict the occurrence of T1ELs in patients with the Najuta stent graft.
Impact on quinolone resistance of plasmid-mediated quinolone resistance gene and mutations in quinolone resistance-determining regions in extended spectrum beta lactamase-producing Klebsiella pneumoniae isolated from urinary tract infection patients
Authors: Onishi Reo , Shigemura Katsumi , Osawa Kayo , Yang Young-Min , Maeda Koki , Tanimoto Hiroshi , Kado Mitsuki , Fang Shiuh-Bin , Sung Shian-Ying , Miyara Takayuki , Fujisawa Masato
Published: July 2022

Klebsiella pneumoniae is a typical pathogen in urinary tract infections (UTI), and the emergence of extended spectrum beta-lactamase (ESBL)-producing strains has been frequently reported, accompanied by higher quinolone resistance rates. There are two major mechanisms of quinolone resistance, mutations in quinolone resistance-determining regions (QRDR) and the presence of the plasmid-mediated quinolone resistance (PMQR) genes. This study aimed to investigate quinolone resistance among 105 ESBL-producing K. pneumoniae specimens isolated from UTI patients in Indonesia. These were characterized for antimicrobial resistance to nalidixic acid, ciprofloxacin, and levofloxacin, QRDR mutations in gyrA and parC and the presence of PMQR genes. We found that 84.8% of the collected isolates were resistant to at least one of the quinolones. QRDR mutation in gyrA was observed in 49.5% of these strains and parC mutations in 61.0%. PMQR genes were identified in 84.8% of strains. The QRDR mutations clearly had a greater effect on resistance than the PMQR genes. In conclusion, we found high quinolone resistance rates in Indonesian ESBL-producing K. pneumoniae, in which QRDR mutation played a major role.
A Genome for Edith’s Checkerspot Butterfly: An Insect with Complex Host-Adaptive Suites and Rapid Evolutionary Responses to Environmental Changes
Authors: Tunstrom Kalle , Wheat Christopher W , Parmesan Camille , Singer Michael C , Mikheyev Alexander S
Published: July 2022

Insects have been key players in the assessments of biodiversity impacts of anthropogenically driven environmental change, including the evolutionary and ecological impacts of climate change. Populations of Edith’s Checkerspot Butterfly (Euphydryas editha) adapt rapidly to diverse environmental conditions, with numerous high-impact studies documenting these dynamics over several decades. However, studies of the underlying genetic bases of these responses have been hampered by missing genomic resources, limiting the ability to connect genomic responses to environmental change. Using a combination of Oxford Nanopore long reads, haplotype merging, HiC scaffolding followed by Illumina polishing, we generated a highly contiguous and complete assembly (contigs n = 142, N50 = 21.2 Mb, total length = 607.8 Mb; BUSCOs n = 5,286, single copy complete = 97.8%, duplicated = 0.9%, fragmented = 0.3%, missing = 1.0%). A total of 98% of the assembled genome was placed into 31 chromosomes, which displayed large-scale synteny with other well-characterized lepidopteran genomes. The E. editha genome, annotation, and functional descriptions now fill a missing gap for one of the leading field-based ecological model systems in North America.
Integrated collaborative care intervention for depression and obesity in primary care: translation from research to practice
Authors: Ronneberg Corina R , Lv Nan , Ajilore Olusola A , Gerber Ben S , Venditti Elizabeth M , Snowden Mark B , Steinman Lesley E , Wittels Nancy E , Barve Amruta , Dosala Sushanth , Rosas Lisa G , Kringle Emily A , Ma Jun
Published: July 2022

The objective of this study was to present lessons learned about engagement, delivery modality and pandemic impact while delivering a collaborative care intervention with a socioeconomically, racially and ethnically diverse sample. Participants completed a post-intervention survey (n = 41) on experiences and preferred intervention delivery modality, coronavirus 2019 (COVID-19) Impact Survey (n = 50) and provided open-ended feedback about the intervention (n = 27). Intervention process data included attendance, modality, and withdrawals. Data were analyzed using descriptive statistics and inductive content analyses. Of 71 intervention participants, 6 (8%) withdrew before session 1. Completers adhered to intervention timeline better than withdrawals. Participants liked the in-person interaction, efficient coach support, accountability of in-person and Zoom vs. phone sessions and the flexibility and convenience of phone and Zoom vs. in-person sessions. A majority of participants reported experiencing pandemic impacts such as heightened emotional distress, decreased activity engagement, poorer eating behaviors and being unable to meet basic needs. Participants deviating from intervention timelines may be re-engaged by targeted outreach attempts. Videoconference has the potential for providing as-needed coaching. Future interventions may be optimized to account for and address areas impacted by the pandemic. Findings revealed specific strategies that can be implemented in future interventions to improve emotional and physical health among diverse populations.
Quality level and outsourcing strategies in a three-tier low-carbon supply chain
Authors: Wu Xinjian , Yu Chao , Zhang Suyong
Published: July 2022

We analyze the quality risk and outsourcing strategies in a three-tier low-carbon supply chain comprising an original equipment manufacturer (OEM), a contract manufacturer (CM) and a supplier under two competitive scenarios. The following two outsourcing strategies that are currently implemented by OEM are considered: consignment and turnkey. Under the consignment strategy, the OEM procures the components from the supplier and then outsources the product manufacturing to the CM. Under the turnkey strategy, the OEM outsources the component procurement and product manufacturing to the CM and CM procures the components from the supplier. We compare the quality level and two outsourcing strategies under non-competitive scenario in which the CM does not have its own brand products and competitive scenario in which the CM sells its own brand production. It is shown that, in the non-competitive scenario, OEM prefers the turnkey strategy than the consignment strategy in the low-carbon supply chain. In the competitive scenario, the OEM’s outsourcing strategy depends on the CM’s quality investment cost coefficient.
Targeted SARS-CoV-2 treatment is associated with decreased mortality in immunocompromised patients with COVID-19
Authors: Lafont Emmanuel , Pere Hélène , Lebeaux David , Cheminet Geoffrey , Thervet Eric , Guillemain Romain , Flahault Adrien
Published: July 2022

Background

Little is known about targeted (antiviral or monoclonal antibody) anti-SARS-CoV-2 treatment in immunocompromised patients with COVID-19.

Objectives

To assess the real-life efficacy and tolerance of targeted treatment of COVID-19 in immunocompromised patients.

Patients and methods

Single-centre retrospective case series of immunocompromised patients with COVID-19 between December 2021 and March 2022. We recorded all cases of COVID-19 among immunocompromised patients treatment between 20 December 2021 and 15 March 2022. Choice of treatment was left to the physician’s decision, according to internal treatment protocol, treatment availability and circulating variants. Main outcome was death from COVID-19 after no treatment or targeted treatment.

Results

Sixty-seven immunocompromised patients [38 male; median (IQR) age, 53 (43–63) years], with a median (IQR) follow-up of 60 (47–80) days. Ten patients did not receive any targeted treatment. Targeted treatment consisted of IV curative remdesivir (n = 22), sotrovimab (n = 16), tixagevimab/cilgavimab (n = 13) and casirivimab/imdevimab (n = 1). Ten patients (15%) presented severe COVID-19 and 2 (3%) died from Omicron COVID-19. Comparing patients who received targeted anti-SARS-CoV-2 treatment and no prophylaxis, (n = 42; 81%) with those who did not (n = 10; 19%), death rate was significantly lower in treated patients [n = 0 (0%) versus n = 2 (20%); P = 0.034]. No severe adverse events were reported among treated patients. Among 15 patients who received tixagevimab/cilgavimab as pre-exposure prophylaxis, 6 received an additional curative treatment and none died from COVID-19.

Conclusions

Our results suggest that targeted COVID-19 treatment, including direct antivirals or monoclonal antibodies, is safe and efficient and could be proposed in high-risk immunocompromised patients.
Juvenile drift of an invasive crayfishFaxonius virilis(Hagen, 1870) (Decapoda: Astacidea: Cambaridae) in the middle Pecos River, New Mexico, USA
Authors: Ricklefs Sara A , Filbrun Jesse E
Published: July 2022

Ecologists have long recognized that dispersal capabilities influence range expansion by nonnative species. Some of the most disruptive crayfish invaders are highly mobile as adults within and across watershed networks. In this study, we contribute a new facet to our understanding of crayfish early life history and invasions by documenting strong evidence of synchronized, behavioral downstream drift by early juveniles. During 2019, we observed a relatively dense springtime pulse of juvenile crayfish in drift nets set at two sites in the middle Pecos River near Fort Sumner, New Mexico. To determine whether this was an anomalous episode or an annual event, we sampled in 2020 and 2021 to: 1) determine the timing and extent of drifting behavior relative to environmental variation, and 2) identify the drifters to species level using DNA barcoding. Across three years, we collected juvenile crayfish (2.4–13.1 mm carapace length) after sunset during April through June in relatively clear water conditions (5–64 NTU) that coincided with minimum flows (41–152 cfs) and seasonally typical temperatures for this region (15–26 °C). To identify specimens to species level, we sequenced the barcoding region of the cytochrome c oxidase I (COI) DNA barcode for 35 juveniles and 6 adult male vouchers that represented all years. Based on morphological identifications of adult males and COI sequence comparisons to published reference specimens, nearly all drifting juveniles were identified as Virile Crayfish Faxonius virilis (Hagen, 1870). Drifters matched the sizes of second-molt juveniles newly released in the laboratory from two brooding females that we captured in the field. Faxonius virilis has been collected throughout the Rio Grande watershed, but not yet been reported in the Pecos River. As drifting early life stages are common across crustaceans, we suspect juvenile crayfish drift is probably not unique to F. virilis nor to our study system. We encourage others to perform targeted surveys of juvenile drift across a broad range of study systems, and to identify causal factors and ecological consequences of juvenile drift using controlled experiments.
“Music Therapy Was Never on the Table”: Perspectives of Parents of Young Autistic Children
Authors: Hernandez-Ruiz Eugenia , Lehrer Gabriel
Published: July 2022

Parent coaching of music interventions is emerging as a viable model for families with young autistic children, yet recruitment difficulties have been apparent in previous studies. Understanding parent perspectives of early intervention services is critical to ensure that interventions are acceptable, feasible, and effective for all family members. In order to understand possible parental resistance to this type of parent education, we explored perspectives regarding music therapy, research, and parent coaching in parents of young autistic children. Fourteen parents attended virtual focus groups to discuss their experiences. We used a descriptive phenomenological approach to uncover the essence of their experience. Our findings indicate that, contrary to our preconceptions, participants did not show negative dispositions towards music therapy, research, or parent coaching. Instead, most participants had very little or no knowledge of music therapy services. They had limited experience with research in general, and only two participants had experienced music therapy directly. Several participants had varying amounts of experience with parent participation or parent coaching outside of music therapy and shared positive experiences with it. Parents seemed willing and eager to learn music strategies to support their children and saw value in the use of music for their child’s development. First-contact providers (i.e., early interventionists and diagnosticians) and social media seem influential in parents’ decision-making as they navigate early intervention services soon after diagnosis. Music therapy organizations are encouraged to design targeted efforts to make information on music therapy available through these sources.
Working toward Socially Responsive Recruitment Practices of Psychology Interns in an Academic Medical Center
Authors: Glover Jenna , Lynn Courtney , Holzman Jacob B W , Germone Monique , Talmi Ayelet
Published: July 2022

Objective

This study describes a quality improvement (QI) process to reduce bias and increase inclusion and equity in the recruitment of health service psychology interns in an American Psychological Association-accredited psychology internship program at a national children’s hospital.

Methods

This QI project utilized two Plan-Do-Study-Act (PDSA) cycles targeting the application review and the interview processes primarily using supervisor engagement and feedback to inform these processes. The goal of the PDSA cycles was to increase diversity in psychology doctoral interns offered interviews and ultimately recruited to the internship program.

Results

The application rating form was revised to place a greater emphasis on factors related to diversity, such as increasing the number of points applicants could earn for being bilingual. Regarding the interview process, structured interview questions were created, and a new, unified rubric was used to score interviewees. The changes in demographics of applicants selected for interviews and feedback from applicants who interviewed are reported.

Conclusions

The QI process resulted in tangible changes to improve equitable and inclusive internship recruitment. Lessons learned throughout this process included the need for continual auditing of practices through an equity lens, engaging supervisors at all stages of the process, and implementing incremental actions.
The missing base molecules in atmospheric acid–base nucleation
Authors: Cai Runlong , Yin Rujing , Yan Chao , Yang Dongsen , Deng Chenjuan , Dada Lubna , Kangasluoma Juha , Kontkanen Jenni , Halonen Roope , Ma Yan , Zhang Xiuhui , Paasonen Pauli , Petäjä Tuukka , Kerminen Veli-Matti , Liu Yongchun , Bianchi Federico , Zheng Jun , Wang Lin , Hao Jiming , Smith James N , Donahue Neil M , Kulmala Markku , Worsnop Douglas R , Jiang Jingkun
Published: July 2022

Transformation of low-volatility gaseous precursors to new particles affects aerosol number concentration, cloud formation and hence the climate. The clustering of acid and base molecules is a major mechanism driving fast nucleation and initial growth of new particles in the atmosphere. However, the acid–base cluster composition, measured using state-of-the-art mass spectrometers, cannot explain the measured high formation rate of new particles. Here we present strong evidence for the existence of base molecules such as amines in the smallest atmospheric sulfuric acid clusters prior to their detection by mass spectrometers. We demonstrate that forming (H2SO4)1(amine)1 is the rate-limiting step in atmospheric H2SO4-amine nucleation and the uptake of (H2SO4)1(amine)1 is a major pathway for the initial growth of H2SO4 clusters. The proposed mechanism is very consistent with measured new particle formation in urban Beijing, in which dimethylamine is the key base for H2SO4 nucleation while other bases such as ammonia may contribute to the growth of larger clusters. Our findings further underline the fact that strong amines, even at low concentrations and when undetected in the smallest clusters, can be crucial to particle formation in the planetary boundary layer.
Robust and dynamic underwater adhesives enabled by catechol-functionalized poly(disulfides) network
Authors: Shi Chen-Yu , He Dan-Dan , Zhang Qi , Tong Fei , Shi Zhao-Tao , Tian He , Qu Da-Hui
Published: July 2022

Developing molecular approaches to the creation of robust and water-resistant adhesive materials promotes a fundamental understanding of interfacial adhesion mechanisms as well as future applications of biomedical adhesive materials. Here, we present a simple and robust strategy that combines natural thioctic acid and mussel-inspired iron-catechol complexes to enable ultra-strong adhesive materials that can be used underwater and simultaneously exhibit unprecedentedly high adhesion strength on diverse surfaces. Our experimental results show that the robust crosslinking interaction of the iron-catechol complexes, as well as high-density hydrogen bonding, are responsible for the ultra-high interfacial adhesion strength. The embedding effect of the hydrophobic solvent-free network of poly(disulfides) further enhances the water-resistance. The dynamic covalent poly(disulfides) network also makes the resulting materials reconfigurable, thus enabling reusability via repeated heating and cooling. This molecule-engineering strategy offers a general and versatile solution to the design and construction of dynamic supramolecular adhesive materials.
Treatment With a Three-Drug Regimen for Pulmonary Tuberculosis Based on Rapid Molecular Detection of Isoniazid Resistance: A Noninferiority Randomized Trial (FAST-TB)
Authors: De Castro N , Mechaï F , Bachelet D , Canestri A , Joly V , Vandenhende M , Boutoille D , Kerjouan M , Veziris N , Molina J M , Grall N , Tattevin P , Laouénan C , Yazdanpanah Y ,   for the FAST TB Study Group
Published: July 2022

Background

The rationale behind the use of ethambutol in the standard tuberculosis treatment is to prevent the emergence of resistance to rifampicin in case of primary resistance to isoniazid. We evaluated whether early detection of isoniazid resistance using molecular testing allows the use an ethambutol-free regimen.

Methods

FAST-TB, a phase 4, French, multicenter, open-label, non-inferiority trial, compared 2 strategies: (1) polymerase chain reaction (PCR)-based detection of isoniazid and rifampicin resistance at baseline using Genotype MTBDRplus version 2.0 followed by ethambutol discontinuation if no resistance was detected (PCR arm) and (2) a standard 4-drug combination, pending phenotypic drug-susceptibility results (C arm). Adult patients with smear-positive pulmonary tuberculosis were enrolled. The primary endpoint was the proportion of patients with treatment success defined as bacteriological or clinical cure at the end of treatment. A non-inferiority margin of 10% was used.

Results

Two hundred three patients were randomized, 104 in the PCR arm and 99 in the C arm: 26.6% were female, median age was 37 (interquartile range, 28–51) years, 72.4% were born in Africa, and 5.4% were infected with human immunodeficiency virus. Chest x-ray showed cavities in 64.5% of the cases. Overall, 169 patients met criteria of treatment success: 87 of 104 (83.7%) in the PCR arm and 82 of 99 (82.8%) in the C arm with a difference of +0.8% (90% confidence interval, −7.9 to 9.6), meeting the noninferiority criteria in the intention-to-treat population (P = .02).

Conclusions

In a setting with low prevalence of primary isoniazid resistance, a 3-drug combination with isoniazid, rifampicin, and pyrazinamide, based on rapid detection of isoniazid resistance using molecular testing, was noninferior to starting the recommended 4-drug regimen.
Aggregating Human Judgment Probabilistic Predictions of Coronavirus Disease 2019 Transmission, Burden, and Preventive Measures
Authors: Codi Allison , Luk Damon , Braun David , Cambeiro Juan , Besiroglu Tamay , Chen Eva , de Cesaris Luis Enrique Urtubey , Bocchini Paolo , McAndrew Thomas
Published: July 2022

Aggregated human judgment forecasts for coronavirus disease 2019 (COVID-19) targets of public health importance are accurate, often outperforming computational models. Our work shows that aggregated human judgment forecasts for infectious agents are timely, accurate, and adaptable, and can be used as a tool to aid public health decision making during outbreaks.
Private Practice Dentists Improve Antibiotic Use After Dental Antibiotic Stewardship Education From Infectious Diseases Experts
Authors: Goff Debra A , Mangino Julie E , Trolli Elizabeth , Scheetz Richard , Goff Douglas
Published: July 2022

Background

Private practice dentists represent 72% of United States dentists. We conducted a prospective cohort study of private practice dentists comparing antibiotic use before and after dental antibiotic stewardship education by infectious diseases (ID) antibiotic stewardship experts.

Methods

Study phases were as follows: phase 1 (preeducation), 3 months of retrospective antibiotic data and a presurvey assessed baseline antibiotic knowledge; phase 2 (education), dentists attended 3 evening Zoom sessions; phase 3, (posteducation/interventions), 3 months of prospective audits with weekly feedback; phase 4, postsurvey and recommendations to reach more dentists.

Results

Fifteen dentists participated. Ten had practiced >20 years. Presurvey, 14 were unfamiliar with dental stewardship. The number of antibiotic prescriptions pre/post decreased from 2124 to 1816 (P < .00001), whereas procedures increased from 8526 to 9063. Overall, appropriate use (prophylaxis and treatment) increased from 19% pre to 87.9% post (P < .0001). Appropriate prophylaxis was 46.6% pre and 76.7% post (P < .0001). Joint implant prophylaxis decreased from 164 pre to 78 post (P < .0001). Appropriate treatment antibiotics pre/post improved 5-fold from 15% to 90.2% (P = .0001). Antibiotic duration pre/post decreased from 7.7 days (standard deviation [SD], 2.2 days) to 5.1 days (SD, 1.6 days) (P < .0001). Clindamycin use decreased 90% from 183 pre to 18 post (P < .0001). Postsurvey responses recommended making antibiotic stewardship a required annual continuing education. Study participants invited ID antibiotic stewardship experts to teach an additional 2125 dentists via dental study clubs.

Conclusions

After learning dental antibiotic stewardship from ID antibiotic stewardship experts, dentists rapidly optimized antibiotic prescribing. Private practice dental study clubs are expanding dental antibiotic stewardship training to additional dentists, hygienists, and patients across the United States.
Clinical features at diagnosis of sickle cell disease prior to universal newborn screening in Alberta
Authors: Monagel Dania A , Monteiro Jessica , Thull-Freedman Jennifer , Ruzycki Angela , Leaker Michael , Steele MacGregor
Published: July 2022

Objectives

Sickle cell disease (SCD) is an inherited multisystem disorder with complications starting in the first year of life. Newborn screening (NBS) can identify infants with SCD and is associated with decreased morbidity and mortality. Variation in availability of NBS in Canada, and lack of standardized screening for immigrant children, may lead to delayed diagnosis.

Methods

This was a retrospective cohort study of 126 children aged 0–18 years with SCD registered with the SCD clinic at the Alberta Children’s Hospital between January 2003 and January 2018, prior to province-wide universal NBS for SCD. Patient demographic information, circumstances of diagnosis, and other contextual information were collected from patient health records. Descriptive statistics were used to summarize data, with Mood’s median test used to compare medians between groups.

Results

Forty-three (35%) patients were born in Alberta. Patients were mostly (95.3%) of African descent. Of patients born in Alberta, 63% (26/43) were diagnosed at >12 months of age, with a median age at diagnosis of 18 months (IQR = 4–39). This was significantly older (P < 0.001) than children born in the USA or in Canadian provinces with SCD NBS programs, where the median age at diagnosis was zero months (N = 36). Of the 42% of patients born outside North America, 64% were diagnosed following an acute complication.

Conclusions

This study highlights the importance of NBS for early detection and management of SCD, and the importance of screening at-risk immigrants who may not have received NBS for SCD.
Electron tomography of prolamellar bodies and their transformation into grana thylakoids in cryofixed Arabidopsis cotyledons
Authors: Liang Zizhen , Yeung Wai-Tsun , Ma Juncai , Mai Keith Ka Ki , Liu Zhongyuan , Chong Yau-Lun Felix , Cai Xiaohao , Kang Byung-Ho
Published: July 2022

The para-crystalline structures of prolamellar bodies (PLBs) and light-induced etioplast-to-chloroplast transformation have been investigated via electron microscopy. However, such studies suffer from chemical fixation artifacts and limited volumes of 3D reconstruction. Here, we examined Arabidopsis thaliana cotyledon cells by electron tomography (ET) to visualize etioplasts and their conversion into chloroplasts. We employed scanning transmission ET to image large volumes and high-pressure freezing to improve sample preservation. PLB tubules were arranged in a zinc blende-type lattice-like carbon atoms in diamonds. Within 2 h after illumination, the lattice collapsed from the PLB exterior and the disorganized tubules merged to form thylakoid sheets (pre-granal thylakoids), which folded and overlapped with each other to create grana stacks. Since the nascent pre-granal thylakoids contained curved membranes in their tips, we examined the expression and localization of CURT1 (CURVATURE THYLAKOID1) proteins. CURT1A transcripts were most abundant in de-etiolating cotyledon samples, and CURT1A was concentrated at the PLB periphery. In curt1a etioplasts, PLB-associated thylakoids were swollen and failed to form grana stacks. In contrast, PLBs had cracks in their lattices in curt1c etioplasts. Our data provide evidence that CURT1A is required for pre-granal thylakoid assembly from PLB tubules during de-etiolation, while CURT1C contributes to cubic crystal growth in the dark.
A nuclear import pathway exploited by pathogenic noncoding RNAs
Authors: Ma Junfei , Dissanayaka Mudiyanselage Shachinthaka D , Park Woong June , Wang Mo , Takeda Ryuta , Liu Bin , Wang Ying
Published: July 2022

The prevailing view of intracellular RNA trafficking in eukaryotic cells is that RNAs transcribed in the nucleus either stay in the nucleus or cross the nuclear envelope, entering the cytoplasm for function. However, emerging evidence illustrates that numerous functional RNAs move in the reverse direction, from the cytoplasm to the nucleus. The mechanism underlying RNA nuclear import has not been well elucidated. Viroids are single-stranded circular noncoding RNAs that infect plants. Using Nicotiana benthamiana, tomato (Solanum lycopersicum), and nuclear-replicating viroids as a model, we showed that cellular IMPORTIN ALPHA-4 (IMPa-4) is likely involved in viroid RNA nuclear import, empirically supporting the involvement of Importin-based cellular pathway in RNA nuclear import. We also confirmed the involvement of a cellular protein (viroid RNA-binding protein 1 [VIRP1]) that binds both IMPa-4 and viroids. Moreover, a conserved C-loop in nuclear-replicating viroids serves as a key signal for nuclear import. Disrupting C-loop impairs VIRP1 binding, viroid nuclear accumulation, and infectivity. Further, C-loop exists in a subviral satellite noncoding RNA that relies on VIRP1 for nuclear import. These results advance our understanding of subviral RNA infection and the regulation of RNA nuclear import.
A mutant-based analysis of the establishment of Nod-independent symbiosis in the legume Aeschynomene evenia
Authors: Quilbé Johan , Nouwen Nico , Pervent Marjorie , Guyonnet Rémi , Cullimore Julie , Gressent Frédéric , Araújo Natasha Horta , Gully Djamel , Klopp Christophe , Giraud Eric , Arrighi Jean-François
Published: July 2022

Intensive research on nitrogen-fixing symbiosis in two model legumes has uncovered the molecular mechanisms, whereby rhizobial Nod factors activate a plant symbiotic signaling pathway that controls infection and nodule organogenesis. In contrast, the so-called Nod-independent symbiosis found between Aeschynomene evenia and photosynthetic bradyrhizobia, which does not involve Nod factor recognition nor infection thread formation, is less well known. To gain knowledge on how Nod-independent symbiosis is established, we conducted a phenotypic and molecular characterization of A. evenia lines carrying mutations in different nodulation genes. Besides investigating the effect of the mutations on rhizobial symbiosis, we examined their consequences on mycorrhizal symbiosis and in nonsymbiotic conditions. Analyzing allelic mutant series for AePOLLUX, Ca2+/calmodulin dependent kinase, AeCYCLOPS, nodulation signaling pathway 2 (AeNSP2), and nodule inception demonstrated that these genes intervene at several stages of intercellular infection and during bacterial accommodation. We provide evidence that AeNSP2 has an additional nitrogen-dependent regulatory function in the formation of axillary root hairs at lateral root bases, which are rhizobia-colonized infection sites. Our investigation of the recently discovered symbiotic actor cysteine-rich receptor-like kinase specified that it is not involved in mycorrhization; however, it is essential for both symbiotic signaling and early infection during nodulation. These findings provide important insights on the modus operandi of Nod-independent symbiosis and contribute to the general understanding of how rhizobial–legume symbioses are established by complementing the information acquired in model legumes.
Pyruvate, phosphate dikinase regulatory protein impacts light response of C4 photosynthesis in Setaria viridis
Authors: Om Kuenzang , Arias Nico N , Jambor Chaney C , MacGregor Alexandra , Rezachek Ashley N , Haugrud Carlan , Kunz Hans-Henning , Wang Zhonghui , Huang Pu , Zhang Quan , Rosnow Josh , Brutnell Thomas P , Cousins Asaph B , Chastain Chris J
Published: July 2022

In C4 plants, the pyruvate (Pyr), phosphate dikinase regulatory protein (PDRP) regulates the activity of the C4 pathway enzyme Pyr, phosphate dikinase (PPDK) in a light-/dark-dependent manner. The importance of this regulatory action to C4 pathway function and overall C4 photosynthesis is unknown. To resolve this question, we assessed in vivo PPDK phospho-regulation and whole leaf photophysiology in a CRISPR–Cas9 PDRP knockout (KO) mutant of the NADP-ME C4 grass green millet (Setaria viridis). PDRP enzyme activity was undetectable in leaf extracts from PDRP KO lines. Likewise, PPDK phosphorylated at the PDRP-regulatory Thr residue was immunologically undetectable in leaf extracts. PPDK enzyme activity in rapid leaf extracts was constitutively high in the PDRP KO lines, irrespective of light or dark pretreatment of leaves. Gas exchange analysis of net CO2 assimilation revealed PDRP KO leaves had markedly slower light induction kinetics when leaves transition from dark to high-light or low-light to high-light. In the initial 30 min of the light induction phase, KO leaves had an ∼15% lower net CO2 assimilation rate versus the wild-type (WT). Despite the impaired slower induction kinetics, we found growth and vigor of the KO lines to be visibly indistinguishable from the WT when grown in normal air and under standard growth chamber conditions. However, the PDRP KO plants grown under a fluctuating light regime exhibited a gradual multi-day decline in Fv/Fm, indicative of progressive photosystem II damage due to the absence of PDRP. Collectively, our results demonstrate that one of PDRP’s functions in C4 photosynthesis is to ensure optimal photosynthetic light induction kinetics during dynamic changes in incident light.
Shared decision-making to improve medication adherence
Authors: Slyer Jason T.
Published: July 2022

Shared decision-making is recommended in many clinical practice guidelines. Using a case study of medication adherence, this paper demonstrates how providers can utilize the concepts of shared decision-making to improve treatment decisions and increase patient self-efficacy in carrying out the plan of care.
Point-of-care ultrasound
Authors: Fraleigh Courteney D.M. , Duff Elsie
Published: July 2022

Point-of-care ultrasound (PoCUS) is a cost-effective diagnostic technology that, with training, is accessible, portable, and a convenient diagnostic modality to complement physical assessments. PoCUS is beneficial in that it can reduce the number of imaging tests required, while also mitigating barriers to healthcare for rural and remote communities.
Measurable Lumbar Motion Remains 1 Year After Vertebral Body Tethering
Authors: Mathew Smitha E. , Milbrandt Todd A. , Larson A. Noelle
Published: July 2022

Introduction:

Vertebral body tethering (VBT) is growing in popularity for skeletally immature patients with scoliosis because of presumed preservation of spinal motion. Although results have shown preserved thoracic motion, there is minimal data to support motion over the lumbar instrumented segments after VBT. The purpose of this study was to analyze the range of motion of the thoracolumbar and lumbar spine after lumbar VBT.

Methods:

Retrospective review of patients treated with lumbar VBT underwent low-dose biplanar flexion-extension and lateral bending radiographs at 1 year after surgery to assess motion. Coronal motion at 1 year was compared with preoperative side-bending radiographs. The angle subtended by the screws at the upper instrumented vertebra and lower instrumented vertebra was measured on left-bending and right-bending radiographs to evaluate the coronal arc of motion and was compared with preoperative values over the same levels measured from the end plates. At 1 year postoperatively, the sagittal angle was measured over the instrumented levels on flexion and extension radiographs.

Results:

Of the 71 scoliosis patients who underwent VBT at our center eligible for 1-year follow-up, 20 had lumbar instrumentation, all of whom had lumbar bending films available at 1 year after surgery. Seven patients had both thoracic and lumbar VBT on the same day and 13 had lumbar or thoracolumbar tether only. Mean age was 13.5±1.9 years. Mean preoperative major coronal curve measured 52+8 degrees (range: 42 to 70) and mean 27 degrees (range: 13 to 40) at latest follow-up. Mean levels instrumented was 8 (range: 5 to 12), with the lowest instrumented level typically L3 (N=14). The mean preoperative coronal arc of motion over the instrumented segments was 38±13 degrees (range: 19 to 73 degrees) and decreased after surgery to a mean arc of 17±7 degrees (range: 7 to 31 degrees). However, 19 of the 20 (95%) had at least a 10-degree coronal arc of motion. Patients maintained on average 46% (range: 22% to 100%) of their preoperative coronal arc of lumbar motion over the instrumented lumbar segments. On flexion-extension lateral radiographs taken at 1 year postoperatively, there was a mean postoperative arc of motion of 30±13 degrees.

Conclusions:

Lumbar VBT resulted in preserved flexion and extension motion at 1 year postoperatively. We also noted some preserved coronal plane motion, but this was decreased compared with preoperative values by ~50%. These findings provide proof of concept that some spinal motion is preserved after lumbar VBT in contrast to lumbar fusion where no motion is retained over the instrumented segments.