bluuebunny/crossref_metadata_2025 huggingface dataset:
Slow body magnetohydrodynamic waves in solar photospheric flux tubes with density inhomogeneity
Authors: Asiri F , Ballai I , Fedun V , Verth G , Ruzheinikov S N , Albidah A B
Published: February 2024

Pores and sunspots are ideal environments for the propagation of guided magnetohydrodynamic (MHD) waves. However, modelling such photospheric waveguides with varying background quantities such as plasma density and magnetic field has thus far been very limited. Such modelling is required to correctly interpret MHD waves observed in pores and sunspots with resolved inhomogeneities such as light bridges and umbral dots. This study will investigate the propagation characteristics and the spatial structure of slow body MHD modes in a magnetic flux tube with a circular cross-section with inhomogeneous equilibrium density distribution under solar photospheric conditions in the short wavelength limit. For simplicity, the equilibrium density profile is taken to have a circular density enhancement or depletion. The advantage of this is that the strength, size, and position of the density inhomogeneity can be easily changed. Calculating the eigenfrequencies and eigenfunctions of the slow body modes is addressed numerically with use of the Fourier–Chebyshev Spectral method. The radial and azimuthal variation of eigenfunctions is obtained by solving a Helmholtz-type partial differential equation with Dirichlet boundary conditions. The inhomogeneous equilibrium density profile results in modified eigenvalues and eigenvectors. It was found that a localized density inhomogeneity leads to a decrease in the eigenvalues and the spatial structure of modes ceases to be a global harmonic oscillation, as the modes migrate towards regions of lower density. Comparing the homogeneous case and the cases corresponding to depleted density enhancement, the dimensionless phase speed undergoes a significant drop in its value (at least 40  per cent).
Convective mixing: the formation channel of Li-rich giants
Authors: Li Xue-Feng , Shi Jian-Rong , Li Yan , Yan Hong-Liang , Zhang Jing-Hua
Published: February 2024

Increasing observed data indicate that part of giants has abnormally high lithium (Li) inside their surface, and their proportion is around 1 per cent. Instead of pursuing the feasible mechanisms for extra Li enrichment, we focus on how to inhibit Li depletion from the main-sequence phase of giants. With this in mind, we find that convective mixing is capable of achieving this goal and forming Li-rich giants, which is mainly attributed to the convection model with the convective boundary defined by the Ledoux criterion. Another factor in the formation of Li-rich giants in our convection models is related to the Li abundances of their progenitors. If the Li abundances of the progenitors exceed the meteoritic value ($\rm 3.3\ dex$), then the majority of giants will be rich in Li. This is the general pattern of stellar Li abundance evolution without factoring in extra Li depletion. We propose that other Li depletion processes should also be adopted in the future, as they may be the key to the 1 per cent puzzle.
Chemical modification patterns for microRNA therapeutic mimics: a structure-activity relationship (SAR) case-study on miR-200c
Authors: Garreau Marion , Weidner Julie , Hamilton Russell , Kolosionek Ewa , Toki Naoko , Stavenhagen Kathrin , Paris Clément , Bonetti Alessandro , Czechtizky Werngard , Gnerlich Felix , Rydzik Anna
Published: February 2024

microRNA (miRNA) mimics are an emerging class of oligonucleotide therapeutics, with a few compounds already in clinical stages. Synthetic miRNAs are able to restore downregulated levels of intrinsic miRNAs, allowing for parallel regulation of multiple genes involved in a particular disease. In this work, we examined the influence of chemical modifications patterns in miR-200c mimics, assessing the regulation of a selection of target messenger RNAs (mRNA) and, subsequently, of the whole transcriptome in A549 cells. We have probed 37 mimics and provided an initial set of instructions for designing miRNA mimics with potency and selectivity similar to an unmodified miRNA duplex. Additionally, we have examined the stability of selected mimics in serum. Finally, the selected two modification patterns were translated to two other miRNAs, miR-34a and miR-155. To differing degrees, these designs acted on target mRNAs in a similar manner to the unmodified mimic. Here, for the first time, we describe a structured overview of ‘miRNA mimics modification templates’ that are chemically stabilised and optimised for use in an in vitro set up and highlight the need of further sequence specific optimization when mimics are to be used beyond in vitro tool experiments.
Hepatitis C and Cigarette Smoking Behavior: Themes From Focus Groups
Authors: Cohen Julia F , Ward Kathleen M , Gittleman Jennifer , Perez Esther , Pia Tyler , Shuter Jonathan , Weinberger Andrea H , Sulkowski Mark
Published: February 2024

Introduction

People with chronic hepatitis C virus (HCV; PWHC) use cigarettes at a much higher prevalence than other individuals, and smoking can exacerbate the harms specifically related to HCV (eg, hepatocellular carcinoma). Little is known about factors related to cigarette use among PWHC.

Aims and Methods

This study examined focus group data to explore beliefs and behaviors related to cigarette use among PWHC. Qualitative data from two focus groups of PWHC reporting current cigarette smoking (n = 15, 60% male) were collected using a semi-structured interview guide. Participants were asked about reasons for smoking, barriers to quitting smoking, and the relationship of HCV to smoking. Focus groups were transcribed verbatim and coded in NVivo 12. Four coders examined themes that arose in the focus groups. Common themes are described and supported with quotes.

Results

Reasons for smoking included addiction to cigarettes, stress, substituting cigarettes for other drugs, and social norms, while reasons for quitting included health and being free from the use of all drugs. Barriers to quitting included concerns about coping with stress, weight gain, and having a lack of support for and education about quitting. Many participants believed there was a link between smoking and HCV and discussed smoking in relation to the stress of an HCV diagnosis.

Conclusions

Participants identified both HCV-related and non-HCV-related aspects of cigarette smoking and cessation-related behaviors that could be targeted in cessation treatment. More research is needed to identify the best treatment approaches that reduce the significant medical consequences of cigarette use among PWHC.

Implications

People with chronic hepatitis C virus (HCV; PWHC) smoke cigarettes at a high prevalence, yet little is known about their smoking behaviors. Moreover, there are no cessation treatments targeting PWHC. This is the first study to collect focus group data from PWHC who smoke in order to identify reasons for cigarette use (HCV-related and non-HCV-related), and motivators and barriers to quitting cigarettes. PWHC reports using cigarettes to cope with the stress of an HCV diagnosis and to celebrate HCV cure. These findings suggest there are specific times during the HCV care continuum where providers can aid with cessation efforts.
Postcumulus Processes Recorded in Whole-Rock Geochemistry: a Case Study from the Mirabela Layered Intrusion, Brazil
Authors: Barnes Stephen J , Williams Morgan
Published: February 2024

According to the ‘trapped liquid’ paradigm, whole-rock chemical compositions of cumulate rocks in layered intrusions can be represented as closed-system multicomponent mixtures of the cumulus phases and the liquids from which they crystallised. Alternative open-system models for cumulate solidification assert that intercumulus liquid is continuously mobile as a result of compaction of crystal mushes. In the closed-system models, all excluded elements, i.e. those incompatible in the cumulus phases, should be correlated with one another, whereas in open systems the more incompatible elements should be decoupled from the more compatible ones and correlations should be poor. These alternative hypotheses are tested using a database of >63 000 whole-rock analyses of mostly ultramafic cumulates from a single package of layers across the entire width of the Mirabela layered intrusion, a 2.5-km-wide by >2-km-thick intrusion with Great Dyke-like stratigraphy. Variably compatible elements Al, Na, Ti and P are found to show strong correlations with one other in olivine-pyroxene cumulates across the spectrum from mesocumulate to orthocumulate rocks, where drill-core sample intervals are composited over 3 m; weaker correlations are found over 1-m sample intervals. The closed-system trapped liquid model is robust for this suite of rocks at the scale of 3-m lengths of drill core (~1 kg of sample). Furthermore, a very smooth and symmetrical variation is observed from dominantly ad- to mesocumulate rocks in the geometrical centre of the intrusion towards orthocumulates at both margins, attributable to increase in cooling rate towards the margins. The most adcumulate rocks are gabbronorites at the base of the mafic sequence in the centre of the intrusion. There is no corresponding decrease in layer thickness towards the centre that would be predicted by a compaction model. The only incompatible element showing partial decoupling is K, which appears to have been mobile at a very late stage, probably in an aqueous fluid phase. There is no evidence for mobilisation of platinum group elements or other chalcophile elements by this fluid despite the presence of disseminated sulfide throughout the sampled interval.
Metamorphism of Dolomitic and Magnesitic Rocks in Collisional Orogens and Implications for Orogenic CO2 Degassing
Authors: Tamang Shashi , Groppo Chiara , Girault Frédéric , Perrier Frédéric , Rolfo Franco
Published: February 2024

Carbonate-bearing sediments, containing calcite, dolomite or magnesite as major carbonate components, are important constituents of sedimentary sequences deposited on passive margins through Earth’s history. When involved in collisional orogenic processes, these sediments are metamorphosed at variable temperatures and pressures, and undergo decarbonation reactions. While the orogenic metamorphism of some of these lithologies (i.e. impure limestones and dolostones, marls sensu stricto and calcareous pelites) is relatively well understood, very little is known about the metamorphic evolution and decarbonation history of mixed carbonate–silicate rocks in which either dolomite or magnesite is the dominant carbonate component.

Here we present the results of a petrologic study of representative samples of metasediments from Central Nepal, derived from Proterozoic dolomitic and magnesitic protoliths metamorphosed during the Himalayan orogeny. The main metamorphic assemblages developed in sediments originally containing different amounts of dolomite or magnesite are characterised in detail. Forward thermodynamic modelling applied to seven samples allows constraints to be placed on (i) the main decarbonation reactions, (ii) the P–T conditions under which these reactions took place, (iii) the composition of the fluids, and (iv) the amounts of CO2 released.

We conclude that the CO2 productivity of dolomitic and magnesitic pelites and marls originally containing 15–40% carbonate is significant (>5.5 ± 1.0 CO2 wt% and up to 10.5 ± 1.5 CO2 wt%), whereas for carbonate contents above 60–70%, CO2 productivity is negligible unless aqueous fluids infiltrate from the outside and trigger decarbonation reactions. Since the dolomitic and magnesitic protoliths are significantly abundant in the sedimentary sequences involved in the still active Himalayan orogen, the decarbonation processes described here could contribute to the diffuse CO2 degassing currently observed at the surface. Furthermore, we propose for the first time that the peculiar magnesium-rich assemblages investigated in this study may derive from evaporitic protoliths, and that the whole Upper Lesser Himalayan Sequence may therefore represent the metamorphic product of a Proterozoic sequence consisting of alternating layers of carbonatic, evaporitic and pelitic sediments.
Do Men Care about Childcare? Women’s Relative Resources and Men’s Preferences for Work–Family Reconciliation Policies
Authors: Estévez-Abe Margarita , Lim Tae Hyun
Published: February 2024

Existing literature on the politics of work–family reconciliation policies focuses primarily on women and their policy preferences as the main driver of recent policy expansions. But what do we know about male preferences? This article explores this question in an innovative way by integrating insights from economic and sociological studies of division of labor and bargaining within the household. It investigates the link between women’s relative resources within the household and their male partners’ preferences for different types of reconciliation policies. Drawing on regression analysis of nineteen OECD countries using the International Social Survey Program data (Family and Changing Gender Roles IV), we find that: (1) men in dual-earner households, men in college-educated educational homogamy, and men in educational hypogamy (the woman is better educated) are more likely to support reconciliation policies; and (2) women’s earnings and education have different effects on men’s preferences.
Towards a more effective REACH legislation in protecting human health
Authors: Godderis Lode , De Ryck Evi , Baeyens Willy , Geerts Lieve , Jacobs Griet , Maesen Phillippe , Mertens Birgit , Schroyen Guy , Van Belleghem Frank , Vanoirbeek Jeroen , Van Larebeke Nicolas
Published: February 2024

There is growing evidence indicating the substantial contribution of man-made products to an increase in the risk of diseases of civilization. In this article, the Belgian Scientific Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Committee gives a critical view on the working of REACH. The current regulatory framework needs to further evolve taking into account data generated using modern science and technology. There is a need for improved assessment process not only before but also after entering the market. Objectivity, transparency, and the follow-up after market access can be optimized. Additionally, no guidance documents exist for regulation of mixture effects. Further, the lengthiness before regulatory action is a big concern. Decision-making often takes several years leading to uncertainties for both producers and end users. A first proposed improvement is the implementation of independent toxicity testing, to assure objectivity, transparency, and check and improve compliance. A “no data, no market” principle could prevent access of hazardous chemicals to the market. Additionally, the introduction of novel testing could improve information on endpoints such as endocrine disrupting abilities, neurotoxicity, and immunotoxicity. An adapted regulatory framework that integrates data from different sources and comparing the outputs with estimates of exposure is required. Fast toxicology battery testing and toxicokinetic testing could improve speed of decision-making. Hereby, several improvements have been proposed that could improve the current REACH legislation.
XThe Seventeenth Century, Part II
Authors: Baker William , Stelzer Emily , Airey Jennifer , Parry David , Urban David V
Published: February 2024

This chapter has four sections: 1. General and Poetry; 2. Restoration Drama Excluding Dryden; 3. Dryden; 4. Prose. Section 1 is by William Baker, with Emily Stelzer covering Marvell and Herrick, and with William Baker and Emily Stelzer covering Crashaw; sections 2 and 3 are by Jennifer Airey; section 4 is by William Baker on Hobbes and Locke, David Parry on Bunyan, and David V. Urban on Pepys. There is no ‘Miscellaneous’ section this year.
Cervical Spine Stenosis Causing Diaphragmatic Paralysis: A Case Study and Narrative Review of Clinical Presentations and Outcomes
Authors: Lamb Colin D. , Schupper Alexander J. , Quinones Addison , Zhang Jack Y. , Steinberger Jeremy , Margetis Konstantinos
Published: February 2024

Study Design:

Case report and narrative review.

Objective:

To explore the therapeutic role of surgical and nonsurgical treatment of diaphragmatic paralysis secondary to spinal cord and nerve root compression.

Summary of Background Data:

Phrenic nerve dysfunction due to central or neuroforaminal stenosis is a rare yet unappreciated etiology of diaphragmatic paralysis and chronic dyspnea. Surgical spine decompression, diaphragmatic pacing, and intensive physiotherapy are potential treatment options with varying degrees of evidence.

Methods:

The case of a 70-year-old male with progressive dyspnea, reduced hemi-diaphragmatic excursion, and C3-C7 stenosis, who underwent a microscopic foraminotomy is discussed. Literature review (MEDLINE, PubMed, Google Scholar) identified 19 similar reports and discussed alternative treatments and outcomes.

Results and Conclusions:

Phrenic nerve root decompression and improvement in neuromonitoring signals were observed intraoperatively. The patient’s postoperative course was uncomplicated, and after 15 months, he experienced significant symptomatic improvement and minor improvement in hemi-diaphragmatic paralysis and pulmonary function tests. All case reports of patients treated with spinal decompression showed symptomatic and/or functional improvement, while one of the 2 patients treated with physiotherapy showed improvement. More studies are needed to further describe the course and outcomes of these interventions, but early identification and spinal decompression can be an effective treatment.

OCEBM Level of Evidence:

Level—4.
AHN LifeFlight, 45 Years in the Making
Authors: Yobbi Annale
Published: February 2024

In Pittsburgh, Pennsylvania, the skies have become a battleground against time in a world where every second counts. Since its inception in 1978, a revolution has occurred in emergency medical services, with LifeFlight Helicopters soaring to new heights in emergency treatment and transport. This article will explore the transformation of helicopter emergency medical services through the decades, where every rotor blade spins with a mission to save lives and rewrite the rules of survival. Allegheny Health Network's LifeFlight is a rotor-wing (helicopter) aeromedical transport service that provides rapid emergent transport for critically ill and injured persons. The program hub of operations is primarily in Western Pennsylvania. Since its inception in 1978, the program has grown and transformed into the sophisticated, highly technical, expanded scope of practice, critical care transport service it is today. The crews spend a significant portion of clinical care focusing on preparing the patient to survive the transport and ensure stability during transit; this phase of transport is equally crucial as the patient care during the actual flight. This article introduces the evolution and innovations that LifeFlight's medical crews and aviation practices have undergone since the program started.
LifeFlight Case Studies
Authors: Mikolich Brian , Shank Geoff , Thomas David
Published: February 2024

Air medical providers are responsible for the care of an incredibly diverse patient population. When it is time to transport a patient, providers must be prepared for complex situations, each requiring different skills, medications, and critical thinking. Scene flights will have providers landing and providing care in the prehospital setting where an interfacility transport requires the patient to be taken from one hospital to another. Specialty flights require special equipment, personnel, and aircraft preparedness to be completed. The case studies provided within this article highlight the complexity and diversity that is encountered each shift at Allegheny LifeFlight.
Top 10 Tips on Safety From the Air Medical Transport Industry
Authors: Hough Peter , Nawrocki Philip , McCardell Tyler , Parker Gregory
Published: February 2024

The air medical transport industry places a high value on developing and maintaining a culture of safety due to the higher risk nature of its operations. The dynamic nature of response and transport, inherent risks involved with flight, lack of supporting resources, weather conditions, and austere nature of the transport environment are all factors that highlight the need for enhanced safety. As such, the air medical transport industry has developed a robust and unique approach to provider and patient safety involving many tactics not otherwise used in other areas of health care. This article describes some of the unique safety features and approaches that are commonplace in the air medical transport industry and proposes a means for these initiatives to other areas of the health care system.
Transitions in Video Laryngoscope Technology to Improve First-Pass Success
Authors: Jones Brandon , Asberry Cassandra
Published: February 2024

Prehospital intubation is a high-risk, relatively low frequency procedure. Provider experience plays a key role in first-pass success rates, especially in the setting of a difficult airway. While strong foundational knowledge is necessary to equip providers with an adequate understanding of intubation procedures and the skill set needed to manage a difficult airway, effective equipment may provide an extra boost in first-pass success for novice airway providers. First-pass success is correlated with decreased adverse events and should be maximized in the prehospital setting. After evaluating overall first-pass success of 66% to 83% from 2016 to 2020, AHN LifeFlight enacted changes in education, training, and video laryngoscopy equipment to successfully increase first-pass success to over 90%.
Effect of phenylephrine rescue injection on hypotension after spinal anaesthesia for caesarean delivery when guided by both heart rate and SBP during an early warning window
Authors: Tang Wenxi , Liu Haiying , Zhang Zheng , Lyu Wenyuan , Wei Penghui , Zhou Haipeng , Zhou Jinfeng , Li Jianjun
Published: February 2024

BACKGROUND

Spinal anaesthesia is now the most common technique for caesarean delivery. However, because of the intermittent nature of noninvasive blood pressure (NIBP) measurements, maternal blood pressure may become hypotensive between the measurements. There is thus an inbuilt delay before the anaesthesiologist can intervene to counteract the hypotension. Based on the principle that changes in blood pressure can induce compensatory changes in the heart rate (HR), combining the NIBP with real-time HR, we designed two warning windows to predict hypotension and hypertension.

OBJECTIVE

To evaluate whether phenylephrine administration guided by these warning windows would help maintain haemodynamic stability.

SETTING

A teaching hospital.

DESIGN

A randomised controlled trial.

PATIENTS

One hundred and ten pregnant women scheduled for elective caesarean delivery were enrolled, from which, after exclusions, 86 were eligible for the study.

INTERVENTIONS

All eligible patients received a continuous intravenous infusion of phenylephrine as soon as spinal anaesthesia was initiated. Thereafter, patients were randomly assigned to two groups. In the test group (Win-Group): rescue phenylephrine administration was triggered by an early warning window of HR above 100 beats per minute (bpm) and SBP 90 to 110 mmHg; pausing the infusion phenylephrine was triggered by a HR lower than 60 bpm and SBP greater than 90 mmHg. In the control group, phenylephrine was guided by BP only when it appeared on the monitor: SBP less than 90 mmHg was the trigger for administering rescue phenylephrine; SBP greater than 110 mmHg was the trigger for pausing the phenylephrine infusion.

MAIN OUTCOME MEASURES

The primary outcome was incidence of hypotension. Secondary outcomes were the incidence of hypertension and other adverse haemodynamic events.

RESULTS

The incidence of hypotension was significantly lower in the Win-Group than in the BP-Group (27.8 vs. 66.7%, P = 0.001). The minimum SBP was significantly higher in Win-Group than in BP-Group (93.9 ± 9.49 vs. 86.7 ± 11.16 mmHg, P 
= 0.004). There was no significant difference in the incidence of hypertension between groups.

CONCLUSION

After spinal anaesthesia for caesarean delivery, when phenylephrine infusion is guided by HR along with BP from a warning window it effectively reduces the incidence of hypotension without any significant effect on incidence of hypertension.

TRIAL REGISTRATION

Chictr.org.cn; Identifier: ChiCTR 2100041812.
Transcriptome Analysis Reveals Enhancement of Cardiogenesis-Related Signaling Pathways by S-Nitroso-N-Pivaloyl-d-Penicillamine: Implications for Improved Diastolic Function and Cardiac Performance
Authors: Takenaka Yasuhiro , Hirasaki Masataka , Bono Hidemasa , Nakamura Shigeo , Kakinuma Yoshihiko
Published: February 2024

We previously reported a novel compound called S-nitroso-N-pivaloyl-d-penicillamine (SNPiP), which was screened from a group of nitric oxide donor compounds with a basic chemical structure of S-nitroso-N-acetylpenicillamine, to activate the nonneuronal acetylcholine system. SNPiP-treated mice exhibited improved cardiac output and enhanced diastolic function, without an increase in heart rate. The nonneuronal acetylcholine–activating effects included increased resilience to ischemia, modulation of energy metabolism preference, and activation of angiogenesis. Here, we performed transcriptome analysis of SNPiP-treated mice ventricles to elucidate how SNPiP exerts beneficial effects on cardiac function. A time–course study (24 and 48 hours after SNPiP administration) revealed that SNPiP initially induced Wnt and cyclic guanosine monophosphate–protein kinase G signaling pathways, along with upregulation of genes involved in cardiac muscle tissue development and oxytocin signaling pathway. We also observed enrichment of glycolysis-related genes in response to SNPiP treatment, resulting in a metabolic shift from oxidative phosphorylation to glycolysis, which was suggested by reduced cardiac glucose contents while maintaining adenosine tri-phosphate levels. In addition, SNPiP significantly upregulated atrial natriuretic peptide and sarcolipin, which play crucial roles in calcium handling and cardiac performance. These findings suggest that SNPiP may have therapeutic potential based on the pleiotropic mechanisms elucidated in this study.
Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice
Authors: Wu Pau Yen , Caceres Ana Isabel , Chen Jiegen , Sokoloff Jamie , Huang Mingjian , Baht Gurpreet Singh , Nackley Andrea G. , Jordt Sven-Eric , Terrando Niccolò
Published: February 2024

Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery. We established a tibial fracture mouse model that recapitulates clinically relevant orthopedic trauma surgery, which causes changes in neuropeptide levels in dorsal root ganglia and sustained neuroinflammation in the spinal cord. Here, we monitored extended pain behavior in this model, observing chronic bilateral hindpaw mechanical allodynia in both male and female C57BL/6J mice that persisted for >3 months after surgery. We also tested the analgesic effects of a novel, minimally invasive, bioelectronic approach to percutaneously stimulate the vagus nerve (termed percutaneous vagus nerve stimulation [pVNS]). Weekly pVNS treatment for 30 minutes at 10 Hz for 3 weeks after the surgery strongly reduced pain behaviors compared with untreated controls. Percutaneous vagus nerve stimulation also improved locomotor coordination and accelerated bone healing. In the dorsal root ganglia, vagal stimulation inhibited the activation of glial fibrillary acidic protein-positive satellite cells but without affecting microglial activation. Overall, these data provide novel evidence supportive of the use of pVNS to prevent postoperative pain and inform translational studies to test antinociceptive effects of bioelectronic medicine in the clinic.
Predicting Conversion to Insulin Sensitivity With Metformin
Authors: Gannon Jessica M. , Sanchez Marcos , Lines Katherine , Cairns Kathleen , Reardon Claire , Chengappa K.N. Roy , Calkin Cynthia V.
Published: February 2024

Background

Insulin resistance (IR) changes the trajectory of responsive bipolar disorder to a treatment-resistant course. A clinical trial conducted by our group demonstrated that IR reversal by metformin improved clinical and functional outcomes in treatment-resistant bipolar depression (TRBD). To aid clinicians identify which metformin-treated TRBD patients might reverse IR, and given strong external evidence for their association with IR, we developed a predictive tool using body mass index (BMI) and homeostatic model assessment–insulin resistance (HOMA-IR).

Methods

The predictive performance of baseline BMI and HOMA-IR was tested with a logistic regression model using known metrics: area under the receiver operating curve, sensitivity, and specificity. In view of the high benefit to low risk of metformin in reversing IR, high sensitivity was favored over specificity.

Results

In this BMI and HOMA-IR model for IR reversal, the area under the receiver operating curve is 0.79. At a cutoff probability of conversion of 0.17, the model's sensitivity is 91% (95% confidence interval [CI], 57%–99%), and the specificity is 56% (95% CI, 36%–73%). For each unit increase in BMI or HOMA-IR, there is a 15% (OR, 0.85; 95% CI, 0.71–0.99) or 43% (OR, 0.57; CI, 0.18–1.36) decrease in the odds of conversion, respectively.

Conclusions

In individuals with TRBD, this tool using BMI and HOMA-IR predicts IR reversal with metformin with high sensitivity. Furthermore, these data suggest early intervention with metformin at lower BMI, and HOMA-IR would likely reverse IR in TRBD.
Development and First Clinical Use of an Extracorporeal Artificial Multiorgan System in Acute-on-Chronic Liver Failure Patients
Authors: Ahmad Suhail , Novokhodko Alexander , Liou Iris W. , Smith Nancy Colobong , Carithers Robert L. , Reyes Jorge , Bakthavatsalam Ramasamy , Martin Carl , Bhattacharya Renuka , Du Nanye , Hao Shaohang , Gao Dayong
Published: February 2024

Multiple organ failure (MOF) is a common and deadly condition. Patients with liver cirrhosis with acute-on-chronic liver failure (AOCLF) are particularly susceptible. Excess fluid accumulation in tissues makes routine hemodialysis generally ineffective because of cardiovascular instability. Patients with three or more organ failures face a mortality rate of more than 90%. Many cannot survive liver transplantation. Extracorporeal support systems like MARS (Baxter, Deerfield, IL) and Prometheus (Bad Homburg, Germany) have shown promise but fall short in bridging patients to transplantation. A novel Artificial Multi-organ Replacement System (AMOR) was developed at the University of Washington Medical Center. AMOR removes protein-bound toxins through a combination of albumin dialysis, a charcoal sorbent column, and a novel rinsing method to prevent sorbent column saturation. It removes excess fluid through hemodialysis. Ten AOCLF patients with over three organ failures were treated by the AMOR system. All patients showed significant clinical improvement. Fifty percent of the cohort received liver transplants or recovered liver function. AMOR was successful in removing large amounts of excess body fluid, which regular hemodialysis could not. AMOR is cost-effective and user-friendly. It removes excess fluid, supporting the other vital organs such as liver, kidneys, lungs, and heart. This pilot study’s results encourage further exploration of AMOR for treating MOF patients.
Handheld Ultrasound Devices for Peripheral Intravenous Cannulation
Authors: Ray-Barruel Gillian , Pather Priscilla , Schults Jessica A. , Rickard Claire M.
Published: February 2024

Ultrasound-guided insertion of peripheral intravenous catheters (PIVCs) is recommended for patients with difficult intravenous access, but access to ultrasound equipment is often limited to specialty departments. Compact, affordable handheld ultrasound devices are available, but the extent of their clinical adoption and impact on patient outcomes is unknown. This scoping review aimed to explore evidence regarding handheld and pocket ultrasound devices for PIVC insertion. Databases were searched for studies published in English between January 2000 and January 2023 evaluating handheld or pocket ultrasound devices weighing ≤3 kg for PIVC insertion. Data were extracted using standardized forms and summarized using descriptive statistics. Seventeen studies reporting the use of handheld or pocket ultrasound devices were identified. Most studies were conducted in adult inpatient facilities; 3 included pediatrics, and 2 reported out-of-hospital use. Participants with difficult intravenous access featured in 9 studies. Ultrasound training programs were described in 12 studies, with competency defined by number of successful PIVC insertions. Five studies reported clinician and/or patient perspectives. Ultrasound for PIVC insertion is not widely accessible in nonspecialist areas, but more compact and affordable handheld models could provide a solution, especially for patients with difficult access. More research evidence using handheld ultrasound is needed.
Explaining racial and ethnic disparities in antiretroviral therapy adherence and viral suppression among U.S. men who have sex with men
Authors: Patel Deesha , Beer Linda , Yuan Xin , Tie Yunfeng , Baugher Amy R. , Jeffries William L. , Dailey Andre , Henny Kirk D. ,   for the Medical Monitoring Project
Published: February 2024

Objective:

To identify factors – including social determinants of health (SDOH) – that explain racial/ethnic disparities in antiretroviral therapy (ART) adherence and sustained viral suppression (SVS) among U.S. men who have sex with men (MSM) with HIV.

Design:

We used weighted data from 2017–2021 cycles of the Medical Monitoring Project.

Methods:

Among MSM taking ART, we calculated prevalence differences (PDs) with 95% confidence intervals (CIs) of ART adherence (100% ART adherence, past 30 days) and SVS (all viral loads in past 12 months <200 copies/ml or undetectable) for Black MSM (BMSM) and Hispanic/Latino MSM (HMSM) compared with White MSM (WMSM). Using forward stepwise selection, we calculated adjusted PDs with 95% CIs to examine if controlling for selected variables reduced PDs.

Results:

After adjusting for age, any unmet service need, federal poverty level (FPL), food insecurity, homelessness, time since HIV diagnosis, gap in health coverage, and education, the BMSM/WMSM PD for ART adherence reduced from −16.9 to −8.2 (51.5%). For SVS, the BMSM/WMSM PD reduced from −8.3 to −3.6 (56.6%) after adjusting for ART adherence, age, homelessness, food insecurity, gap in health coverage, FPL, any unmet service need, time since diagnosis, and ER visit(s). The HMSM/WMSM PD for ART adherence reduced from −9.3 to −2.9 (68.8%) after adjusting for age and FPL. The unadjusted HMSM/WMSM PD for SVS was not statistically significant.

Conclusions:

Adjusting for SDOH and other factors greatly reduced racial/ethnic disparities in ART adherence and SVS. Addressing these factors − particularly among BMSM − could substantially improve health equity among MSM with HIV.
Diversity in Plastic Surgery and the 2023 US Supreme Court Decision
Authors: Swanson Eric
Published: February 2024

The number of publications on the topic of diversity, equity, and inclusion in plastic surgery has increased exponentially in the last 5 years. Numerous changes have been implemented. On June 29, 2023, the US Supreme Court ruled that affirmative action in college admissions is unconstitutional. Writing for the majority, Justice Roberts concluded that eliminating racial discrimination means eliminating all of it, and the Equal Protection Clause applies without regard to any differences of race, of color, or of nationality. Justice Thomas authored a concurrence, stating that such policies are contrary to our colorblind constitution and our nation's equality ideal. Justice Sotomayor was joined by Justice Kagan and Justice Jackson in their dissenting opinion that ignoring race will not equalize a society that is racially unequal and that students of various racial backgrounds can offer different perspectives because of that identity. The reaction was largely partisan. Michelle Steel and Young Kim, Republican Asian American Congresswomen from California, lauded the decision, along with Republican Senator Tim Scott from South Carolina. Senate Majority Leader Democrat Chuck Schumer opined that the Supreme Court decision has put a “giant roadblock in our country's march toward racial justice.” Cory Booker, New Jersey Democrat, called the decision a devastating blow. President Joe Biden and former First Lady Michelle Obama also disagreed with the decision. Profound ramifications across our institutions of higher learning and in medical specialties are likely to follow. Legally, it will be difficult or impossible to defend race-based preferences going forward. This is true regardless of whether such policies were put in place with the best of intentions.
Efficiency and novelty of using environmental swabs for dry-surface biofilm recovery
Authors: Watson Fergus , Wilks Sandra , Chewins John , Keevil Bill
Published: February 2024

Studies on the epidemiology of dry-surface biofilms (DSBs) within healthcare settings have shown an almost universal distribution across frequently touched items. Despite a growing body of evidence for DSBs in hospitals, little attention has been paid to the recovery capacity of techniques used to detect these microbial communities. Biofilms are inherently difficult to remove from surfaces due to adhesive substances within their matrix and may act as sources of infection, but to what extent is largely unknown. In this study, we evaluate the recovery efficiencies of commonly used environmental swabs against DSBs containing 7.24 log10
Acinetobacter baumannii cm−2, using a drip flow reactor and desiccation cycle. Biofilm presence was visually confirmed using episcopic differential interference contrast microscopy combined with epifluorescence and quantified using sonicated viable plate counts. The swab materials used comprised foam, viscose and cotton, all of which were pre-moistened using a buffer solution. The surfaces were vigorously swabbed by each material type and the resultant microbe populations for both swabs and remaining DSBs were quantified. Our results found foam-tipped swabs to be superior, detecting on average 30 % of the original DSB contamination; followed by viscose (6 %) and cotton (3 %). However, no distinct difference was revealed in the concentration of microbes remaining on the surface after swabbing for each swab type, suggesting there is variation in the capacity for each swab to release biofilm-associated micro-organisms. We conclude whilst environmental swabs do possess the ability to detect biofilms on dry surfaces, the reduced efficiencies are likely to cause an underestimation of the microbes present and should be considered during clinical application.
On the limits of 16S rRNA gene-based metagenome prediction and functional profiling
Authors: Matchado Monica Steffi , Rühlemann Malte , Reitmeier Sandra , Kacprowski Tim , Frost Fabian , Haller Dirk , Baumbach Jan , List Markus
Published: February 2024

Molecular profiling techniques such as metagenomics, metatranscriptomics or metabolomics offer important insights into the functional diversity of the microbiome. In contrast, 16S rRNA gene sequencing, a widespread and cost-effective technique to measure microbial diversity, only allows for indirect estimation of microbial function. To mitigate this, tools such as PICRUSt2, Tax4Fun2, PanFP and MetGEM infer functional profiles from 16S rRNA gene sequencing data using different algorithms. Prior studies have cast doubts on the quality of these predictions, motivating us to systematically evaluate these tools using matched 16S rRNA gene sequencing, metagenomic datasets, and simulated data. Our contribution is threefold: (i) using simulated data, we investigate if technical biases could explain the discordance between inferred and expected results; (ii) considering human cohorts for type two diabetes, colorectal cancer and obesity, we test if health-related differential abundance measures of functional categories are concordant between 16S rRNA gene-inferred and metagenome-derived profiles and; (iii) since 16S rRNA gene copy number is an important confounder in functional profiles inference, we investigate if a customised copy number normalisation with the rrnDB database could improve the results. Our results show that 16S rRNA gene-based functional inference tools generally do not have the necessary sensitivity to delineate health-related functional changes in the microbiome and should thus be used with care. Furthermore, we outline important differences in the individual tools tested and offer recommendations for tool selection.
Rapidin situmutation detection in extracellular vesicle-DNA
Authors: Rahman Md. Mofizur , Wang Lixue , Rahman Md. Motiar , Chen Yundi , Zhang Wenlong , Wang Jing , Lee Luke P. , Wan Yuan
Published: February 2024

A PCR- and sequencing-free mutation detection assay facilitates cancer diagnosis and reduces over-reliance on specialized equipment. This benefit was highlighted during the pandemic when high demand for viral nucleic acid testing often sidelined mutation analysis. This shift led to substantial challenges for patients on targeted therapy in tracking mutations. Here, we report a 30-minute DNA mutation detection technique using Cas12a-loaded liposomes in a microplate reader, a fundamental laboratory tool. CRISPR-Cas12a complex and fluorescence-quenching (FQ) probes are introduced into tumor-derived extracellular vesicles (EV) through membrane fusion. When CRISPR-RNA hybridizes with the DNA target, activated Cas12a cantrans-cleave FQ probes, resulting in fluorescence signals for the quantification of DNA mutation. Future advancements in multiplex and high-throughput mutation detection using this assay will streamline self-diagnosis and treatment monitoring at home.
Identification of robust cellular programs using reproducible LDA that impact sex-specific disease progression in different genotypes of a mouse model of AD
Authors: Rezaie Narges , Rebboah Elisabeth , Williams Brian A. , Liang Heidi Yahan , Reese Fairlie , Balderrama-Gutierrez Gabriela , Dionne Louise A. , Reinholdt Laura , Trout Diane , Wold Barbara J. , Mortazavi Ali
Published: February 2024

The gene expression profiles of distinct cell types reflect complex genomic interactions among multiple simultaneous biological processes within each cell that can be altered by disease progression as well as genetic background. The identification of these active cellular programs is an open challenge in the analysis of single-cell RNA-seq data. Latent Dirichlet Allocation (LDA) is a generative method used to identify recurring patterns in counts data, commonly referred to as topics that can be used to interpret the state of each cell. However, LDA’s interpretability is hindered by several key factors including the hyperparameter selection of the number of topics as well as the variability in topic definitions due to random initialization. We developed Topyfic, a Reproducible LDA (rLDA) package, to accurately infer the identity and activity of cellular programs in single-cell data, providing insights into the relative contributions of each program in individual cells. We apply Topyfic to brain single-cell and single-nucleus datasets of two 5xFAD mouse models of Alzheimer’s disease crossed with C57BL6/J or CAST/EiJ mice to identify distinct cell types and states in different cell types such as microglia. We find that 8-month 5xFAD/Cast F1 males show higher level of microglial activation than matching 5xFAD/BL6 F1 males, whereas female mice show similar levels of microglial activation. We show that regulatory genes such as TFs, microRNA host genes, and chromatin regulatory genes alone capture cell types and cell states. Our study highlights how topic modeling with a limited vocabulary of regulatory genes can identify gene expression programs in singlecell data in order to quantify similar and divergent cell states in distinct genotypes.
COVID-19 vaccine uptake and associated risk factors among first antenatal care attendees in Zambia, 2021-2022: a repeated cross-sectional study
Authors: Tembo Tannia , Somwe Paul , Bosomprah Samuel , Kalenga Kalubi , Moyo Nyembezi , Kabamba Bupe , Seffren Victoria , Fwoloshi Sombo , Rutagwera Marie-Reine , Musunse Maximillian , Mwiinga Linos , Gutman Julie R. , Hines Jonas Z. , Sikazwe Izukanji
Published: February 2024

Introduction

Pregnant women are considered a high-risk group for COVID-19, and a priority for vaccination. Routine antenatal (ANC) care provides an opportunity to track trends and factors associated with vaccine uptake. We sought to evaluate COVID-19 vaccine uptake among pregnant women attending ANC in Zambia.

Methods

We conducted a repeated cross-sectional study in 39 public health facilities in four districts in Zambia from September 2021 to September 2022. Pregnant women who were aged 15-49 years were enrolled during their first ANC visit. Every month, ∼20 women per facility were interviewed during individual HIV testing and counseling. We estimated vaccine uptake as the proportion of eligible participants who self-reported having received the COVID-19 vaccine.

Results

A total of 9,203 pregnant women were screened, of which 9,111 (99%) were eligible and had vaccination status. Of the 9,111 included in the analysis, 1,818 (20%) had received the COVID-19 vaccine during the study period, with a trend of increasing coverage with time (0.5% in September 2020, 27% in September 2022). Conversely, 3,789 (42%) reported not being offered a COVID-19 vaccine. We found that older age, education, employment status, and prior COVID-19 infection were significantly associated with vaccine uptake.

Conclusion

COVID-19 vaccine uptake among pregnant women was lower than estimates from the general population (27% across the four districts in September 2022), pointing to missed opportunities to protect this high-risk group. ANC visits were a viable point for conducting COVID-19 surveillance. Incorporating the vaccine as part of the routine ANC package might increase coverage in this group.

Teaser key message

Antenatal care clinics could be an easy and sustainable platform for increasing COVID-19 vaccine uptake among pregnant women.

Key Findings

Despite evidence that COVID-19 vaccines are safe in pregnancy, vaccine uptake was low among pregnant women in Zambia through the end of 2022.

Various demographic characteristics were associated with the uptake of COVID-19 vaccines.

Key Implications

It is acceptable and feasible to assess COVID-19 vaccination uptake and hesitancy among pregnant women attending ANC. ANC may provide an easy, sustainable platform for routinely monitoring COVID-19 and other disease outbreaks.

Key vaccination messages and mass vaccination strategies can be designed and adopted for pregnant women to reduce vaccine hesitancy and consequently, increase vaccine uptake.

COVID-19 vaccination could be incorporated into routine antenatal care to help increase vaccination coverage among pregnant women seeking antenatal care services.