bluuebunny/crossref_metadata_2025 huggingface dataset:
808 Analysis of Medulloblastomas Subgroups in Pediatric Patients in Latin-America
Authors: Passinho Juliana , Purificacao Junior Antonio F. , Oliveira Renato Guedes , Gorender Ethel , Waldir Beira Renato Melaragno , Carvalho Laube Kaito Alves , Manfroi Gregori , Rehder Roberta , Epelman Sidnei
Published: March 2023

INTRODUCTION:

The 4 groups molecular-based classification of medulloblastomas is widely accepted. However, technology inaccessibility and low-quality formalin-fixed and paraffin-embedded (FFPE) samples, unable its application for most Latin-American cancer centers.

METHODS:

The goal of this study was to perform a feasibility analysis based on 18 mRNA expression by qPCR integrated with immunohistochemistry (IH) and fluorescent hybridization in situ (FISH) (c-MYC, n-MYC and monosomy 6) for molecular stratification to create an International Treatment Protocol at a low cost for low-income centers.

RESULTS:

Fifty-four FFPE samples were classified according to histologic and molecular aspects. Classic medulloblastoma was the commonest histology (53.7%), followed by desmoplastic/extensive nodularity (24.1%), NOS (16,7%) and anaplastic (5,6%). IH markers classified patients in three groups (WNT, SHH and non-WNT/non-SHH) in 98% of cases. PCR-based method confirmed results from IH in 81.5%. Additionally, it detected WNT activation in 2 more patients, previously classified as SHH. For both cases, the presence of monosomy 6 confirmed WNT subgroup. The integration of these three techniques resulted in the following frequencies: WNT (13.0%), SHH (38.9%), group 3 (9.3%), group 4 (20.3%) and non-WNT/non-SHH (18.5%). From 40 patients with clinical follow-up available, 3-year overall survival (n = 40) for low, intermediate and high-risk groups were 100%, 60% and 20%, respectively (p < 0.05), based only in molecular criteria, which confirmed the prognostic importance of this method at a low cost.

CONCLUSIONS:

The prognosis of the treatment of medulloblastomas has changed after novel studies on the molecular subgroups and the introduction of target-based therapy. The current protocol will enable different centers to implement treatment based on the knowledge of molecular subgroups.
834 Inhibition of the Epileptic Engram Prevents Seizures in a Mouse Model of Temporal Lobe Epilepsy
Authors: Harward Stephen C. , Clark Katie , Shalita Chidyaonga , Lin Thiri , McNamara Jim O.
Published: March 2023

INTRODUCTION:

The cellular basis of temporal lobe epilepsy (TLE) remains elusive and consequently has hindered efforts to develop novel therapies. Similar challenges have plagued the field of learning and memory until recent work identified plasticity of a subset of neurons in a multi-focal network as the cellular source for memory (the memory engram). Building on these results, we ask if an engram exists for TLE and if it can be targeted to modulate the epileptic phenotype?

METHODS:

We used the intra-amygdala kainic acid status-epilepticus (SE) model in which a brief episode of SE results in spontaneous seizures days later. To identify cells active during epileptogenesis and thus possibly comprising the engram, we performed immunohistochemistry for the immediate early gene product c-Fos (a marker of cellular activity) at various time points after SE (1 to 96 hours). To modulate the persistently active cells, we used a chemical-genetic approach to first label these cells with an inhibitory DREADD (designer receptors exclusively activated by designer drugs) and then inhibit their activity with clozapine-N-oxide (a small molecular activator of DREADDs).

RESULTS:

We found a pattern of c-Fos expression that first appears after SE in the dentate gyrus, begins to localize in subsets of CA3 and CA1 pyramidal neurons by 12 hours, and then persists in these cells for approximately 72 hours. With our chemical-genetic approach, we successfully labeled the cells active after SE with an inhibitory DREADD and then silenced their activity once the animals were epileptic. Such silencing proved effective in significantly reducing the occurrence of subsequent seizure activity.

CONCLUSIONS:

Following an epilepsy-inducing insult, a subset of hippocampal neurons remains persistently active for several days. Subsequent inhibition of these neurons in epileptic animals prevents seizures, consistent with them comprising the epileptic engram.
868 Analysis of the Surgical Edge of Adult-Type Diffuse Astrocytomas and its Correlation With Prognosis
Authors: Salazar Ramirez Zita Elizabeth , Janis Sandoval Ramirez Christian J. , Feria Romero Iris Angelica , Nettel-Rueda Barbara
Published: March 2023

INTRODUCTION:

Glioma cells extend beyond the macroscopic margins of the tumor, making it impossible to pursue a cure based only on surgical treatment in patients with the diagnosis of Adult-Type Diffuse Glioma (ATDG). The tumor volume left behind in the surgical bed is a significant predictor of recurrence and survival. In the present study, we analyzed the grade of malignancy in the surgical edge (SE) after tumor removal and correlated it with progression-free survival (PFS) in patients diagnosed with ATDG.

METHODS:

Surgical edge biopsy samples were obtained after tumor removal in 15 patients (3 A2; 2 A3; 2 A4; and 8 GBM, WHO CNS 5); the samples were analyzed by three neuropathologists and were classified in a GOM (2, 3, or 4). An MRI was performed within 48 hours after surgery in all patients to assess the extent of resection. PFS was obtained from clinical and MRI follow-up. Data analysis was conducted using a nonparametric Spearman rank coefficient correlation test.

RESULTS:

Correlation analysis between the highest grade of malignancy found in the SE and PFS was -0.8080 (95% CI = -0.9359 to -0.4920, p < 0.0001). See Image 1.

CONCLUSIONS:

A strong correlation between the GOM in the SE and PFS was found in ATDG Astrocytomas. See Image 2 and 3.
874 Direct Visualization of Planned Resection Volumes with Microbubble-Enhanced MR-Guided Focused Ultrasound Blood-Brain Barrier Opening and Sodium Fluorescein in Infiltrating Gliomas
Authors: Ahmed Abdul-Kareem , Anastasaidis Pavlos , Gandhi Dheeraj , Woodworth Graeme
Published: March 2023

INTRODUCTION:

Surgical resection of infiltrating gliomas (IG,Grade II-IV) can be challenging, as many do not consistently enhance on gadolinium-enhanced MRI. Evidence of survival benefit of supratotal resection is mounting. No method exists to preoperatively demarcate a planned surgical resection volume. Such physical demarcation could significantly improve the resection of IGs.

METHODS:

Four patients were treated (3M:1F), with a mean age of 32.5 (29-36). All were suspected of having or were previously diagnosed with a supratentorial IG. Patients underwent awake transcranial MB-FUS BBBO of the lesion bed and perilesional areas planned for resection at the discretion of the operating neurosurgeon (GFW). Subsequently, patients were transported directly to the operating room. For each patient, sodium fluorescein was administered, and then tumors were resected with standard craniotomies under general anesthesia, using neuronavigation and fluorescent microscopy.

RESULTS:

Patients tolerated the procedure well without adverse events with a median follow-up of 15.7 months. The mean tumor volume was 18.2 cm3 (6.8-32.9). The demarcated planned resection volume was visualized with fluorescent microscopy. Fluorescing tissue was completely resected. Gross-total or supratotal resection was achieved in all patients. Pathologies included diffuse astrocytoma, oligodendroglioma, and anaplastic oligodendroglioma.

CONCLUSIONS:

MB-FUS BBBO and sodium fluorescein present a safe and novel method of demarcating a preoperatively planned surgical resection volume with resultant intraoperative visualization in IGs. This method is resilient to brain shift, and is an addition to the current repertoire for visualizing non-contrast-enhancing gliomas. The same method can be investigated for use in epilepsy surgery.
879 Monitoring Flash Visual Evoked Potentials During Endoscopic Skull Base Surgery Reduces the Risk of Visual Pathway Injury
Authors: Ochoa-Sanchez; Mazen Alotaibi Rafael , Kilty Shaun , Agbi Charles B. , Lamothe Andre , Schramm David , Alkherayf Fahad A.
Published: March 2023

INTRODUCTION:

Minimally invasive endoscopic endonasal skull base surgery offer safer and more effective access to the skull base to remove benign and malignant tumors. However, endoscopic skull base surgery around the visual pathway may increase the risk of injury of the visual pathway. Monitoring of flash visual evoked potentials (FVEPs) during surgery may detect a possible injury to the visual pathway, allowing the surgeon to take corrective measures during surgery to reverse or minimize it.

METHODS:

We identified patients with chiasmatic or pre-chiasmatic lesions who underwent minimally invasive endoscopic skull base surgery. Patients were subjected to eye exam (color vision, visual acuity, and visual field evaluation) within 3 months before surgery, and within 6-12 weeks and 6-9 months after surgery to explore short- and long-term surgical outcomes on eyesight. During surgery, FVEPs were recorded from electrodes placed in the scalp overlying the visual cortex after flashing red light stimulation (Cadwell LED stimulating goggles), as reported previously. We examined the relationship between FVEPs amplitude change and visual outcome on these patients.

RESULTS:

102 patients have been enrolled in this retrospective study. The median age at admission was 57 years (range: 22-86 years) and 68.4% of the patients were female. Most of the patients had either pituitary adenoma (64.7%) or skull base meningioma (23.5%). Preliminary eye evaluations (pre- and post-surgery) showed that the patients did not develop short- or long-term eyesight impairments.

CONCLUSIONS:

Our study provides a new method for rapidly acquiring reproducible FVEP waves for which allows for timely reporting significant FVEP changes resulting in prompt signal action. Thus, monitoring FVEPs during endoscopic endonasal skull base surgery reduces the risk of visual pathway injury.
880 Electrophysiological Patterns of Glioma-Induced Neuronal Network Remodeling are a General Property of Brain Tumors Regardless of Subtype
Authors: Aabedi Alexander Arash , Lipkin Benjamin , Young Jacob , Hinkley Leighton , Findlay Anne , Daniel Andy , Krishna Saritha , Umbach Gray , Surapaneni Akhil , Kaur Jasleen , Berger Mitchel , Molinaro Annette , Brang David , Nagarajan Srikantan S. , Hervey-Jumper Shawn L.
Published: March 2023

INTRODUCTION:

Recent evidence indicates that diffuse gliomas engage with neurons at the single-unit and circuit level through differing mechanisms. Certain malignant gliomas form glioma-neuron excitatory glutamatergic synapses and modulate neuron-neuron synapses through activity-dependent paracrine signaling, while others establish glioma-glioma connections via tumor microtubes. It is therefore possible that diffuse gliomas remodel neuronal circuits in a defined and predictable manner and demonstrate distinct electrophysiological profiles with prognostic and therapeutic significance.

METHODS:

Following spatial-temporal registration, an elastic net logistic regression classifier was used to distinguish between power spectra arising from glioma-remodeled cortex and within-subject control conditions (N = 140). Model significance was determined non-parametrically by re-training each model 1,000 times with randomly permuted class labels and testing the true phi coefficient against the null distribution.

RESULTS:

In the discovery dataset, glioma infiltration was accurately classified based on tumor intrinsic neuronal activity (p < 0.05) in 127 patients (90.7%). Thirty electrophysiological features were identified, which revealed increased power in the delta range (1-4 Hz) and decreased power in the beta range (12-20 Hz) as a unique signature of glioma remodeling (p < 0.05) which was preserved in the validation dataset as well as across WHO 2021 diffuse glioma subtypes. To identify gene expression programs and signaling mechanisms that may contribute to glioma-induced remodeling but are potentially not identified in the current clinical classification scheme, targeted, next generation sequencing was performed and used as covariates, which again demonstrated the significance of the delta-beta spectral features.

CONCLUSIONS:

These data support converging mechanisms of glioma-induced neuronal network remodeling across tumor subtypes, setting the stage for novel therapies such as neuromodulation.
886 Stereotactic Radiosurgery Reprograms Macrophage, Microglia, and T Cell Populations in the Glioblastoma Immune Microenvironment
Authors: Young Jacob , Cho Nam Woo , Lucas Calixto-Hope , Seo Kyounghee , Santos Raquel , Phillips Joanna , Ozawa Tomoko , Berger Mitchel , Raleigh David R.
Published: March 2023

INTRODUCTION:

Daily ionizing radiation, the first-line treatment for glioblastoma, prevents durable immune infiltration of the tumor microenvironment. Hypofractionated radiotherapy is used to treat glioblastomas at recurrence, but the impact of hypofractionated radiotherapy on the glioblastoma immune microenvironment is incompletely understood.

METHODS:

Syngeneic GL261 (3x105 cells/mouse) or SB28 glioblastoma cells (3 x 104 cells/mouse) were implanted into the frontal lobe of immunocompetent C57BL/6J mice. Bioluminescence was used to assess glioblastoma growth. After tumor engraftment, glioblastomas were treated with conformal SRS (18Gy/1Fx) or sham. Glioblastomas were collected for histologic, single-cell, or molecular analyses 5 days after treatment or at the time of euthanasia after monitoring for survival. Glioblastoma immune microenvironment responses were assessed using (1) H&E, (2) single cell mass cytometry (CyTOF) or IHC to define or validate immune cell changes, respectively, or (3) multiplexed cytokine assays to elucidate molecular mechanisms reprograming the glioblastoma immune microenvironment in response to SRS.

RESULTS:

SRS attenuated glioblastoma growth and prolonged survival compared to sham treatment in both immunocompetent intracranial mouse models (GL261: 14 days versus 27 days, p < 0.001, SB28: 19 days versus 22 days, p = 0.001). CyTOF showed SRS decreased immunosuppressive macrophage infiltration and increased microglia or CD8+ T cell infiltration of the glioblastoma immune microenvironment in GL261 tumors , however, there were very few changes in the lymphoid compartment of SB28 tumors . Histologic analyses validated T cell and microglia infiltration after SRS . Glioblastoma cytokine analysis revealed inhibition of pro-tumor/anti-inflammatory cytokines (IL6, LIF) after SRS in SB28 tumors .

CONCLUSIONS:

Single-fraction SRS reprograms glioblastoma macrophage, microglia, and CD8+ T cell populations in preclinical models, suggesting SRS or inhibition of pro-tumor/anti-inflammatory mechanisms underlying the immunosuppressive glioblastoma microenvironment represent immunogenic therapies that may offer a benefit to patients with glioblastoma.
887 Mizuho Minimally Invasive Brain Tumor Surgery Award
Authors: Yoon Wan Soo
Published: March 2023

INTRODUCTION:

Early descent of the diaphragm sellae (DS) during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary macroadenoma surgery is occasionally a troublesome event by blocking the surgical field. This can block access for remnant tumor or cause cerebrospinal fluid leak due to uneventful rupture of the DS. Some methods are reported previously, but they have many limitations.

METHODS:

We designed a simple and rigid pituitary retractor with the least space occupation in the nasal cavity to be compatible in EETS. The pituitary retractor was held by external holder system to support the herniated DS stably. We retrospectively reviewed a clinical 22 cases of pituitary macroadenomas underwent EETS using the pituitary retractor.

RESULTS:

The pituitary retractor stably pushed up the herniated DS in all cases, and the surgeon proceeded the procedure with bimanual maneuver. The pituitary retractor was helpful to remove tumors around the medial cavernous sinus and behind the DS in 16 and seven cases, respectively. In four cases, the meticulous hemostasis was completed with the direct visualization by the DS elevation with this retractor. Gross total tumor resection was performed in 20/22 patients (91%). The impaired visual function and hypopituitarism were improved in 18/20 (90%) and 7/14 (50%) patients after surgery, respectively. There was no complication related with the pituitary retractor.

CONCLUSIONS:

During EETS for pituitary macroadenomas, the novel pituitary retractor reported in this study is a very useful technique when the herniated DS block the surgical field and bimanual maneuver. This pituitary retractor can help to result in the excellent surgical outcomes with minimal morbidity.
889 Significance of Cortico-Bulbar Motor Evoked Potential (CoMEP) Monitoring in Vestibular Schwannoma Surgery for Prediction of Postoperative Facial Nerve Palsy
Authors: Roessler Karl , Shawarba Julia , Strasser Elisabeth , Hirschmann Dorian , Hertha Johannes , Reitbauer Stefan , Novak Klaus
Published: March 2023

INTRODUCTION:

Direct facial nerve stimulation during vestibular schwannoma surgery (VSS) allows preservation of the nerve in its continuity. However, prognostication of post- operative nerve function remains challinging.

METHODS:

In total, 51 patients (median age 52yrs; 19-84) with unilateral VS (median size 20mm;10-50) were included. Intraoperative neuromonitoring consisted of auditory evoked potentials (AEPs), direct facial nerve stimulation and CoMEPs. An anodal stimulation via subdermal corkscrew electrodes on position C3 or C4 and a cathode near Cz with a train of 6 pulses, each with a duration ono 500us, at a frequency of 5000 Hz and an interstimulus-interval of 2 ms was used.

RESULTS:

Complete resection was achieved in >90% of patients. Preoperative hearing was preserved in 78% (40/51) patients and postoperative serviceable hearing was preserved in 35% (18/49) patients and was closely related to preserved wave V of the AEPs. Additionally, MEPs were successfully monitored in every patient for the entire duration of the surgery. In 16% of the patients, more than 50% reduction of MEP baseline amplitude was recorded, correlating directly with moderate to severe postoperative facial palsy (House Brackman 3-5). No facial palsy without MEP amplitude reduction was observed. During 6 months FU, recovery of 1-2 HB Grades was observed in all cases. All patients with intraoperative MEP amplitude reduction had significant larger VS than patients without MEP amplitude reduction (27 vs 22 mm, p = 0.02)

CONCLUSIONS:

In addition to direct facial nerve stimulation, intraoperative CoMEP monitoring during VSS seems to be of high significance and value for intraoperative facial nerve preservation and prognosis estimation of postoperative short- and long-term facial palsy.
892 Validation of Docetaxel as a Radiosensitizer in High-Risk Meningiomas Based on DNA Methylation Profiling
Authors: Youngblood Mark W. , Tran Anh , Wang Wenxia , An Shejuan , Scholtens Denise , Zhang Lyndsee , O’Shea; Jenny Pokorny Kaitlyn , Magill Stephen , Sachdev Sean , Lukas Rimas Vincas , Ahmed Atique , Unruh Dusten , Walshon Jordain , McCortney Kathleen , Wang Yufen , Baran Aneta , Sahm Felix , Aldape Kenneth , Chandler James P. , James David , Heimberger Amy B. , Horbinski Craig
Published: March 2023

INTRODUCTION:

Genome-wide methylation profiling has emerged as a transformative prognostic tool in meningiomas, and has identified discrete epigenetic clusters that share distinct clinical and biological features. The association of these signatures with underlying pathological mechanisms has not been well-explored.

METHODS:

From a collection of over two-hundred well-annotated tumors, we found 981 genes in which methylation signal was predictive of recurrence. Using pathway enrichment analysis, Docetaxel was identified as a candidate therapeutic agent; a medication that is frequently utilized in other common malignancies. This chemotherapy was validated in vitro and in vivo using patient derived meningiomas, and also tested in combination with radiotherapy.

RESULTS:

Based on 15 patient-derived cultures from our institution and 2 public cell lines, we found that Docetaxel could inhibit meningioma growth at concentrations that were favorable relative to other cancers. This drug triggered apoptosis in meningiomas of all tumor grades and methylation classes, with IC50 values ranging from 0.8 nm to 4.4 nm in vitro. Combining Docetaxel with radiation therapy resulted in synergistic cytotoxic effects on meningioma cultures, associated with elevated markers of cell death and dsDNA breaks. We confirmed our results via orthotopic meningioma models of the cell lines CH157 and IOMM-Lee, which exhibited dose-dependent improvements in mortality and tumor volume in response to Docetaxel and radiation.

CONCLUSIONS:

Our results leverage DNA methylation patterns to repurpose FDA-approved medications in the treatment of meningiomas, and suggest a clinical trial of Docetaxel with radiotherapy may be efficacious in aggressive lesions.
893 Development of a Rabbit Human Glioblastoma Model for Testing of Endovascular Selective Intra-Arterial Infusion (ESIA) of Novel Stem Cell-Based Therapeutics
Authors: Srinivasan Visish M. , Kan Peter , Gumin Joy , Collins Dalis E. , Chen Stephen , Chen Melissa M. , Garcia Robert , Fueyo Juan , Lang Frederick F.
Published: March 2023

INTRODUCTION:

Poor outcomes for glioblastoma (GBM) are partly due to the inability to deliver therapeutic agents to the tumor because of the blood brain barrier (BBB) as well as ineffective agents. We have evaluated bone marrow-derived mesenchymal stem cells (MSCs) as transport vehicles of biological therapeutics, particularly Delta-24-RGD (D24), an engineered tumor-selective oncolytic adenovirus that replicates and lyses only in human tumor cells. In mice, we have shown that MSCs loaded with D24 (MSCs-D24) home to GBMs after intra-arterial (IA) carotid infusion, resulting in widespread distribution in the tumor and oncolysis. Intravenous infusion is ineffective, rendering IA delivery the only effective systemic option. To understand the applicability of IA infusions of MSCs-D24 requires a large animal, human brain tumor model recapitulating the challenges of clinical use.

METHODS:

Rabbits underwent stereotactic xenoimplantation of human GBM cell lines. Tumor creation was confirmed on magnetic resonance imaging (MRI), histologic and immunohistochemistry analysis. Selective internal carotid artery MSCs-D24 infusion ipsilateral to the tumor was performed assess efficacy and safety.

RESULTS:

We report on successful xenoimplantation of human glioblastoma cell lines (U87, GSC17, and GSC8-11) in 28 immunosuppressed rabbits using Mycophenolate Mofetil, Dexamethasone, and Tacrolimus. The implanted rabbits were followed for 35 days prior to tumor assessment with MRI, angiography, and histological analysis. On MRI, the tumors were hyperintense on T2-weighted image and enhanced (evidence of BBB breakdown). On histological analysis, tumors showed phenotypic traits of human GBM and display varying levels of vascularity, an important feature for testing IA therapy. Selective internal carotid artery MSCs-D24 infusion was safe in the model, and MSCs-D24 homed to the implanted tumor at 24 hours.

CONCLUSIONS:

The intracranial immunosuppressed rabbit human GBM model allows testing of ESIA infusion of novel therapeutics (eg. MSCs-D24) in a clinically relevant fashion.
Distinct myofibre domains of the human myotendinous junction revealed by single-nucleus RNA sequencing
Authors: Karlsen Anders , Yeung Ching-Yan Chloé , Schjerling Peter , Denz Linda , Hoegsbjerg Christian , Jakobsen Jens R. , Krogsgaard Michael R. , Koch Manuel , Schiaffino Stefano , Kjaer Michael , Mackey Abigail L.
Published: March 2023

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell–matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle–tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.
Diet in the prevention and treatment of depression - systematic review
Authors: Szulc Izabela , Swacha Weronika , Kozłowska Julia , Pacek Katarzyna , Piekarska Małgorzata , Kasperski Radosław , Jedlina Klaudia , Rusin Klaudia , Budziłło Julia , Lewandowska Monika
Published: March 2023

Depression is one of the leading causes of disability worldwide. It affects, according to WHO, nearly 300 million people worldwide, a number close to 3,8 % of the world’s population. Depression is not exclusively a mental disorder limited to psychiatry, nowadays it is present in all medical fields. It has a significant association with many comorbidities, as an example cardiovascular diseases and metabolic disorders. Additionally, depression often is manifested with psychosomatic symptoms. Both aspects lead clinicians to major diagnostic and therapeutic challenges. Each one of dietary element: omega-3 fatty acids, zinc, selenium, iron, vitamin B12, vitamin D, folate, creatine was found to correspond with mental health in patients and the level of mentioned diet components is negatively correlated with depression risk of individuals. Each of the dietary aspect considered in the article has a significant correlation with depression disorder and might support the new multidisciplinary attitude toward it in mental health.
DEVELOPMENT OF A LEADERSHIP MINDSET SCALE
Authors: Kangas Nathan M. , Kumar V. Krishna , Moore Betsy J. , Flickinger Christopher A. , Barnett Jennifer L.
Published: March 2023

The purpose of the study was to construct a Leadership Mindset Scale (LMS) and to assess its reliability and construct validity. Participants were 100 employees in a variety of leadership and non-leadership positions at various organizations in three states. An item and factor analysis on the 13 LMS items led to a scale with 11 items (Cronbach α = .80). A Principal Axis Factor analysis with Promax rotation suggested three factors: Leadership Mindset Teachability (LMS-T), a belief in leadership teachability; Leadership Mindset Improvability (LMS-I), a belief in leadership improvability over time; and Leadership Mindset Predictability (LMS-P), a belief that leadership cannot be predicted at an early age. Convergent validity of LMS-Total and Teachability was evidenced by significant correlations with the implicit theories of intelligence and anxiety scales, and developmental leadership and transactional leadership scales. Divergent validity was evidenced by a non-significant correlation with social desirability. The results suggest that the LMS measures a construct different from those of other leadership scales used in the study. The LMS can be helpful in leadership training programs to promote a growth mindset about the trainability of leadership skills.
Store-Wide Shelf-Space Allocation with Ripple Effects Driving Traffic
Authors: Flamand Tülay , Ghoniem Ahmed , Maddah Bacel
Published: March 2023

How Product Locations Drive Traffic Throughout a Retail Store

In “Store-Wide Shelf-Space Allocation with Ripple Effects Driving Traffic,” Flamand, Ghoniem, and Maddah develop a framework for deciding where to place products in a store, in addition to apportioning the shelf space among products, in a way that maximizes impulse profit, a phenomenon that may account for 50% of transactions. By analyzing a large data set of customer receipts from a grocery store in Beirut, the authors develop a regression model that estimates traffic at a shelf based on its location and the “attraction” from products allocated nearby. The traffic model is embedded within a mixed-integer nonlinear program, which they solve via specialized linear approximations. For the store in Beirut, a 65% improvement in impulse profit is anticipated, and the location of products is found to be significantly more important in driving store-wide traffic than the relative shelf-space allocation.
A cautionary tale of two canines: a case report
Authors: Hoare Sophie , Larmour Colin
Published: March 2023

This orthodontic case report highlights the unpredictable behaviour of ectopic maxillary permanent canines. An 11-year-old male patient had bilateral ectopic maxillary canine teeth that were in high positions and initially left in situ and monitored. During orthodontic treatment, there was rapid spontaneous eruption of both teeth with resulting resorption to an adjacent lateral incisor. This case report details the clinical findings and progress of treatment and management. A review of the literature reinforces the importance of maintaining regular radiographic review to assess for migration of ectopic teeth, and to ensure appropriate treatment planning and assessment of potential complications.

CPD/Clinical Relevance: This report highlights the need for regular radiographic review of impacted canines in younger patients.
The simplified basic periodontal examination in children and adolescents: an update
Authors: Pathak Divya , Bhujel Nabina
Published: March 2023

The ‘Guidelines for periodontal screening and management of children and adolescents under 18 years of age’ was updated by the British Society of Periodontology and Implant Dentistry and the British Society of Paediatric Dentistry in September 2021. The updated guidance acknowledged changes outlined in the 2017 World Workshop Classification of Periodontal Diseases and Conditions. The guideline outlines the use of the simplified BPE (sBPE) as a screening tool for periodontal disease in children, with treatment and management recommendations determined by sBPE codes 0–4*. It is an essential tool in primary dental care.

CPD/Clinical Relevance: The dental team should be aware of the recent changes in national guidance and carry out periodontal screening in children appropriately.
Education Select Committee Inquiry
Authors: Cowley Sue
Published: March 2023

With the affordability of childcare currently making headlines, a new inquiry by the Education Select Committee seeks to find answers to some of the pressing problems facing the sector. Sue Cowley explains more about the areas that the inquiry will explore and summarises the first session of oral evidence.
Giving our children oracy and agency in their learning
Authors: McClure Ali
Published: March 2023

Following her talk for Eton College's Centre for International Research in Learning and the launch of her eBook, Ali McClure introduces her FingerTips - Reflective Learners Talking Tool.
Primary knee arthroplasty for osteoarthritis restores patients’ health-related quality of life to normal population levels
Authors: Yapp Liam Z. , Scott Chloe E. H. , MacDonald Deborah J. , Howie Colin R. , Simpson A. Hamish R. W. , Clement Nick D.
Published: March 2023

Aims

This study investigates whether primary knee arthroplasty (KA) restores health-related quality of life (HRQoL) to levels expected in the general population.

Methods

This retrospective case-control study compared HRQoL data from two sources: patients undergoing primary KA in a university-teaching hospital (2013 to 2019), and the Health Survey for England (HSE; 2010 to 2012). Patient-level data from the HSE were used to represent the general population. Propensity score matching was used to balance covariates and facilitate group comparisons. A propensity score was estimated using logistic regression based upon the covariates sex, age, and BMI. Two matched cohorts with 3,029 patients each were obtained for the adjusted analyses (median age 70.3 (interquartile range (IQR) 64 to 77); number of female patients 3,233 (53.4%); median BMI 29.7 kg/m2 (IQR 26.5 to 33.7)). HRQoL was measured using the three-level version of the EuroQol five-dimension questionnaire (EQ-5D-3L), and summarized using the Index and EuroQol visual analogue scale (EQ-VAS) scores.

Results

Patients awaiting KA had significantly lower EQ-5D-3L Index scores than the general population (median 0.620 (IQR 0.16 to 0.69) vs median 0.796 (IQR 0.69 to 1.00); p < 0.001). By one year postoperatively, the median EQ-5D-3L Index score improved significantly in the KA cohort (mean change 0.32 (SD 0.33); p < 0.001), and demonstrated no clinically relevant differences when compared to the general population (median 0.796 (IQR 0.69 to 1.00) vs median 0.796 (IQR 0.69 to 1.00)). Compared to the general population cohort, the postoperative EQ-VAS was significantly higher in the KA cohort (p < 0.001). Subgroup comparisons demonstrated that older age groups had statistically better EQ-VAS scores than matched peers in the general population.

Conclusion

Patients awaiting KA for osteoarthritis had significantly poorer HRQoL than the general population. However, within one year of surgery, primary KA restored HRQoL to levels expected for the patient’s age-, BMI-, and sex-matched peers.

Cite this article: Bone Joint J 2023;105-B(4):365–372.
Impact of the number of previous lumbar operations on patient-reported outcomes after surgery for lumbar spinal stenosis or lumbar disc herniation
Authors: Riksaasen Anniken S. , Kaur Simran , Solberg Tore K. , Austevoll Ivar , Brox Jens-Ivar , Dolatowski Filip C. , Hellum Christian , Kolstad Frode , Lonne Greger , Nygaard Øystein P. , Ingebrigtsen Tor
Published: March 2023

Aims

Repeated lumbar spine surgery has been associated with inferior clinical outcomes. This study aimed to examine and quantify the impact of this association in a national clinical register cohort.

Methods

This is a population-based study from the Norwegian Registry for Spine surgery (NORspine). We included 26,723 consecutive cases operated for lumbar spinal stenosis or lumbar disc herniation from January 2007 to December 2018. The primary outcome was the Oswestry Disability Index (ODI), presented as the proportions reaching a patient-acceptable symptom state (PASS; defined as an ODI raw score ≤ 22) and ODI raw and change scores at 12-month follow-up. Secondary outcomes were the Global Perceived Effect scale, the numerical rating scale for pain, the EuroQoL five-dimensions health questionnaire, occurrence of perioperative complications and wound infections, and working capability. Binary logistic regression analysis was conducted to examine how the number of previous operations influenced the odds of not reaching a PASS.

Results

The proportion reaching a PASS decreased from 66.0% (95% confidence interval (CI) 65.4 to 66.7) in cases with no previous operation to 22.0% (95% CI 15.2 to 30.3) in cases with four or more previous operations (p < 0.001). The odds of not reaching a PASS were 2.1 (95% CI 1.9 to 2.2) in cases with one previous operation, 2.6 (95% CI 2.3 to 3.0) in cases with two, 4.4 (95% CI 3.4 to 5.5) in cases with three, and 6.9 (95% CI 4.5 to 10.5) in cases with four or more previous operations. The ODI raw and change scores and the secondary outcomes showed similar trends.

Conclusion

We found a dose-response relationship between increasing number of previous operations and inferior outcomes among patients operated for degenerative conditions in the lumbar spine. This information should be considered in the shared decision-making process prior to elective spine surgery.

Cite this article: Bone Joint J 2023;105-B(4):422–430.
Factors affecting a patient’s experience following the open Latarjet procedure to treat recurrent anterior shoulder instability
Authors: Makaram Navnit S. , Nicholson Jamie A. , Yapp Liam Z. , Gillespie Matthew , Shah Chandrarajan P. , Robinson C. M.
Published: March 2023

Aims

The open Latarjet procedure is a widely used treatment for recurrent anterior instability of the shoulder. Although satisfactory outcomes are reported, factors which influence a patient’s experience are poorly quantified. The aim of this study was to evaluate the effect of a range of demographic factors and measures of the severity of instability on patient-reported outcome measures in patients who underwent an open Latarjet procedure at a minimum follow-up of two years.

Methods

A total of 350 patients with anterior instability of the shoulder who underwent an open Latarjet procedure between 2005 and 2018 were reviewed prospectively, with the collection of demographic and psychosocial data, preoperative CT, and complications during follow-up of two years. The primary outcome measure was the Western Ontario Shoulder Instability Index (WOSI), assessed preoperatively, at two years postoperatively, and at mid-term follow-up at a mean of 50.6 months (SD 24.8) postoperatively. The secondary outcome measure was the abbreviated version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score. The influence of the demographic details of the patients, measurements of the severity of instability, and the complications of surgery were assessed in a multivariate analysis.

Results

The mean age of the patients was 25.5 years (22 to 32) and 27 (7.7%) were female. The median time to surgery after injury was 19 months (interquartile range (IQR) 13 to 39). Seven patients developed clinically significant complications requiring further intervention within two years of surgery. The median percentage WOSI deficiency was 8.0% (IQR 4 to 20) and median QuickDASH was 3.0 (IQR 0 to 9) at mid-term assessment. A minority of patients reported a poorer experience, and 22 (6.3%) had a > 50% deficiency in WOSI score. Multivariate analysis revealed that consumption of ≥ 20 units of alcohol/week, a pre-existing affective disorder or epilepsy, medicolegal litigation, increasing time to surgery, and residing in a more socioeconomically deprived area were independently predictive of a poorer WOSI score.

Conclusion

Although most patients treated by an open Latarjet procedure have excellent outcomes at mid-term follow-up, a minority have poorer outcomes, which are mainly predictable from pre-existing demographic factors, rather than measures of the severity of instability.

Cite this article: Bone Joint J 2023;105-B(4):389–399.
The value of national arthroplasty registry data in 2023
Authors: Baker Paul N. , Jeyapalan Rathan , Jameson Simon S.
Published: March 2023

The importance of registries has been brought into focus by recent UK national reports focusing on implant (Cumberlege) and surgeon (Paterson) performance. National arthroplasty registries provide real-time, real-world information about implant, hospital, and surgeon performance and allow case identification in the event of product recall or adverse surgical outcomes. They are a valuable resource for research and service improvement given the volume of data recorded and the longitunidal nature of data collection. This review discusses the current value of registry data as it relates to both clinical practice and research.

Cite this article: Bone Joint J 2023;105-B(4):356–360.
A randomized clinical trial of glenohumeral joint steroid injection versus suprascapular nerve block in patients with frozen shoulder: a protocol for the Therapeutic Injections For Frozen Shoulder (TIFFS) study
Authors: Jump Christopher M. , Mati Wael , Maley Alex , Taylor Rebecca , Gratrix Karen , Blundell Clare , Lane Suzanne , Solanki Nilesh , Khan Maqsood , Choudhry Muhammad , Shetty Vishwanath , Malik Rayaz A. , Charalambous Charalambos P.
Published: March 2023

Aims

Frozen shoulder is a common, painful condition that results in impairment of function. Corticosteroid injections are commonly used for frozen shoulder and can be given as glenohumeral joint (GHJ) injection or suprascapular nerve block (SSNB). Both injection types have been shown to significantly improve shoulder pain and range of motion. It is not currently known which is superior in terms of relieving patients’ symptoms. This is the protocol for a randomized clinical trial to investigate the clinical effectiveness of corticosteroid injection given as either a GHJ injection or SSNB.

Methods

The Therapeutic Injections For Frozen Shoulder (TIFFS) study is a single centre, parallel, two-arm, randomized clinical trial. Participants will be allocated on a 1:1 basis to either a GHJ corticosteroid injection or SSNB. Participants in both trial arms will then receive physiotherapy as normal for frozen shoulder. The primary analysis will compare the Oxford Shoulder Score (OSS) at three months after injection. Secondary outcomes include OSS at six and 12 months, range of shoulder movement at three months, and Numeric Pain Rating Scale, abbreviated Disabilities of Arm, Shoulder and Hand score, and EuroQol five-level five-dimension health index at three months, six months, and one year after injection. A minimum of 40 patients will be recruited to obtain 80% power to detect a minimally important difference of ten points on the OSS between the groups at three months after injection. The study is registered under ClinicalTrials.gov with the identifier NCT04965376.

Conclusion

The results of this trial will demonstrate if there is a difference in shoulder pain and function after GHJ injection or SSNB in patients with frozen shoulder. This will help provide effective treatment to patients with frozen shoulder.

Cite this article: Bone Jt Open 2023;4(3):205–209.
Detailed analysis of the R1f/ΔI1 WMS technique and demonstration of significantly higher detection sensitivity compared to 2f WMS for calibration-free trace gas sensing
Authors: De Shruti , Selvaraj Ramya , Grattan Kenneth T. V. , Chakraborty Arup Lal
Published: March 2023

Recognizing that wavelength modulation spectroscopy (WMS) is particularly important in the development of high-sensitivity gas sensing systems, this paper presents a detailed analysis of the R1f/ΔI1 WMS technique that has recently been successfully demonstrated for calibration-free measurements of the parameters that support detecting multiple gases under challenging conditions. In this approach, the magnitude of the 1f WMS signal (R1f) was normalized by using the laser’s linear intensity modulation (ΔI1) to obtain the quantity R1f/ΔI1 that is shown to be unaffected by large variations in R1f itself due to the variations in the intensity of the received light. In this paper, different simulations have been used to explain the approach taken and the advantages that it shows. A 40 mW, 1531.52 nm near-infrared distributed feedback (DFB) semiconductor laser was used to extract the mole fraction of acetylene in a single-pass configuration. The work has shown a detection sensitivity of 0.32 ppm for 28 cm (0.089 ppm-m) with an optimum integration time of 58 s. The detection limit achieved has been shown to be better than the value of 1.53 ppm (0.428 ppm-m) for R2f WMS by a factor of 4.7, which is a significant improvement.
Wavefront accuracy of mechanically assembled all-cordierite reflective optical system for cryogenic applications
Authors: Sarugaku Yuki , Ikeda Yuji , Kobayashi Naoto , Kondo Sohei , Otsubo Shogo , Yasui Chikako , Kawakita Hideyo
Published: March 2023

Although a reflective optical system can theoretically realize ideal
optical designs, it is not always the optimal choice compared with a
refractive one because of the difficulty in achieving high wavefront
accuracy. A promising solution is to build reflective optical systems
by mechanically assembling all the optical and structural components
made of cordierite, which is a ceramic with a very low thermal
expansion coefficient. Interferometric evaluations of an experimental
product demonstrated that diffraction-limited performance in the
visible wavelength was achieved and maintained even after cooling to
80 K. This new technique may be the most cost-effective method
for utilizing reflective optical systems, especially for cryogenic
applications.
Hypothalamic Menin regulates systemic aging and cognitive decline
Authors: Leng Lige , Yuan Ziqi , Su Xiao , Chen Zhenlei , Yang Shangchen , Chen Meiqin , Zhuang Kai , Lin Hui , Sun Hao , Li Huifang , Xue Maoqiang , Xu Jun , Yan Jingqi , Chen Zhenyi , Yuan Tifei , Zhang Jie
Published: March 2023

Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits. Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.