bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergence in interspecific and intersubspecific gene expression between two closely related horseshoe bats (Rhinolophus)
Authors: Li Jun , Sun Keping , Dai Wentao , Leng Haixia , Feng Jiang
Published: December 2022

Closely related species have been used as representative systems to investigate the genetic mechanisms involved in the early stages of species differentiation. Previous studies have indicated that variation in gene expression might be a sensitive indicator of initial species divergence, although the role of expression divergence, and especially that associated with phenotypic variation remained relatively undefined. For three organs (cochlea, brain, and liver) from two closely related bat species (Rhinolophus siamensis and R. episcopus), the interspecific and intersubspecific gene expression profiles were compared using transcriptomics in this study. Striking organ specificity of expression was observed, and expression profiles exhibited similarities between cochlea and brain tissues. Numerous differentially expressed genes (DEGs) were identified for each organ in the interspecific comparison (cochlea/brain/liver: 1,069/647/692) and intersubspecific comparison (608/528/368). Functional enrichment analysis indicated vital variation in expression related to the immune system, ion activities, neuronal function, and multisensory system regulation in both comparisons. DEGs relevant to the variation in echolocation calls (RF) were found, and some of them were involved in the pivotal patterns of expression variation. The regulation of immune, ion channel, neural activity, and sophisticated sensory functions at the expression level might be key mechanisms in the early species divergence of bats, and the expression variation related to acoustical signal could have played a crucial part. This study expands our knowledge of gene expression and patterns of variation for three key organs to echolocation at both the interspecific and intersubspecific levels. Further, the framework described here provides insight into the genetic basis of phenotypic variation during the incipient stage of species differentiation.
Assessment of Truck-Mounted Area-Wide S-methoprene Applications to Manage West Nile Virus Vector Species in the Suburbs of Chicago, IL, USA
Authors: Johnson Haley E , Clifton Mark , Harbison Justin E , Erkapic Anastazia , Barrett-Wilt Gregory A , Paskewitz Susan , Bartholomay Lyric
Published: December 2022

West Nile virus remains the leading cause of arboviral neuroinvasive disease in the United States, despite extensive efforts to control the mosquito vectors involved in transmission. In this study, we evaluated the effectiveness of Altosid SR-20 (active ingredient, S-methoprene 20%) larvicide applications using truck-mounted ultra-low volume (ULV) dispersal equipment to target Culex pipiens Linnaeus (Diptera: Culicidae) and Cx. restuans (Theobald)larvae. A combination of emergence bioassays, open-field measurements of deposited S-methoprene and spray distribution using gas chromatography–mass spectrometry, and assessments of adult Culex spp. populations in response to applications were conducted over the summer of 2020 within the North Shore Mosquito Abatement District (IL, USA). Open-field applications revealed that dispersed Altosid SR-20 using ULV equipment was effective (75% emergence inhibition in susceptible lab strain Cx. pipiens larvae) up to 53 m. In suburban neighborhood applications, we found that S-methoprene deposition and larval emergence inhibition (EI) in front yards did not differ significantly from backyards. An overall EI of 46% and 28% were observed for laboratory strain Cx. pipiens and wild Cx. restuans larvae respectively, and both had an EI significantly higher than the untreated control group. The EI of exposed wild Cx. pipiens larvae did not differ from the untreated controls, suggesting an increased tolerance to S-methoprene. No difference in abundance of gravid or host-seeking adult Culex spp. post-application was detected between treated and untreated sites. These results document the ability of area-wide application to distribute S-methoprene, but this strategy will need further modifications and evaluation for Culex spp. management.
Illustrations of rheumatoid arthritis symptoms to promote communication between patients and physicians
Authors: Kaneko Yuko , Hasegawa Mieko , Ikeda Kei , Nakano Kazuhisa , Kadono Yuho , Tanaka Yoshiya , Takeuchi Tsutomu
Published: December 2022

Objectives

To develop an illustrative tool presenting visualized rheumatoid arthritis (RA) symptoms using pictures to promote better understanding between patients and physicians.

Methods

A tool named ‘Okomarigoto Sheet’ was developed through an internet survey of patients with RA and certified rheumatologists by repeated in-person interviews.

Results

An internet survey on the reality of communication between patients with RA and physicians in 200 patients and 200 certified rheumatologists revealed various local and systemic symptoms of RA and difficulties in sharing those symptoms between patients and physicians during a short consultation. Interviews from patients and certified rheumatologists suggested that illustrations of symptoms would be helpful for better communication between them; therefore, an illustrative tool presenting visualized RA symptoms was drafted. The draft illustrations were refined through multiple rounds of interviews with the patients. The final version of the tool was discussed and evaluated at a joint meeting of patients and rheumatologists.

Conclusions

A picture sheet presenting RA symptoms was developed. Future prospective studies should evaluate the usefulness of the sheet in clinical practice to promote better communication between patients and physicians.
PAM-independent ultra-specific activation of CRISPR-Cas12a via sticky-end dsDNA
Authors: Zhang Wei , Mu Yaoqin , Dong Kejun , Zhang Lei , Yan Bei , Hu Hao , Liao Yangwei , Zhao Rong , Shu Wan , Ye Zhengxin , Lu Yaping , Wan Chong , Sun Qiangqiang , Li Longjie , Wang Hongbo , Xiao Xianjin
Published: December 2022

Although CRISPR-Cas12a [clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 12a] combining pre-amplification technology has the advantage of high sensitivity in biosensing, its generality and specificity are insufficient, which greatly restrains its application range. Here, we discovered a new targeting substrate for LbaCas12a (Lachnospiraceae bacterium Cas12a), namely double-stranded DNA (dsDNA) with a sticky-end region (PAM−SE+ dsDNA). We discovered that CRISPR-Cas12a had special enzymatic properties for this substrate DNA, including the ability to recognize and cleave it without needing a protospacer adjacent motif (PAM) sequence and a high sensitivity to single-base mismatches in that substrate. Further mechanism studies revealed that guide RNA (gRNA) formed a triple-stranded flap structure with the substrate dsDNA. We also discovered the property of low-temperature activation of CRISPR-Cas12a and, by coupling with the unique DNA hybridization kinetics at low temperature, we constructed a complete workflow for low-abundance point mutation detection in real samples, which was fast, convenient and free of single-stranded DNA (ssDNA) transformation. The detection limits were 0.005–0.01% for synthesized strands and 0.01–0.05% for plasmid genomic DNA, and the mutation abundances provided by our system for 28 clinical samples were in accordance with next-generation sequencing results. We believe that our work not only reveals novel information about the target recognition mechanism of the CRISPR-Cas12a system, but also greatly broadens its application scenarios.
A convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1
Authors: Closa Adria , Reixachs-Solé Marina , Fuentes-Fayos Antonio C , Hayer Katharina E , Melero Juan L , Adriaanse Fabienne R S , Bos Romy S , Torres-Diz Manuel , Hunger Stephen P , Roberts Kathryn G , Mullighan Charles G , Stam Ronald W , Thomas-Tikhonenko Andrei , Castaño Justo P , Luque Raúl M , Eyras Eduardo
Published: December 2022

A significant proportion of infant B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene expression, gene fusions, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We identified 87 fusions with significant allele frequency across patients and shared functional impacts, suggesting common mechanisms across fusions. We further identified a gene expression signature that predicts high risk independently of the gene fusion background and includes the upregulation of the splicing factor SRRM1. Experiments in B-ALL cell lines provided further evidence for the role of SRRM1 on cell survival, proliferation, and invasion. Supplementary analysis revealed that SRRM1 potentially modulates splicing events associated with poor outcomes through protein-protein interactions with other splicing factors. Our findings reveal a potential convergent mechanism of aberrant RNA processing that sustains a malignant phenotype independently of the underlying gene fusion and that could potentially complement current clinical strategies in infant B-ALL.
Identification of RNU44 as an Endogenous Reference Gene for Normalizing Cell-Free RNA in Tuberculosis
Authors: Gu Wei , Tu Xilin , Lu Weinan , Yin Yian , Meng Qingtai , Wang Xinyang , Zhang Fengmin , Fu Yingmei
Published: December 2022

Background

Normalization of cell-free RNA (cf-RNA) concentration can be affected by variable experimental conditions and thus impact the performance of their diagnostic potential. Our study aimed to identify appropriate endogenous reference genes for cf-RNA biomarker evaluation in the diagnosis of tuberculosis (TB).

Methods

Subjects consisting of patients with TB with and without malignancy, patients with pneumonia, and healthy controls were recruited. Candidate reference genes were screened and identified by literature reviewing and RNA-Seq analysis. Expression levels of the candidate genes were determined by reverse-transcription real-time quantitative polymerase chain reaction in plasma from patients with TB and healthy controls. The stability of gene expression was assessed by geNorm, NormFinder, BestKeeper, the Comparative Delta Ct method, and RefFinder. Differential expression of 2 small RNAs (sRNAs) encoding by genome of Mycobacterium tuberculosis in plasma of patients with TB were determined by both absolute quantification and relative quantification with candidate reference genes.

Results

According to the stability ranking analyzed with the 5 computational programs, the top 4 candidates—miR-93, RNU44, miR-16, and glyceraldehyde 3-phosphate dehydrogenase—were used to normalize the transcript levels of 2 mycobacterial sRNAs, MTS2823 and MTS1338, which were observed to have higher copy numbers in the plasma of patients with TB. Normalization with RNU44 displayed significantly higher levels of the 2 M tuberculosis sRNAs in the patients’ plasma than those of healthy controls.

Conclusions

RNU44 was demonstrated as a proper endogenous gene for cf-RNA normalization in TB diagnosis.
Quantifying Gram-Negative Resistance to Empiric Treatment After Repeat ExpoSure To AntimicRobial Therapy (RESTART)
Authors: Wibisono Arya , Harb Gaielle , Crotty Matthew , Rahmanzadeh Kristen , Alexander Julie , Hunter Leigh , Dominguez Edward
Published: December 2022

Background

Antibiotic exposure is a primary predictor of subsequent antibiotic resistance; however, development of cross-resistance between antibiotic classes is also observed. The impact of changing to a different antibiotic from that of previous exposure is not established.

Methods

This was a retrospective, single-center cohort study of hospitalized adult patients previously exposed to an antipseudomonal β-lactam (APBL) for at least 48 hours in the 90 days prior to the index infection with a gram-negative bloodstream or respiratory infection. Susceptibility rates to empiric therapy were compared between patients receiving the same (repeat group) versus a different antibiotic from prior exposure (change group).

Results

A total of 197 patients were included (n = 94 [repeat group] and n = 103 [change group]). Pathogen susceptibility to empiric therapy was higher in the repeat group compared to the change group (76.6% vs 60.2%; P = .014). After multivariable logistic regression, repeat APBL was associated with an increased likelihood of pathogen susceptibility (adjusted odds ratio, 2.513; P = .012). In contrast, there was no difference in susceptibility rates between the repeat group and the subgroup of change patients who received an empiric APBL (76.6% vs 78.5%; P = .900). Longer APBL exposure duration (P = .012) and chronic kidney disease (P = .002) were associated with higher nonsusceptibility to the exposure APBL. In-hospital mortality was not significantly different between the repeat and change groups (18.1% vs 23.3%; P = .368).

Conclusions

The common practice of changing to a different APBL from that of recent exposure may not be warranted.
SEC14-GOLD protein PATELLIN2 binds IRON-REGULATED TRANSPORTER1 linking root iron uptake to vitamin E
Authors: Hornbergs Jannik , Montag Karolin , Loschwitz Jennifer , Mohr Inga , Poschmann Gereon , Schnake Anika , Gratz Regina , Brumbarova Tzvetina , Eutebach Monique , Angrand Kalina , Fink-Straube Claudia , Stühler Kai , Zeier Jürgen , Hartmann Laura , Strodel Birgit , Ivanov Rumen , Bauer Petra
Published: December 2022

Organisms require micronutrients, and Arabidopsis (Arabidopsis thaliana) IRON-REGULATED TRANSPORTER1 (IRT1) is essential for iron (Fe2+) acquisition into root cells. Uptake of reactive Fe2+ exposes cells to the risk of membrane lipid peroxidation. Surprisingly little is known about how this is avoided. IRT1 activity is controlled by an intracellular variable region (IRT1vr) that acts as a regulatory protein interaction platform. Here, we describe that IRT1vr interacted with peripheral plasma membrane SEC14-Golgi dynamics (SEC14-GOLD) protein PATELLIN2 (PATL2). SEC14 proteins bind lipophilic substrates and transport or present them at the membrane. To date, no direct roles have been attributed to SEC14 proteins in Fe import. PATL2 affected root Fe acquisition responses, interacted with ROS response proteins in roots, and alleviated root lipid peroxidation. PATL2 had high affinity in vitro for the major lipophilic antioxidant vitamin E compound α-tocopherol. Molecular dynamics simulations provided insight into energetic constraints and the orientation and stability of the PATL2-ligand interaction in atomic detail. Hence, this work highlights a compelling mechanism connecting vitamin E with root metal ion transport at the plasma membrane with the participation of an IRT1-interacting and α-tocopherol-binding SEC14 protein.
Development of a Tool to Assess Medical Oral Language Proficiency
Authors: Diamond Lisa C. , Gregorich Steven E. , Karliner Leah , González Javier , Pérez-Cordón Cristina , Iniguez Reniell , Alberto Figueroa José , Izquierdo Karen , Ortega Pilar
Published: December 2022

Purpose

To communicate with linguistically diverse patients, medical students and physicians often use their non-English-language skills. However, there is no standard protocol to determine whether those skills are adequate before patient care. This causes many physicians, institutions, educators, and learners to forgo non-English-language proficiency assessment altogether. The purpose of this study is to report on the development, refinement, and interrater reliability of the Physician Oral Language Observation Matrix (POLOM), a rater-based tool assessing 6 language skill categories observed during clinical interactions: comprehension, fluency/fluidity, vocabulary, pronunciation, grammar, and communication. This study focused on the use of the POLOM in Spanish interactions.

Method

The authors adapted an existing language observation tool for use in clinical settings, creating the preliminary POLOM. Next, they iteratively refined the tool from April to July 2021 using videorecorded medical student-standardized patient encounters from a U.S.-based medical Spanish program. In each refinement iteration, 4 bilingual raters (2 physicians and 2 linguists) independently rated 3 to 6 encounters and convened to discuss ratings with the goals of improving instrument instructions, descriptors, and subsequent rater agreement. Using the final POLOM, raters independently rated 50 videos in rotating interdisciplinary pairs. Generalizability theory was applied to estimate reliability via interrater agreement (dependability) coefficients (range 0–1) for each POLOM category and the total score.

Results

POLOM total score dependability equaled 0.927 (single rater) and 0.962 (averaged across 2 raters). The highest mean score was observed for the comprehension category (4.15; range 1–5) while the lowest was for communication (3.01; range 1–5).

Conclusions

Raters achieved a high level of agreement on POLOM assessments of students’ medical oral Spanish proficiency. The POLOM is the first assessment tool that provides examinees and instructors with both a holistic and detailed review of clinician non-English oral language skills as contextualized for patient care.
Clinical and prognostic features of E-cadherin in adenocarcinoma of the esophagogastric junction patients
Authors: Hu Kang , Zheng Qi-Ming , Wang Ye-Peng , Zhao Meng-Meng , Sun Zhi-Gang
Published: December 2022

Objective

The expression, activity, and functional role of E-cadherin in adenocarcinoma of the esophagogastric junction (AEG) are unclear. In this research, we evaluated the expression of E-cadherin in AEG, as well as its clinicopathological significance and prognostic value.

Methods

A total of 65 AEG samples and 10 normal paracancerous tissues undergoing AEG resection in thoracic surgery were collected. The samples were immunohistochemically examined for expression levels of E-cadherin. The Chi-square test was used to determine if E-cadherin expression correlated with the clinicopathological features of AEG patients. The link between clinicopathological features and 5-year survival rates was investigated using Kaplan–Meier survival curves and multifactorial Cox regression analysis.

Results

In AEG tissues, E-cadherin expression was considerably reduced. Differentiation grade (P = 0.013), infiltration depth (P = 0.033), and clinicopathological stage (P = 0.045) were substantially linked to the level of E-cadherin expression. Five-year survival rates of AEG patients were affected by E-cadherin expression (P = 0.037), tumor differentiation (P = 0.010), lymph node metastasis (P < 0.001), and clinicopathological stage (P = 0.037). Tumor differentiation (P = 0.033) and lymph node metastasis (P = 0.001) were independent risk factors for shorter overall survival.

Conclusion

E-cadherin expression in AEG was significantly decreased, which was strongly related to tumor differentiation, infiltration, and clinicopathological stage. An E-cadherin deficiency would lead to poor prognosis in AEG patients. E-cadherin may play a crucial role in AEG invasion and metastasis. Low expression of E-cadherin may be a potential early biomarker and overall survival predictor for AEG patients.
Prognostic implications of elevated pulmonary artery systolic pressure on 6-month mortality in elderly patients with acute myocardial infarction
Authors: Wang Shengji , Lian Yonggang , Wang Hongfei , Fan Xiaoting , Zhao Haiying
Published: December 2022

Background

Pulmonary artery systolic pressure (PASP) has often been evaluated as an indicator of heart failure, but the relationship between PASP and the prognosis of elderly patients with acute myocardial infarction (AMI) is not well understood.

Methods

The medical data of 3460 hospitalized elderly patients diagnosed with AMI between January 2013 and June 2018 were reviewed. PASP was calculated using transthoracic color Doppler ultrasonography. Patients were grouped according to their admission PASP results as follows: Group A, PASP ≤30 mmHg; Group B, 30 mmHg <PASP ≤50 mmHg; and Group C, PASP ≥51 mmHg. The primary endpoint was all-cause death 6 months following AMI. Multiple Cox regression analysis was used to identify independent risk factors for 6-month mortality in elderly patients with AMI.

Results

PASP was associated with age, Killip classification, AMI site, and decreased ejection fraction in elderly patients. After adjusting for clinical and echocardiographic parameters in the Cox model, PASP was found to be significantly related to all-cause mortality. In receiver operating characteristic analysis, a PASP of >34 mmHg had a sensitivity of 62.3% and specificity of 65.7% for predicting 6-month all-cause death after AMI.

Conclusion

PASP at admission is a useful marker for predicting short-term mortality in elderly patients with AMI. This finding could be used to help identify high-risk patients and make appropriate clinical decisions.
The evidence of implanting a different intraocular lens in each eye
Authors: Melvani Rakhi , Farid Marjan
Published: December 2022

Purpose of review

To evaluate the growing body of evidence investigating implanting a different intraocular lens (IOL) in each eye.

Recent findings

Many surgeons have turned to the mix-and-match approach of implanting two different types of IOLs with the goal of achieving an improved range of distances. A number of studies have compared different types of mix-and-match IOL approaches, with promising results that seem to show maintenance of excellent vision at all distances, and high levels of spectacle independence.

The mix-and-match IOL approach appears to be a promising option for patients, maintaining good vision at all distances, especially near and intermediate, which is highly desired by patients. Few studies also showed intriguing secondary endpoints such as decreased unwanted visual phenomena using this method.
Pharmacokinetics, efficacy and safety of a novel fibrinogen concentrate in pediatric patients with congenital afibrinogenemia
Authors: Khayat Claudia Djambas , Navarro-Puerto Jordi , Ross Cecil Reuben , Subramanian Kannan , Kalappanavar Nijalingappa K. , Rucker Karen , Liang Wei , Mondou Elsa
Published: December 2022

Introduction

Congenital afibrinogenemia treatment with plasma-derived fibrinogen concentrates in pediatric patients is limited. This study investigated the pharmacokinetics, surrogate efficacy, and safety of a plasma-derived fibrinogen concentrate (FIB Grifols) in pediatric patients with congenital afibrinogenemia.

Methods

Patients aged <18 years old diagnosed with congenital afibrinogenemia were included in this prospective, multinational, phase 1–2, single-arm study. After a single dose of a plasma-derived fibrinogen concentrate (70 mg/kg body weight), pharmacokinetic parameters were determined from plasma fibrinogen activity (Clauss method) and antigen method (ELISA), and calculated by noncompartmental and population pharmacokinetic (popPK) models. Patients were followed up over 14 days. Efficacy variables were the mean change on thromboelastographic variables (maximum clot firmness [MCF], alpha angle [α]) and coagulation tests (prothrombin time, activated partial thromboplastin time, and thrombin time) 1 h postinfusion. Safety parameters were assessed.

Results

Eleven patients with a median (range) age 8.80 (3.7–12.7) years were treated with the plasma-derived fibrinogen concentrate. Using the popPK modeling, fibrinogen activity reached a mean (standard deviation) C
max of 1.3 (0.225) g/l, half-life (t
1/2) of 60.6 (4.48) h and incremental in vivo recovery (IVR) of 1.86 (0.322) (mg/dl)/(mg/kg). Surrogate efficacy was demonstrated by significant increase in MCF (9.23 [3.94] mm; P < 0.001; 95% confidence interval 6.58, 11.87). All coagulation times were significantly shortened after fibrinogen concentrate infusion. Adverse events were mild or moderate in severity, and unrelated to fibrinogen concentrate.

Conclusions

In pediatric patients with congenital afibrinogenemia, plasma-derived fibrinogen concentrate revealed a favorable and specific pharmacokinetic profile, demonstrated efficacy in coagulation and was safe and well tolerated.
Exploring the potential cost-effectiveness of a novel platelet assay for guiding dual antiplatelet therapy duration in acute coronary syndrome patients following percutaneous coronary intervention
Authors: Vilain Katherine A. , DiBattiste Peter M. , Schneider David J. , Cohen David J.
Published: December 2022

Objective

Duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) influences ischemic and bleeding events. Platelet expression of constant fragment of immunoglobulin, low affinity IIa, receptor (FcγRIIa) independently predicts risk of ischemic complications and is proposed as a tool to guide individualized care.

Methods

We used a Markov model to predict lifetime ischemic and bleeding events and healthcare costs in acute myocardial infarction (MI) patients treated with PCI and DAPT and to project cost-effectiveness of platelet FcγRIIa-assay-guided care (30:3 months DAPT for patients at high: low ischemic risk) versus current standard care (12 months DAPT) from the perspective of the US healthcare system. Model inputs included assay sensitivity and specificity, ischemic and bleeding event rates, and impacts on quality of life, mortality, and costs. Assay cost was $90. Sensitivity analyses were conducted over a range of plausible clinical and cost assumptions.

Results

Under base case assumptions, platelet FcγRIIa-assay-guided DAPT duration was projected to increase lifetime costs by $19 versus standard care, with an associated incremental cost-effectiveness ratio (ICER) of $436 per quality-adjusted life-year (QALY) gained. Assay-guided DAPT duration was consistent with high-value care (ICER < $50 000/QALY gained) over a broad range of alternative assumptions.

Conclusion

Based on a decision-analytic model, for patients with MI treated with PCI, the additional costs of the platelet FcγRIIa assay for guiding DAPT duration would be largely offset by reductions in downstream event-related costs, and assay-guided care would be highly cost-effective by current standards. These findings require confirmation in prospective studies and in a randomized clinical trial of assay-guided versus nonassay-guided DAPT duration.
Prevalence of low-attenuation plaques and statin therapy in plaque rupture type of acute coronary syndrome
Authors: Kashiwagi Manabu , Taruya Akira , Kuroi Akio , Katayama Yosuke , Terada Kosei , Wada Teruaki , Takahata Masahiro , Shiono Yasutsugu , Tanimoto Takashi , Tanaka Atsushi
Published: December 2022

Background

We sought to investigate the differences in coronary plaque morphology on coronary computed tomography angiography (CCTA) and medical therapy between acute coronary syndrome (ACS) and stable ischemic heart disease (SIHD). We also explored the relationship between plaque morphology on CCTA at the initial phase and lesion morphology in the acute phase of ACS.

Methods

In 5967 patients who underwent invasive coronary angiography, 58 ACS and 91 SIHD patients who had prior CCTA imaging of the culprit lesion and denied ischemic heart disease at CCTA scanning were enrolled.

Results

Although the prevalence of positive remodeling was not different (P = 0.27), low-attenuation plaques (LAP) on prior CCTA were significantly higher in ACS than in SIHD (52% vs. 24%, P < 0.01). The frequency of coronary stenosis grading did not differ between the two groups (P = 0.14). In ACS patients, the frequencies of plaque rupture and lipid-rich plaque assessed by optical coherence tomography (OCT) were significantly higher in LAP than in non-LAP (73% vs. 23%, P < 0.01; 82% and 23%, P < 0.01). Multivariate regression analysis revealed that statin use and LAP on prior CCTA were predictors of future ACS events (P < 0.01, and P < 0.05, respectively).

Conclusions

LAP on CCTA, not positive arterial remodeling, and lack of statin therapy were associated with ACS development. In addition, LAP more frequently led to the development of the plaque rupture type of ACS compared with non-LAP. Lipid-lowering therapy with statins might be useful to prevent plaque rupture in patients with LAP regardless of coronary stenosis.
Tips and tricks for management of the dysfunctional maxillary sinus
Authors: Chung Sei Y. , Halderman Ashleigh A.
Published: December 2022

Purpose of the review

To review the various factors associated with the most common cause of maxillary sinus dysfunction; recalcitrant chronic maxillary sinusitis (RCMS). In addition, available medical and surgical management options are discussed along with various tips and tricks for optimal management.

Recent findings

Defects in mucociliary clearance, immunodeficiency, anatomic factors, and infectious etiologies have been implicated in dysfunction of the maxillary sinus leading to RCMS. Medical management including oral antibiotics or topical drugs have shown varying degrees of success. Endoscopic modified medial maxillectomy (EMMM) has been shown to significantly improve symptoms in patients with RCMS.

A dysfunctional maxillary sinus presents a clinical challenge. A thorough evaluation of any potential contributing factors must be done in addition to an assessment of the adequacy of prior surgical treatment of the maxillary sinus. Beyond the middle meatal antrostomy, EMMM can be used to effectively address RCMS. In cases that fail EMMM, removal of the condemned mucosa to encourage auto-obliteration of the sinus can be considered.
Interprofessional Naloxone Student Training to Manage Suspected Opioid Overdose
Authors: Riley Elizabeth , Trotter Stephanie , Dayer Lindsey , Teigen Amber , Nagel Corey , Stickley Kimberly , LaBorde Pamela , Richardson Leah , McFerguson Rochelle , Ward Nicole , Anders Michael
Published: December 2022

Purpose

The study purpose was to examine the effect of interprofessional naloxone training on students' knowledge, confidence, and interprofessional collaboration competency. The overarching goal was to decrease mortality related to opioid overdoses.

Design/Methods

A training session for interprofessional students consisted of a lecture presentation, demonstration, and hands-on practice regarding appropriate administration of naloxone for suspected opioid overdose. A questionnaire elicited baseline and change in knowledge, confidence, and interprofessional collaboration competency scores at pretraining and posttraining. In addition, changes in knowledge and confidence were also measured 3 weeks after the training. Thematic analysis explored training components that students perceived as valuable or needing improvement.

Results

Participants (N = 100) were nursing (n = 33), physician assistant (n = 37), and pharmacy (n = 30) students. Pretraining and posttraining comparison demonstrated increased knowledge (P < .001), confidence (P < .001), and collaboration scores (P < .001). At 3 weeks, knowledge and confidence remained higher than pretraining (P < .001). Knowledge was trending downward compared with posttraining (P = .09). Thematic analysis identified 4 themes: (a) indications for administration of different naloxone types, (b) learning modalities, (c) knowledge application, and (d) improvements.

Conclusions

An interprofessional naloxone administration training resulted in increased knowledge, confidence, and interprofessional teamwork. Educators can adapt this training for a variety of future or current healthcare professionals to improve immediate intervention and outcomes in suspected opioid overdoses.
What the Joint Commission Medication Management Titration Standards Mean to Quality Care for Complex Patients
Authors: Chechel Laura , McLean Barbara , Slazinski Theresa , Rincon Teresa
Published: December 2022

The Joint Commission (TJC), the nation’s largest healthcare accreditor, was founded in the 1950s. Its Standards for Medication Management (MM) of titratable medications focused on prescriptive ordering practices versus reliance on nurse clinical decision making. The use of measurable endpoints to guide nurse decision making regarding medication titration has been the standard of care since the inception of TJC. Evidence to support altering these practice patterns is lacking. Using the 6 aims for the healthcare system (safe, timely, effective, efficient, equitable, and patient-centered) from the National Academy of Medicine, formerly the Institute of Medicine, and the American Association of Critical-Care Nurses Healthy Work Environment essential standards (skilled communication, true collaboration, effective decision making, appropriate staffing, meaningful recognition, authentic leadership), this article examines the impact of TJC MM standards on system design in critical care environments.
A new era of HIV care for age-associated multimorbidity
Authors: Collini Paul , Mawson Rebecca L.
Published: December 2022

Purpose of review

The management of people with HIV has shifted focus from acute AIDS-defining illness towards improving detection of chronic disease and reducing impact of multimorbidity. In this review, we explore this shifting paradigm of HIV care and the evidence for alternative models proposed to provide integrated holistic services for people with HIV (PWH) with multimorbidity.

Recent findings

Despite 25 years of the antiretroviral treatment (ART) era an increased incidence of noncommunicable disease (NCD) and multimorbidity in PWH persists. As the world moves closer to universal ART coverage this phenomenon is now reported in low- and middle-income settings. Multimorbidity affects PWH disproportionately compared to the general population and results in reduced health related quality of life (HRQoL), greater hospitalization and higher mortality. There is evidence that NCD care provision and outcomes may be inferior for PWH than their HIV negative counterparts. Various models of integrated multimorbidity care have developed and are grouped into four categories; HIV specialist clinics incorporating NCD care, primary care services incorporating HIV care, community NCD clinics offering integrated HIV care, and multidisciplinary care integrated with HIV in secondary care. Evidence is limited as to the best way to provide multimorbidity care for PWH.

A new era of HIV care for an ageing population with multimorbidity brings challenges for health providers who need to develop holistic patient focused services which span a range of coexisting conditions.
Coronary Artery Calcium Evaluation Using New Generation Photon-counting Computed Tomography Yields Lower Radiation Dose Compared With Standard Computed Tomography
Authors: Schwartz Fides R. , Daubert Melissa A. , Molvin Lior , Ramirez-Giraldo Juan C. , Samei Ehsan , Marin Daniele , Tailor Tina D.
Published: December 2022

Prospective head-to-head comparison of coronary calcium scores between standard computed tomography (CT) and photon-counting CT show no significant differences, while photon-counting CT administers substantially lower radiation dose.
Multidisciplinary approaches to the Amazonian past: introduction to the theme issue
Authors: Emlen Nicholas Q. , Arias Leonardo , van Gijn Rik
Published: December 2022

This theme issue presents collaborative research by anthropologists, linguists, archaeologists, geneticists, historians and biogeographers, who work across disciplinary boundaries to investigate the Amazonian past. Amazonia is a fertile ground in which to develop such multidisciplinary approaches because its relative paucity of documentary records makes other sources of evidence regarding the past more important; because multidisciplinary approaches are well suited to address important unanswered questions in Amazonian history; and because a recent and dramatic reappraisal of the region's past make this an exciting time to conduct this sort of research. The papers in this theme issue feature different combinations of academic disciplines, and they address different geographical regions and historical periods, but all of them show how combining insights from different fields can help illuminate aspects of the Amazonian past that would otherwise remain obscure to them all.
Factors associated with support-seeking behavior among AIAN women survivors of IPV
Authors: Park Susanna Y
Published: December 2022

Objectives

To understand how Native women seek support as survivors of intimate partner violence by examining factors associated with seeking formal support (e.g., medical, police), informal support (e.g., family, friends), or both types of support.

Methods

Data from the 2010 National Intimate and Sexual Violence Survey were analyzed among the AIAN oversamples. Descriptive statistics and odds ratio analyses were conducted to observe significant factors that are associated with adult Native women survivors seeking support.

Results

Survivors have higher odds of seeking informal supports than formal supports. Formal support is not often sought, however survivors had significantly higher odds of seeking therapy. Conclusions. While there are various avenues in which survivors may seek support, not all types of support are helpful to the survivor’s needs. However, this study is still valuable in distinguishing factors related to support-seeking and observing general relationships. Focused and intentional public health research on support for AIAN women survivors is needed to further understand how programs and policies can be improved.
Habitat edges affect tree diversity more than biomass regeneration in a reforested wet neotropical timber plantation
Authors: Medina Nicholas , Capetz Emma , Johnson Andrea , Mendoza Agustín , Villalobos Max
Published: December 2022

About half of all forests are tropical and secondary, making tropical forest regeneration integral to future forests. Tree stand biomass and taxonomic richness can recover in a few decades, but relative abundances may lag indefinitely. Since most forests are within a km of a habitat edge, edge effects likely affect community composition regeneration. However, most studies assess how degraded edges affect intact forests, leaving it unclear whether higher-quality edges could facilitate regeneration of nearby degraded forests. Notably, higher quality edges near intact forests could promote processes like dispersal and wood biomass accumulation that effectively accelerate succession, leading to better performance of shade-tolerant taxa compared to pioneer taxa in the early stages of forested plantation regeneration. This study addressed how wet tropical forested plantation regeneration was affected by distance to adjacent intact forest edge. It was hypothesized that old timber plantations facilitate regeneration by increasing available shade, favoring the presence and biomass of later-successional taxa, ultimately changing community composition overall. A wet neotropical timber plantation reforested after 20 years and adjacent to primary forest was censused for trees along a 300 m edge distance gradient, and analysis matched identified taxa to broad dispersal mode and wood density traits using relevant literature.

As distance from primary forest edge increased, stem and wood density tended to increase significantly, with ~10% variation explained, while biomass and canopy light surprisingly tended to stay the same. Stand tree richness also tended to increase significantly, but diversity decreased steeply and non-linearly, explained in part by wood density, and taxonomic composition varied notably. Finally, tree taxa associated with both early and late successional stages decreased significantly, as well as genus Ficus, but biomass by dispersal mode did not tend to change. Overall this study supports that stand composition is less resilient and more subject to edge effects than biomass and richness, suggesting that global forests will likely be distinctly new assemblages in the future, with timber and biodiversity trade-offs occurring based on local and regional management activity.
ModelCIF: An extension of PDBx/mmCIF data representation for computed structure models
Authors: Vallat Brinda , Tauriello Gerardo , Bienert Stefan , Haas Juergen , Webb Benjamin M. , Žídek Augustin , Zheng Wei , Peisach Ezra , Piehl Dennis W. , Anischanka Ivan , Sillitoe Ian , Tolchard James , Varadi Mihaly , Baker David , Orengo Christine , Zhang Yang , Hoch Jeffrey C. , Kurisu Genji , Patwardhan Ardan , Velankar Sameer , Burley Stephen K. , Sali Andrej , Schwede Torsten , Berman Helen M. , Westbrook John D.
Published: December 2022

ModelCIF (github.com/ihmwg/ModelCIF) is a data information framework developed for and by computational structural biologists to enable delivery ofFindable, Accessible, Interoperable, andReusable(FAIR) data to users worldwide. It is an extension of the Protein Data Bank Exchange / macromolecular Crystallographic Information Framework (PDBx/mmCIF), which is the global data standard for representing experimentally-determined, three-dimensional (3D) structures of macromolecules and associated metadata. ModelCIF provides an extensible data representation for deposition, archiving, and public dissemination of predicted 3D models of proteins. The PDBx/mmCIF framework and its extensions (e.g., ModelCIF) are managed by the Worldwide Protein Data Bank partnership (wwPDB,wwpdb.org) in collaboration with relevant community stakeholders such as the wwPDB ModelCIF Working Group (wwpdb.org/task/modelcif). This semantically rich and extensible data framework for representing computed structure models (CSMs) accelerates the pace of scientific discovery. Herein, we describe the architecture, contents, and governance of ModelCIF, and tools and processes for maintaining and extending the data standard. Community tools and software libraries that support ModelCIF are also described.
The energetic and allosteric landscape for KRAS inhibition
Authors: Weng Chenchun , Faure Andre J. , Lehner Ben
Published: December 2022

Thousands of proteins have now been genetically-validated as therapeutic targets in hundreds of human diseases. However, very few have actually been successfully targeted and many are considered ‘undruggable’. This is particularly true for proteins that function via protein-protein interactions: direct inhibition of binding interfaces is difficult, requiring the identification of allosteric sites. However, most proteins have no known allosteric sites and a comprehensive allosteric map does not exist for any protein. Here we address this shortcoming by charting multiple global atlases of inhibitory allosteric communication in KRAS, a protein mutated in 1 in 10 human cancers. We quantified the impact of >26,000 mutations on the folding of KRAS and its binding to six interaction partners. Genetic interactions in double mutants allowed us to perform biophysical measurements at scale, inferring >22,000 causal free energy changes, a similar number of measurements as the total made for proteins to date. These energy landscapes quantify how mutations tune the binding specificity of a signalling protein and map the inhibitory allosteric sites for an important therapeutic target. Allosteric propagation is particularly effective across the central beta sheet of KRAS and multiple surface pockets are genetically-validated as allosterically active, including a distal pocket in the C-terminal lobe of the protein. Allosteric mutations typically inhibit binding to all tested effectors but they can also change the binding specificity, revealing the regulatory, evolutionary and therapeutic potential to tune pathway activation. Using the approach described here it should be possible to rapidly and comprehensively identify allosteric target sites in many important proteins.
Spatial and Spectral Components of the BOLD Global Signal in Rat Resting-State Functional MRI
Authors: Anumba Nmachi , Maltbie Eric , Pan Wen-Ju , LaGrow Theodore J. , Xu Nan , Keilholz Shella
Published: December 2022

In resting-state fMRI (rs-fMRI), the global signal average captures widespread fluctuations related to unwanted sources of variance such as motion and respiration, and has long been used as a regressor to reduce noise during data preprocessing. However, coherent neural activity in spatially-extended functional networks can also contribute to the global signal. The relative contributions of neural and non-neural sources to the global signal remain poorly understood. This study sought to tackle this problem through the comparison of the blood oxygenation level dependent (BOLD) global signal to an adjacent non-brain tissue signal from the same scan in rs-fMRI obtained from anesthetized rats. In this dataset motion was minimal and ventilation was phase-locked to image acquisition to minimize respiratory fluctuations. In addition to contrasting the spatial and spectral components of these two signals, we also observed these differences across the use of three different anesthetics: isoflurane, dexmedetomidine, and a combination of dexmedetomidine and light isoflurane. Here, we report differences in the spectral composition of the two signals as evaluated by a power spectral density (PSD) estimate and a fractional amplitude of low-frequency fluctuations (fALFF) calculation. Additionally, we show spatial selectivity for specific brain structures that show an increased correlation to the global signal both statically and dynamically, through Pearson’s correlation and co-activation pattern analysis, respectively. All of the observed differences between the BOLD global signal and the adjacent non-brain tissue signal were maintained across all three anesthetic conditions, showing that the global signal is distinct from the noise contained in the tissue signal. This study provides a unique perspective to the contents of the global signal and their origins.
Transposable elements contribute to the establishment of the glycine shuttle in Brassicaceae species
Authors: Triesch Sebastian , Denton Alisandra K. , Bouvier Jacques W. , Buchmann Jan P. , Reichel-Deland Vanessa , Martins Guerreiro Ricardo Nuno Ferreira , Busch Noah , Schlüter Urte , Stich Benjamin , Kelly Steven , Weber Andreas P.M.
Published: December 2022

C3-C4intermediate photosynthesis has evolved at least five times convergently in the Brassicaceae, despite this family lackingbona fideC4species. The establishment of this carbon concentrating mechanism is known to require a complex suite of ultrastructural modifications as well as changes in spatial expression patterns, which are both thought to be underpinned by a reconfiguration of existing gene-regulatory networks. However, to date, the mechanisms which underpin the reconfiguration of these gene networks are largely unknown. In this study, we used a pan-genomic association approach to identify genomic features that could confer differential gene expression toward the C3-C4 intermediate state by analysing eight C3 species and seven C3-C4 species from five independent origins in the Brassicaceae. We found a strong correlation between transposable element (TE) insertions incis-regulatory regions and the C3-C4intermediacy. Specifically, our study revealed 113 gene models in which presence of a TE within a gene correlates with C3-C4intermediate photosynthesis. In this set, genes involved in the photorespiratory glycine shuttle are enriched, including the glycine decarboxylase P-protein whose expression domain undergoes a spatial shift during the transition to C3-C4photosynthesis. When further interrogating this gene, we discovered independent TE insertions in its upstream region which we conclude to be responsible for causing the spatial shift inGLDP1gene expression. Our findings hint at a pivotal role of TEs in the evolution of C3-C4intermediacy, especially in mediating differential spatial gene expression.