bluuebunny/crossref_metadata_2025 huggingface dataset:
Decomposition-based framework for tumor classification and prediction of treatment response from longitudinal MRI
Authors: Rahbek Sofie , Mahmood Faisal , Tomaszewski Michal R , Hanson Lars G , Madsen Kristoffer H
Published: December 2022

Objective. In the field of radiation oncology, the benefit of MRI goes beyond that of providing high soft-tissue contrast images for staging and treatment planning. With the recent clinical introduction of hybrid MRI linear accelerators it has become feasible to map physiological parameters describing diffusion, perfusion, and relaxation during the entire course of radiotherapy, for example. However, advanced data analysis tools are required for extracting qualified prognostic and predictive imaging biomarkers from longitudinal MRI data. In this study, we propose a new prediction framework tailored to exploit temporal dynamics of tissue features from repeated measurements. We demonstrate the framework using a newly developed decomposition method for tumor characterization. Approach. Two previously published MRI datasets with multiple measurements during and after radiotherapy, were used for development and testing: T
2-weighted multi-echo images obtained for two mouse models of pancreatic cancer, and diffusion-weighted images for patients with brain metastases. Initially, the data was decomposed using the novel monotonous slope non-negative matrix factorization (msNMF) tailored for MR data. The following processing consisted of a tumor heterogeneity assessment using descriptive statistical measures, robust linear modelling to capture temporal changes of these, and finally logistic regression analysis for stratification of tumors and volumetric outcome. Main Results. The framework was able to classify the two pancreatic tumor types with an area under curve (AUC) of 0.999, P < 0.001 and predict the tumor volume change with a correlation coefficient of 0.513, P = 0.034. A classification of the human brain metastases into responders and non-responders resulted in an AUC of 0.74, P = 0.065. Significance. A general data processing framework for analyses of longitudinal MRI data has been developed and applications were demonstrated by classification of tumor type and prediction of radiotherapy response. Further, as part of the assessment, the merits of msNMF for tumor tissue decomposition were demonstrated.
Accelerated cardiac diffusion tensor imaging using deep neural network
Authors: Liu Shaonan , Liu Yuanyuan , Xu Xi , Chen Rui , Liang Dong , Jin Qiyu , Liu Hui , Chen Guoqing , Zhu Yanjie
Published: December 2022

Cardiac diffusion tensor imaging (DTI) is a noninvasive method for measuring the microstructure of the myocardium. However, its long scan time significantly hinders its wide application. In this study, we developed a deep learning framework to obtain high-quality DTI parameter maps from six diffusion-weighted images (DWIs) by combining deep-learning-based image generation and tensor fitting, and named the new framework FG-Net. In contrast to frameworks explored in previous deep-learning-based fast DTI studies, FG-Net generates inter-directional DWIs from six input DWIs to supplement the loss information and improve estimation accuracy for DTI parameters. FG-Net was evaluated using two datasets of ex vivo human hearts. The results showed that FG-Net can generate fractional anisotropy, mean diffusivity maps, and helix angle maps from only six raw DWIs, with a quantification error of less than 5%. FG-Net outperformed conventional tensor fitting and black-box network fitting in both qualitative and quantitative metrics. We also demonstrated that the proposed FG-Net can achieve highly accurate fractional anisotropy and helix angle maps in DWIs with different b-values.
Multi-mode architectures for noise-resilient superconducting qubits
Authors: Calzona Alessio , Carrega Matteo
Published: December 2022

Great interest revolves around the development of new strategies to efficiently store and manipulate quantum information in a robust and decoherence-free fashion. Several proposals have been put forward to encode information into qubits that are simultaneously insensitive to relaxation and to dephasing processes. Among all, given their versatility and high-degree of control, superconducting qubits have been largely investigated in this direction. Here, we present a survey on the basic concepts and ideas behind the implementation of novel superconducting circuits with intrinsic protection against decoherence at a hardware level. In particular, the main focus is on multi-mode superconducting circuits, the paradigmatic example being the so-called

0
−
π

circuit. We report on their working principle and possible physical implementations based on conventional Josephson elements, presenting recent experimental realizations, discussing both fabrication methods and characterizations.
Computational study of temperature and density perturbations on atmospheric dynamics
Authors: Abawari Admasu , Elfaged Yitagesu
Published: December 2022

This study examines the perturbation effect of temperature and density of moist air on atmospheric variables at 9°1’48″N, 38°44’24″E and 6.324 km above the Earth’s surface. The atmosphere is a compressible neutral moist air flowing on a rotating Earth as a model and it’s basic atmospheric parameters such as gas constant, transport coefficients, mixing ratio and specific heat capacities are considered to be temperature dependent and the Earth’s gravity changes with latitude and altitude. To describe the dynamics, we carried out a numerical computation using finite difference method on an unstaggered grid. Our results revealed that the response of all the variables have a plane wave pattern, in which specific heat capacities (SHCs), resultant wind speed (RWS) and water vapor mixing ratio (MR) increase with time at each latitude but vertical wind speed (VWS), specific enthalpy (SE) and pressure decrease with time at each latitude. The increase of MR with time is the result of water vapor flux into the air parcel and the decrease of SE and increase of RWS with time is the result of thermal energy to mechanical energy transformation. The decrease of VWS with time is the effect of the viscous force due to temperature dependence of viscosity.
Fabrication of high-surface-area, SiO2 supported polyimide carbon aerogel microspheres: electrochemical application
Authors: Liu Shi , Ji Jianqi , Wang Yixing , Yan Cenqi , Bai Huitao , Qin Jiaqiang , Cheng Pei
Published: December 2022

A series of polyimide (PI)/SiO2 aerogel microspheres were prepared by using polyamide acid salt and hydrolyzed tetraethyl orthosilicate based on the reverse-phase emulsion method. Then, PI/SiO2 aerogel microspheres were carbonized and etched to obtain carbon aerogel microspheres (CAMs). Scanning electron microscope, transmission electron microscope and nitrogen isothermal adsorption were used to characterize the micro-morphology and pore structure of the microspheres; and electrochemical workstation was used to test the electrochemical performance of the CAMs. The results showed that CAMs with different pore structures and specific surface area were obtained by adjusting the content of SiO2. Highest specific surface area of 1166.9 m2 g−1 and a total pore volume of 1.2369 cm3 g−1 were achieved at a SiO2 content of 50%. When used as the electrode materials for supercapacitors, these CAMs demonstrated a maximum specific capacitance of 125.1 F g−1 in a three-electrode system and a maximum capacitance of 53.3% at 30 A g−1. This article provides a new strategy for the preparation of CAMs with high specific surface area by using linear PI precursor and SiO2 support skeleton.
Spatiotemporal varying coefficient model for respiratory disease mapping in Taiwan
Authors: Wang Feifei , Duan Congyuan , Li Yang , Huang Hui , Shia Ben-Chang
Published: December 2022

Respiratory diseases have been global public health problems for a long time. In recent years, air pollutants as important risk factors have drawn lots of attention. In this study, we investigate the influence of $\pm2.5$ (particulate matters in diameter less than 2.5 ${\rm{\mu }} m$) on hospital visit rates for respiratory diseases in Taiwan. To reveal the spatiotemporal pattern of data, we propose a Bayesian disease mapping model with spatially varying coefficients and a parametric temporal trend. Model fitting is conducted using the integrated nested Laplace approximation, which is a widely applied technique for large-scale data sets due to its high computational efficiency. The finite sample performance of the proposed method is studied through a series of simulations. As demonstrated by simulations, the proposed model can improve both the parameter estimation performance and the prediction performance. We apply the proposed model on the respiratory disease data in 328 third-level administrative regions in Taiwan and find significant associations between hospital visit rates and $\pm2.5$.
Sweet taste perception in mice is blunted by PTBP1-regulated skipping of Tas1r2 exon 4
Authors: Zheng Xin , Zhu Jianhui , Liu Jiaxin , Wang Hong , Qin Yumei , Jiang Peihua , Xiao Li , Gong Tao , Li Yuqing , Peng Xian , Xu Xin , Cheng Lei , Huang Liquan , Chen Qianming , Zhou Xuedong , Margolskee Robert F
Published: December 2022

Taste perception, initiated by activation of taste receptors in taste bud cells, is crucial for regulating nutrient intake. Genetic polymorphisms in taste receptor genes cannot fully explain the wide individual variations of taste sensitivity. Alternative splicing (AS) is a ubiquitous posttranscriptional mode of gene regulation that enriches the functional diversity of proteins. Here, we report the identification of a novel splicing variant of sweet taste receptor gene Tas1r2 (Tas1r2_∆e4) in mouse taste buds and the mechanism by which it diminishes sweet taste responses in vitro and in vivo. Skipping of Tas1r2 exon 4 in Tas1r2_∆e4 led to loss of amino acids in the extracellular Venus flytrap domain, and the truncated isoform reduced the response of sweet taste receptors (STRs) to all sweet compounds tested by generating nonfunctional T1R2/T1R3 STR heterodimers. The splicing factor PTBP1 (polypyrimidine tract-binding protein 1) promoted Tas1r2_∆e4 generation through binding to a polypyrimidine-rich splicing silencer in Tas1r2 exon 4, thus decreasing STR function and sweet taste perception in mice. Taken together, these data reveal the existence of a regulated AS event in Tas1r2 expression and its effect on sweet taste perception, providing a novel mechanism for modulating taste sensitivity at the posttranscriptional level.
Transoral septotomy with septum traction is an effective treatment for recurrent Zenker diverticulum
Authors: Salvador Renato , Provenzano Luca , Bonventre Giulia , Cutrone Cesare , Moletta Lucia , Sari Marianna , Costantini Andrea , Forattini Francesca , Vittori Arianna , Valmasoni Michele , Costantini Mario , Capovilla Giovanni
Published: December 2022

Symptoms of Zenker diverticulum can recur whatever the type of primary treatment administered. A modified transoral stapler-assisted septotomy (TS) was introduced in clinical practice a few years ago to improve the results of this mini-invasive technique. The aim of this prospective, controlled study was to assess the outcome of TS in patients with recurrent Zenker diverticulum (RZD), as compared with patients with treatment-naïve Zenker diverticulum (NZD). Patients diagnosed with NZD or RZD, and treated with TS between 2015 and 2021 were compared. Symptoms were recorded and scored using a detailed questionnaire. Barium swallow and endoscopy were performed before and after the TS procedure. In sum, 89 patients were enrolled during the study period: 68 had NZD and 21 had RZD. The patients’ demographic and clinical data were similar in the two groups. Three mucosal lesions were detected intra-operatively, and one came to light at post-operative radiological assessment in the NZD group. No mucosal lesions were detected in the RZD group. The median follow-up was 36 months (interquartile range 23–60). The treatment was successful in 97% NZD patients and 95% of RZD patients (P = 0.56). This is the first comparative study based on prospectively collected data to assess the outcome of TS in patients with RZD. Traction on the septum during the procedure proved effective in the treatment of RZD, achieving a success rate that was excellent, and comparable with the outcome in treating NZD.
A case report of recovery of sinus node abnormalities associated with right atrial involvement of ‘early-stage’ cardiac sarcoidosis
Authors: Nakahara Miyuki , Takemoto Masao , Fujishima Shin-ichiro , Tsuchihashi Takuya
Published: December 2022

Background

Cardiac sarcoidosis (CS) is a chronic inflammatory disease characterized by impaired contractility of the myocardium secondary to cardiac conduction system abnormalities, which result in atrio-ventricular (AV) conduction block and ventricular tachyarrhythmias. Notably, sinus node (SN) abnormalities are rarely associated with CS.

Case summary

We herein present a case of CS presenting with SN abnormalities associated with atrial involvement of the CS and describe the utility of cardiac magnetic resonance imaging (cMRI), fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG-PET-CT) scans, and cardiac biopsy, in making an initial early diagnosis of early-stage CS. Fortunately, an initial appropriate immunosuppression therapy with methylprednisolone for the CS thus far can help the SN and AV conduction function recover and has provided a good clinical course without the implantation of a pacemaker or implantable cardio-defibrillator.

Discussion

Although the diagnosis of CS may be elusive, the initial clinical suspicion and use of advanced imaging may be important for an early diagnosis of CS. Furthermore, because CS may sometimes rapidly progress, the early diagnosis and treatment of early-stage CS may also be important to help the SN and AV conduction function recover, and avoid implantation of a pacemaker, as in this present case.
Lifting spirits and building community: the social, emotional and practical benefits of all-female group singing
Authors: Helitzer Elizabeth , Moss Hilary , O’Donoghue Jessica
Published: December 2022

A mixed-methods concurrent identical design was implemented to explore the following research question: what are the emotional, social, and practical impacts of group singing for women from a regeneration area? Members of an all-female community choir based in an area of disadvantage participated in a focus group and survey. The most significant quantitative finding was an increase in the overall perceived level of health, which seemed linked to qualitative themes of ‘positive emotions’, ‘redefining and reclaiming identity’, ‘choir as an extended family’ and ‘community interaction and impact’. Three themes arose from qualitative data: social impact, health and well-being aspects, and practical issues. Integrating qualitative and quantitative findings identified an overarching concept that ‘choir participation may increase emotional and social health and well-being’. Group singing was found beneficial, with a potential to serve as a resource in cultivating resilience in individuals living in areas of disadvantage.
Socioeconomic dilemmas of commercial markets for invasive species: lessons from lionfish in Mexico
Authors: Quintana Anastasia , Marcos Sergio , Malpica-Cruz Luis , Tamayo Lizbeth , Canto Noh José Ángel , Fernández-Rivera Melo Francisco , Fulton Stuart
Published: December 2022

“If you can’t beat ‘em, eat ‘em”: the development of commercial markets is an emerging strategy to control invasive species. This strategy may have fewer unintended ecological impacts than genetic modification and biological control; however, its unintended social impacts are poorly understood. We discuss the social dilemmas and opportunities created by commercializing invasive species, based on the experiences of fishing cooperatives’ harvest of invasive lionfish (Pterois sp.) in the Mexican Caribbean. In Cozumel, Mexico, a pilot commercial fishery began in 2012, and by 2015 had seemingly succeeded at reducing local lionfish abundance. However, three social dilemmas have accompanied this process. First, though designed to support sustainability, this market disproportionately benefits fishers that use fishing gear considered "unsustainable". Second, this strategy reinforces the narrative of fishers trapped in a “tragedy of the commons,” while simultaneously depending on the fishers’ participation. Finally, the programme's very success has led to its own demise, disproportionately affecting the programme's most invested participants. These and similar dilemmas may be inevitable when systems in place for sustainable resource harvest are repurposed for resource collapse. However, fishing cooperatives have managed to navigate these dilemmas in partnership with governmental and non-governmental organization (NGO) advocates to position themselves as conservation leaders.
Resistance to Prostaglandin E2 Promotes Monocyte Activation During Chronic HIV Infection
Authors: Di Diego Garcia Facundo , Cabrerizo Gonzalo , Paletta Ana , Pérez Paula S , Varese Augusto , Geffner Jorge , Bello Natalia , Fridman Vanesa , Stecher Daniel , Ceballos Ana , Remes Lenicov Federico
Published: December 2022

Background

Monocyte activation is a driver of inflammation in the course of chronic HIV infection. Prostaglandin E2 (PGE2) is known to mediate anti-inflammatory effects, notably the inhibition of tumor necrosis factor-α (TNF-α) production by monocytes. We aim to investigate the effects of PGE2 on activation of monocytes in chronic HIV infection and the mechanisms through which PGE2 modulates their inflammatory signature.

Methods

We recruited a group of people with HIV (PWH) and matched healthy uninfected persons. We compared plasma levels of PGE2, monocyte activation, and sensitivity of monocytes to the inhibitory actions mediated by PGE2.

Results

We found increased plasma levels of PGE2 in PWH, and an activated phenotype in circulating monocytes, compared with uninfected individuals. Monocytes from PWH showed a significant resistance to the inhibitory actions mediated by PGE2; the concentration of PGE2 able to inhibit 50% of the production of TNF-α by lipopolysaccharide-stimulated monocytes was 10 times higher in PWH compared with uninfected controls. Furthermore, the expression of phosphodiesterase 4B, a negative regulator of PGE2 activity, was significantly increased in monocytes from PWH.

Conclusions

Resistance to the inhibitory actions mediated by PGE2 could account, at least in part, for the inflammatory profile of circulating monocytes in PWH.
Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus (RSV) Vaccine in Healthy RSV-Seropositive Children 12–23 Months of Age
Authors: Díez-Domingo Javier , Sáez-Llorens Xavier , Rodriguez-Weber Miguel A , Epalza Cristina , Chatterjee Archana , Chiu Cheng-Hsun , Lin Chien-Yu , Berry Andrea A , Martinón-Torres Federico , Baquero-Artigao Fernando , Langley Joanne M , Ramos Amador José T , Domachowske Joseph B , Huang Li-Min , Chiu Nan-Chang , Esposito Susanna , Moris Philippe , Lien-Anh Nguyen Thi , Nikic Vanja , Woo Wayne , Zhou Yingjun , Dieussaert Ilse , Leach Amanda , Gonzalez Lopez Antonio , Vanhoutte Nicolas
Published: December 2022

Background

Safe and effective respiratory syncytial virus (RSV) vaccines remain elusive. This was a phase I/II trial (NCT02927873) of ChAd155-RSV, an investigational chimpanzee adenovirus-RSV vaccine expressing 3 proteins (fusion, nucleoprotein, and M2-1), administered to 12–23-month-old RSV-seropositive children followed up for 2 years after vaccination.

Methods

Children were randomized to receive 2 doses of ChAd155-RSV or placebo (at a 1:1 ratio) (days 1 and 31). Doses escalated from 0.5 × 1010 (low dose [LD]) to 1.5 × 1010 (medium dose [MD]) to 5 × 1010 (high dose [HD]) viral particles after safety assessment. Study end points included anti–RSV-A neutralizing antibody (Nab) titers through year 1 and safety through year 2.

Results

Eighty-two participants were vaccinated, including 11, 14, and 18 in the RSV-LD, RSV-MD, and RSV-HD groups, respectively, and 39 in the placebo groups. Solicited adverse events were similar across groups, except for fever (more frequent with RSV-HD). Most fevers were mild (≤38.5°C). No vaccine-related serious adverse events or RSV-related hospitalizations were reported. There was a dose-dependent increase in RSV-A Nab titers in all groups after dose 1, without further increase after dose 2. RSV-A Nab titers remained higher than prevaccination levels at year 1.

Conclusions

Three ChAd155-RSV dosages were found to be well tolerated. A dose-dependent immune response was observed after dose 1, with no observed booster effect after dose 2. Further investigation of ChAd155-RSV in RSV-seronegative children is warranted.

Clinical Trials Registration

NCT02927873.
Target RNA-guided protease activity in type III-E CRISPR–Cas system
Authors: Wang Xiaoshen , Yu Guimei , Wen Yanan , An Qiyin , Li Xuzichao , Liao Fumeng , Lian Chengwei , Zhang Kai , Yin Hang , Wei Yong , Deng Zengqin , Zhang Heng
Published: December 2022

The type III-E CRISPR–Cas systems are newly identified adaptive immune systems in prokaryotes that use a single Cas7–11 protein to specifically cleave target RNA. Cas7–11 could associate with Csx29, a putative caspase-like protein encoded by the gene frequently found in the type III-E loci, suggesting a functional linkage between the RNase and protease activities in type III-E systems. Here, we demonstrated that target RNA recognition would stimulate the proteolytic activity of Csx29, and protein Csx30 is the endogenous substrate. More interestingly, while the cognate target RNA recognition would activate Csx29, non-cognate target RNA with the complementary 3′ anti-tag sequence inhibits the enzymatic activity. Csx30 could bind to the sigma factor RpoE, which may initiate the stress response after proteolytic cleavage. Combined with biochemical and structural studies, we have elucidated the mechanisms underlying the target RNA-guided proteolytic activity of Csx29. Our work will guide further developments leveraging this simple RNA targeting system for RNA and protein-related applications.
Site-directed biochemical analyses reveal that the switchable C-terminus of Rpc31 contributes to RNA polymerase III transcription initiation
Authors: Shekhar Arvind Chandra , Sun Yuan-En , Khoo Seok-Kooi , Lin Yu-Chun , Malau Ester Betaria , Chang Wei-Hau , Chen Hung-Ta
Published: December 2022

Rpc31 is a subunit in the TFIIE-related Rpc82/34/31 heterotrimeric subcomplex of Saccharomyces cerevisiae RNA polymerase III (pol III). Structural analyses of pol III have indicated that the N-terminal region of Rpc31 anchors on Rpc82 and further interacts with the polymerase core and stalk subcomplex. However, structural and functional information for the C-terminal region of Rpc31 is sparse. We conducted a mutational analysis on Rpc31, which uncovered a functional peptide adjacent to the highly conserved Asp-Glu-rich acidic C-terminus. This C-terminal peptide region, termed ‘pre-acidic’, is important for optimal cell growth, tRNA synthesis, and stable association of Rpc31 in the pre-initiation complex (PIC). Our site-directed photo-cross-linking to map protein interactions within the PIC reveal that this pre-acidic region specifically targets Rpc34 during transcription initiation, but also interacts with the DNA entry surface in free pol III. Thus, we have uncovered a switchable Rpc31 C-terminal region that functions in an initiation-specific protein interaction for pol III transcription.
The Impact of Reducing Nicotine Content on Adolescent Cigarette Smoking and Nicotine Exposure: Results From a Randomized Controlled Trial
Authors: Cassidy Rachel N , Tidey Jennifer W , Jackson Kristina M , Cioe Patricia A , Murphy Sharon E , Krishnan-Sarin Suchitra , Hatsukami Dorothy , Colby Suzanne M
Published: December 2022

Introduction

As the science base around the potential benefits of a reduced-nicotine standard for cigarettes grows, information on the potential effects on adolescent smokers is a high priority. The aim of this randomized trial was to test the influence of 3-week exposure to reduced nicotine cigarettes in a sample of adolescent daily smokers.

Aims and Methods

In this double-blind, two-arm, randomized controlled trial (NCT0258731), following a 1-week baseline, adolescent daily smokers not currently intending to quit (ages 15–19 years, n = 66 randomized) were urn randomized to use either very low nicotine content (VLNC; 0.4 mg/g; n = 33) or normal nicotine content (NNC, 15.8 mg/g; n = 33) research cigarettes for 3 weeks. Participants attended five study sessions at our clinical laboratory. The primary outcome was average total cigarettes smoked per day (CPD; including both study and non-study cigarettes) at week 3.

Results

Stepwise regression results demonstrated that compared with NNC cigarettes (n = 31), assignment to VLNC cigarettes (n = 29), was associated with 2.4 fewer CPD on average than NNC assignment (p < .05) week 3 when controlling for covariates (p < .01, Cohen’s d = 0.52 n = 60 completed all procedures). VLNC cigarettes were also associated with lower levels of craving reduction than NNC cigarettes (Questionnaire on Smoking Urges Factor 2, p < .05). No group differences were found for secondary outcomes.

Conclusions

Adolescent participants assigned to VLNC use for 3 weeks smoked fewer total CPD relative to the NNC group. Overall, data suggest that a VLNC policy would reduce cigarette smoking in adolescents who smoke, but high rates of incomplete adherence suggest that youth may seek alternative sources of nicotine in this scenario.

Implications

The US Food and Drug Administration may enact a reduced-nicotine product standard that would affect all commercially available cigarettes. One important population affected by this policy would be adolescents who smoke. This study, the first clinical trial of VLNC cigarettes in adolescents, demonstrates that adolescents switched to VLNC cigarettes for 3 weeks reduced their CPD relative to the normal-nicotine cigarette control group, without leading to increased respiratory symptoms or increased withdrawal. Biomarkers indicated the use of other sources of nicotine, suggesting that such a policy will need to consider approaches to assist in transitioning away from smoking.
Using Daily Ratings to Examine Treatment Dose and Response in Cognitive Behavioral Therapy for Chronic Pain: A Secondary Analysis of the Co-Operative Pain Education and Self-Management Clinical Trial
Authors: MacLean R Ross , Buta Eugenia , Higgins Diana M , Driscoll Mary A , Edmond Sara N , LaChappelle Kathryn M , Ankawi Brett , Krein Sarah L , Piette John D , Heapy Alicia A
Published: December 2022

Background

Cognitive behavioral therapy for chronic pain (CBT-CP) has a strong evidence base, but little is known about when treatment benefits are achieved. The present study is a secondary analysis of individuals with chronic back pain recruited for a noninferiority trial comparing interactive voice response (IVR) CBT-CP with in-person CBT-CP.

Methods

On the basis of data from daily IVR surveys, a clinically meaningful change was defined as a 30% reduction in pain intensity (n = 108) or a 45% increase in daily steps (n = 104) compared with the baseline week. We identified individuals who achieved a meaningful change at any point during treatment, and then we compared those who maintained a meaningful change in their final treatment week (i.e., responders) with those who did not or who achieved a meaningful change but lapsed (i.e., nonresponders).

Results

During treatment, 46% of participants achieved a clinically meaningful decrease in pain intensity, and 66% achieved a clinically significant increase in number of steps per day. A total of 54% of patients were classified as responders in terms of decreases in pain intensity, and 70% were responders in terms of increases in step count. Survival analyses found that 50% of responders first achieved a clinically meaningful change by week 4 for pain intensity and week 2 for daily steps. Dropout and demographic variables were unrelated to responder status, and there was low agreement between the two measures of treatment response.

Conclusions

Collectively, results suggest that most responders improve within 4 weeks. Evaluating treatment response is highly specific to the outcome measure, with little correlation across outcomes.
Advances in drug therapy and delivery for cataract treatment
Authors: Lee Bryanna J. , Afshari Natalie A.
Published: December 2022

Purpose of review

Cataract is one of the leading causes of blindness worldwide and surgery is the only available treatment. Pharmacological therapy has emerged as a potential approach to combat the global shortage of surgery due to a lack of access and resources. This review summarizes recent findings in pharmacological treatment and delivery, focusing on drugs that target oxidative stress and the aggregation of crystallins.

Recent findings

Antioxidants and oxysterols have been shown to improve or reverse lens opacity in cataract models. N-acetylcysteine amide and N-acetylcarnosine are two compounds that have increased bioavailability over their precursors, alleviating the challenges that have come with topical administration. Studies have shown promising results, with topical N-acetylcarnosine clinically decreasing lens opacity. Furthermore, lanosterol, and more recently 5-cholesten-3b,25-diol (VP1-001), have been reported to combat the aggregation of crystallins in vivo and ex vivo. Delivery has improved with the use of nanotechnology, but further research is needed to solidify these compounds’ therapeutic effects on cataracts and improve delivery methods to the lens.

Although further research in drug dosage, delivery, and mechanisms will need to be conducted, pharmacologic therapies have provided new strategies and treatments for the reversal of cataracts.
Recurrent spontaneous coronary artery dissection
Authors: Xu Minmin , Wang Jian , Yuan Kangzheng , Luo Xiaoyan , Liu Fangmei , Deng Min , Wang Daxin
Published: December 2022

Spontaneous coronary artery dissection (SCAD) is a significant cause of myocardial infarction (MI) and is more prevalent in pregnancy. The disease is being increasingly appreciated and diagnosed with the development and application of coronary angiography and intravascular imaging. Recurrent spontaneous coronary artery dissection (R-SCAD) is relatively common, with recurrence rates ranging from 8 to 27%. R-SCAD usually involves anatomical sites different from the original SCAD lesion and can cause MI, ventricular arrhythmias, and cardiogenic shock. This study aims to conduct a comprehensive review of R-SCAD to identify early risk factors and guide prevention policies and interventions. In addition, the risk of R-SCAD in subsequent pregnancies in women with a history of SCAD is discussed.
Closed-loop ventilation
Authors: Arnal Jean-Michel , Katayama Shinshu , Howard Christopher
Published: December 2022

Purpose of review

The last 25 years have seen considerable development in modes of closed-loop ventilation and there are now several of them commercially available. They not only offer potential benefits for the individual patient, but may also improve the organization within the intensive care unit (ICU). Clinicians are showing both greater interest and willingness to address the issues of a caregiver shortage and overload of bedside work in the ICU. This article reviews the clinical benefits of using closed-loop ventilation modes, with a focus on control of oxygenation, lung protection, and weaning.

Recent findings

Closed-loop ventilation modes are able to maintain important physiological variables, such as oxygen saturation measured by pulse oximetry, tidal volume (VT), driving pressure (ΔP), and mechanical power (MP), within target ranges aimed at ensuring continuous lung protection. In addition, these modes adapt the ventilator support to the patient's needs, promoting diaphragm activity and preventing over-assistance. Some studies have shown the potential of these modes to reduce the duration of both weaning and mechanical ventilation.

Recent studies have primarily demonstrated the safety, efficacy, and feasibility of using closed-loop ventilation modes in the ICU and postsurgery patients. Large, multicenter randomized controlled trials are needed to assess their impact on important short- and long-term clinical outcomes, the organization of the ICU, and cost-effectiveness.
Successful Clinical Nurse Specialist Recruitment
Authors: Fischer-Cartlidge Erica , Short Kathleen
Published: December 2022

Background

The future of the clinical nurse specialist (CNS) role depends on nurses enrolling in CNS programs and having access to clinical experiences. At 1 institution, challenges with CNS recruitment and variations in how students were precepted were noted. This article describes a successful CNS student program and its value in creating a talent pipeline.

Project

A revision to student placements was initiated to create a formalized program including enhanced academic partnerships, standardized expectations and goals, assigned clinical projects and end-of-semester presentations, appointment of a student coordinator, and structured preceptor preparation.

Outcomes

Outcomes included 100 placements for 50 different students; the primary source of recruitment for the organization is now prior students, with 17 being hired since program inception. A 325% increase was also noted in qualified preceptors. Student productivity increased, and 11 students were accepted for national presentations. Academic sites have reported increased satisfaction.

Conclusion

Organizations looking to increase CNS recruitment should consider the revision of their student program. A centralized CNS responsible for student experiences can ensure standardization and provide preceptor support. The CNSs have an essential role in securing their future nationally and can do so through growing new talent and aiding in preparation for practice.
HIV Pre-exposure Prophylaxis Services for Black and Hispanic or Latino Gay, Bisexual, and Other Men Who Have Sex With Men and Transgender Women in THRIVE, 2015-2020
Authors: Tanner Mary R. , Zhu Weiming , Iqbal Kashif , Dominguez Kenneth L. , Yu Lei , Hayes Tameka D. , Wiener Jeffrey , Koenig Linda J. , Batey Scott , Burgess Samuel , Elamin Fatima , Fox Anthony , Price Ashley , Wood Lucila , Hoover Karen W.
Published: December 2022

Background and setting:

From 2015 to 2020, the THRIVE project supported 7 US health departments to improve HIV prevention services for Black or African American (Black) and Hispanic or Latino gay, bisexual, and other men who have sex with men (GBM) and transgender women (TGW).

Methods:

We described services provided in the THRIVE PrEP continuum. Using Poisson regression models, we estimated associations between race or ethnicity and age and PrEP screening, linkage, and prescription. We examined associations between colocation of services and PrEP linkage and prescription for 2 sites.

Results:

THRIVE served 12,972 GBM without HIV; 37% of PrEP-eligible GBM were prescribed PrEP. THRIVE served 1185 TGW without HIV; 45% of PrEP-eligible TGW were prescribed PrEP. Black and Hispanic or Latino GBM were 29% (RR = 0.71, 95% CI: 0.66–0.77) and 19% (RR = 0.81, 95% CI: 0.75–0.87) less likely, respectively, to be prescribed PrEP than White GBM. GBM aged 18–24 years and 55 years or older were 19% (RR = 0.81, 95% CI: 0.75–0.87) and 22% (RR = 0.78, 95% CI: 0.67–0.9) less likely, respectively, to be prescribed PrEP compared with those aged 35–44 years. Colocated services were associated with a 54% (RR = 1.54, 95% CI: 1.44–1.64) and a 31% (RR = 1.31, 95% CI: 1.19–1.43) greater likelihood of PrEP linkage and prescription, respectively, compared with services at different locations.

Conclusions:

THRIVE provided PrEP to higher proportions of PrEP-eligible persons than current national estimates; however, PrEP use disparities persist. Colocation of services may be a useful component of jurisdictional strategies to increase PrEP coverage.
A novel fluorescently-labeled long-chain fatty acid analog for the study of fatty acid metabolism in cultured cells
Authors: Hara Yasuhiro , Hirano Ken-ichi
Published: December 2022

123I-15-(p-iodophenyl)-(R,S)-methyl pentadecanoic acid (BMIPP) is a long-chain fatty acid (LCFA) analog developed to examine myocardial LCFA metabolism and has been used as a tracer for nuclear cardiology. However, its use is limited because of the specialized features of cardiac scintigraphy. In this study, a novel BMIPP-based probe was utilized, in which iodine-123 was replaced with a fluorescent compound, to extend the use of123I-BMIPP to a wider variety of cellsex vivo. To confirm that this fluorescent LCFA analog (fluorescent BMPP) was imported into cells, fluorescence-activated cell sorting (FACS) analysis and fluorescent cell imaging were performed using cultured cells. The analysis showed that the import of fluorescent BMPP into the cells occurred in a concentration-dependent manner. This import into cells was inhibited by Sulfosuccinimidyl Oleate in a dose-dependent manner, which is an inhibitor of CD36, a well-known LCFA transporter, suggesting that fluorescent BMPP could be imported into cells via the same pathway as LCFA. FACS and cell imaging intensities of the cells importing fluorescent BMPP were attenuated after incubation in the non-Alexa680-BMPP medium. These results suggest that fluorescent BMPP can be transported into and from cells, reflecting the metabolism of LCFA. Fluorescently-labeled BMPP has the potential to be used as a probe for studying LCFA metabolism in various cells.
Near-universal same day linkage to ART care among newly diagnosed adults living with HIV: A cross sectional study from primary health facilities, in urban Malawi
Authors: Chihana Rachel , Katumbi Chaplain , Dadabhai Sufia , Kaumba Agness , Mughogho Atusaye , Singano Victor , Mwapasa Victor , Malisita Ken
Published: December 2022

Malawi HIV treatment guidelines recommend same-day antiretroviral therapy (ART) initiation. Overall 97.9 % of Malawians living with HIV (PLHIV) are on ART, same-day ART initiation prevalence and factors that facilitate it have not been fully described. We assessed same-day ART initiation and described individual, health system and health facility infrastructural factors at health facilities supported by expert clients (EC). ECs are lay PLHIV who support other PLHIV. The study was conducted in urban and semi-urban primary health facilities, in Blantyre, Malawi. It was a cross-sectional, descriptive survey of PLHIV and health facility leaders. Eligibility criteria included age ≥ 18 years, new diagnosis of HIV, received counselling from ECs, and offered same day ART. The study was conducted from December 2018 to June 2021, and 321 study participants enrolled. Mean age (standard deviation) was 33 years (10) with 59% females. In total, 315 (98.1%) initiated same day ART. Four participants did not because of mental unpreparedness, one wanted to try herbal medicine and one was concerned about stigma. Participants reported health facility accessibility (99%,318/321), privacy (91%, 292/321) and quality of counselling by EC as excellent (40%,128/321). Same day ART was nearly universal. Participants’ satisfaction with health services delivery, the presence of EC, and infrastructural characteristics such as good privacy were cited as reasons favoring same day linkage to ART. The most cited reason for not starting same day ART was mental unpreparedness.
Effects of temperature on the development ofHeliconius eratobutterflies
Authors: Huang Yuqian , McPherson Josie , Jiggins Chris D. , Montejo-Kovacevich Gabriela
Published: December 2022

Anthropogenic climate change is thought to present a significant threat to biodiversity, in particular to tropical ectotherms, and the effects of long-term developmental heat stress on this group have received relatively little research attention.

Here we study the effects of experimentally raising developmental temperatures in a tropical butterfly. We measured survival, development time, adult body mass, and wing size of a neotropical butterfly,Heliconius erato demophoon, across three temperature treatments.

Egg survival was lower in the hotter treatments, with 83%, 73%, and 49% of eggs eclosing in the 20-30°C, 23-33°C, and 26-36°C treatments, respectively. Larval survival was five times lower in the 26-36°C treatment (4%) compared to the 20-30°C treatment (22%), and we did not detect differences in pupal survival across treatments due to high mortality in earlier stages.

Adults in the 20-30°C treatment had a lower body mass and larvae had a lower growth rate compared to the intermediate 23-33°C treatment, but were heavier than the few surviving adults in the 26-36°C treatment. Females were heavier and grew faster as larvae than males in the 23-33°C treatment, but there was no associated increase in wing size.

In summary, high developmental temperatures are particularly lethal for eggs and less so for larvae, and also affect adult morphology. This highlights the importance of understanding the effects of temperature variation across ontogeny in tropical ectotherms.
Multiple Instance Learning Framework can Facilitate Explainability in Murmur Detection
Authors: Rohr Maurice , Müller Benedikt , Dill Sebastian , Güney Gökhan , Antink Christoph Hoog
Published: December 2022

Objective

Cardiovascular diseases (CVDs) account for a high fatality rate worldwide. Heart murmurs can be detected from phonocardiograms (PCGs) and may indicate CVDs. Still they are often overlooked as their detection and correct clinical interpretation requires expert skills. In this work, we aim to predict the presence of murmurs and clinical outcome from multiple PCG recordings employing an explainable multitask model.

Approach

Our approach consists of a two-stage multitask model. In the first stage, we predict the murmur presence in single PCGs using a multiple instance learning (MIL) framework. MIL also allows us to derive sample-wise classifications (i.e. murmur locations) while only needing one annotation per recording (“weak label”) during training. In the second stage, we fuse explainable hand-crafted features with features from a pooling-based artificial neural network (PANN) derived from the MIL framework. Finally, we predict the presence of murmurs as well as the clinical outcome for a single patient based on multiple recordings using a simple feed-forward neural network.

Main results

We show qualitatively and quantitatively that the MIL approach yields useful features and can be used to detect murmurs on multiple time instances and may thus guide a practitioner through PCGs. We analyze the second stage of the model in terms of murmur classification and clinical outcome. We achieved a weighted accuracy of 0.714 and an outcome cost of 13612 when using the PANN model and demographic features on the CirCor dataset (hidden testset of the George B. Moody PhysioNet challenge 2022, team “Heart2Beat”, rank 12 / 40).

Significance

To the best of our knowledge, we are the first to demonstrate the usefulness of MIL in PCG classification. Also, we showcase how the explainability of the model can be analyzed quantitatively, thus avoiding confirmation bias inherent to many post-hoc methods. Finally, our overall results demonstrate the merit of employing MIL combined with handcrafted features for the generation of explainable features as well as for a competitive classification performance.
Metabolomic Profiling to Identify Early Urinary Biomarkers and Metabolic Pathway Alterations in Autosomal Dominant Polycystic Kidney Disease
Authors: Houske Eden A. , Glimm Matthew G. , Bergstrom Annika R. , Slipher Sally K. , Welhaven Hope D. , Greenwood Mark C. , Linse Greta M. , June Ronald K. , Yu Alan S.L. , Wallace Darren P. , Hahn Alyssa K.
Published: December 2022

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of numerous fluid-filled cysts that lead to progressive loss of functional nephrons. Currently, there is an unmet need for diagnostic and prognostic indicators of early stages of the disease. Metabolites were extracted from the urine of early-stage ADPKD patients (n=48) and age- and sex-matched normal controls (n=47) and analyzed by liquid chromatography-mass spectrometry. Orthogonal partial least squares-discriminant analysis was employed to generate a global metabolomic profile of early ADPKD for the identification of metabolic pathway alterations and discriminatory metabolites as candidates of diagnostic and prognostic biomarkers. The global metabolomic profile exhibited alterations in steroid hormone biosynthesis and metabolism, fatty acid metabolism, pyruvate metabolism, amino acid metabolism, and the urea cycle. A panel of 46 metabolite features were identified as candidate diagnostic biomarkers. Notable putative identities of candidate diagnostic biomarkers for early detection include creatinine, cAMP, dCMP, various androgens (testosterone, 5alpha-androstane-3,17,dione, trans-dehydroandrosterone), betaine aldehyde, phosphoric acid, choline, 18-hydroxycorticosterone, and cortisol. Metabolic pathways associated with variable rates of disease progression included steroid hormone biosynthesis and metabolism, vitamin D3 metabolism, fatty acid metabolism, the pentose phosphate pathway, tricarboxylic acid cycle, amino acid metabolism, sialic acid metabolism, and chondroitin sulfate and heparin sulfate degradation. A panel of 41 metabolite features were identified as candidate prognostic biomarkers. Notable putative identities of candidate prognostic biomarkers include ethanolamine, C20:4 anandamide phosphate, progesterone, various androgens (5alpha-dihydrotestosterone, androsterone, etiocholanolone, epiandrosterone), betaine aldehyde, inflammatory lipids (eicosapentaenoic acid, linoleic acid, stearolic acid), and choline. Our exploratory data support metabolic reprogramming in early ADPKD and demonstrate the ability of liquid chromatography-mass spectrometry-based global metabolomic profiling to detect metabolic pathway alterations as new therapeutic targets and biomarkers for early diagnosis and tracking disease progression of ADPKD.
Sexual misconduct reporting: the silencing effects of hegemonic masculinity
Authors: Smith Chelsie J. , Dupré Kathryne E. , Dionisi Angela M.
Published: December 2022

Purpose

Drawing on hegemonic masculinity theory, this study provides evidence supporting how gender, race and sexual identity, may shape the rates of sexual misconduct reporting, by keeping those targets who traditionally enjoy positions of power (i.e. white, cisgender men) silent.

Design/methodology/approach

Across 3,230 gender harassment, 890 sexual advance harassment and 570 sexual assault incidents that occurred within a traditionally masculine organization, the authors conducted tests of independence and hierarchical regression analyses to examine whether targets' social identity characteristics (i.e. sex, race, sexuality and gender alignment), predicted the reporting of sexual misconduct.

Findings

Although reporting rates varied based on the type of incident, white men were less likely than their colleagues to report workplace sexual misconduct. In general, men were approximately half as likely as women to report. Lower rates of reporting were similarly seen among all white (vs BIPOC) targets and all cisgender and heterosexual (vs LGBT) targets, when controlling for other identity characteristics.

Originality/value

Research on sexual misconduct has largely privileged the experiences of (white, heterosexual) women, despite knowledge that men, too, can experience this mistreatment. This research broadens this lens and challenges the notion that sexual misconduct reporting rates are uniform across employee groups. By articulating how the pressures of hegemonic masculinity serve to silence certain targets – including and especially white, cisgender men – the authors provide means of better understanding and addressing workplace sexual misconduct underreporting.