bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actuator Size of Magnetic Controlled Growth Rod (7 cm vs. 9 cm) is Not Predictive of Unplanned Return to the Operating Room: A Retrospective Multicenter Comparative Cohort Study
Authors: Garg Sumeet , Heffernan Michael , Feddema Tyler , Luhmann Scott , Sturm Peter , Vitale Michael , Andras Lindsay , White Klane ,   The Pediatric Spine Study Group, Carry Patrick 
Published: October 2024

Background:
Magnetic controlled growth rods (MCGR) are the most common type of implant used for operative treatment of patients with early-onset scoliosis (EOS). Rods can have either a 7-cm actuator, allowing 2.8 cm of potential expansion, or a 9-cm actuator which allows 4.8 cm potential expansion. We hypothesized that the rate of unplanned return to the operating room (UPROR) will be increased when the 9-cm actuator is implanted in smaller patients. In addition, we aimed to identify a cutoff for spine length between planned upper and lower instrumented MCGR levels that best differentiated between patients having a high versus low risk of UPROR.

Methods:
We identified 167 patients from a prospectively collected registry of EOS patients who began MCGR treatment at 9 years of age or younger, with greater than 1 year of follow-up, and had adequate radiographs. Demographic, clinical, and surgical characteristics were analyzed for 7-cm and 9-cm actuator patients. Chi-square tests and Student t tests were used to test for differences between the 2 actuator rod groups. A predictive model for UPROR within 2 years was developed based on variables significantly predictive of UPROR.

Results:
The average follow-up was 2.6 years (range, 1 to 5 y) in both the 7 cm (n=74) and 9 cm (n=93) groups. Twenty-five complications in 14 patients led to UPROR within 2 years of MCGR insertion, 8% incidence (95% CI, 4%-13%). Device-related complications (n=15) were the most common reason for UPROR, followed by wound complications (n=4), pain-related complications (n=3), junctional kyphosis (n=2), and incarcerated umbilical hernia (n=1). After adjusting for age, spine height, number of spine anchors, sex, and diagnosis, there was no significant difference in UPROR rates between groups. Fewer proximal anchors, smaller T1-S1 height, and more caudal mid-point of primary coronal curvature were significantly associated with UPROR in the predictive model.

Conclusion:
MCGR actuator size is not a significant factor in predicted UPROR. Smaller height, fewer anchors, and caudal apex increased UPROR risk.

Level of Evidence:
This is a retrospective, multicenter comparative cohort study (Level III therapeutic).
VITRECTOMY COMBINED WITH INVERTED INTERNAL LIMITING MEMBRANE FLAP INSERTION OR SINGLE-LAYERED FLAP COVERING TECHNIQUE FOR HIGHLY MYOPIC MACULAR HOLES WITH MACULAR RETINOSCHISIS
Authors: Jia Qinlang , Zhang Ke , Qi Biying , Yang Xiaohan , Wu Xijin , Wang Xinbo , Feng Xiao , Liu Wu 
Published: October 2024

Purpose:
To investigate the anatomical and visual outcomes of inverted internal limiting membrane flap insertion versus single-layered i-internal limiting membrane flap covering in highly myopic macular holes associated with macular retinoschisis.

Methods:
A retrospective study compared 23 G vitrectomy with inverted-internal limiting membrane flap insertion (30 eyes) or covering (31 eyes) in highly myopic macular holes patients. Pre- and postoperative optical coherence tomography images and best-corrected visual acuity (BCVA) were evaluated. Macular hole schisis was classified into three types based on the extent of outer layer schisis. Regression analysis identified predictors of closure rate and postoperative BCVA.

Results:
The baseline data of the two groups were matched, including BCVA, axial length, and minimum linear diameter, except for a higher hole height in insertion group (P = 0.038). After a mean follow-up of 11.7 months, type I closure rates were 83.3% (25/30) in the insertion group and 90.3% (28/31) in the covering group (P = 0.335), respectively. The intact external limiting membrane in the covering group (7/28) was higher compared with the insertion group (1/28) finally (P = 0.026). Final BCVA improved significantly in both groups (P < 0.001); the BCVA was better in closed highly myopic macular holes in the covering group (P = 0.011). Multivariate linear regression analysis revealed that preoperative BCVA (β = 0.386, P = 0.001) and Macular hole schisis stage (β = 0.309, P = 0.004) were independent predictive factors for the final BCVA.

Conclusion:
The single-layered inverted-internal limiting membrane flap covering favored foveal structure recovery and provided a better visual prognosis in closed highly myopic macular holes compared with insertion. The preoperative BCVA and macular hole schisis stage were independent predictors of visual outcomes in patients with highly myopic macular holes.
Finger-controlled nonultrasonic lens extractor
Authors: Beniz Luiz A.F. , Chatzea Marina S. , Zarei-Ghanavati Siamak , Jammal Alessandro A. , Yoo Sonia H. 
Published: October 2024

Purpose:
To report initial surgical experience and learning curve with a new finger-controlled, ultrasoundless lens extractor device and provide insights for future surgical endeavors.

Setting:
Bascom Palmer Eye Institute, Miami, Florida.

Design:
Single-center, noncomparative, retrospective, consecutive case series.

Methods:
61 eyes of 51 individuals with cataract. All surgeries were performed with the miCOR 700 lens extractor by a single experienced physician. Nuclear density was graded preoperatively. Corrected distance visual acuity (CDVA), intraocular pressure (IOP), and pachymetry were evaluated preoperatively and postoperatively. Surgical videos were reviewed to collect data on time for each surgical step and complications. Regression analyses assessed the learning curve, performance improvement, and effects of nuclear density on surgical time and postoperative pachymetric variation.

Results:
Patients had a mean age of 72.2 ± 7.6 years. Increased surgical experience significantly reduced procedure time (P < .001), nuclear removal time (P = .018), and cortex removal time (P = .002). Higher nuclear density resulted in a longer procedure (P < .001) and nuclear removal time (P < .001). One posterior capsular rent occurred, not attributed to the lens extractor. No thermal damage to the corneal wound was observed. Postoperative CDVA improved significantly (P < .001 for eyes without ocular comorbidities, P = .016 for eyes with ocular comorbidities). All cases of corneal edema and IOP spikes resolved within a month.

Conclusions:
The miCOR 700 lens extractor offers an innovative, cost-effective approach to cataract surgery. Further research is needed to compare it with conventional phacoemulsification techniques.
NaV1.8/NaV1.9 double deletion mildly affects acute pain responses in mice
Authors: Alves-Simões Marta , Teege Laura , Tomni Cecilia , Lürkens Martha , Schmidt Annika , Iseppon Federico , Millet Queensta , Kühs Samuel , Katona Istvan , Weis Joachim , Heinemann Stefan H. , Hübner Christian A. , Wood John , Leipold Enrico , Kurth Ingo , Haag Natja 
Published: October 2024

Abstract
The 2 tetrodotoxin-resistant (TTXr) voltage-gated sodium channel subtypes NaV1.8 and NaV1.9 are important for peripheral pain signaling. As determinants of sensory neuron excitability, they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and the release of neurotransmitters from sensory neuron terminals. NaV1.8 and NaV1.9, which are encoded by SCN10A and SCN11A, respectively, are predominantly expressed in pain-sensitive (nociceptive) neurons localized in the dorsal root ganglia (DRG) along the spinal cord and in the trigeminal ganglia. Mutations in these genes cause various pain disorders in humans. Gain-of-function missense variants in SCN10A result in small fiber neuropathy, while distinct SCN11A mutations cause, i. a., congenital insensitivity to pain, episodic pain, painful neuropathy, and cold-induced pain. To determine the impact of loss-of-function of both channels, we generated NaV1.8/NaV1.9 double knockout (DKO) mice using clustered regularly interspaced short palindromic repeats/Cas-mediated gene editing to achieve simultaneous gene disruption. Successful knockout of both channels was verified by whole-cell recordings demonstrating the absence of NaV1.8- and NaV1.9-mediated Na+ currents in NaV1.8/NaV1.9 DKO DRG neurons. Global RNA sequencing identified significant deregulation of C-LTMR marker genes as well as of pain-modulating neuropeptides in NaV1.8/NaV1.9 DKO DRG neurons, which fits to the overall only moderately impaired acute pain behavior observed in DKO mice. Besides addressing the function of both sodium channels in pain perception, we further demonstrate that the null-background is a very valuable tool for investigations on the functional properties of individual human disease-causing variants in NaV1.8 or NaV1.9 in their native physiological environment.
Increasing Diabetic Retinopathy Screening in Resident-Run Clinic Through Partnership With Ophthalmology Clinic: A Pilot Study
Authors: Mahoney Catherine , Toomey Caitlin 
Published: October 2024

ABSTRACT
Despite the importance of early detection of diabetic retinopathy, many diabetic patients fail to receive the recommended screening. The objective of this quality-improvement initiative was to increase diabetic retinopathy screening through a partnership between primary care and ophthalmology, where primary care clinic staff may schedule patients directly for screening appointments at point of referral. To our knowledge, this intervention is the first described to use an interspecialty partnership to increase screening. We implemented the intervention at a resident-run primary care clinic with a medically underserved patient population. The pilot intervention took place over a 6-month time frame. The completion rate of diabetic retinopathy screening examinations was compared before and after intervention and was found to increase in a statistically significant manner from 34.7% to 40.5% (p = .01). The no-show rate did improve from 66.7% preintervention to 46.0% postintervention; however, this change was not statistically significant (p = .44). During this pilot, the intervention was able to increase diabetic retinopathy screening completion rate; however, further efforts should be aimed at addressing no-shows. Overall, this initiative was a positive step toward the goal of every diabetic patient undergoing the appropriate screening examinations.
Use of calculated free testosterone in men: advantages and limitations
Authors: Nyamaah Jennifer Afrakoma , Narinx Nick , Antonio Leen , Vanderschueren Dirk 
Published: October 2024

Purpose of review
Due to technical requirements and high cost, equilibrium dialysis-free testosterone (T) measurements are not commonly available in clinical practice. Clinicians rely on calculated free T (cFT) as a proxy. This review discusses using free T as a second-line assessment, highlighting its relevance in preventing misdiagnosis and overtreatment of male hypogonadism.

Recent findings
While there is consensus on measuring total T – comprising sex hormone-binding globulin (SHBG)-bound, albumin-bound, and free T – as a first step in diagnosing male hypogonadism, evidence confirms that aging and conditions like obesity influence both total T and SHBG levels. Furthermore, low free T has been associated with symptoms of androgen deficiency, even in men with normal total T. Clinicians should, however, be aware of limitations of free T calculations, particularly the lack of standardization. Recent developments include establishing age-stratified free T reference ranges measured by equilibrium dialysis.

Summary
Free T remains a subject of longstanding controversy. Factors such as age and obesity can alter total T and SHBG levels. Free T serves as a second-line indicator of androgen exposure, taking SHBG fluctuations into account. Given that commonly used free T calculators only provide approximations of free T, there is a need to further standardize free T calculators.
Fibro-osseous lesions of the sinonasal tract: a contemporary review
Authors: Motwani Kartik , Adelman Avraham E. , Chapurin Nikita 
Published: October 2024

Purpose of review
Fibro-osseous lesions (FOL) are benign, slow-growing lesions that are often incidentally discovered in the sinonasal cavity. They may necessitate surgical resection in patients with postobstructive sinusitis, or in cases of cranial nerve and orbital compression. We examine the recent advancements in otolaryngology relating to diagnostic characteristics and treatments for FOL, with emphasis on new technologies to improve outcomes and reduce recurrence.

Recent findings
We discuss distinguishing characteristics across FOL subtypes, including osteomas, fibrous dysplasia, and ossifying fibroma. Recent literature encompasses clinical case series and animal model studies examining mechanistic, diagnostic, and therapeutic findings in FOL. Recent advancements include emerging pharmacological therapies, development of imaging guidance for surgical planning, and focus on the importance of complete surgical resection for improved outcomes.

Summary
Management of most FOL may be approached by endoscopic techniques, harnessing recent improvements in image guidance and surgical innovation. Improved diagnostic imaging, including the use of 3-D surgical planning, has been shown to enhance treatment outcomes. Improved understanding of the genetic and pathophysiological characteristics of FOL could further reveal targeted therapies, reducing recurrence and improving patient quality of life.
Emerging Artificial Intelligence-Based Pedagogies in Didactic Nursing Education
Authors: Gerdes Michele , Bayne Andrew , Henry Kristina , Ludwig Barbara , Stephenson Leigh , Vance Allison , Wessol Jennifer , Winston Sarah 
Published: October 2024

Background:
Artificial intelligence pedagogies are increasingly commonplace in health care education, and limited information guides their application in didactic nursing environments.

Purpose:
To examine the current state of artificial intelligence–based pedagogies used in didactic nursing education.

Design:
The review was conducted using Arksey and O’Malley’s scoping review framework and the Joanna Briggs Institute’s System for the Unified Management, Assessment, and Review of Information platform. Literature is reported using the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews.

Methods:
The review included articles published between January 1, 2013, and July 23, 2024, in MEDLINE (via PubMed), Cumulative Index to Nursing and Allied Health Literature, Education Resources Information Center, World Science, and Google Scholar. Two reviewers independently assessed all articles.

Results:
Themes for the 16 included articles were generative artificial intelligence and pairing artificial intelligence with other pedagogical strategies.

Conclusions:
More research is needed to examine artificial intelligence–based pedagogies in didactic nursing education.
Innovative and best models of palliative and end-of-life care – with focus on rural and remote communities
Authors: Mogan Caroline , Davies Nathan , Dening Karen Harrison , Lloyd-Williams Mari 
Published: October 2024

Purpose of review
The review aims to synthesize the most recent innovative models of palliative care being delivered in rural and remote locations.

Recent findings
Worldwide, as the ageing population grows, more people will require palliative care. However, equal availability of high-quality palliative care services remains a significant challenge, particularly in rural and remote communities. Innovative models of palliative care have been developed to address the projected need of people in rural and remote areas. Models that leverage the use of digital healthcare (such as telecare and Artificial Intelligence), the non-specialized palliative care workforce (such as GPs, pharmacists, and family carers), and community driven approaches have demonstrated success in achieving positive palliative care outcomes, such as reduced physical and emotional distress, and family carers feeling more supported.

Summary
There is a need to support people to remain within their rural and remote communities towards the end-of-life (EOL). While some models of care have been identified to help with this, there continues to be significant difficulties in access to health and social care in rural and remote areas. It is important we build on this research to understand more broadly the models of support for those living in remote and rural communities at the EOL.
The association between peripheral neuropathy and daily-life gait quality characteristics in people with diabetes
Authors: Hulshof Chantal M , van der Leeden Marike , van Netten Jaap J , Gijssel Maarten , Evers Jordi , Bus Sicco A , Pijnappels Mirjam 
Published: October 2024

0.AbstractBackgroundPeripheral neuropathy is a common complication of diabetes and increases the risk of falls, possibly through gait (quality) impairments in daily life. Characteristics of gait quality have been associated with peripheral neuropathy in a laboratory setting, but little is known about the more relevant association with gait quality in daily life.Research questionWhat is the association between peripheral neuropathy and gait quality characteristics in daily life in people with diabetes?MethodsData from two cross-sectional studies were combined in an exploratory analysis, including a total of 98 participants with diabetes (mean age: 68 (SD 7) years, 32 females), of which 68 with peripheral neuropathy. Participants wore a tri-axial accelerometer for seven consecutive days. Walking episodes ≥5 seconds were identified and analysed to determine various gait quality characteristics. Associations were assessed using linear regression analyses, adjusted for walking speed and other potential confounders.ResultsPeripheral neuropathy was significantly associated with a lower walking speed (people with neuropathy: 0.81 vs without neuropathy: 0.88 m/s; β (95% confidence interval (CI)): -0.114 (−0.202 to -0.026)), a lower stride frequency (0.81 vs 0.85 strides/s; β (95% CI): -0.030 (−0.057 to -0.003)), lower gait intensity (i.e. lower root mean square) in vertical direction (1.38 vs 1.63 m/s2; β (95% CI): -0.074 (−0.143 to -0.006)), and less gait symmetry (i.e. lower harmonic ratio) in vertical direction (1.82 vs 2.27; β (95% CI): -0.322 (−0.474 to -0.170)). People with peripheral neuropathy had non-significantly poorer gait quality for most of the other 21 gait quality characteristics.SignificancePeripheral neuropathy seems to negatively affect several gait quality characteristics measured in daily life. These results need to be replicated in future studies and may help to develop targeted gait training to improve gait quality and potentially reduce fall risk in people with diabetes and peripheral neuropathy.
Circadian clock features define novel breast cancer subtypes and shape drug sensitivity
Authors: Ector Carolin , Didier Jeff , Landtsheer Sébastien De , Nordentoft Malthe S. , Schmal Christoph , Keilholz Ulrich , Herzel Hanspeter , Kramer Achim , Sauter Thomas , Granada Adrián E. 
Published: October 2024

AbstractThe circadian clock regulates key physiological processes, including cellular responses to DNA damage. Circadian-based therapeutic strategies optimize treatment timing to enhance drug efficacy and minimize side effects, offering potential for precision cancer treatment. However, applying these strategies in cancer remains limited due to limited understanding of the clock’s function across cancer types and incomplete insights into how the circadian clock affects drug responses. To address this, we conducted deep circadian phenotyping across a panel of breast cancer cell lines using two complementary reporters. Observing diverse circadian dynamics, we developed metrics to assess circadian rhythm strength and stability. This led to the identification of four distinct circadian-based phenotypes in breast cancer: functional, weak, unstable, and dysfunctional clocks. Furthermore, we demonstrate that the circadian clock plays a critical role in shaping pharmacological responses to various anti-cancer drugs and identify circadian features that accurately predict drug sensitivity. Collectively, our findings establish a foundation for advancing the use of chronotherapeutic strategies in breast cancer treatment, expanding their potential application to improve therapeutic outcomes in breast cancer.
Regulating IL-2 immune signaling function via a core allosteric structural network
Authors: Woodward Claire H. , Solieva Shahlo O. , Hwang Daniel , De Paula Viviane S. , Fabilane Charina S. , Young Michael C. , Trent Tony , Teeley Ella C. , Majumdar Ananya , Spangler Jamie B. , Bowman Gregory R. , Sgourakis Nikolaos G. 
Published: October 2024

AbstractHuman interleukin-2 (IL-2) is a crucial cytokine for T cell regulation, with therapeutic potential in cancer and autoimmune diseases. However, IL-2’s pleiotropic effects across different immune cell types often lead to toxicity and limited efficacy. Previous efforts to enhance IL-2’s therapeutic profile have focused on modifying its receptor binding sites. Yet, the underlying dynamics and intramolecular networks contributing to IL-2 receptor recognition remain unexplored. This study presents a detailed characterization of IL-2 dynamics compared to two engineered IL-2 mutants, “superkines” S15 and S1, which exhibit biased signaling towards effector T cells. Using NMR spectroscopy and molecular dynamics simulations, we demonstrate significant variations in core dynamic pathways and conformational exchange rates across these three IL-2 variants. We identify distinct allosteric networks and excited state conformations in the superkines, despite their structural similarity to wild-type IL-2. Furthermore, we rationally design a mutation (L56A) in the S1 superkine’s core network, which partially reverts its dynamics, receptor binding affinity, and T cell signaling behavior towards that of wild-type IL-2. Our results reveal that IL-2 superkine core dynamics play a critical role in their enhanced receptor binding and function, suggesting that modulating IL-2 dynamics and core allostery represents an untapped approach for designing immunotherapies with improved immune cell selectivity profiles.HighlightsNMR and molecular dynamics simulations revealed distinct conformational dynamics and allosteric networks in computationally re-designed IL-2 superkines compared to wild-type IL-2, despite their similar crystal structures.The superkines S1 and S15 exhibit altered sampling of excited state conformations at an intermediate timescale, with slower conformational exchange rates compared to wild-type IL-2.A rationally designed mutation (L56A) in the S1 superkine’s core allosteric network partially reverted its dynamics, receptor binding affinity, and T cell signaling behavior towards that of wild-type IL-2.Our study demonstrates that IL-2 core dynamics play a critical role in receptor binding and signaling function, providing a foundation for engineering more selective IL-2-based immunotherapies.Graphical Abstract