bluuebunny/crossref_metadata_2025 huggingface dataset:
Lumbar Fusion Debris Resulting in Painful Foreign-body Reaction in Abdominal Scar
Authors: Drayton Ka’la D. , Babigian Alan
Published: February 2025

Scar formation is a foreseeable outcome in wound healing. Patients frequently undergo scar revision to improve aesthetic appearance or function. Herein, we present the case of a 49-year-old woman who presented with a painful scar on the abdominal wall. High-resolution computed tomography failed to reveal any underlying source of the abdominal pain. During scar revision, she was found to have extensive fibrosis resulting from a foreign-body response to spinal debris.
Management of diabetic tractional retinal detachments: surgical experiences from a large tertiary academic institution
Authors: Liao Albert , Fortes Blake , Au Adrian , Hou Kirk
Published: February 2025

Purpose of review

Management of diabetic tractional retinal detachments (TRDs) remains technically challenging. The purpose of this review is to provide an updated overview of current surgical techniques and important considerations when treating this condition.

Recent findings

Recent advances in imaging have provided critical insights into hyaloid status and tractional forces in diabetic TRDs, greatly aiding surgical planning. Updates in vitrectomy instruments have also greatly improved anatomic success rates. However, a comprehensive preoperative evaluation and plan remains key in optimizing visual outcomes for this difficult condition.

The surgical management of diabetic TRDs requires several key elements for successful outcomes. Timely intervention and presurgical planning are crucial, particularly in rapidly progressing cases. The use of advanced imaging and instruments enhances visualization and precision during surgery. Finally, a collaborative multispecialty approach with clear communication with patients about their prognosis is fundamental to effective care. These strategies collectively improve patient outcomes and promote visual recovery in those affected by diabetic TRDs.
A Neuman Systems Model-Based Forensic Nursing Course
Authors: McDowell Betsy M.
Published: February 2025

Because nursing theory is integral to effective nursing practice, education, and research, today's faculty are expected to weave nursing theory throughout the nursing curricula at both advanced and entry academic levels. However, incorporating nursing theory across all courses may be unfamiliar for many faculty. In this article, a senior-year elective course in forensic nursing included in a prelicensure baccalaureate curriculum with a Neuman Systems Model focus is presented. Suggested forensic nursing metaparadigm concepts, a possible schedule of topics and activities, and samples of Neuman Systems Model-based assignments are provided. This example could easily be adapted to other nursing theories and/or to other courses across the curriculum. Also emphasized is the importance of nurses providing trauma-informed care for all clients and reinforces the value of accurate evidence collection techniques and documentation. Finally, this course offers students a view of forensic nursing as a viable career choice.
Performance of Government-Financed Cervical Cancer Screening in Hunan, China and Optimization of Triage Strategies
Authors: Liao Zexi , Zou Kehan , Lei Ming , Wu Yinglan , Yang Wenqing , Zhang Yu
Published: February 2025

Objectives

Cervical cancer is a preventable and manageable public health concern. This study aimed to evaluate the performance of a government-financed cervical cancer screening program and to discuss optimal primary screening approach and triage strategies for large-scale population screening.

Methods

This population-based study was conducted from 2015 to 2020 and included 6,373,279 eligible women. The performance of the cervical cancer screening program in Hunan Province was evaluated by comparing cancer incidence and mortality rates. The screening powers of primary human papillomavirus (HPV) testing and cytology were compared by calculating positive outcomes and cervical intraepithelial neoplasia 2 or worse (CIN2+) detection rates. Triage strategies for individuals positive for HPV-16/18 after primary HPV testing were discussed by comparing the CIN2+ detection rates and associated costs.

Results

The cervical cancer screening program has contributed to lower cancer mortality rates in Hunan Province. The HPV testing showed a higher CIN2+ detection rate than cytology as the primary screening approach (0.604% vs. 0.324%). For individuals positive for HPV-16/18, reflex cytology demonstrated a higher CIN2+ detection rate than direct colposcopy (51.11% vs 41.25%), although it was more expensive. For individuals with high-risk HPV types other than HPV-16/18, direct colposcopy exhibited a similar CIN2+ detection power as reflex cytology, but cost less.

Conclusions

The cervical cancer screening program should be expanded because the benefits outweigh the costs. Statistical data indicate that HPV testing is a cost-effective preliminary screening approach for large-scale population screening.
Clinician Characteristics Associated With Adoption of Updated National Colposcopy Guidelines
Authors: Fuzzell Lindsay , Brownstein Naomi C. , Fontenot Holly B. , Lake Paige , Michel Alexandra , Perkins Rebecca B. , Vadaparampil Susan T.
Published: February 2025

Objective

To evaluate adherence to the 2019 ASCCP risk-based management consensus guidelines for management of patients following colpscopic cervical biopsy among US colposcopists.

Methods

To elucidate factors associated with utilization of the 2019 guidelines for patients undergoing colposcopic cervical biopsy, we cross-sectionally surveyed physicians and advanced practice professionals who perform colposcopy. Clinicians responded to clinical vignettes describing scenarios for which management recommendations differed between 2019 and prior management guidelines. Vignette 1 involved deferral of repeat colposcopy for patients with a low-risk biopsy, HPV, and cytology results. Vignette 2 involved deferral of excisional treatment on a patient with repeated low-grade biopsy results. Binomial logistic regression models determined factors associated with utilization of 2019 guidelines.

Results

A total of 670 colposcopists participated from across the United States. For Vignettes 1 and 2, guideline-adherent responses were given by 30.5% and 66.1% of participants, respectively. Colpsocopists practicing in community health centers were more likely to perform guideline-concordant care for Vignettes 1 and 2. Hispanic compared to non-Hispanic colposcopists and Internal or Family medicine compared to OB-GYN colposcopists are less likely to perform guideline-concordant care in Vignette 2. Irrespective of their chosen response, most believed they were guideline-adherent.

Conclusions

Many colposcopists may not realize their current management strategies are inconsistent with 2019 guidelines. Tailored education initiatives could address knowledge gaps, maximize patient benefits, and minimize harms.
Effects of Insertion Depth and Modiolar Proximity on Cochlear Implant Speech Recognition Outcomes With a Precurved Electrode Array
Authors: Canfarotta Michael W. , Dillon Margaret T. , Thompson Nicholas J. , Selleck A. Morgan , Dedmon Matthew M. , Brown Kevin D.
Published: February 2025

Objectives

To examine the relationship between angular insertion depth (AID), modiolar proximity, and speech recognition outcomes for cochlear implant (CI) recipients of a precurved electrode array.

Study Design

Retrospective review.

Setting

Tertiary academic referral center.

Patients

Thirty-five adult CI recipients (n = 40 ears) of precurved electrode arrays listening with a CI-alone device.

Interventions

Cochlear implantation with postoperative computed tomography.

Main Outcome Measures

Consonant-nucleus-consonant (CNC) word recognition at 6 months post-activation.

Results

A multivariate regression model demonstrated that both deeper apical AID and closer modiolar proximity in the basal turn were independently associated with better CNC word scores at 6 months (F
2,37 = 7.264, p = 0.002). A deeper basal insertion depth was positively correlated with apical AID (r = 0.754, p < 0.001) but negatively correlated with modiolar proximity in the basal turn (r = −0.766, p < 0.001).

Conclusions

These data suggest that both apical cochlear coverage and modiolar proximity independently confer speech recognition benefit with a precurved array. However, these benefits are mutually exclusive for current precurved array designs as a deeper basal insertion depth results in greater apical coverage but lateralization of electrodes away from the modiolus in the basal turn. Future work is needed to elucidate mechanisms behind these findings that may motivate electrode array design modifications to further optimize outcomes for CI users.
Otologic Symptoms Following Teprotumumab Administration in Patients with Thyroid Eye Disease
Authors: Epperson Madison V. , Hughes Sara , Valenzuela Carla V. , Stucken Emily Z.
Published: February 2025

Objective

Comprehensively characterize subjective otologic adverse events following teprotumumab administration with standardized patient reported outcome metrics. Understand the impact on patients’ quality of life and perception of the medication.

Study Design

Retrospective case series.

Setting

Tertiary referral center.

Patients

Thirty-two adults with thyroid eye disease treated with teprotumumab from 2020 to 2023.

Main Outcome Measures

Subjective hearing loss, tinnitus, dizziness (Dizziness Handicap Inventory), patulous eustachian tube (Eustachian Tube Dysfunction Questionnaire-7, Patulous Eustachian Tube Handicap Inventory-10), effect of hearing loss on quality of life, and decisional regret.

Results

Half reported hearing loss (n = 16, 50%) while receiving teprotumumab. Onset was gradual in 75% of patients with onset at the sixth [IQR 5–7] infusion. It was nonfluctuating (93.8%), bilateral (100%), and did not return to baseline (93.8%). Of those reporting hearing loss, 37.5% reported dizziness and 87.5% reported tinnitus; 87.5% felt it affected quality of life, and 33.3% would opt to not receive the medication again. The median DHI score was 9 [0–35] in those with hearing loss compared to 0 [0–5] in those without hearing loss (p = 0.02, Wilcoxon rank sum). Based on the ETDQ-7, 37.5% of patients experienced eustachian tube dysfunction; 15.6% experienced symptoms of a patulous eustachian tube with a median PHI-10 score of 15 [3–24], indicating a mild handicap.

Conclusions

Many patients experience subjective hearing loss following teprotumumab administration, typically gradual in onset, nonfluctuating, bilateral, persistent, and significantly affecting quality of life. Patients may also experience comorbid vertigo and symptoms of eustachian tube dysfunction or patulous eustachian tube with variable severity.
Epidemiology, clinic, therapeutic, and outcome of pelvic organ prolapse: a retrospective single-center cohort study
Authors: Amadou Issa Abdou , Soumana Diaouga Hamidou , Lankonde Salifou Zelika , Abdoul-Wahab Mahamadou Moumouni , Oumara Maina , Oumarou Garba Souleymane , Harouna Salifou Jamila , Abdoulaye Maman Bachir , Nouhou Hassan , Nayama Madi
Published: February 2025

Introduction:

Pelvic organ prolapse (POP) is a major public health problem. This study aims to determine the incidence, sociodemographic profile of patients, the management and outcomes of POP in a maternity hospital with limited resources in Niger.

Methodology:

This was an eight-year retrospective cohort study involving the analysis of medical records from patients who underwent management of POP between 1 January 2015 and 31 December 2022 in our department. The epidemiological data, treatment, and outcomes of POP were collated and subjected to analysis.

Results:

During the study period, 358 cases of POP were recorded out of a total of 12 536 patients treated in the department, representing a frequency of 2.8%. The mean age of the patients was 46.14 years (range: 17–90 years). The patients were identified as married (307 cases, 85.75%), unemployed (353 cases, 98.6%) and not attending school (332 cases, 92.74%). The largest number of cases were observed in large multiparous women (60.05%, 215 patients). The average parity was 6.5 children. The vast majority of patients (269 cases, 75.14%) lived in rural areas. The most frequent motif for consultation was the sensation of mass in the vagina (146 cases, 40.78%) and vulvar swelling (138 cases, 38.55%). The most frequent genital prolapses type was middle, made of the hysterocele essentially (150 cases, 41.90%). The stage III of genital prolapses was the most frequent in 76.51% (274 cases). All patients underwent surgical treatment (100%), and the vaginal access was most used in 57.55% (206 cases) of cases. Conservative treatment was performed in the majority of patients (197 cases, 55.02%). The intraoperative complications were vesical lesions (0.56%, two cases) and ureteral and vascular lesion (0.28%, one case).

Conclusion:

POP is a common occurrence in our region. Surgical treatment is the most practiced and hysterectomy by vaginal surgical approach is the most practiced.
A Transition Guide
Authors: Gilroy Heidi , De Joya Anna
Published: February 2025

To succeed in the face of recent challenges, healthcare organizations need highly trained, educated, and competent staff. Nursing professional development (NPD) practitioners and departments are a key component to achieving this goal. Little evidence exists on the most efficient and effective way to organize NPD departments in the hospital setting. This article describes 1 hospital's journey through centralization of an NPD department, which resulted in high satisfaction, cost savings, and enhanced quality outcomes.
Creation of a Novel Virtual Reality Simulation to Increase Nursing Skills in Management of Workplace Violence
Authors: Tobias Jane , DiDonato Stephen , Whitfield-Harris Lisa , Okupniak Carol , Santulli Gabrielle , Das Nimmy , Marino Marie
Published: February 2025

OBJECTIVE

This article presents the design, development, and implementation of a novel and innovative virtual reality (VR) simulation aimed at increasing nursing skills in identifying, managing, and deescalating workplace violence (WPV) incidents and mitigating the effects after critical incidents.

BACKGROUND

The ANA reports that 1 in 4 nurses in the United States experience workplace assault annually, highlighting the novel role of VR simulations in educating and preparing nurses to recognize, address, and minimize the impact of WPV.

METHODS

A multidisciplinary team designed and implemented a VR simulation based on real WPV incidents reported by nurses in an urban health system, enlisting a film and video company's expertise to bring scenarios to life, addressing a critical gap.

CONCLUSIONS

This article discusses the collaborative creation of simulations using VR as a novel strategy for educating nurses on identification, management, and deescalation of incidents of WPV and mitigating the effects of WPV after critical incidents.
Focal Intense FDG Uptake of the Tongue Muscle Due to Repeated Tooth-Licking Mimicking Malignancy
Authors: Huo Yajing , Dong Aisheng , Han Yan
Published: February 2025

A 55-year-old woman underwent FDG PET/CT to detect possible multiple myeloma due to IgM κ paraproteinemia. FDG PET/CT showed a focal intense activity with SUVmax of 21.3 in her anterior tongue, suspicious for malignancy. MRI and physical examination of the tongue were normal. On further inquiry, the patient reported she had a habit of licking her anterior mandibular teeth and licked her teeth repeatedly before and after injection of FDG. Consequently, the tongue activity was interpreted as physiological tongue muscle activity due to repeated tooth-licking.
Multi-physics modeling for ion homeostasis in multi-compartment plant cells using an energy function
Authors: Mestdagh Guillaume , De Angeli Alexis , Godin Christophe
Published: February 2025

Plant cells control their volume by regulating the osmotic potential of their cytoplasm and vacuole. Water is attracted into the cell as the result of a cascade of solute exchanges between the cell subcompartments and the cell surroundings, which are governed by chemical, electrostatic and mechanical forces. Due to this multi-physics aspect and to couplings between changes of volumes and chemical effects, modeling these exchanges remains a challenge that has only been partially adressed. In this paper, we introduce an energy-based approach to couple chemical, electrical and mechanical processes taking place between several subcompartments of a plant cell. The contributions of all physical effects are gathered in an energy function that allows us to derive the equations satisfied by each variable in a systematical way. This results in a modular, unified approach that can be interpreted analytically. We illustrate these properties on the modeling of ion and water transport in a guard cell during stoma opening. We represent the stoma opening process as a quasi-static evolution driven by hydrogen pumps in the plasma and vacuolar membranes, resulting in an interpretable model with few parameters. We perform numerical simulations to investigate the role of each hydrogen pump in this process. We show that this energy-based approach allows us to highlight a hierarchy between the forces involved in the system, that can be exploited to interpret the emergent properties of this complex multi-physics system.
Long-term restricted mean survival time survival of anterior large vessel occlusion strokes treated with endovascular thrombectomy
Authors: Wellington Daniel James , Diprose William , Campbell Douglas , Hong Jae Beom , Boyle Luke , Barber Peter Alan
Published: February 2025

Introduction

Endovascular thrombectomy (EVT) has revolutionized the treatment of patients with large vessel occlusion (LVO) stroke. Three-month functional independence ranges between 33 and 60%, and mortality between 12 and 25%. Few studies have presented outcomes beyond five years and their reported odds or hazard ratios are difficult to apply clinically. Median survival is also challenging to interpret correctly. Restricted mean survival time (RMST) is a clinically intuitive metric that gives survival times up to specified cutoff points. We aimed to determine RMST at one, two and five years after EVT for anterior circulation stroke patients and evaluate survival impact of various risk factors.

Methods

This cohort study examined survival of patients treated with EVT for anterior circulation LVO stroke from 2011-2024 from the New Zealand national stroke database. Unadjusted RMST was determined for all age brackets. Cox regression adjusted survival curves were used to determine RMST and survival probabilities at one, two and five years for significant covariates.

Results

There were 1457 anterior circulation LVO patients treated with EVT included for analysis (median follow-up 8.9 years [95% CI 7.57 – inf]). At five years, 415 (28%) patients had died. Patients aged 90 years or older had a RMST of 1.64 years, and a five-year survival probability of 33% compared with a 97% survival probability for those aged 15-39 years. Five-year RMST survival differences were; independent level of function versus dependent (0.77 years), low comorbidity versus high (0.71 years), mild-moderate NIHSS versus higher (0.49 years), smaller infarct cores versus large (0.48 years), and good reperfusion versus (0.67 years).

Discussion

RMST provided clinically useful survival estimates and subgroup survival differences after EVT, especially in those of advanced age. RMST is easy to communicate, captures survival nuances, and can provide absolute differences that are not possible when outcomes are measured using median survival alone.
Spike-specific IgG4 generated post BNT162b2 mRNA vaccination is inhibitory when directly competing with functional IgG subclasses
Authors: Tam Jerry C. H. , Sibayan Abbie C. , Seow Jeffrey , Graham Carl , Kurshan Ashwini , Merrick Blair , Stanton Richard J. , Doores Katie J.
Published: February 2025

The rapid development of vaccines against SARS-CoV-2 during the COVID-19 pandemic proved vital in controlling viral spread and reducing mortality and morbidity. Both neutralising activity and effector function activity of Spike-specific antibodies have been shown to be important for their protective and therapeutic activity. However, several recent studies have reported that vaccination with mRNA based COVID-19 vaccines can lead to elevated levels of Spike-specific IgG4, an isotype which is often considered anti-inflammatory due to its reduced binding to Fcγ receptors on immune cells. Here we show that the level of Spike-specific IgG4 produced following BNT162b2 vaccination is impacted by the interval between and frequency of vaccines boosts, prior SARS-CoV-2 infection (hybrid immunity), breakthrough infection and bivalent vaccine boosters. Despite the increase in Spike-specific IgG4 between the 2ndand 3rdBNT162b2 vaccine dose, neutralisation, ADCD and ADCP activity all increased. Through expression of SARS-CoV-2 monoclonal antibodies cloned as IgG1, IgG2, IgG3 and IgG4, we demonstrated that whilst Spike-specific IgG4 had reduced effector function activity, including ADCC, ADCD and ADCP, IgG4 was only inhibitory when directly competing with functional IgG subclasses binding to an overlapping epitope. In the context of polyclonal plasma, ADCC and ADCD activity could not be depleted by addition of high concentrations of a Spike-specific IgG4 mAb cocktail suggesting the non-stimulatory effect of Spike-specific IgG4 may be hidden in more complex scenarios, such as polyclonal mixes in serum.
Evolution of cross-tolerance to metals in yeast
Authors: Bazzicalupo Anna L. , Kahn Penelope C. , Ao Eully , Campbell Joel , Otto Sarah P.
Published: February 2025

Organisms often face multiple selective pressures simultaneously (e.g., mine tailings with multiple heavy metal contaminants), yet we know little about when adaptation to one stressor provides cross-tolerance or cross-intolerance to other stressors. To explore the potential for cross-tolerance, we first adaptedSaccharomyces cerevisiaeto high concentrations of six single metals in a short-term evolutionary rescue experiment. We then measured the cross-tolerance of each metal-adapted line in the other five metals. We generated and tested three predictors for the degree of cross-tolerance, based on the similarity between pairs of metal environments in (1) their physiochemical properties, (2) the overlap in genes known to impact tolerance to both metals, and (3) their co-occurrence in the environment. None of these predictors explained significant variation in cross-tolerance. Instead, we observed that adapted lines in one metal were frequently cross-tolerant to certain metals (manganese and nickel) and intolerant to others (cobalt and zinc). Furthermore, cross-tolerance between pairs of metals was not reciprocal, with mutations accumulating in one metal (e.g., copper) providing adaptation to another metal (e.g., manganese), but notvice versa. Evolved lines also differed in their degree of specialization, with lines evolved in manganese or copper more specialized to that metal, but lines evolved in cobalt or zinc more generally tolerant. To determine the genetic basis of these metal adaptations, we sequenced the genomes of 109 metal-adapted yeast lines. The SNP mutation spectrum was significantly different in cadmium, cobalt, and manganese than expected in a mutation accumulation experiment inS. cerevisiae. In addition, two lines were highly mutated, bearing defects in DNA repair genes (both in manganese). Thirteen genes exhibited parallel adaptation to different metals; three of these genes generated broad cross-tolerance. Several mutations were found in vacuolar transporter genes, suggesting an important role for vacuolar proteins in adapting to metal stress. Our results with these metal-adapted lines indicate that cross-tolerance is challenging to predict, depending on the combined stressors experienced and the nature of the mutations involved.
Control of the force-bearing properties of microtubule-associated proteins via stalk/linker regions: insights from the NDC80 complex
Authors: Kovalenko Ilya B. , Kholina Ekaterina G. , Fedorov Vladimir A. , Pozdnyakov Egor M. , Orekhov Philipp S. , Gudimchuk Nikita B.
Published: February 2025

Many microtubule-associated proteins (MAPs) function under mechanical loads. Among them, motor proteins and passive couplers link microtubules with other cytoskeletal filaments, membranous structures and diverse scaffolds to enable cell shape changes, locomotion and other important processes. A key kinetochore complex, NDC80, transmits forces from microtubule disassembly to chromosome motion during cell division. Recently, this complex has been shown to detach from microtubules more easily when pulled toward the minus-end of the microtubule than when pulled in the plus-end direction. Here, we used coarse-grained molecular dynamics and Brownian dynamics simulations to explain the asymmetric effect of the directional load on the unbinding of the NDC80 complex from microtubules and then generalized our findings to other MAPs. We found that the lever arm created by the stiff stalk of NDC80 tilted toward the plus-end of the microtubule is critical for asymmetric unbinding of this complex, similar to that of dynein. In contrast, EB-proteins, the microtubule crosslinker PRC1, and kinesins are predicted to lack pronounced unbinding asymmetry, either due to their almost perpendicular anchorage to the microtubule wall or due to the high flexibility of their linker regions proximal to the microtubule-binding domains. Thus, our study highlights some of the design principles of MAPs, explaining how their distal parts can impart, modulate or eliminate the dependence of unbinding on the direction of external loads. This information deepens our understanding of the load-bearing properties and functions of diverse MAPs and may guide the design of synthetic protein systems with predefined mechanical characteristics.
Neurod2/6 transcription factors control basal progenitor differentiation and sequential production of neocortical cell subtypes
Authors: Yan Kuo , Newman Andrew G , Tutukova Svetlana , Gavrish Maria , Bormuth Ingo , Bormuth Olga , Tarabykin Victor
Published: February 2025

Neurod2 and Neurod6 (Neurod2/6) are key transcription factors that promote neuronal differentiation, however, their role in the developing neocortex is not fully understood. Both genes have similar expression patterns during development as well as binding motifs. In order to investigate their role in cortical neurogenesis, we generated a mouse model deficient for both Neurod2/6. Here we demonstrate that differentiation of Tbr2-positive (Tbr2+) basal progenitors (BPs), but not Pax6+ apical progenitors, was severely defected, resulting in ectopically expanded BPs in perinatal Neurod2/6 deficient brains. The sequential fate specification of cortical neurons was also impaired in the absence of Neurod2/6. Ectopic Tbr2+ BPs expressed multiple proliferation markers and were able to self-renew. Olig2+ glial precursors were consequently over-produced in Neurod2/6 deficient brains. Restoration of Neurod2/6 in the double deficient brains downregulated Tbr2 expression, and exhibited substantial rescue effects on defected laminar subtype specification and excessive gliogenesis. Our work indicates that Neurod2/6 regulate BP differentiation and sequential production of cortical cell subtypes via inhibiting Tbr2-dependent genetic program.
Impact of the Microtubule Cytoskeleton on Insulin Transport in Beta Cells: A 3D Computational Study
Authors: Thieu Thoa , Holmes William R.
Published: February 2025

Glucose-stimulated insulin secretion (GSIS) in pancreaticβcells is vital to metabolic homeostasis. Recent evidence has highlighted the critical role of the cells’ microtubule (MT) cytoskeleton in regulating transport and availability of insulin containing vesicles. How these vesicles move within the cell and how that mobility is influenced by the MT network is however not well understood. The MT network in these cells is dense and randomly oriented. Further insulin vesicles are relatively large compared to the spaces in this dense meshwork. Here we develop a 3D computational model that simulates vesicle motions in the dense MT network of theβcell. The structure of this MT network, along with the dynamics of vesicle motions, are calibrated to microscopy data fromβcells to ensure physiological relevance. Our results reveal a number of key observations. 1) The MT network inβcells likely impairs motion of larger vesicles (200 − 300nmin diameter). 2) This is in part a consequence of their “caging” by the MT network. 3) This results in a substantial reduction in the likelihood of vesicles transiting from the cells interior to the plasma membrane, a pre-cursor to GSIS. 4) Dynamic remodeling of the MT network reduces the strength of these effects. 5) That same remodeling however introduces anomalous (sub-diffusion) motion characteristics. Taken together, these results indicate that the dense MT network of theβcell substantially inhibits mobility and availability (for GSIS) of insulin. It further sheds light on how the complex filament network in cells leads to statistically anomalous motions. Finally, this modeling further provides a test-bed for determining how potential manipulations of the structure and dynamics of this network would tune GSIS.

SIGNIFICANCE

Insulin release from pancreaticβcells is crucial for blood sugar regulation, and recent research suggests the microtubule network inside these cells plays a key role in how insulin is transported and released. This study developed a 3D computational model to explore how insulin vesicles move through this dense network. Results show that the microtubules can “cage” larger vesicles, making it difficult for them to reach the cell surface for insulin release. Dynamic remodeling of the network can however increase insulin mobility and availability. These findings highlight the impact of the microtubule network on insulin transport and secretion and provide insight into potential ways to tune this process.
Exploiting attP landing sites and gypsy retrovirus insulators to identify and study viral suppressors of RNA silencing
Authors: Gupta Adarsh K. , Chennuri Pratima R. , Monfardini Raquel D. , Myles Kevin M.
Published: February 2025

RNA interference (RNAi) pathways are crucial for regulating viral infections in both animals and plants, acting as defense mechanisms that limit pathogen replication. This has led to the evolution of viral suppressors of RNA silencing (VSRs) across various plant and insect viruses, with potential analogs in arthropod-borne human pathogens. However, while functionally similar, VSRs often lack genetic conservation due to convergent evolution. Research on VSRs typically involves analyzing individual proteins expressed in host cells with secondary reporter constructs, but the lack of a standardized system can lead to inconsistent findings. Our study examined how genomic insertion sites affect VSR activity using a transgenicDrosophila melanogasterreporter system. We integrated the VSR protein DCV-1A into three different attP sites and assessed silencing. The results showed significant variation in VSR activity across loci due to position effects. However, by flanking the transgenes with gypsy retrovirus insulators, we achieved consistent high-level silencing across all sites. These findings suggest the potential for establishing a standardized reporter system inDrosophila, facilitating the identification, study and comparison of VSR proteins. However, our results also highlight the limitations of using isolated proteins in reporter systems, emphasizing the need for a comprehensive holistic approach to definitively determine VSR functions.
Impact of the establishment of a national lead agency on the emergency medical service system in Khon Kaen Province, Thailand
Authors: Yapanan Papawadee , Impool Tawatchai , Pattanarattanamolee Ratrawee , Thanakanjanaphakdee Wuttikul , Tokuno Shinichi , Nakahara Shinji
Published: February 2025

Purpose

National Institute for Emergency Medicine (NIEM) was established as the national lead agency for emergency medicine in 2008 in Thailand. This study aimed to evaluate the longitudinal effect of establishing NIEM on emergency medical service (EMS) use and case fatalities among patients with severe trauma.

Method

Data were extracted from Khon Kaen Hospital’s Injury Surveillance Database. The analysis included injured patients with an Injury Severity Score of >15, directly transferred to its emergency department between January 1997 and December 2021. Changes in formal EMS use, total EMS use, and in-hospital deaths were investigated using segmented regression analysis. The change point in 2008 divided the study period into two segments.

Result

The proportion of formal EMS use among severely injured patients increased by approximately 1.5% annually before 2008, with a level change of 52.9 percentage point (pp) increases in 2008, and without a significant slope change. The total EMS use, including informal EMS, increased by approximately 3.4% annually before 2008, with a level change of 17.9ppincrease in 2008, and a significant slope change in the decreasing direction of the increasing trend. The proportion of in-hospital deaths showed no significant changes before 2008, with an increase of 8.0ppin 2008, with significant slope change and decreasing trends after 2008.

Conclusions

The trends indicated a significant increase in EMS use among patients with severe trauma after establishing NIEM in 2008, which reflects the integration of informal EMS units into the formal system. However, a reduction in fatalities in 2008 was not observed.
Inequities in Effective Coverage of Family Planning Services in Low-and Middle-Income Countries: Linking Households and Facility Surveys
Authors: Tian Shenning , Hazel Elizabeth A , Munos Melinda , Maïga Abdoulaye , Jiwani Safia S , Wilson Emily B , Mady Gouda Roland Mesmer , Amouzou Agbessi
Published: February 2025

Background

Despite decades of family planning (FP) program successes in low-and middle-income countries (LIMCs), unmet need for contraceptives persists with inequalities in coverage. Including elements of service readiness in family planning intervention coverage measures will better inform population-level program performance.

Methods

Five LMICs countries were identified with a health facility and household survey conducted within five years of one another within the last 10 years: Bangladesh, Haiti, Malawi, Nepal and Tanzania, with time trend data available for Nepal. We used ecological linking methods to develop quality readiness adjusted FP coverage measures by linking health facility assessments (readiness) and household surveys (intervention coverage). Linking units were defined by facility type, managing authority and geographic location using women’s reported source of contraceptives. Intervention coverage was defined as the percentage of women 15-49 years of age in need of contraceptive services who were using a modern method and we used the average FP readiness score in each linking unit to calculate readiness-adjusted intervention coverage. We used a coverage cascade model to understand gaps in health service readiness and access, and performed a health equity analysis for wealth, locality and age.

Findings

We found large gaps in FP intervention coverage and readiness in all settings. Facility readiness scores ranged from 0.60 and 0.75 with gaps in coverage and readiness-adjusted coverage ranging from 49 percentage points (pp) in Bangladesh to 34pp in Malawi. Urban, wealthier and adolescent women had lower readiness-adjusted coverage since they also obtained their contraceptives outside of health facilities. We found little change in the coverage cascades for Nepal from 2015 to 2021.

Conclusions

This analysis demonstrates calculating readiness-adjusted FP coverage using a cascade model in five geographically diverse countries with time trends in one country. As previous studies have shown, we found large gaps in intervention and readiness-adjusted coverage with related inequalities.
Identification of novel vertebral development factors through UK Biobank driven genetic and body imaging analysis reveals markers for back pain
Authors: Sun Zhuopin , Han Jiru , Fearnley Liam G. , McGlinn Edwina , Bahlo Melanie
Published: February 2025

Numerical variations and transitional anatomy in the human vertebral column, observed in up to 36% of individuals, represent a significant yet understudied aspect of skeletal development with potential effects on multiple physiological systems. Utilising UK Biobank data, we integrated genetic analysis with deep learning-based multi-modal body imaging to investigate genetic factors associated with thoracic and lumbar spine anatomy. We identified three key genes—GPC3,NR6A1, andVRTN—associated with numerical variations of the lumbar vertebrae and ribs, withVRTNreported for the first time in humans as influencing vertebral development. Our findings reveal significant associations between these genetic variants, vertebral and rib anomalies, and increased prevalence of chronic pain. This study highlights the genetic underpinnings of vertebral development and demonstrates the utility of combining imaging and genetic data to uncover skeletal variation and its health implications for population health.

Teaser

Integration of genetic and imaging data uncovers novel genetic factors in human vertebral variations and their link to chronic pain.
A Latent Variable Approach for the Investigation of the Multi-factor Impact on Sleep Problems in Individuals with Mild Cognitive Impairment
Authors: Nega Chrysanthi , Moustaka Kleio , Beratis Ion N.
Published: February 2025

The present study aims to explore the impact of neuropsychiatric symptoms, cognitive functioning, and medical status on sleep problems in individuals with Mild Cognitive Impairment (MCI), focusing on insomnia, by implementing a latent variable approach. The 131 Greek patients with MCI, who are consecutive visitors of the Alzheimer’s day clinic, underwent comprehensive assessments in cognitive functioning, neuropsychiatric symptoms, sleeping disturbances, and medical health status. The model was estimated by applying a Partial Least Squares (PLS) approach to structural equation modeling (SEM), incorporating the following latent variables: “psychological burden” (3 indicators: depressive symptoms, anxiety, and stress), “cognitive status” (5 indicators: general cognitive status, phonemic and semantic fluencies, psychomotor speed, and episodic memory), and “sleep problems” (5 indicators: overnight and earlier final awakening(s), decreased daytime functioning and well-being, and insufficient sleep duration). The results supported the SEM effectiveness, with good model fit and high predictive power. The “psychological burden” played the most significant role in the development of sleep problems within the clinical group of MCI, while “cognitive status” appeared to be the second most important SEM predictor, showing a negative association with “sleep problems”. Additionally, MCI age of onset and sleep problems severity were negatively associated. This latent-variable approach allowed us to capture the multidimensional complexity of sleep problems in MCI. Thus, applying integrative evaluations and interventions that target the cognitive status and psychological well-being, may improve the sleep quality of individuals with MCI, and further contribute to a slower cognitive decline course.
Protocol for the development of reporting guidance for interest-holder engagement in practice guidelines: the RIGHT-MuSE checklist
Authors: Yu Xuan , Estill Janne , Akl Elie , Khabsa Joanne , Petkovic Jennifer , Zeidan Lili , Bian Zhaoxiang , Chen Yaolong
Published: February 2025

Background: Guideline developers have increasingly engaged various groups of interest-holders in different stages of guideline development. However, reporting on interest-holder engagement in practice guidelines often lacks transparency. Therefore, the RIGHT (Reporting Items of Practice Guidelines in Healthcare) working group, in collaboration with the MuSE Consortium, plans to develop the RIGHT-MuSE extension. Objectives: This protocol aims to outline the steps for the detailed development of the RIGHT-MuSE checklist, as well as strategies for its effective development, dissemination, and application. Methods: We will follow the methods recommended by the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network, and build on the experience from the development of the original RIGHT statement and its extensions. The development process of RIGHT-MuSE will consist of twelve specific steps: 1. Identifying the need for the checklist; 2. Obtaining funding; 3. Drafting a protocol and registering the project; 4. Establishing the working groups; 5. Reviewing background work; 6. Generating an initial list of items; 7. Conducting consensus surveys; 8. Holding consensus meetings; 9. Drafting the final RIGHT-MuSE checklist; 10. Conducting a pilot test of the checklist; 11. Developing an explanatory document; and 12. Disseminating the checklist. Discussion: The RIGHT-MuSE checklist will provide guideline developers with guidance for the systematic, scientific and transparent reporting of interest-holder engagement in practice guidelines. Additionally, developers and implementers of the RIGHT-MuSE checklist will use this protocol as a reference to ensure that the checklist they develop and implement adheres to the highest standards of transparency and quality. By promoting active and meaningful engagement of interest-holders, the RIGHT-MuSE checklist aims to foster inclusive and people centered processes in healthcare.
Field-Programmable Gate Array-Based Ultra-Low Power Discrete Fourier Transforms for Closed-Loop Neural Sensing
Authors: Yang Richard , Orser Heather D. , Ludwig Kip A. , Coventry Brandon S.
Published: February 2025

Digital implementations of discrete Fourier transforms (DFT) are a mainstay in feature assessment of recorded biopotentials, particularly in the quantification of biomarkers of neurological disease state for adaptive deep brain stimulation. Fast Fourier transform (FFT) algorithms and architectures present a substantial power demand from onboard batteries in implantable medical devices, necessitating the development of ultra-low power Fourier transform methods in resource-constrained environments. Numerous FFT architectures aim to optimize power and resource demand through computational efficiency; however, prioritizing the reduction of logic complexity at the cost of additional computations can be equally or more effective. This paper introduces a minimal architecture single-delay feedback discrete Fourier transform (mSDF-DFT) for use in ultra-low-power field programmable gate array applications and shows energy and power improvements over state-of-the-art FFT methods. We observe a 33% reduction in dynamic power and 4% reduction in resource utilization in a neural sensing application when compared to state-of-the-art FFT algorithms. While designed for use in closed-loop deep brain stimulation and medical device implementations, the mSDF-DFT is also easily extendable to any ultra-low power embedded application.
Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34+Kasumi-3 cells
Authors: Baruah Vargab , Krishna Benjamin A. , Kelly Michael C. , Qi Xu , O’Connor Christine M.
Published: February 2025

Reactivation of latent human cytomegalovirus (CMV) can lead to severe complications in individuals with dysregulated immune systems. While antiviral therapies for CMV are approved, these compounds are limited by their toxicity and inability to specifically target the latent reservoir or prevent reactivation. Herein we show that CMV reactivation in Kasumi-3 cells, a CD34+hematopoietic cell line, requires mitogen-activated protein kinase (MAPK) activation. Importantly, pharmacological inhibition of the MAPK signaling pathway, including MEK and ERK, restricts viral reactivation in Kasumi-3 cells. In sum, our findings show MAPK signaling is critical for CMV reactivation, revealing a potential avenue for therapeutic intervention to prevent viral reactivation and downstream pathogenesis that is often detrimental for immunosuppressed and immunocompromised patients.
A paradigm to study the learning of muscle activity patterns outside of the natural repertoire
Authors: Ghavampour Ali , Emanuele Marco , Sayyid Shuja R. , Orban de Xivry Jean-Jacques , Michaels Jonathan A. , Pruszynski J. Andrew , Diedrichsen Jörn
Published: February 2025

The acquisition of novel muscle activity patterns is a key aspect of motor skill learning which can be seen at play, for example, when beginner musicians learn new guitar or piano chords. To study this process, here we introduce a new paradigm that requires quick and synchronous flexion and extension of multiple fingers. First, participants practiced all the 242 possible combinations of isometric finger flexion and extension around the metacarpophalangeal joint (i.e., chords). We found that some chords were initially extremely challenging, but participants could eventually achieve them with practice, showing that the initial difficulty did not reflect hard biomechanical constraints imposed by the interaction of tendons and ligaments. In a second experiment we found that chord learning was largely chord-specific and did not generalize to untrained chords. Finally, we explored which factors make some chords more difficult than others. Difficulty was well predicted by the muscle activity pattern required by that chord. Interestingly, difficulty related to how similar chords’ muscle activity patterns are to the muscle activity patterns required by everyday hand use, and to the overall size of the muscle activity. Together, our results suggest that the new paradigm introduced in this work may provide a valuable tool to study the neural processes underlying the acquisition of novel muscle activity patterns in the human motor system.
Transcriptomic analysis ofC9orf72-mutated iPSC-derived microglia implicates cell-autonomous upregulation of selected NLRP3 inflammasome genes in motor neuron degeneration
Authors: Pulimood Nisha S , Thiry Louise , Tang Ye Man , Stifani Stefano
Published: February 2025

Hexanucleotide repeat expansion (HRE) in the non-coding region of the geneC9orf72is the most prevalent mutation in Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia. TheC9orf72HRE contributes to motor neuron degeneration in ALS both through cell-autonomous mechanisms and non-cell autonomous disease processes involving glial cells such as microglia. The molecular mechanisms by whichC9orf72HRE microglia contribute to motor neuron death in ALS remain to be fully elucidated. In this study, we generated microglia from humanC9orf72HRE and isogenic iPSCs using three different microglia derivation methods that can generate microglia with distinct intrinsic inflammatory profiles. RNA sequencing analysis reveals a consistent dysregulation of specific genes involved in pathways underlying NLRP3 inflammasome activation inC9orf72HRE microglia independent of priming with any activating cues. In agreement with elevated expression of NLRP3 inflammasome components, conditioned media fromC9orf72HRE microglia enhance the death ofC9orf72HRE motor neurons implicating microglia-secreted molecules in non-cell autonomous mechanisms ofC9orf72HRE pathology. These findings provide evidence thatC9orf72HRE microglia have a cell-autonomous pro-inflammatory phenotype that contributes to non-cell autonomous mechanisms of motor neuron degeneration in ALS through dysregulated expression of specific genes involved in NLRP3 inflammasome-mediated mechanisms.