bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterodimerization domains in MAP4 KINASEs determine subcellular localization and activity in Arabidopsis
Authors: Pan Lixia , Fonseca de Lima Cassio Flavio , Vu Lam Dai , van de Cotte Brigitte , De Winne Nancy , Gevaert Kris , De Jaeger Geert , De Smet Ive
Published: March 2024

Signal transduction relies largely on the activity of kinases and phosphatases that control protein phosphorylation. However, we still know very little about phosphorylation-mediated signaling networks. Plant MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE KINASEs (MAP4Ks) have recently gained more attention, given their role in a wide range of processes, including developmental processes and stress signaling. We analyzed MAP4K expression patterns and mapped protein–MAP4K interactions in Arabidopsis (Arabidopsis thaliana), revealing extensive coexpression and heterodimerization. This heterodimerization is regulated by the C-terminal, intrinsically disordered half of the MAP4K, and specifically by the coiled coil motif. The ability to heterodimerize is required for proper activity and localization of the MAP4Ks. Taken together, our results identify MAP4K-interacting proteins and emphasize the functional importance of MAP4K heterodimerization. Furthermore, we identified MAP4K4/TARGET OF TEMPERATURE3 (TOT3) and MAP4K5/TOT3-INTERACTING PROTEIN 5 (TOI5) as key regulators of the transition from cell division to elongation zones in the primary root tip.
Exploring the role of uncertainty, emotions, and scientific discourse during the COVID-19 pandemic
Authors: Lemor Antoine , Montpetit Éric
Published: March 2024

This article examines the interplay between uncertainty, emotions, and scientific discourse in shaping COVID-19 policies in Quebec, Canada. Through the application of natural language processing (NLP) techniques, indices were developped to measure sentiments of uncertainty among policymakers, their negative sentiments, and the prevalence of scientific statements. The study reveals that while sentiments of uncertainty led to the adoption of stringent policies, scientific statements and the evidence they conveyed were associated with a relaxation of such policies, as they offered reassurance and mitigated negative sentiments. Furthermore, the findings suggest that scientific statements encouraged stricter policies only in contexts of high uncertainty. This research contributes to the theoretical understanding of the interplay between emotional and cognitive dynamics in health crisis policymaking. It emphasizes the need for a nuanced understanding of how science may be used in the face of uncertainty, especially when democratic processes are set aside. Methodologically, it demonstrates the potential of NLP in policy analysis.
Neuropsychiatric symptoms in systemic lupus erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project
Authors: Sloan Melanie , Pollak Thomas A , Massou Efthalia , Leschziner Guy , Andreoli Laura , Harwood Rupert , Bosley Michael , Pitkanen Mervi , Diment Wendy , Bortoluzzi Alessandra , Zandi Michael S , Ubhi Mandeep , Gordon Caroline , Jayne David , Naughton Felix , Barrere Colette , Wincup Chris , Brimicombe James , Bourgeois James A , D’Cruz David
Published: March 2024

Objective

Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge and symptom under-reporting contribute to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures.

Methods

Quantitative and qualitative data analysed included: the prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore the attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system.

Results

We recruited 2817 participants, including 400 clinicians. SLE patients (n = 609) reported significantly higher prevalences of neuropsychiatric symptoms than controls (n = 463) and IA patients (n = 489). SLE and IA patients’ quantitative data demonstrated multiple neuropsychiatric symptoms relapsing/remitting with other disease symptoms such as joint pain. Over 45% of SLE patients reported resolution/improvement of fatigue, positive sensory symptoms, severe headache, and cognitive dysfunction with corticosteroids. Evidence of direct attributability in SLE was highest for hallucinations and severe headache. SLE patients had greater reported improvement from corticosteroids (p= 0.008), and greater relapsing-remitting with disease activity (P < 0.001) in the comparisons with IA patients for severe headache. Clinicians and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritized for discussion and treatment.

Conclusion

We found evidence indicating varying levels of direct attributability of both common and previously unexplored neuropsychiatric symptoms in SLE patients, with hallucinations and severe headache assessed as the most directly attributable. There may also be—currently under-estimated—direct effects on the nervous system in IA and other systemic rheumatological diseases.
Clinical decision support tools useful for identifying sepsis risk
Authors: Heineman Theresa , Orrick Cary , Phan Teresa K. , Denke Linda , Atem Folefac , Draganic Keri
Published: March 2024

Purpose:

Evaluate the effectiveness of the clinical decision support tools (CDSTs), POC Advisor (POCA), and Modified Early Warning System (MEWS) in identifying sepsis risk and influencing time to treatment for inpatients, comparing their respective alert mechanisms.

Methods:

This study was conducted at two academic university medical center hospitals. Data from adult inpatients in medical-surgical and telemetry units were analyzed from January 1, 2020, to December 31, 2020. Criteria included sepsis-related ICD-10 codes, antibiotic administration, and ordered sepsis labs. Subsequent statistical analyses utilized Fisher's exact test and Wilcoxon Rank Sum test, focusing on mortality differences by age, sex, and race/ethnicity.

Results:

Among 744 patients, 143 sepsis events were identified, with 83% already receiving treatment upon CDST alert. Group 1 (POCA alert) showed reduced response time compared with MEWS, while Group 3 (MEWS) experienced longer time to treatment. Group 4 included sepsis events missed by both systems. Mortality differences were not significant among the groups.

Conclusion:

While CDSTs play a role, nursing assessment and clinical judgment are crucial. This study recognized the potential for alarm fatigue due to a high number of CDST-driven alerts, while emphasizing the importance of a collaborative approach for prompt sepsis treatment and potential reduction in sepsis-related mortality.
How Individuals Shape Their Acoustic Environment: Implications for Hearing Aid Comparison in Ecological Momentary Assessment
Authors: Borschke Iris , Jürgens Tim , Schinkel-Bielefeld Nadja
Published: March 2024

Objectives:

When using ecological momentary assessment (EMA) to compare different hearing aid programs, it is usually assumed that for sufficiently long study durations similar situations will be experienced in both programs. However, conscious or subconscious adaptation of situations to one’s hearing ability (e.g., asking a conversation partner to speak up, increasing TV volume)—which might be different across the time spent in different hearing aid programs—may challenge this assumption. In the present study, we investigated how test participants modify their acoustic environment and if these modifications depend on the hearing program.

Design:

Twenty-nine experienced hearing aid users were provided with hearing aids containing two hearing programs differing in directionality and noise reduction (NR). The hearing programs called NR-on and NR-off changed each day automatically. Over the course of 3 weeks, participants were asked to answer a questionnaire every time they encountered an acoustic situation they modified or would have liked to modify to improve the listening situation. Objective data on sound pressure level and classification of the acoustic situation were collected from the hearing aids. At the beginning of the study participants recollected modifications of the acoustic environments they typically do when using their own hearing aids and reported on the frequency of this behavior.

Results:

During the field trial, participants reported on average 2.3 situations per day that they modified or would have liked to modify. Modifications were usually performed quickly after the onset of the situation and significantly improved the pleasantness of the listening situation. While the number of the reported situations did not differ between the programs, modifications increasing the volume of the target signal and increasing the hearing aid volume were more frequent for the NR-on hearing program. Changes in the objective data at the time of the modification were consistent with the reported modifications. Further, the usage time as well as the distribution of the acoustic situations over the entire study period differed between the two hearing programs.

Conclusions:

The large improvement in pleasantness due to the modification might explain the generally positive ratings observed in EMA studies. Furthermore, the results found here suggest that caution is needed when comparing ratings of audiological attributes in EMA, because the different modification behavior across hearing programs may lead to an underestimation of hearing problems and reduced sensitivity when comparing two technologies.
Describing calcium pyrophosphate deposition: undoing the tower of Babel!
Authors: Sirotti Silvia , Terkeltaub Robert , Filippou Georgios
Published: March 2024

Purpose of review

In 1977, McCarty astutely observed, ‘The variety of names suggested for the condition associated with deposits of calcium pyrophosphate dihydrate crystals is exceeded only by the variations of its clinical presentation’. Fast forward to 2024, a standardized nomenclature for calcium pyrophosphate deposition (CPPD) is still lacking. This review aims to delineate the challenges in characterizing CPPD through nomenclature and imaging.

Recent findings

Despite the effort of nomenclature standardization in 2011 by the EULAR, confusion persists in the literature and clinical practice, with pseudo-forms and obscure abbreviations. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) has launched a project to redefine CPPD nomenclature and formulate a user-friendly language for effective communication with patients and other stakeholders. Additionally, recent advancements in imaging, have shed light on various aspects of the disorder.

Almost 60 years from the first description of a clinical manifestation related to calcium pyrophosphate crystals, a common language describing the disorder is still lacking. A redefined CPPD nomenclature, together with lay-friendly terminology, would significantly contribute to the uniformity of CPPD research, enhance public understanding and awareness and improve doctor-patient communication and therefore disease outcomes. Imaging can provide deep insights into CPPD elements, promoting comprehension of this disorder.
Sodium-glucose cotransporter 2 inhibitors: are they ready for prime time in the management of lupus nephritis?
Authors: Wagner Benjamin R. , Rao Panduranga S.
Published: March 2024

Purpose of review

Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis.

Recent findings

SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria. Patients with recent exposure to immunosuppression were excluded from these trials due to concern for risk of infection. In the few, small trials of patients with lupus nephritis, SGLT2 inhibitors were found to be well tolerated. They have been shown to reduce proteinuria and to have modest beneficial effects on blood pressure and BMI among patients with lupus nephritis. They have not been shown to influence disease activity.

SGLT2 inhibitors may have a role in mitigating the chronic renal and cardiovascular effects of lupus nephritis. They should be introduced after kidney function has been stabilized with appropriate immunosuppression, in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. They currently have no role in active disease.
A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy
Authors: Lakshmipathy Damini , Ye Xiaoyi , Kuti Joseph L. , Nicolau David P. , Asempa Tomefa E.
Published: March 2024

OBJECTIVES:

In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (Q
E). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, Q
E intrapatient variability and residual renal function.

DESIGN:

Retrospective observational cohort study.

SETTING:

ICUs within Hartford Hospital (890-bed, acute-care hospital) in Connecticut from 2017 to 2023.

PATIENTS:

Adult ICU patients receiving CRRT for greater than 72 hours.

MEASUREMENTS AND MAIN RESULTS:

CRRT settings including Q
E and urine output (UOP) were extracted from the time of CRRT initiation (0 hr) and trends were assessed. To assess the impact on antibiotic dosing, cefiderocol doses were assigned to 0 hour, 24 hours, 48 hours, and 72 hours Q
E values per product label, and the proportion of antibiotic dose changes required as a result of changes in inpatient’s Q
E was evaluated. Among the 380 ICU patients receiving CRRT for greater than 72 hours, the median (interquartile range) 0 hour Q
E was 2.96 (2.35–3.29) L/hr. Approximately 9 Q
E values were documented per patient per 24-hour window. Q
E changes of greater than 0.75 L/hr were observed in 21.6% of patients over the first 24 hours and in 7.9% (24–48 hr) and 5.8% (48–72 hr) of patients. Approximately 40% of patients had UOP greater than 500 mL at 24 hours post-CRRT initiation. Due to Q
E changes within 24 hours of CRRT initiation, a potential cefiderocol dose adjustment would have been warranted in 38% of patients (increase of 21.3%; decrease of 16.6%). Q
E changes were less common after 24 hours, warranting cefiderocol dose adjustments in less than 15% of patients.

CONCLUSIONS:

Results highlight the temporal and variable dynamics of Q
E and prevalence of residual renal function. Data also demonstrate a risk of antibiotic under-dosing in the first 24 hours of CRRT initiation due to increases in Q
E. For antibiotics with Q
E-based dosing recommendations, empiric dose escalation may be warranted in the first 24 hours of CRRT initiation.
Using Computed-Tomgraphy-Based Pelvimetry and Visceral Obesity Measurements to Predict Total Mesorectal Excision Quality for Patients Undergoing Rectal Cancer Surgery
Authors: Bolshinsky Vladimir , Sweet David , Vitello Dominic , Jia Xue , Holubar Stefan , Church James , Herts Brian R. , Steele Scott R.
Published: March 2024

BACKGROUND:

A complete total mesorectal excision is the gold standard in curative rectal cancer surgery. Ensuring quality is challenging in a narrow pelvis, and obesity amplifies technical difficulties. Pelvimetry is the measurement of pelvic dimensions, but its role in gauging preoperatively difficulty of proctectomy is largely unexplored.

OBJECTIVE:

To determine pelvic structural factors associated with incomplete total mesorectal excision following curative proctectomy and build a predictive model for total mesorectal excision quality.

DESIGN:

Retrospective cohort study.

SETTING:

A quaternary referral center database of patients diagnosed with rectal adenocarcinoma (2009-2017).

PATIENTS:

Curative-intent proctectomy for rectal adenocarcinoma.

INTERVENTIONS:

All radiological measurements were obtained from preoperative CT-images using validated imaging processing software tools. Completeness of total mesorectal excision was obtained from histology reports.

MAIN OUTCOME MEASURES:

Ability of radiological pelvimetry and obesity measurements to predict total mesorectal excision quality.

RESULTS:

Of the 410 cases meeting inclusion criteria, 362 had a complete total mesorectal excision (88%). A multivariable regression identified a deeper sacral curve (per 100 mm2 [OR: 1.14, 95% CI: 1.06-1.23, p < 0.001]), and greater transverse distance of pelvic outlet (per 10 mm [OR:1.41, 95% CI: 1.08-1.84, p = 0.012]) as independently associated with incomplete total mesorectal excision. An increased area of pelvic inlet (per 10 cm2); OR: 0.85, [95% CI: 0.75-0.97, p = 0.02] was associated with a higher rate of complete mesorectal excision. No difference in visceral obesity ratio and visceral obesity (ratio >0.4 vs.<0.4) between body mass index (<30 vs. ≥30) or sex was identified. A model was built to predict mesorectal quality using variables: depth of sacral curve, area of pelvic inlet and transverse distance of pelvic outlet.

LIMITATIONS:

Retrospective analysis not controlled for choice of surgical approach.

CONCLUSIONS:

Pelvimetry is predictive of total mesorectal excision quality in rectal cancer surgery and can alert surgeons preoperatively to cases of unusual difficulty. This predictive model may contribute to treatment strategy and aid in comparison of outcomes between traditional and novel techniques of total mesorectal excision. See Video Abstract
The Effect of Preoperative Chlorhexidine Gluconate Cleanse on Lower Extremity Surgical Site Infections: A Retrospective Cohort Study
Authors: Dempsey Michael P. , Riopelle Alexandria M. , West Margaret , Kumar Aaditya , Schanbacher Carl F.
Published: March 2024

BACKGROUND

Lower extremity surgical sites are at an increased risk of wound infection following Mohs micrographic surgery.

OBJECTIVE

To evaluate the rate of lower extremity surgical site infections following a 14-day regimen of preoperative 4% chlorhexidine gluconate (CHG) rinses and postoperative wound occlusion for 14 days.

MATERIALS AND METHODS

Retrospective data were collected from procedures performed by the senior author from January 2022 through June 2023. To meet inclusion, patients must have completed waist-down CHG soak and rinse for 14 days before surgery, including the day before surgery. In addition, the patient must have kept the dressing clean, dry, and intact until the postoperative appointment at 14 days.

RESULTS

A total of 100 Mohs cases met inclusion criteria. Zero patients developed a surgical site infection.

CONCLUSION

Chlorhexidine gluconate preoperative rinsing and postoperative occlusion for 14 days may minimize the risk of wound infection. Although further research is indicated, an opportunity exists for the adoption of CHG into routine clinical practice in the outpatient dermatology setting.
Autofluorescence Excitation Imaging of Nonmelanoma Skin Cancer for Margin Assessment Before Mohs Micrographic Surgery: A Pilot Study
Authors: Ortiz Arisa E. , Ahluwalia Jusleen , Anderson R. Rox , Franco Walfre , Brian Jiang Shang I.
Published: March 2024

BACKGROUND

Autofluorescence photography can detect specific light–tissue interactions and record important pathophysiological changes associated with nonmelanoma skin cancer (NMSC), which has been ascribed to the fluorescence of an aromatic amino acid, tryptophan.

OBJECTIVE

To assess the impact of a novel, autofluorescence imaging (AFI) device on margin control for NMSCs before Mohs micrographic surgery (MMS) in an effort to decrease overall operating time.

METHODS

Before the initial stage of MMS, NMSCs were measured with a 2-mm margin as standard of care (normal margin). The tumor was then imaged with the AFI device. A 2-mm margin was drawn around the fluorescent area captured by the AFI device and was referred to as the camera margin. The tumor was excised based on the normal margin and evaluated on frozen histological section.

RESULTS

Imaging based on the AFI device resulted in appropriate recommendations for margin control in 8 of 11 tumors. Four of these tumors did not fluoresce and demonstrated a lack of tumor residuum on stage I specimen, as anticipated. There were no side effects from the AFI device.

CONCLUSION

This is an initial pilot study that supports the use of a novel, noninvasive imaging device to help with margin assessment before MMS. On optimization, this device has potential to extend applicability to surgical excisions for tumors that do not fulfill criteria for MMS.
Effect of CYP2D6 genetic variation on patient-reported symptom improvement and side effects among children and adolescents treated with amphetamines
Authors: Gerlach Samuel , Maruf Abdullah Al , Shaheen Sarker M. , McCloud Ryden , Heintz Madison , McAusland Laina , Arnold Paul D. , Bousman Chad A.
Published: March 2024

Objectives

Amphetamine-based medications are recommended as a first-line pharmacotherapy for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. However, the efficacy and tolerability of these medications vary across individuals, which could be related to interindividual differences in amphetamine metabolism. This study examined if genotype-predicted phenotypes of the cytochrome P450 isozyme CYP2D6 were associated with self-reported side effects and symptom improvement in youth treated with amphetamines.

Methods

Two hundred fourteen participants aged 6–24 who had a history of past or current amphetamine treatment were enrolled from Western Canada. Amphetamine dose and duration information was collected from the participants along with questions regarding adherence, concomitant medications, symptom improvement and side effects. DNA was extracted from saliva samples and genotyped for CYP2D6. Binomial logistic regression models were used to determine the effect of CYP2D6 metabolizer phenotype with and without correction for phenoconversion on self-reported symptom improvement and side effects.

Results

Genotype-predicted CYP2D6 poor metabolizers had significantly higher odds of reporting symptom improvement when compared to intermediate metabolizers (OR = 3.67, 95% CI = 1.15–11.7, P = 0.029) after correction for phenoconversion and adjusting for sex, age, dose, duration, and adherence. There was no association between CYP2D6 metabolizer phenotype and self-reported side effects.

Conclusion

Our findings indicate that phenoconverted and genotype-predicted CYP2D6 poor metabolizer phenotype is significantly associated with higher odds of symptom improvement in children and adolescents treated with amphetamine. If replicated, these results could inform the development of future dosing guidelines for amphetamine treatment in children and adolescents.
Picosecond Nd:YAG versus Fractional CO2 Lasers in Management of Postburn Scars
Authors: Tawfik Abeer Attia , Hanafy Noha Sami , Ali Rama Ahmed
Published: March 2024

Background:

The picosecond laser was primarily designed to enhance tattoo removal. Because it has a new innovative mechanism for energy delivery, it has been modified to be used in other conditions such as skin resurfacing, which was usually treated with fractional CO2 laser. Comparing both technologies in managing postburn scars has not been widely addressed.

Methods:

The current prospective comparative randomized intrapatient study was done on 15 patients who presented with unsightly postburn scarring. As a split study, one-half of the affected areas were treated using the picosecond Nd: YAG laser. The other areas were treated with a fractional CO2 laser. After three treatment sessions, the results were analyzed both objectively and subjectively.

Results:

The assessment by the image analysis system (Antera camera) showed improvement in all the parameters in both groups. The melanin relative variation decreased from 11.65 ± 2.86, 15.85 ± 5.63 to 10.60 ± 1.96, 12.56 ± 3.98, respectively in picosecond laser sites and fractional CO2 sites. The percentage change in overall opinion decreased in in favor of the fractional CO2 laser sites, which is a statistically significant improvement. Instead, color scores revealed a greater reduction in the picosecond sites in comparison with the fractional CO2 sites, as it decreased from 7.67 ± 1.76, 7.73 ± 1.83 to 2.87 ± 1.06, 6 ± 1.2, respectively.

Conclusions:

When compared with fractional CO2 lasers, picosecond Nd:YAG shows comparable improvements in scars’ erythema, texture, and height, with some superiority in the management of hyperpigmented scars.
Evaluating Reception Center Models for Radiation Response Screening Capacity and Throughput Predictions
Authors: Finklea Lauren , Goff Robert , Houghton Erica
Published: March 2024

Introduction: The current fleet of nuclear reactors in the United States is mandated to provide evidence that surrounding jurisdictions can screen their populations should an incident occur. Capacity can be measured as throughput in reception centers used for screening. Due to the significant staffing and resources required to exercise screening capacity, most jurisdictions typically perform smaller exercises and use models to estimate their overall throughput. Objective: To evaluate the applicability and realism of current throughput models and practices. Methods: Throughput capacity for radiation screening is estimated with a mathematical model derived by the Federal Emergency Management Agency (FEMA). The Centers for Disease Control and Prevention developed a discrete event simulation model as a tool, SimPLER, to evaluate capacity and make throughput predictions. Model estimates will be compared and evaluated using timing data collected at a large-scale exercise. Results: The FEMA model estimated a throughput 41.2% higher than the actual radiation screening throughput, while the SimPLER model provided identical values. The FEMA and SimPLER models’ predicted throughputs were 50% and 3.8%, respectively, higher than total exercise throughput. Applying each model to the throughput projections for a 12-hour shift, the FEMA model estimates ranged from 665 to 6,646 people and the SimPLER model yielded an estimated throughput of 1,809 people with a standard deviation of 74.6. Conclusion: Discrete event simulation models, such as SimPLER, may provide more realistic and accurate predictions of radiation screening and throughput capacity of reception centers than mathematical models such as the FEMA model.
Clinicopathologic Overlap of Vulvar Psoriasis and Candidiasis
Authors: Day Tania , Chapman-Burgess Erika , Scurry James
Published: March 2024

Objectives

The study’s aim is to assess if vulvar psoriasis and candidiasis may be distinguished by clinical presentation and histopathologic appearance.

Methods

The pathology database identified biopsies with corneal or subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate. Exclusions were age younger than 18 years and unavailable or uninterpretable slides. Clinical data included demographics, comorbid conditions, symptoms, examination, microbiology, treatment, and response. Histopathologic review documented site, thickness, and characteristics of stratum corneum and epidermis, distribution of neutrophils, and infiltrate. Cases were stratified by microbiologic presence or absence of Candida albicans.

Results

Biopsies from 62 women with median age of 60 years were associated with C. albicans on vulvovaginal culture in 28 (45%), whereas 26 (42%) were negative, and 8 (13%) lacked microbiologic assessment. Swab-positive women were more likely to have diabetes, receive prereferral estrogen, and report vulvar pain. Specialist clinical impression was candidiasis in 33 (53%), psoriasis in 11 (18%), comorbid candidiasis and psoriasis in 7 (11%), dermatitis in 10 (16%), and unknown in 2 (3%). Visible fungal organisms occurred in 16 (26%) cases and were associated with diabetes and satellite lesions. Other than presence of organisms, there were no histopathologic differences stratified by microbiologic result.

Conclusions

The histopathologic triad of corneal/subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate is common to vulvar psoriasis and candidiasis, and clinical features do not reliably distinguish between them. Microbiologic assessment and single-agent treatment are useful strategies to clarify the diagnosis.
Psychedelic Therapy: A Primer for Primary Care Clinicians—Historical Perspective and Overview
Authors: Tabaac Burton J. , Shinozuka Kenneth , Arenas Alejandro , Beutler Bryce D. , Cherian Kirsten , Evans Viviana D. , Fasano Chelsey , Muir Owen S.
Published: March 2024

Background:

Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide.

Areas of Uncertainty:

Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far.

Therapeutic Advances:

Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine.

Limitations:

While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%–29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial.

Conclusions:

Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.
Cost-effectiveness Analysis of Single-Use Duodenoscope Applied to Endoscopic Retrograde Cholangiopancreatography
Authors: Nicolás-Pérez David , Gimeno-García Antonio Zebenzuy , Romero-García Rafael Joaquín , Castilla-Rodríguez Iván , Hernandez-Guerra Manuel
Published: March 2024

Objectives

Secondary infections due to transmission via the duodenoscope have been reported in up to 3% of endoscopic retrograde cholangiopancreatographies. The use of single-use duodenoscopes has been suggested. We investigate the cost-effectiveness of these duodenoscopes use in cholangiopancreatography.

Materials and Methods

A cost-effectiveness analysis was implemented to compare the performance of cholangiopancreatographies with reusable duodenoscopes versus single-use duodenoscopes. Effectiveness was analyzed by calculating quality-adjusted life years (QALY) from the perspective of the National Health System. Possibility of crossover from single-use to reusable duodenoscopes was considered. A willingness-to-pay of €25,000/QALY was set, the incremental cost-effectiveness ratio (ICER) was calculated, and deterministic and probabilistic sensitivity analyses were performed.

Results

Considering cholangiopancreatographies with single-use and reusable duodenoscopes at a cost of €2900 and €1333, respectively, and a 10% rate of single-use duodenoscopes, ICER was greater than €3,000,000/QALY. A lower single-use duodenoscope cost of €1211 resulted in an ICER of €23,583/QALY. When the unit cost of the single-use duodenoscope was €1211, a crossover rate of more than 9.5% made the use of the single-use duodenoscope inefficient.

Conclusions

Single-use duodenoscopes are cost-effective in a proportion of cholangiopancreatographies if its cost is reduced. Increased crossover rate makes single-use duodenoscope use not cost-effective.
Pancreatic Cysts Greater Than 1 cm Are Associated With an Increased Risk for Developing Pancreatic Cancer in Individuals From Pancreatic-Cancer Prone Kindreds Undergoing Surveillance
Authors: Aijazi Muaz , Fasanella Kenneth E. , McGrath Kevin , Smith Lynette M. , Singhi Aatur D. , Brand Randall E.
Published: March 2024

Background

The International Cancer of the Pancreas Screening Consortium recommended annual imaging for individuals at increased risk for developing a pancreatic ductal adenocarcinoma (PDAC) who did not have concerning pancreatic findings or a cyst <3 cm without worrisome features. We aimed to determine if 3-cm cyst size accurately predicted advanced precursor lesions in high-risk individuals undergoing surveillance.

Methods

Imaging for high-risk individuals (HRIs) undergoing PDAC surveillance from 2007 to 2021 was reviewed and pancreatic abnormalities were recorded including dominant cyst size and number of cysts. Subjects were excluded if they had the following: (1) no follow-up imaging after baseline, (2) solid lesion at baseline, or (3) development of solid lesion without having cyst on prior imaging.

Results

Five of the 77 HRIs found to have a cystic lesion on surveillance developed a PDAC: 3 with cystic lesion >1 cm as compared with only 2 of 67 HRIs with cystic lesions <1 cm (P < 0.05). None of these cysts developed worrisome findings and 4/5 PDACs did not arise from visualized cystic precursor lesion.

Conclusions

Patients with a cyst ≥1 cm were at increased risk for developing PDAC compared with patients with cyst <1 cm. Pancreatic ductal adenocarcinoma usually did not arise from a recognized cystic lesion.
Effect of pain on activity and participation in individuals with unilateral lower-extremity amputation based on the International Classification of Functioning, Disability, and Health
Authors: Yerli Sibel , Erbahçeci Fatih , Kerem Günel Mintaze
Published: March 2024

Background:

Amputation is a major life-changing event and is regarded as one of the loading causes of permanent disability. However, amputation often causes changes in painful and nonpainful sensory experiences. Pain after amputation has been shown to increase functional limitations caused by limb loss and lower quality of life.

Objective:

This study aimed to examine the effect of pain on activity and participation in individuals with unilateral below-knee amputations according to the International Classification of Functioning, Disability, and Health.

Study Design:

Cross-sectional study.

Methods:

In the study, 64 individuals were divided into 2 groups: those who experienced pain and those who did not. Group 1 included 33 below-knee amputees who experienced pain (27 males, mean age 43.9 ± 12.6 years) and Group 2 included 31 below-knee amputees who did not experience pain (25 males, mean age 47.4 ± 12.1 years). The McGill Pain Questionnaire and visual analog scale were used to assess pain, the Prosthetic Limb Users Survey of Mobility was used to assess activity, and the Reintegration to Normal Living Index was used to assess participation.

Results:

Demographic characteristics of the 2 groups were statistically insignificant (P > 0.05). The nonpainful group had significantly higher activity and participation scores than the painful group (P < 0.001).

Conclusions:

It was found that phantom pain and stump pain in below-knee amputees limited activity and participation. It was also shown that phantom pain has a more negative effect on the activity level of individuals than stump pain.
A scoping review on upper extremity prostheses: Satisfaction, barriers, and their implications in resource-limited countries
Authors: Dizon Lorenzo Martin L. , Leochico Carl Froilan D. , Ramirez Reykjavik S. , Rey-Matias Reynaldo R.
Published: March 2024

The rates of prosthetic abandonment are not extensively understood especially in resource-limited countries. A scoping review was conducted to examine the literature on the satisfaction with and barriers to using specifically upper limb prostheses. A systematic search of the literature identified 425 studies. After reviewing the articles using predetermined inclusion and exclusion criteria, 7 cross-sectional studies were included in the final review. Barriers to the use of upper limb prostheses include the characteristics of the prosthesis (type, comfort, weight, functionality, price, and availability) and individual patient factors (recent prosthetic user, level of amputation, congenital and accidental limb loss, pain, and duration between amputation and prosthetic fitting). Considering tailored prosthetic design and funding may result in improved prosthetic adherence.
Derivation of a Mortality Prediction Model in Critical Care Patients with Cirrhosis and Sepsis
Authors: Piccolo Serafim Laura , Simonetto Douglas A. , Choi Dae Hee , Weister Timothy J. , Hanson Andrew C. , Kamath Patrick S. , Gajic Ognjen , Gallo de Moraes Alice
Published: March 2024

Objective

To develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data.

Design

Retrospective cohort study.

Setting

Medical and mixed ICUs of a tertiary medical center.

Patients

Cirrhotic adults admitted with sepsis to the ICUs from January of 2007 to May of 2017.

Interventions

None.

Measurements and Main Results

Out of 2595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 hours (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were APACHE III score, initial serum lactate, conjugated bilirubin, serum creatinine, MELD score, age, BMI, and serum hemoglobin. The final best model from cross-validation presented an AUC of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with PPV of 0.72 and NPV of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, Sensitivity = 0.43, Specificity = 0.89, PPV = 0.69, NPV = 0.73).

Conclusions

The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, MELD score, age, BMI, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.
Virucidal activity of olanexidine gluconate against SARS-CoV-2
Authors: Watanabe Rika , Yoshida Takuma , Nakaminami Hidemasa
Published: March 2024

Introduction: Antiseptics have been used for infection control against SARS-CoV-2. Ethanol (EtOH) was effective against SARS-CoV-2, while chlorhexidine gluconate (CHG) was less effective. Therefore, there may be differences in virucidal activity between classes of antiseptic agents.
Aim: In this study, we evaluated the efficacy of antiseptics against SARS-CoV-2 and identified effective agents for infection control.
Methods: The following antiseptics were used in this study: 1.5% olanexidine gluconate (OLG); 80% EtOH; 1% sodium hypochlorite (NaClO); 0.2% benzalkonium chloride (BKC); 1% povidone-iodine (PVP-I); 0.5%, 1%, and 1.5% chlorhexidine gluconate (CHG); and 0.5% alkyldiaminoethylglycine hydrochloride (AEG). Virucidal activity was evaluated at 0, 30 s, 1, 2, and 3 min according to EN14476.
Results: After 30 s of exposure, 1.5% OLG, 80% EtOH, 1% NaClO, 0.2% BKC, and 1% PVP-I inactivated SARS-CoV-2 below the detection limit. In contrast, the virus was survived in 0.5% CHG, 1% CHG, and 0.5% AEG after 3 min of exposure. However, the virucidal activity of 1.5% CHG was insufficient after 30 s of exposure.
Conclusion: This study showed that the virucidal activity against SARS-CoV-2 differs depending on the class of antiseptic agent. Despite belonging to the same class of biguanide antiseptics, OLG was more effective against SARS-CoV-2 than CHG.
Assessing the Performance of Zero-Shot Visual Question Answering in Multimodal Large Language Models for 12-Lead ECG Image Interpretation
Authors: Seki Tomohisa , Kawazoe Yoshimasa , Akagi Yu , Takiguchi Toru , Ohe Kazuhiko
Published: March 2024

Large Language Models (LLM) are increasingly multimodal, and Zero-Shot Visual Question Answering (VQA) shows promise for image interpretation. If zero-shot VQA can be applied to a 12-lead electrocardiogram (ECG), a prevalent diagnostic tool in the medical field, the potential benefits to the field would be substantial. This study evaluated the diagnostic performance of zero-shot VQA with multimodal LLMs on 12-lead ECG images. The results revealed that multimodal LLM tended to make more errors in extracting and verbalizing image features than in describing preconditions and making logical inferences. Even when the answers were correct, erroneous descriptions of image features were common. These findings suggest a need for improved control over image hallucination and indicate that performance evaluation using the percentage of correct answers to multiple-choice questions may not be sufficient for performance assessment in VQA tasks.
CHAI: Consensus Clustering Through Similarity Matrix Integration for Cell-Type Identification
Authors: Lodi Musaddiq K , Lodi Muzammil , Osei Kezie , Ranganathan Vaishnavi , Hwang Priscilla , Ghosh Preetam
Published: March 2024

Several methods have been developed to computationally predict cell-types for single cell RNA sequencing (scRNAseq) data. As methods are developed, a common problem for investigators has been identifying the best method they should apply to their specific use-case. To address this challenge, we present CHAI (consensus Clustering tHrough similArIty matrix integratIon for single cell type identification), a wisdom of crowds approach for scRNAseq clustering. CHAI presents two competing methods which aggregate the clustering results from seven state of the art clustering methods: CHAI-AvgSim and CHAI-SNF. Both methods demonstrate improved performance on a diverse selection of benchmarking datasets, besides also outperforming a previous consensus clustering method. We demonstrate CHAI’s practical use case by identifying a leader tumor cell cluster enriched with CDH3. CHAI provides a platform for multiomic integration, and we demonstrate CHAI-SNF to have improved performance when including spatial transcriptomics data. CHAI is intuitive and easily customizable; it provides a way for users to add their own clustering methods to the pipeline, or down-select just the ones they want to use for the clustering aggregation. CHAI is available as an open source R package on GitHub:https://github.com/lodimk2/chai
Heterochromatin dynamics during the initial stages of sexual development inPlasmodium falciparum
Authors: Nhim Sandra , Tintó-Font Elisabet , Casas-Vila Núria , Michel-Todó Lucas , Cortés Alfred
Published: March 2024

Asexual replication ofPlasmodium falciparumin the human blood results in exponential parasite growth and causes all clinical symptoms of malaria. However, at each round of the replicative cycle, some parasites convert into sexual precursors called gametocytes, which are essential for transmission to mosquito vectors. After sexual conversion, parasites develop through the sexual ring stage and then gametocyte stages I to V before they are infective to mosquitoes. Heterochromatin, a type of chromatin generally refractory to gene expression, plays an important role in the regulation of sexual conversion by silencing the master regulator of the process, PfAP2-G, in asexual parasites. Additionally, previous reports have described changes in the genome-wide distribution of heterochromatin in stage II/III or older gametocytes, including expansion of heterochromatin at several subtelomeric regions and reduced occupancy at a few specific loci. However, it is not known if these changes occur concomitantly with sexual conversion or at a later time during gametocyte development. Using a transgenic line in which sexual conversion can be conditionally induced, here we show that the genome-wide distribution of heterochromatin at the initial stages of sexual development (i.e., sexual rings and stage I gametocytes) is almost identical to parasites at asexual blood stages, and major changes do not occur until stage II/III. We also show that transcriptional changes associated with sexual development typically precede, rather than follow, changes in heterochromatin occupancy at their loci, which raises the possibility that PfAP2-G operates as a pioneer factor.

IMPORTANCE

Epigenetic processes and chromatin structure play an important role in the regulation of gene expression in malaria parasites. In particular, a type of chromatin called heterochromatin is involved in the regulation (silencing) of many genes. Parasite sexual development is essential for transmission to mosquito vectors. Here we characterised the global distribution of heterochromatin at different stages of sexual development, and found that initially it is identical to asexual blood stages, but at later transmission stages it is altered. This informs about the putative roles of general heterochromatin redistribution in parasite life cycle progression. By integrating multi-omic datasets, we also found that changes in the expression of several genes precede changes in their heterochromatin occupancy. This indicates that during sexual development some genes can be activated in spite of having heterochromatin.