bluuebunny/crossref_metadata_2025 huggingface dataset:
O Give Me a Home
Authors: McCreless Patrick
Published: February 2023

This essay examines Stephen Lett’s (2023) critique of North American music theory in general, and of the Society for Music Theory in particular, from the point of view of the binary inclusion/exclusion. Drawing on my own experience, I acknowledge that in many respects his critique of the Society for Music Theory (SMT), from its very inception, as creating an exclusionary, “stratified” space, is on target. Yet I contest his reading of the history and current functioning of the Society and of the broader discipline as a wholesale enterprise of coloniality. Although he insists that this metaphor, as applied to the SMT, is not to be read as involving the type of violence inflicted by colonial powers on native peoples, his consistent, governing language of displacement, pushing out, building fences, and defending territory, belies this denial, and produces a narrative that often suggests a level of hostility incompatible with both history and current experience.
Characterization of an atypical but widespread type IV secretion system for transfer of the integrative and conjugative element (ICEclc) inPseudomonas putida
Authors: Daveri Andrea , Benigno Valentina , van der Meer Jan Roelof
Published: February 2023

Conjugation of DNA relies on multicomponent protein complexes bridging two bacterial cytoplasmic compartments. Whereas plasmid conjugation systems have been well documented, those of integrative and conjugative elements (ICEs) have remained poorly studied. We characterize here the conjugation system of the ICEclc element in Pseudomonas putida UWC1 that is a model for a widely distributed family of ICEs. By in frame deletion and complementation, we show the importance on ICE transfer of 22 genes in a 20-kb conserved ICE region. Protein comparisons recognized seven homologs to plasmid type IV secretion system components, another six homologs to frequent accessory proteins, and the rest without detectable counterparts. Stationary phase imaging of P. putida ICEclc with in-frame fluorescent protein fusions to predicted type IV components showed transfer-competent cell subpopulations with multiple fluorescent foci, largely overlapping in dual-labeled subcomponents, which is suggestive for multiple conjugation complexes per cell. Cross-dependencies between subcomponents in ICE-type IV secretion system assembly were revealed by quantitative foci image analysis in a variety of ICEclc mutant backgrounds. In conclusion, the ICEclc family presents an evolutionary distinct type IV conjugative system with transfer competent cells specialized in efficient transfer.
Ultradeep characterisation of translational sequence determinants refutes rare-codon hypothesis and unveils quadruplet base pairing of initiator tRNA and transcript
Authors: Höllerer Simon , Jeschek Markus
Published: February 2023

Translation is a key determinant of gene expression and an important biotechnological engineering target. In bacteria, 5′-untranslated region (5′-UTR) and coding sequence (CDS) are well-known mRNA parts controlling translation and thus cellular protein levels. However, the complex interaction of 5′-UTR and CDS has so far only been studied for few sequences leading to non-generalisable and partly contradictory conclusions. Herein, we systematically assess the dynamic translation from over 1.2 million 5′-UTR-CDS pairs in Escherichia coli to investigate their collective effect using a new method for ultradeep sequence-function mapping. This allows us to disentangle and precisely quantify effects of various sequence determinants of translation. We find that 5′-UTR and CDS individually account for 53% and 20% of variance in translation, respectively, and show conclusively that, contrary to a common hypothesis, tRNA abundance does not explain expression changes between CDSs with different synonymous codons. Moreover, the obtained large-scale data provide clear experimental evidence for a base-pairing interaction between initiator tRNA and mRNA beyond the anticodon-codon interaction, an effect that is often masked for individual sequences and therefore inaccessible to low-throughput approaches. Our study highlights the indispensability of ultradeep sequence-function mapping to accurately determine the contribution of parts and phenomena involved in gene regulation.
Recovering false negatives in CRISPR fitness screens with JLOE
Authors: Dede Merve , Hart Traver
Published: February 2023

It is widely accepted that pooled library CRISPR knockout screens offer greater sensitivity and specificity than prior technologies in detecting genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a ∼20% false negative rate, in addition to library-specific false negatives. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared to false negatives. Cumulative analyses across tissues improves our understanding of core essential genes and suggest only a small number of lineage-specific essential genes, enriched for transcription factors that define pathways of tissue differentiation. To recover false negatives, we introduce a method, Joint Log Odds of Essentiality (JLOE), which builds on our prior work with BAGEL to selectively rescue the false negatives without an increased false discovery rate.
Ribosomes lacking bS21 gain function to regulate protein synthesis inFlavobacterium johnsoniae
Authors: McNutt Zakkary A , Roy Bappaditya , Gemler Bryan T , Shatoff Elan A , Moon Kyung-Mee , Foster Leonard J , Bundschuh Ralf , Fredrick Kurt
Published: February 2023

Ribosomes of Bacteroidia (formerly Bacteroidetes) fail to recognize Shine-Dalgarno (SD) sequences even though they harbor the anti-SD (ASD) of 16S rRNA. Inhibition of SD-ASD pairing is due to sequestration of the 3’ tail of 16S rRNA in a pocket formed by bS21, bS18, and bS6 on the 30S platform. Interestingly, in many Flavobacteriales, the gene encoding bS21, rpsU, contains an extended SD sequence. In this work, we present genetic and biochemical evidence that bS21 synthesis in Flavobacterium johnsoniae is autoregulated via a subpopulation of ribosomes that specifically lack bS21. Mutation or depletion of bS21 in the cell increases translation of reporters with strong SD sequences, such as rpsU’-gfp, but has no effect on other reporters. Purified ribosomes lacking bS21 (or its C-terminal region) exhibit higher rates of initiation on rpsU mRNA and lower rates of initiation on other (SD-less) mRNAs than control ribosomes. The mechanism of autoregulation depends on extensive pairing between mRNA and 16S rRNA, and exceptionally strong SD sequences, with predicted pairing free energies of < –13 kcal/mol, are characteristic of rpsU across the Bacteroidota. This work uncovers a clear example of specialized ribosomes in bacteria.
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials
Authors: Fischer Jordie A J , Cherian Arlin M , Bone Jeffrey N , Karakochuk Crystal D
Published: February 2023

Context

Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.

Objective

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.

Data sources

A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks’ supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.

Data extraction

Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.

Data analysis

Compared with other iron supplements, supplementation with ferrous bisglycinate for 4–20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15–0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17–0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.

Conclusion

Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.

PROSPERO registration no

CRD42020196984.
Outcome of Patients With Malignant Peripheral Nerve Sheath Tumors Enrolled on Sarcoma Alliance for Research Through Collaboration (SARC) Phase II Trials
Authors: Akshintala Srivandana , Mallory Nicole C , Lu Yao , Ballman Karla V , Schuetze Scott M , Chugh Rashmi , Maki Robert G , Reinke Denise K , Widemann Brigitte C , Kim AeRang
Published: February 2023

Background

Evaluation of prior phase II trials for malignant peripheral nerve sheath tumors (MPNST) may help develop more suitable trial endpoints in future studies.

Methods

We analyzed outcomes of patients with recurrent or unresectable/metastatic MPNST enrolled on prior Sarcoma Alliance for Research through Collaboration (SARC) phase II trials and estimated the progression-free survival (PFS). PFS from SARC006 (NCT 00304083), the phase II trial of upfront chemotherapy in chemotherapy naïve patients, was analyzed separately. Impact of baseline enrollment characteristics on PFS was evaluated.

Results

Sixty-four patients (29 male, 35 female, median age 39 years (range 15-81)) with MPNST were enrolled on 1 of 5 trials of single agent or combination therapy that were determined to be inactive. Patients had received a median of 1 (range 0-5) prior systemic therapy, and most had undergone prior surgery (77%) and radiation (61%). Seventy-three percent had metastatic disease at enrollment. Median PFS was 1.77 months (95% CI, 1.61-3.45), and the PFS rate at 4 months was 15%. Greater number of prior systemic therapies and worse performance status were associated with inferior PFS. There was no significant difference in PFS based on age at enrollment, treatment trial, response criteria, presence of metastatic disease, disease site at enrollment, and prior surgery or radiation. In comparison, on the SARC006 trial the PFS rate at 4 months was 94% in 40 patients.

Conclusion

These data provide a historical baseline PFS that may be used as a comparator in future clinical trials for patients with MPNST.
Effects of Electrical Brain Stimulation on Motor Learning
Authors: Karabanov Anke Ninija , Tzvi-Minker Elinor
Published: February 2023

Motor learning is important for many aspects of daily life and includes the acquisition of new skills as well as the adaptation of a known motor pattern to novel environmental conditions. Transcranial electric stimulation (TES) can be applied in connection with motor learning to boost performance in health and disease. In this chapter, we review the ability of TES, in its different forms, to interact with learning, retention, and adaptation of motor skills. We will discuss the influence of stimulation settings, stimulation timing, and the specific cortical target on different forms of motor learning, and relate behavioral effects of stimulation to local brain activity and interregional connectivity. We conclude the chapter highlighting the applied aspect of TES research in motor skill learning on rehabilitation of patients suffering stroke and movement disorders, as well as in experts seeking to boost performance.
Green means go: Green light promotes hypocotyl elongation via brassinosteroid signaling
Authors: Hao Yuhan , Zeng Zexian , Zhang Xiaolin , Xie Dixiang , Li Xu , Ma Libang , Liu Muqing , Liu Hongtao
Published: February 2023

Although many studies have elucidated the mechanisms by which different wavelengths of light (blue, red, far-red, or ultraviolet-B [UV-B]) regulate plant development, whether and how green light regulates plant development remains largely unknown. Previous studies reported that green light participates in regulating growth and development in land plants, but these studies have reported conflicting results, likely due to technical problems. For example, commercial green light-emitting diode light sources emit a little blue or red light. Here, using a pure green light source, we determined that unlike blue, red, far-red, or UV-B light, which inhibits hypocotyl elongation, green light promotes hypocotyl elongation in Arabidopsis thaliana and several other plants during the first 2–3 d after planting. Phytochromes, cryptochromes, and other known photoreceptors do not mediate green-light-promoted hypocotyl elongation, but the brassinosteroid (BR) signaling pathway is involved in this process. Green light promotes the DNA binding activity of BRI1-EMS-SUPPRESSOR 1 (BES1), a master transcription factor of the BR pathway, thus regulating gene transcription to promote hypocotyl elongation. Our results indicate that pure green light promotes elongation via BR signaling and acts as a shade signal to enable plants to adapt their development to a green-light-dominant environment under a canopy.
ETHYLENE RESPONSE FACTORS 4.1/4.2 with an EAR motif repress anthocyanin biosynthesis in red-skinned pears
Authors: Sun Hongye , Hu Kangdi , Wei Shuwei , Yao Gaifang , Zhang Hua
Published: February 2023

Red-skinned pears (Pyrus L.) are preferred to consumers for their attractive color and abundant anthocyanins. Pyrus ETHYLENE RESPONSE FACTOR 3 (PyERF3) positively regulates anthocyanin biosynthesis through interacting with Pyrus myeloblastosis family 114 (PyMYB114) and Pyrus basic helix-loop-helix 3 (PybHLH3) in red-skinned pears. However, the role of APETALA2/ethylene response factors (AP2/ERFs), which negatively regulate anthocyanin biosynthesis, remains unclear in red-skinned pears. Here, we validated that 2 AP2/ERFs, PyERF4.1 and PyERF4.2, screened from the transcriptome data of ‘Starkrimson’ pear (Pyrus communis L.) and its green mutant, inhibit anthocyanin biosynthesis in transgenic pear calli, as well as in overexpression and gene-edited tomato (Solanum lycopersicum) fruits. Meanwhile, the co-transformation of PyERF4.1/PyERF4.2 with PyERF3–PyMYB114–PybHLH3 inhibited anthocyanin biosynthesis in pear fruits and strawberry (Fragaria vesca) receptacles. Further assays showed that PyMYB114 activated the transcription of PyERF4.1/PyERF4.2; PyERF4.1/PyERF4.2 then interacted with PyERF3 to affect the stability of the PyERF3–PyMYB114–PybHLH3 complex, thereby inhibiting the transcription of the anthocyanin biosynthesis gene Pyrus anthocyanidin synthase (PyANS). Furthermore, deletion of the ERF-associated-amphiphilic repression (EAR) motif eliminated the inhibitory effect of PyERF4.1/PyERF4.2 on anthocyanin biosynthesis, and a mutation of the PyERF4.2-EAR motif (LxLxM to LxLxL) strengthened the inhibitory effect, demonstrating that the EAR motif is indispensable for the inhibitory effect of PyERF4.1/PyERF4.2 on anthocyanin biosynthesis in pears. Our study has shed light on a feedback regulatory loop mechanism that balances the excessive accumulation of anthocyanins in red-skinned pears, providing insights into the regulatory mechanism of anthocyanin biosynthesis and the regulatory network of coloration in red-skinned pears.
Dual biologic therapy for the treatment of rheumatic diseases and asthma: a case series
Authors: Malik Mariam , Jones Bryony , Williams Emma , Kurukulaaratchy Ramesh , Holroyd Chris , Mason Alice
Published: February 2023

Objective

Combination biological therapies are being considered increasingly for patients with multiple co-morbidities requiring biologics. There are limited data available on this approach, and concerns remain about the possible risk of adverse events, particularly infection.

Methods

We present three patients on dual biologics for rheumatic disease and asthma. The biologic combinations used were etanercept and mepolizumab, infliximab and omalizumab, and etanercept and omalizumab. The time on combination biologic therapies ranged from 24 to 36 months. Patients were monitored for any serious adverse events.

Results

All three patients were able to tolerate combined biologic therapies, with no serious adverse events. All three patients gained improvement in their rheumatic and asthma disease control, with reduction in disease activity scores and reduction in steroid usage.

Conclusion

The decision to start dual biologic therapy should be considered carefully, on a case-by-case basis. The number of patients who are on combination biological therapy is small, and data are sparse. Real-world data are needed to examine the long-term benefits and risks of different forms of combination biologic therapies.
In-depth characterization of pulmonary arterial hypertension in mixed connective tissue disease: a French national multicentre study
Authors: Chaigne Benjamin , Chevalier Kevin , Boucly Athenaïs , Agard Christian , Baudet Antoine , Bourdin Arnaud , Chabanne Céline , Cottin Vincent , Fesler Pierre , Goupil François , Jego Patrick , Launay David , Lévesque Hervé , Maurac Arnaud , Mohamed Shirine , Tromeur Cécile , Rottat Laurence , Sitbon Olivier , Humbert Marc , Mouthon Luc
Published: February 2023

Objective

Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients.

Methods

MCTD patients enrolled in the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan–Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses.

Results

Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH.

Conclusion

PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH.
High prevalence and mortality of Pneumocystis jirovecii pneumonia in anti-MDA5 antibody-positive dermatomyositis
Authors: Chen Xixia , Shu Xiaoming , He Linrong , Yang Hanbo , Lu Xin , Wang Guochun , Ge Yongpeng
Published: February 2023

Objectives

To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS).

Methods

Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods.

Results

91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P < 0.001).

Conclusion

PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.
Tax principles, policy feedback and self-interest: cross-national experimental evidence on wealth tax preferences
Authors: Schechtl Manuel , Tisch Daria
Published: February 2023

Rising wealth inequality and squeezed public budgets has brought wealth tax back into policy discussions. A net wealth tax might help to boost state revenue and reduce wealth inequality. Yet little is known about citizens’ attitudes towards the design of a net wealth tax (i.e. the tax unit, exemption and rate). Using a novel multifactorial survey experiment, we examine citizens’ endorsement of fundamental principles of taxation. Building on policy feedback theory, we examine if preferences differ in three policy arenas (USA, Germany and UK) and whether individuals’ reasoning is dependent on self-interest. While a clear majority in all three countries generally endorses a wealth tax, our findings show that citizens care more about the amount exempted than the tax unit or rate. We do not identify a preference for any specific tax unit. Furthermore, tax preferences seem to be strikingly similar among citizens of all three countries. Yet we show that individuals are mostly concerned about not being personally affected by such a tax, which is reflected in their preference for substantial exemptions. We discuss our findings with regard to our understanding of wealth inequality, tax equity and the potential implications for policymakers.
Effective Management of Powdery Mildew in Cantaloupe Plants Using Nighttime Applications of UV Light
Authors: Lopes Ueder P. , Alonzo Galvin , Onofre Rodrigo B. , Mello Paulo P. , Gadoury David M. , Vallad Gary E. , Peres Natalia A.
Published: February 2023

Ultraviolet light at wavelengths from 254 to 283 nm/has been reported to effectively suppress powdery mildews in several crops, including some cucurbits. Its use to suppress powdery mildew (Podosphaera xanthii) specifically in cantaloupe has not been previously reported. We evaluated the foregoing technology in cantaloupe fields for suppression of powdery mildew and possible effects on plant growth and yield. In a controlled laboratory study, greenhouse-grown cantaloupe plants were exposed to a gradient of UV-C (254 nm) doses during darkness, and the effects upon powdery mildew development and the plant were evaluated. We also evaluated the efficacy of nighttime applications of UV-C at 100 and 200 J/m2 against powdery mildew on adaxial leaf surfaces in greenhouse, high-tunnel, and open-field plantings. UV-C at the foregoing doses reduced sporulation and germination of P. xanthii conidia without damaging plants. On cantaloupe seedlings in the greenhouse, disease severity was equivalently suppressed at all doses and frequencies of applications of the light. In high-tunnel and open-field experiments, the most effective control of powdery mildew was provided by UV-C applied at 200 J/m2 twice every week, where suppression provided by UV-C was generally equal to and sometimes better than the fungicide treatment. The foregoing UV-C dose and frequency of application also provided the highest yield under field conditions, indicating that UV-C treatment is a promising technology for commercially relevant suppression of powdery mildew on cantaloupe in a variety of growing systems.
A Telemedicine Standardized Patient Experience: Enhancing the Virtual Classroom and Preparing for Alternative Modalities of Care
Authors: Maynard Kristi , Knickerbocker Joshua
Published: February 2023

This pilot study explored the use of standardized patients in the virtual classroom in efforts to increase family nurse practitioner preparedness to engage in telemedicine care delivery. Using a mixed-methods approach, we determined this innovation significantly increased students’ confidence in their ability to perform a telemedicine visit while also improving their satisfaction with the virtual classroom.
Updates in diagnosis and management of paediatric mastocytosis
Authors: Tiano Rasa , Krase Ifat Z. , Sacco Keith
Published: February 2023

Purpose of review

Paediatric mastocytosis is a rare clonal disorder characterized by the overproduction and organ infiltration of mast cells. Symptoms are due to mast cell mediator release. Cutaneous mastocytosis is the most common presentation in children with systemic disease being rare. Our aim is to provide a practical guideline in differentiating subtypes of paediatric mastocytosis while providing actionable recommendations on diagnosis, clinical management, follow-up and prognosis.

Recent findings

Longitudinal cohort studies of paediatric cutaneous mastocytosis have shown spontaneous remission with favourable prognosis. Hereditary alpha-tryptasemia may coexist with mastocytosis; thus, screening for this disorder is recommended. There is an emerging role for serum tryptase in asthma endotyping and potential for using therapeutic tryptase inhibitors.

Morbidity in paediatric mastocytosis typically arises from symptoms secondary to mast cell mediator release. Prognosis for nonaggressive disease is typically favourable; however, risks for anaphylaxis and psychosocial morbidity may be underestimated. Symptomatic management and anticipatory guidance may help support patients and families throughout the disease course.
Lung ultrasound monitoring: impact on economics and outcomes
Authors: Cammarota Gianmaria , Vetrugno Luigi , Longhini Federico
Published: February 2023

Purpose of review

This review aims to summarize the impact of lung ultrasonography (LUS) on economics and possible impact on patients’ outcomes, proven its diagnostic accuracy in patients with acute respiratory failure.

Recent findings

Despite some previous ethical concerns on LUS examination, today this technique has showed several advantages. First, it is now clear that the daily use of LUS can provide a relevant cost reduction in healthcare of patients with acute respiratory failure, while reducing the risk of transport of patients to radiological departments for chest CT scan. In addition, LUS reduces the exposition to x-rays since can replace the bedside chest X-ray examination in many cases. Indeed, LUS is characterized by a diagnostic accuracy that is even superior to portable chest X-ray when performed by well trained personnel. Finally, LUS examination is a useful tool to predict the course of patients with pneumonia, including the need for hospitalization and ICU admission, noninvasive ventilation failure and orotracheal intubation, weaning success, and mortality.

LUS should be implemented not only in Intensive Care Units, but also in other setting like emergency departments. Since most data comes from the recent coronavirus disease 2019 pandemic, further investigations are required in Acute Respiratory Failure of different etiologies.
Harm Reduction Approach to Increasing Self-reported Safe Medication Storage Among Pregnant and Parenting People Receiving Opioid Use Disorder Treatment
Authors: Grist Elizabeth , Thakkar Bhushan , Dacha Phoebe , Lutins Erika , Maxwell Madison , Martin Caitlin E.
Published: February 2023

Objectives

The expansion of access to buprenorphine-naloxone (BUP-NAL) for the treatment of opioid use disorder (OUD) is critical to combat the overdose crisis. Evidence is lacking to guide providers on how to best promote BUP-NAL medication safety for their patients. This study assessed (1) the current medication storage practices among a sample of pregnant and parenting people receiving BUP-NAL for OUD; (2) the feasibility and acceptability of providing a lockbox for safe medication storage.

Methods

Pregnant and/or parenting patients receiving sublingual BUP-NAL in an outpatient OUD clinic were recruited between June and November 2021. Participants completed a baseline survey, received a lockbox, and a follow-up survey 3 to 8 weeks later. The primary outcome of current self-reported safe medication storage practice was defined by storing BUP-NAL in a locked/latched place “almost always” or “always” on the baseline survey. Outcomes were analyzed using simple proportions.

Results

Sixty-three participants completed the baseline survey, and 50 completed the follow-up survey. Baseline survey results indicated that only a quarter of patients (26.6%) were practicing safe BUP-NAL medication storage practices. At follow up, 93.6% of patients were using the lockbox provided by the study, 93.4% reported being satisfied with the lockbox, and most participants (89.3%) reported safe BUP-NAL medication storage practices.

Conclusions

Many pregnant and parenting patients with OUD receiving BUP-NAL do not store their medications safely. The provision of a lockbox as part of OUD treatment is a feasible, acceptable, and potentially effective harm reduction intervention.
A Mixed-methods Evaluation of an Addiction/Cardiology Pilot Clinic With Contingency Management for Patients With Stimulant-associated Cardiomyopathy
Authors: Leyde Sarah , Abbs Elizabeth , Suen Leslie W. , Martin Marlene , Mitchell Andreas , Davis Jonathan , Azari Soraya
Published: February 2023

Objectives

Contingency management (CM) is one of the most effective treatments for stimulant use disorder but has not been leveraged for people with stimulant-associated cardiomyopathy (SA-CMP), a chronic health condition with significant morbidity and mortality. We aimed to determine the feasibility and acceptability of a multidisciplinary addiction/cardiology clinic with CM for patients with SA-CMP and to explore barriers and facilitators to engagement and recovery.

Methods

We recruited patients with a hospitalization in the past 6 months, heart failure with reduced ejection fraction (<40%) and stimulant use disorder to participate in Heart Plus, a 12-week addiction/cardiology clinic with CM in an urban, safety-net, hospital-based cardiology clinic, which took place March 2021 through June 2021. Contingency management entailed gift card rewards for attendance and negative point-of-care urine drug screens. Our mixed-methods study used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. We obtained data from the medical record, staff surveys, and qualitative interviews with participants.

Results

Thirty-eight patients were referred, 17 scheduled an appointment, and 12 attended the intake appointment and enrolled in the study. Mean treatment duration was 8 of 12 weeks. Of the 9 participants who attended more than one visit, the median attendance was 82% of available visits for in-person visits and 83% for telephone visits, and all patients reported decreased stimulant use.

Conclusions

Delivering CM through a multidisciplinary addiction/cardiology clinic for patients with SA-CMP was feasible and engaged patients in care. Further research is needed to assess whether this program is associated with improved heart failure outcomes.
Integrative Analysis of Proteome-wide Association Studies and Functional Enrichment Analysis to Identify Genes and Chemicals Associated with Alcohol Dependence
Authors: Zhang Jingxi , Meng Peilin , Yao Yao , Zhang Huijie , Pan Chuyu , Li Chun'e , Chen Yujing , Zhang Zhen , Cheng Shiqiang , Liu Li , Yang Xuena , Jia Yumeng , Zhang Feng
Published: February 2023

Objectives

Alcohol dependence accounts for a large proportion of the global burden of disease and disability. This study aims to investigate the candidate genes and chemicals associated with alcohol dependence.

Methods

Using data from published alcohol dependence genome-wide association studies, we first conducted a proteome-wide association study of alcohol dependence by integrating alcohol dependence genome-wide association studies with 2 human brain reference proteomes of dorsolateral prefrontal cortex from the Religious Order Study and Rush Memory and Aging Project and the Banner Sun Health Research Institute. Then, based on the identified genes in proteome-wide association study, we conducted functional enrichment analysis and chemical-related functional enrichment analysis to detect the related Gene Ontology terms and chemicals.

Results

Proteome-wide association study identified several potential candidate genes for alcohol dependence, such as GOT2 (P = 7.59 × 10−6) and C3orf33 (P = 5.00 × 10−3). Furthermore, functional enrichment analysis identified multiple candidate Gene Ontology terms associated with alcohol dependence, such as glyoxylate metabolic process (adjusted P = 2.99 × 10−6) and oxoglutarate metabolic process (adjusted P = 9.95 × 10−6). Chemical-related functional enrichment analysis detected several alcohol dependence–related candidate chemicals, such as pitavastatin (P = 2.00 × 10−4), cannabinoids (P = 4.00 × 10−4), 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (P = 4.00 × 10−4), and gabapentin (P = 2.00 × 10−3).

Conclusions

Our study reports multiple candidate genes and chemicals associated with alcohol dependence, providing novel clues for understanding the biological mechanism of alcohol dependence.
Defining Prescription Drug Misuse: A Naturalistic Evaluation of National Survey on Drug Use and Health Data From 2012–2014 to 2015–2017
Authors: McHugh R. Kathryn , Votaw Victoria R. , McCarthy Megan D. , Bichon Juliette A. , Bailey Allen J. , Fitzmaurice Garrett M.
Published: February 2023

Objectives

Prescription drug misuse (PDM) is a significant public health problem. As research has evolved, the definitions of misuse have varied over time, yet the implications of this variability have not been systematically studied. The objective of this study was to leverage a change in the measurement of PDM in a large population survey to identify its impact on the prevalence and correlates of this behavior.

Methods

Data from the National Survey on Drug Use and Health were compared before and after a change in the definition of PDM from one that restricted the source and motive for use to one that captured any misuse other than directed by a prescriber. Three-year cohorts were constructed, representing a restricted definition of PDM (2012–2014) and a broad definition of PDM (2015–2017).

Results

Segmented logistic regression models indicated a significant increase in PDM prevalence for all 3 drug types examined (opioids, tranquilizers, and sedatives). Although the magnitude of differences varied somewhat based on drug type, the broader definition was generally associated with older age, higher prevalence of health insurance, and higher odds of misusing one's own prescription. Some worsening of mental health indicators was observed, but results indicated few other clinical or substance use differences.

Conclusions

Definitions of prescription drug misuse have a substantial impact on the prevalence of misuse and some impact on the characteristics of the population. Further research is needed to understand the optimal strategy for measuring this behavior, based on the scientific or public health question or interest.
Rapid Low-dose Buprenorphine Initiation for Hospitalized Patients With Opioid Use Disorder
Authors: Sokolski Eleasa , Skogrand Emily , Goff Amelia , Englander Honora
Published: February 2023

Introduction

Low-dose buprenorphine initiation allows patients to start buprenorphine for treatment of opioid use disorder (OUD) while continuing full-agonist opioids. This strategy is beneficial for hospitalized patients who may have acute pain and are not able to tolerate withdrawal. However, most protocols require 7–10 to complete, which may create barriers in patients with shorter or unpredictable lengths of stay.

Objective

This cohort study examined the efficacy and feasibility of a rapid low-dose buprenorphine initiation protocol in the hospital setting.

Methods

We performed a retrospective cohort study of hospitalized patients with OUD (diagnosed by DSM-5 criteria) seen by an addiction medicine consult service at a single academic medical center who started buprenorphine via a rapid low-dose initiation between November 2021 and May 2022. Patients were prospectively tracked using an electronic registry, and data were abstracted from the electronic health record.

Results

Twenty-four patients underwent rapid low-dose initiation during the study period. All patients received full-agonist opioids before starting buprenorphine. Thirteen (54%) patients reported using fentanyl, with 5 patients reported endorsing use within 48 hours preceding buprenorphine initiation. Nineteen (79%) patients completed initiation with an average time to completion of 72 hours. Among patients who reported fentanyl use in the 48 hours before starting buprenorphine, 60% completed initiation and 40% elected to transition to methadone. No patients experienced precipitated withdrawal.

Conclusions

Rapid low-dose buprenorphine initiation provides a feasible and well-tolerated alternative to traditional and slower low-dose initiations for hospitalized patients.
Letrozole Compared With Clomiphene Citrate for Polycystic Ovarian Syndrome
Authors: Liu Zhuo , Geng Yuli , Huang Yanjing , Hu Runan , Li Fan , Song Yufan , Zhang Mingmin
Published: February 2023

OBJECTIVE:

To estimate the effect of letrozole and clomiphene citrate in women with infertility and polycystic ovarian syndrome (PCOS).

METHODS OF STUDY SELECTION:

MEDLINE through PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched for relevant studies from inception to February 1, 2022. Two reviewers retrieved, filtered, and extracted data independently using the bibliographic software EndNote X9 and Excel workbook. We included randomized controlled trials (RCTs) reporting ovulation induction outcomes in women with infertility and PCOS treated with either letrozole or clomiphene citrate followed by timed intercourse or intrauterine insemination. The data were merged into a mean difference or risk ratio (RR) with 95% CI, depending on variable types.

TABULATION, INTEGRATION, AND RESULTS:

Data collection and organization were conducted in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Twenty-nine RCTs were eligible, which included 3,952 women and 7,633 ovulation induction cycles. We acquired evidence from 22 RCTs for the ovulation rate, 28 RCTs for the clinical pregnancy rate, and eight RCTs for live-birth rate. Pooled analysis indicated that letrozole treatment prevailed against clomiphene citrate in ovulation rate (RR 1.14, 95% CI 1.06–1.21, P<.001), clinical pregnancy rate (RR 1.48, 95% CI 1.34–1.63, P<.001), and live-birth rate (RR 1.49, 95% CI 1.27–1.74, P<.001).

CONCLUSIONS:

Letrozole was associated with improved ovulation, pregnancy, and live-birth rates compared with clomiphene citrate. We recommend letrozole over clomiphene citrate as an ovulation induction drug in women with infertility and PCOS, although the quality of the evidence is mixed.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42022308777.
Texas Senate Bill 8 and Abortion Experiences in Patients With Fetal Diagnoses
Authors: Baker Courtney C. , Smith Emma , Creinin Mitchell D. , Moayedi Ghazaleh , Chen Melissa J.
Published: February 2023

OBJECTIVE:

To describe experiences with abortion counseling and access in patients with lethal or life-limiting fetal diagnoses in Texas after enactment of Senate Bill 8 (SB8).

METHODS:

In this qualitative study, we interviewed patients who obtained abortions after enactment of SB8, using semi-structured interviews to explore how restrictions affected abortion care. Two researchers coded all transcripts using an inductive technique and analyzed themes in an iterative approach.

RESULTS:

We interviewed 16 participants who reported gestational durations from 13 to 29 weeks at the time of abortion. Participants described loss of the therapeutic patient–physician relationship and feelings of isolation while pursuing abortion due to the limitations imposed by SB8. For example, participants felt there was a physician “gag rule” regarding abortion (“the unspoken word of termination”), resulting in the need to find information about pregnancy options outside of the medical community and further highlighting the privilege of financial resources necessary to obtain an abortion on their own. Participants also expressed fears regarding confidentiality with their support systems and clinicians (“I would joke around and say, well don't sue me, but halfway mean it”) and personal safety when self-referring for abortion (“…am I making the right choice on where I need to go? Is it safe?”).

CONCLUSION:

Abortion restrictions and bans such as SB8 erode the patient–physician relationship, evoking fear and safety concerns during a vulnerable time for those undergoing abortion for lethal or life-limiting fetal diagnoses. They force patients to shoulder the significant burden of understanding pregnancy options and navigating the process of abortion alone, which is likely to have greater effects on those with fewer resources.
Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group
Authors: Boller Marie J. , Xu Fei , Lee Catherine , Sridhar Sneha , Greenberg Mara B. , Hedderson Monique M.
Published: February 2023

OBJECTIVE:

To evaluate perinatal outcomes associated with pregnancy after bariatric surgery within a large integrated health care system using propensity score matching.

METHODS:

We conducted a retrospective cohort study that evaluated perinatal outcomes in pregnant patients after bariatric surgery from January 2012 through December 2018. History of bariatric surgery was identified by using International Classification of Diseases codes and a clinical database. Primary outcomes were preterm birth (PTB), gestational hypertension, preeclampsia, impaired glucose tolerance or gestational diabetes, a large-for-gestational-age (LGA) or small-for-gestational-age (SGA) neonates, and cesarean birth. Propensity scores were estimated by using logistic regression that accounted for age at delivery, prepregnancy body mass index, year of delivery, parity, neighborhood deprivation index, race and ethnicity, insurance status, initiation of prenatal visit in the first trimester, smoking during pregnancy, chronic hypertension, and preexisting diabetes. Five patients in the control group were matched to each patient in the case group on linear propensity score, and modified Poisson regression was used to adjust for covariates. Sensitivity analyses by timing and type of surgery were performed.

RESULTS:

We identified a case cohort of 1,591 pregnancies in patients after bariatric surgery and a matched cohort of 7,955 pregnancies in patients who had not undergone bariatric surgery. Demographic characteristics were similar in both groups. In multivariate models, pregnancy after bariatric surgery was associated with a decreased risk of preeclampsia (7.5% vs 10.2%, adjusted relative risk [aRR] 0.72, 95% CI 0.60–0.86), gestational diabetes or impaired fasting glucose (23.5% vs 35.0%, aRR 0.73, 95% CI 0.66–0.80), and LGA (10.6% vs 19.9%, aRR 0.56, 95% CI 0.48–0.65) and an increased risk of SGA (10.9% vs 6.6%, aRR 1.51, 95% CI 1.28–1.78). No significant differences were observed in PTB, gestational hypertension and cesarean delivery.

CONCLUSION:

Pregnancy after bariatric surgery in a racially and ethnically diverse cohort of patients is associated with decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates; it is also associated with an increased risk of SGA neonates compared with pregnant patients in a matched control group.
Initial Displacement of Humeral Shaft Fractures Is Associated With Failure of Nonoperative Management
Authors: Kim Ye Joon , Taniguchi Kevin , Bowers Mathew R. , Lauder Alexander , Parry Joshua A.
Published: February 2023

Objectives:

To determine whether the initial radiographic displacement of humeral shaft fractures is associated with failure of nonoperative management.

Design:

Retrospective cohort study.

Setting:

Urban level 1 trauma center.

Patients/Participants:

106 patients with humeral shaft fractures (OTA/AO 12) initially managed nonoperatively.

Intervention:

Functional bracing.

Main Outcome Measurements:

Failure of nonoperative management, defined as conversion to surgery, malunion, and delayed union/nonunion.

Results:

Nonoperative management failed in 33 (31%) of 106 included patients with 27 patients (25%) requiring surgery. On multivariate analysis, female sex [odds ratio (OR): 3.50, 95% confidence interval (CI): 1.09 to 11.21], American Society of Anesthesiologist classification >1 (OR: 7.16, CI: 1.95 to 26.29), initial fracture medial/lateral (ML) translation (OR: 1.09, CI: 1.01 to 1.17, per unit change), and initial fracture anterior–posterior (AP) angulation (OR: 1.09, CI: 1.02 to 1.15, per unit change) were independently associated with failure of nonoperative management. Initial fracture displacement values that maximized the sensitivity (SN) and specificity (SP) for failure included an AP angulation >11 degrees (SN 75%, SP 64%) and ML translation >12 mm (SN 55%, SP 75%). The failure rate in patients with none, 1, or both of these fracture parameters was 3.1% (1/32), 35.6% (20/56), and 66.6% (12/18), respectively.

Conclusions:

Nearly one-third of patients experienced failure of initial nonoperative management. Failure was found to be associated with greater initial fracture AP angulation and ML translation. Fracture displacement cut-off values were established that may be used by surgeons to counsel patients with these injuries.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.