bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute visual field loss as first presentation of cancer associated retinopathy
Authors: Moreno Sergio Inat , Fonseca Cristobal Andres Neira , Laguna Candela Congost , Peláez Blanca Casado , Gil Romana Garcia , Mirete Patricia Udaondo
Published: January 2025

Aims/Purpose: To describe a case of cancer‐associated retinopathy (CAR) due to advanced bilateral ovarian cancer presenting with visual field loss, photopsia and nyctalopia.

Methods: A case report of a 53‐year‐old female with bilateral serous surface papillary ovarian cancer stage IIIC with one week history of visual field defect, photopsia and nyctalopia. Patient has undergone multiple surgical interventions and chemotherapy cycles plus bevacizumab in the last 7 years.

Results: At the presentation, best‐corrected visual acuity (BCVA) was 20/20 in both eyes, normal pupils with no relative afferent pupillary defect and no dyscromatopsia. She denied pain with ocular movements. Examination of anterior and posterior segment was unremarkable. Humphrey visual field test showed a bilateral concentric peripheral field loss. Macular spectral domain optic coherence tomography (SD‐OCT) was normal, however peripheral SD‐OCT revealed marked thinning of the outer retinal layers. Fundus Autofluorescence (FAF) exhibited hyperfluorescence in mid‐peripheral retina more notorious in perivascular areas. Full‐field electroretinogram showed asimmetrical cone and rod dysfunction. Given these clinical findings and the history of ovarian cancer, CAR diagnosis was made. Treatment was started with high dose corticosteroids, immunoglobulins and Rituximab achieving improvement of visual phenomena, stabilization of visual acuity and interruption of retinal damage on OCT and FAF after 3 months of follow‐up.

Conclusions: CAR is a paraneoplastic syndrome with poor visual prognosis. A cross reaction occurs between tumor and retinal antigens triggering an autoimmune response leading to a retinal degeneration, being alpha enolase and anti recoverin the most common. More than fifty percent of cases test positive to these antibodies. Despite negative results, treatment is important because patients with visual improvement are described in literature.
Symptom management in melanoma associated retinopathy following intravitreal dexamethasone
Authors: Ilyas Ameerah , Mahroo Omar , Tan Jit Kai , Trepatchayakorn Supawat , Bloch Edward , Robson Anthony G. , Plant Gordon , Virgo Jonathon , Webster Andrew R. , Pavesio Carlos , Mohamed Moin
Published: January 2025

Aims/Purpose: Patients with melanoma‐associated retinopathy (MAR) experience visual impairment, which can persist even following remission of the melanoma. Here we report two patients in whom symptoms improved following intravitreal dexamethasone implants.

Methods: An 81 year old man reported recent onset visual disturbance. Electroretinograms (ERGs) revealed loss of ON bipolar signals, raising the possibility of MAR. Further investigation revealed metastatic melanoma. The patient underwent treatment, resulting in melanoma remission. The second patient (an 87 year old man) was diagnosed with metastatic melanoma and later developed visual symptoms in his better eye (the other eye had a prior ischaemic retinal vein occlusion). ERGs revealed selective ON bipolar signal loss, consistent with MAR. In both patients, despite systemic melanoma treatment, visual symptoms persisted.

Results: The first patient underwent cycles of plasma exchange, but vision continued to deteriorate, with visual acuity reaching 20/120 and 20/600 in right and left eye respectively. In light of prior reports of intravitreal steroids improving some cases of MAR, he underwent intravitreal dexamethasone implants. This was associated with subjective improvement of symptoms as well as improved acuity. Multiple treatments were performed to both eyes, with visual acuity stabilising around 20/80 in both eyes. The second patient found his symptoms of photopsia and impaired colour vision troubling. Visual acuity dropped to 20/40. After one intravitreal dexamethasone implant, symptoms improved markedly, with acuity also improving slightly to 20/30. Both patients remain under review.

Conclusions: The cases highlight the importance of considering possible paraneoplastic retinopathy in visual dysfunction and apparently unremarkable examination (in the first case, the symptoms preceded the melanoma diagnosis). The cases add to the few existing case reports of possible benefit from intravitreal steroid in MAR.

References

Ameerah Ilyas,1 Jit Kai Tan,1–3 Supawat Trepatchayakorn,2 Edward Bloch,1–3 Anthony G. Robson,1,4 Gordon T. Plant,5 Jonny Virgo,3 Andrew R. Webster,1,2 Carlos Pavesio,1,2 Moin D. Mohamed,3 Omar A. Mahroo1–4

UCL Institute of Ophthalmology

Retinal Service, Moorfields Eye Hospital
Assessment of ophthalmology residents' perspectives on the utilization of artificial intelligence in contemporary practices
Authors: Fendouli Ines , Aoun Safa Ben , Maamouri Rim , Sakji Fatma , Slim Selmi , Amri Monia Cheour
Published: January 2025

Aims/Purpose: To survey ophthalmology residents on their perspectives of artificial intelligence (AI) and their implications regarding its potential use in ophthalmology.

Methods: Online anonymous questionnaire sent out via e‐mail toTunisian ophthalmology residents from all different educational levels (1st to 5th year) between May and June 2024. The survey contained 18items, assessing the extent participants either "Yes" or "No" or multiple choice with statements on the perceived benefits and concerns of AI in ophthalmology. Responses were analyzed using descriptive statistics. Data were analyzed using SPSS 26.0

Results: Thirty ophthalmology residents were included. Of the participants, 70% were female,and 30% were male. The mean age was 28.26 years ± 3 years. Among the participants, 73.3% consider themselves to have enough potentials to understand AI, and 86.7% recognize the importance of adapting to AI in ophthalmology. According to Tunisian ophthalmology residents, AI most important applications in this field include diabetic retinopathy (30%) and optical coherence tomography angiography (26.7%). Eight residents thought that AI can improve the practice of ophthalmology by 50%. All participants agreed on that AI could save time for patients; 96.7% believed AI cannot replace physicians. For83.3% of residents, considering learning AI basics ought to be mandatory during the medical curriculum, as 90 % believed that this tool can help making more accurate diagnosis; 93.3% believed it may reduce consultation time for residents, and 90 % agreed it may help in management and treatment prescription. More than ¾ tried to adapt AI in clinical practice and almost 97% of residents are willing to adapt AI to facilitate research.

Conclusions: Learning and applying AI for clinical practice may be a promising technology for ophthalmology residents, in order to save time, facilitate diagnosis and management. Moreover, Tunisian residents seem to be willing to improve their competences in this field and adapt this tool for research and medical publications.

Reference

Ting DSW, Pasquale LR, Peng L, Campbell JP, Lee AY, Raman R, Tan GSW, Schmetterer L, Keane PA, Wong TY. Artificial intelligence and deep learning in ophthalmology. Br J Ophthalmol. 2019 Feb; 103(2): 167‐175.
Regulation of the stress response of müller cells after retinal detachment by amniotic membrane secretome in vitro
Authors: Hillenmayer Anna , Christian Wertheimer , Thomas Sterz , Azza Dammak , Armin Wolf
Published: January 2025

Aims/Purpose: Müller cells play a key role in retinal homeostasis, structural support and immune response. They respond to retinal detachment and subsequent hypoxic conditions with increased stress response leading to structural changes. Due to the stabilizing properties of the amniotic membrane, first potential intraocular applications in vitreoretinal pathologies have been published. The aim was to investigate possible effects of amnion on Müller cells in the context of hypoxic damage after retinal detachment in vitro.

Methods: Secretome was isolated from cryopreserved amniotic membranes. Immortalized Müller cells (MIO‐M1) with and without hypoxia treatment were incubated with the secretome and toxicity was excluded by a life/death assay and a cell death detection ELISA. A Wst‐1 and BrdU assay were performed for cell activity and proliferation; Western blot analysis and immunofluorescence staining were used to detect changes in protein expression of alpha‐SMA, SOX‐2 and GFAP.

Results: Both hypoxia and the addition of amniotic secretome significantly reduced the metabolic activity of the cells. Incubation with secretome led to a statistically significant stagnation under both normoxic (p = 0.005) and hypoxic conditions (p > 0.01) in cell proliferation. Hypoxia led to increased expression of alpha‐SMA (p = 0.6), GFAP (p = 0.02) and SOX‐2 (p = 0.03) in Western blot analysis while secretome led to a normalization of alpha‐SMA (p = 0.03), GFAP (p = 0.1) and SOX‐2 (p = 0.001) under normoxic as well as hypoxic conditions. This observation was affirmed in immunofluorescence. Toxicity was excluded.

Conclusions: In vitro simulation of hypoxic conditions in retinal detachment leads to stress responses of Müller cells. The amniotic secretome appears to regulate Müller cell behavior in vitro by supporting a stable phenotype under normoxic and hypoxic conditions. Further studies are needed to evaluate the clinical potential of the amniotic secretome after retinal detachment.
Evaluation of macular ganglion cell layer‐inner plexiform layer (GCL‐IPL) thickness in patients treated with ozurdex: A retrospective study from a swiss cohort of patients
Authors: Rizzato Angelica , Kochkorov Asan , Katamay Robert , Katja Hatz
Published: January 2025

Aims/Purpose: To investigate the effect of Dexamethasone intravitreal implants (Ozurdex®) on macular GCL‐IPL thickness in patients treated for diabetic macular edema (DME), retinal vein occlusion (RVO), and non‐infectious uveitic macular edema (UME).

Methods: All eyes receiving Ozurdex® between 2013 and 2021 were included and assigned to group 1 ( ≤ 5 implants) or group 2 ( > 5 implants). Clinical records were reviewed, and SD‐OCT images manually segmented. Data were evaluated at baseline and at 3 years ± 4 months. Exclusion criteria were poor imaging quality, lack of adequate follow‐up, and absence of dry SD‐OCT at the timepoints. Primary outcome is change in macular GCL‐IPL thickness between baseline and 3‐year follow‐up, compared using paired t‐test. Secondary outcome: incidence of ocular hypertension (IOP > 25mmHg) at three years, compared using Fisher's exact test.

Results: 82 eyes of 73 patients were included (mean age 67.5 years). 30 eyes with DME, 26 with RVO, and 26 with UME. Group 1 (40 eyes) received a mean of 3.0 injections (SD = 1.5; range = 1‐5), while group 2 (42 eyes) received a mean of 7.9 injections (SD = 1.7; range = 6‐14). Macular GCL‐IPL thickness in group 1 was not significantly reduced after 3 years (mean difference: ‐1.8μm, 95% CI: ‐4.4; 0.8, p = 0.18), while group 2 showed significant reduction (mean difference: ‐5.9μm, 95% CI: ‐10.5; ‐1.3, p < 0.05). However, no significant difference in new ocular hypertension cases between group 1 (42.5%) and group 2 (38.0%), p = 0.82 was found.

Conclusions: The study shows that repeated Ozurdex® injections are associated with significant reduction in macular GCL‐IPL thickness over 3 years, however, despite increased ocular hypertension in both groups, no significant differences between groups were found. These findings highlight the need for long‐term monitoring of macular GCL‐IPL thickness and intraocular pressure in patients receiving multiple Ozurdex® injections for DME, RVO, and UME.
Association between atherosclerotic cardiovascular disease risk and diabetic retinopathy in patients with type 2 diabetes mellitus
Authors: Agapitou Chrysa , Lampsas Stamatios , Risi‐Koziona Alexia , Kyratzidis Fotis , Pappelis Konstantinos , Theodossiadis Panagiotis , Chatziralli Irini
Published: January 2025

Aims/Purpose: The purpose of this study is to examine the association between diabetic retinopathy (DR) and the atherosclerotic cardiovascular disease (ASCVD) risk in patients with type 2 diabetes mellitus (DM) and to assess risk factors potentially associated with DR.

Methods: Participants in the study were 215 patients with type 2 DM, who underwent a thorough ophthalmic examination, including best‐corrected visual acuity (BCVA) measurement, dilated fundoscopy, fundus photography, optical coherence tomography (OCT) and OCT angiography (OCTA). DR was graded as no apparent retinopathy (NDR), mild non‐proliferative (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR). In addition, a detailed medical history of patients was recorded, while the ASCVD risk estimator plus by the American College of Cardiology was used to calculate the ASCVD risk.

Results: Multivariate logistic regression analysis showed that factors associated with DR independently were: DM duration (multivariate OR = 3.16, 95% CI: 1.55‐6.44, p = 0.002), HbA1c levels (multivariate OR = 2.94, 95% CI: 1.37‐6.32, p = 0.006) and presence of neuropathy (multivariate OR = 3.59, 95% CI: 1.43‐9.05, p = 0.007). At the multivariate multinomial logistic regression analysis, NPDR development was associated with duration of DM (multivariate RR = 3.31, 95% CI: 1.57‐6.97, p = 0.002), HbA1c levels (multivariate RR = 2.24, 95% CI: 1.00‐5.02, p = 0.050) and neuropathy (multivariate RR: 3.94, 95% CI: 1.54‐10.11, p = 0.004), while PDR development was only associated with HbA1c levels (multivariate RR = 6.88, 95% CI: 2.19‐21.63, p = 0.001). The ASCVD score was not found to be significantly correlated with DR (p = 0.191).

Conclusions: Factors associated with DR were DM duration, HbA1c levels and presence of neuropathy, while the ASCVD score was not found to be significantly associated with DR.
Optical coherence tomography findings in persistent hyaloid artery: A prospective study
Authors: Sakji Fatma , Aoun Safa Ben , Maamouri Rym , Ferchichi Molka , Fendouli Ines , Cheour Monia
Published: January 2025

Aims/Purpose: To describe the features of peripapillary persistent hyaloid artery and its effects on disc parameters using Swept‐source optical coherence tomography (SS‐OCT) and SS‐OCT angiography (SS‐OCT A).

Methods: Seven eyes of 7 patients diagnosed with Persistent hyaloid artery were prospectively reviewed at the department of Ophthalmology in the Habib Thameur Hospital, Tunisia, between January 2024 and June 2024. All patients were assessed for peripapillary retinal nerve fibers layer (pRNFL) thickness by SS‐OCT, and blood flow by papillary OCT‐A, 4.5 mm*4.5 mm cubes.

Results: Mean age was 36.33 years, with 4 women and 3 men. SS‐OCT showed peripapillary hyperreflective tubular material of the persistent hyaloid artery in the right eye of 3 patients and in the left eye of 4 patients. On analysis of the pRNFL thickness, the mean average thickness was 110.8, Inferior quadrant (150.8), superior quadrant (134), nasal quadrant (83.4) and temporal quadrant (74.8). pRNFL were thickened in one eye, altered in one eye in the superior quadrant, and preserved in five eyes. SS‐OCT A revealed no blood flow at the lesion in all eyes.

Conclusions: A persistent hyaloid artery is an uncommon lesion whose diagnosis, evaluation and monitoring have become easily possible using SS‐OCT and SS‐OCT A. Evaluating the vascular flow at the level of the optic nerve head would be of great importance in order to prevent certain complications, notably vitreous hemorrhage and retinal detachment.

References

Jeon, H., Kim, J., & Kwon, S. OCT angiography of persistent hyaloid artery: a case report. BMC Ophthalmol. 2019 Jul 4; 19(1): 141.

Gamidov AA, Durzhinskaya MH, Makashova NV, Sakalova ED, Velieva IA. Persistent hyaloid artery in an adult (a case report). Vestn Oftalmol. 2020; 136(4): 214.
Assessing retinal thickness and vascular structures in an Alzheimer's disease mouse model APP NL‐F/NL‐F
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , Jiménez María González , Salobrar‐Garcia Elena , Matamoros José A. , Lozano María Pilar Rojas , Fernández‐Albarral José A. , Elvira‐Hurtado Lorena , Ramirez Ana Isabel , Salazar Juan Jose , Nieto‐Vaquero Carmen , Desviat María Isabel Cuartero , Moro María Ángeles , Saito Takashi , Saido Takaomi C. , Ramirez Jose Manuel , de Hoz Rosa
Published: January 2025

Aims/Purpose: In Alzheimer's disease (AD), there are histopathological aspects that cannot be studied in patients, demanding the use of murine models of the disease. The APPNL‐F/NL‐F model reproduces the pathophysiology quite faithfully. The aim of the present study was to analyze the retinal vascular structures and retinal thickness in an AD model at different ages and compares these findings to age‐matched wild type (WT) controls.

Methods: A diachronic study was conducted using spectral‐domain OCT angiography (SD‐OCTA) and AngioTool software to assess retinal vascular structures, alongside OCT for measuring inner and outer retina thickness. We include two study groups: the APPNL‐F/NL‐F AD model and WT controls at 6, 9, 12, 15, 17, and 20 months old. The analysis focused on the three vascular plexus and retinal thickness, using the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. We considered statistically significant a p‐value < 0.05.

Results: Compared to WT, the APPNL‐F/NL‐F group exhibited both vascular and structural changes starting as early as 6 months, with these changes persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, particularly in the superficial vascular complex (SVC), were noted. There was a marked decrease in vessel area and total vessel length in the SVC, as well as in the intermediate and deep capillary plexus. Additionally, the inner retina predominantly showed a thickness decrease, while the outer retina demonstrated an increased thickness at most time points compared to the control group.

Conclusions: The study identifies early retinal vascular and structural changes in the APPNL‐F/NL‐F model that precede cognitive changes observed at later stages. These findings suggest that the retinal changes in this model more closely resemble those in human AD compared to other transgenic models, highlighting the potential of retinal assessments in early AD diagnosis.
Post‐secondary education in young patients with inflammatory bowel disease: A population‐based cohort study
Authors: Rasmussen Julie , Nørgård Bente Mertz , Gaardskær Nielsen Rasmus , Qvist Niels , Bøggild Henrik , Fonager Kirsten
Published: January 2025

Aim

Inflammatory bowel disease (IBD) diagnosed in adolescence may have adverse effects on educational attainment. The study aims to examine post‐secondary educational attainment in patients with IBD and how it is affected by disease severity and comorbid mental health disorders.

Methods

This cohort study used nationwide Danish registries. In a cohort of patients with IBD and matched references, the time to attainment of post‐secondary education was examined using Cox regression. In the analysis for disease severity and mental health disorders, the relative risk of attainment of post‐secondary education was evaluated using binomial regression.

Results

We identified 1136 patients with IBD and 8791 references. Overall, patients with Crohn's disease (CD) or ulcerative colitis (UC) attained a post‐secondary education as often as references (CD: hazard ratio (HR) 1.10 (95% confidence interval (CI) 0.99–1.22); UC: HR 0.97 (95% CI 0.88–1.06)). Patients with both severe IBD and mental health disorders had a significantly lower chance of attaining a post‐secondary education compared to patients with severe IBD without mental health disorders.

Conclusions

Patients with IBD attained a post‐secondary education at the same rate as references. Having both severe IBD and mental health disorder negatively affected post‐secondary educational attainment.
Pharmacological profiling of small molecule modulators of the TMEM16A channel and their implications for the control of artery and capillary function
Authors: Al‐Hosni Rumaitha , Agostinelli Emilio , Ilkan Zeki , Scofano Lara , Kaye Rachel , Dinsdale Ria L. , Acheson Kathryn , MacDonald Andrew , Rivers Dean , Biosa Alice , Gunthorpe Martin J. , Platt Frances , Tammaro Paolo
Published: January 2025

Background and purpose

TMEM16A chloride channels constitute a depolarising mechanism in arterial smooth muscle cells (SMCs) and contractile cerebral pericytes. TMEM16A pharmacology is incompletely defined. We elucidated the mode of action and selectivity of a recently identified positive allosteric modulator of TMEM16A (PAM_16A) and of a range of TMEM16A inhibitors. We also explore the consequences of selective modulation of TMEM16A activity on arterial and capillary function.

Experimental approach

Patch‐clamp electrophysiology, isometric tension recordings, live imaging of cerebral cortical capillaries and assessment of cell death were employed to explore the effect of selective pharmacological control of TMEM16A on vascular function.

Key Results

In low intracellular free Ca2+ concentrations ([Ca2+]i), nanomolar concentrations of PAM_16A activated heterologous TMEM16A channels, while being almost ineffective on the closely related TMEM16B channel. In either the absence of Ca2+ or in saturating [Ca2+]i, PAM_16A had no effect on TMEM16A currents at physiological potentials. PAM_16A selectively activated TMEM16A currents in SMCs and enhanced aortic contraction caused by phenylephrine or angiotensin‐II and capillary (pericyte) constriction evoked by endothelin‐1 or oxygen–glucose deprivation (OGD) to simulate cerebral ischaemia. Conversely, selective TMEM16A inhibition with Ani9 facilitated aortic, mesenteric and pericyte relaxation, and protected against OGD‐mediated pericyte cell death. Unlike PAM_16A and Ani9, a range of other available modulators were found to interfere with endogenous cationic currents in SMCs.

Conclusions and implications

Arterial tone and capillary diameter can be controlled with TMEM16A modulators, highlighting TMEM16A as a target for disorders with a vascular component, including hypertension, stroke, Alzheimer's disease and vascular dementia.
Clinical value of the Japanese version of patient‐reported multiple sclerosis neuropsychological screening questionnaire
Authors: Muryoi Atsuya , Nei Michiko , Fujimori Juichi , Nakashima Ichiro
Published: January 2025

Background

Neuropsychological abnormalities are common in patients with multiple sclerosis (MS); however, unlike motor and sensory deficits, their measurement in a clinical setting can be difficult.

Methods

We evaluated 80 patients with MS using the newly created Japanese version of a patient‐report form of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and compared the results with those of processing speed tests (PST), namely, CogEval, and health‐related quality of life (QOL). QOL was evaluated using the Medical Outcomes Study Short Form‐36 Health Survey (SF‐36).

Results

The partial correlation coefficient, after excluding the effect of disease duration, showed that the total MSNQ score was significantly correlated with PST (r = −0.2798, P = .0125), mental component summary (MCS) (r = −0.2913, P = .0092), and social role component summary (RCS) (r = −0.2591, P = .0211) in SF‐36. Multiple linear regression analyses showed that physical component summary was significantly associated with age (P = .0158), EDSS (P = .0005), and CogEval raw score (P = .0029), whereas MCS was significantly associated with MSNQ (P = .0007). When patients with MS were divided into two groups using a median total MSNQ score threshold of 17, those with high MSNQ scores showed significantly higher EDSS scores (P = .0101), lower PST scores (P = .0426), and lower MCS scores in SF‐36 (P = .0083).

Conclusion

The Japanese version of the patient‐reported MSNQ can be useful in identifying patients with decreased mental QOL, which might be more difficult than to capture physical QOL.
An interdisciplinary approach to improving conservation outcomes for parasites
Authors: Brown Timothy M. , Dunn Alison M. , Quinnell Rupert J. , Clarke Ellen , Cunningham Andrew A. , Goodman Simon J.
Published: January 2025

Parasites represent a significant proportion of Earth's biodiversity and play important roles in the ecology and biology of ecosystems and hosts, making them an important target for conservation. Despite increasing calls to prioritize protection for parasites in the academic literature, they remain undervalued and underrepresented in global biodiversity conservation efforts, not least due to the perception that the interests of parasite and host conservation are opposing and the common misconception that parasites are a threat, rather than a benefit, to conservation. We considered whether taking an interdisciplinary approach to parasite conservation research will generate novel insights and solutions concerning why and how parasite conservation should be practiced for the benefit of parasites, their hosts, ecosystems, and people. We argue that 2 of the main barriers to more widespread parasite conservation are the knowledge gap concerning the role of sociocultural factors affecting the willingness to enact parasite conservation and the lack of a consistent and cohesive philosophical basis for parasite conservation. Possible sociocultural barriers to parasite conservation include misconceptions of the risks posed by parasites, taxonomic bias, differences in conservation values, economic constraints, and technical challenges. The use of social science can generate insights into levels of awareness and support for parasite conservation and improve understanding of how human values and attitudes mediate conservation practices concerning parasites. Such knowledge will have a critical role in addressing sociocultural barriers and improving support for parasite conservation. Issues with the current philosophical basis for parasite conservation include contradictory accounts of which parasites merit conservation, insufficient explanation of how different conservation values apply to parasite biodiversity, and the existence of a false antagonism between host and parasite conservation. Greater engagement with philosophical work on environmental ethics and biological unitization will strengthen existing arguments for parasite conservation and will support conservation decision‐making processes.
Dapagliflozin modulates hepatic lipid metabolism through the proprotein convertase subtilisin/kexin type 9/low density lipoprotein receptor pathway
Authors: Lu Fengyuan , Li En , Gao Yifeng , Zhang Yan , Kong Lijuan , Yang Xiaoyu
Published: January 2025

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is mainly secreted by the liver, and plays a crucial role in lipid metabolism disorder. Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) can regulate lipid metabolism through various pathways, including reducing visceral fat accumulation, modulating serum lipoprotein levels and alleviating hepatic steatosis. However, the specific regulatory mechanisms remain unclear.

Methods

We built a model of glucose and lipid metabolism disorder in vivo and in vitro, and explored the regulatory mechanism of dapagliflozin in regulating liver lipid metabolism.

Results

We found that the SGLT2i dapagliflozin significantly reduced serum levels of PCSK9, total cholesterol (TC), low density lipoprotein cholesterol (LDL‐C) in high‐fat diet (HFD)‐fed mice, while also improving hepatic steatosis. In vitro studies confirmed that dapagliflozin increased LDL receptor (LDLR) expression in HepG2 cells, enhancing their ability to uptake LDL‐C.

Conclusions

Further mechanistic studies revealed that the hepatocyte nuclear factor‐1‐alpha (HNF1α)/PCSK9/LDLR signalling pathway may be involved in dapagliflozin's regulation of lipid metabolism homeostasis.
Development and Preliminary Validation of a Novel Instrument to Assess Re‐Injury Associated Anxiety Following Traumatic Orofacial and Dental Injury in Young Boxers
Authors: Ravi Mugilan , Tewari Nitesh , Mathur Vijay Prakash , Haldar Partha , Bhargava Rachna , Deep Raman , Rahul Morankar , Bansal Kalpana , Goel Shubhi , Raghuthaman Sruthila
Published: January 2025

Background/Aim

An injury sustained during sports activity can lead to the development of reinjury anxiety and hamper performance. Although tools exist to assess re‐injury anxiety, a domain of interest in the field of sports medicine, research in the psychological impact of an orofacial injury is rudimentary. The present study envisaged to develop an instrument to assess the presence of reinjury anxiety following orofacial and dental injury in boxers aged between 10 and 16 years.

Methods

In Phase 1, items were generated following literature search and focus‐group discussions (FGD). In Phase 2, a group discussion was conducted with three experienced boxing coaches to assess face validity, followed by two rounds of scrutiny by expert groups to assess the content validity through the content‐validity‐index (CVI), respectively. In Phase 3, the modified tool was pre‐tested on an independent sample of young boxers. Finally, in Phase 4, to determine dimensionality, the modified tool was administered to 183 young boxers and their responses were subject to an exploratory factor analysis through Principal component analysis, followed by Promax rotation to determine the factor loading. Internal consistency reliability was measured through calculation of Cronbach's‐alpha.

Results

From the 29‐items devised initially, the tool was sequentially modified. Analysis of the responses by the second expert group, an average Scale‐level‐CVI of 0.9 and Universal agreement of 0.526 was obtained, which resulted in the inclusion of 20 items for the final phase of the study. From the factor analysis, the items were found to fit to a five‐factor structure, which explained 56.4% of the variance in the constructs. Internal consistency of the tool was measured to be 0.74.

Conclusion

A 10‐item oral re‐injury anxiety scale for young boxers (ORAS‐YB) tool was developed. It was found to have high face and content validity, and acceptable reliability. Further research with a larger sample is required to confirm the factor structure and determine test–retest reliability of the developed tool.
Living in Biological Darkness II: Impact of Winter Habitual Daytime Light on Night‐Time Sleep
Authors: Nowozin Claudia , Wahnschaffe Amely , de Zeeuw Jan , Papakonstantinou Alexandra , Hädel Sven , Rodenbeck Andrea , Bes Frederik , Kunz Dieter
Published: January 2025

Timing and architecture of sleep are co‐driven by circadian rhythms modulated by their major Zeitgeber light and darkness. In a natural environment, one is exposed to 3.000 lx (cloudy winter sky) to 100.000 lx (bright sunny sky). The aim of the study was to assess (1) habitual daytime light exposure in urban winter and (2) impact of daytime urban light on objective night‐time sleep. Eleven healthy participants (mean age ± SD: 25.4 ± 2.8 years; 6 male) wore eyeglass frames continuously recording daytime illuminance levels vertically to the eye by mounted sensors (range: 1–40.000 lx) during four consecutive days in winter 2008 in Berlin, Germany. In‐lab polysomnography was performed over two nights in nine participants. Median light exposure over 4 days was the following: full day 7:00–19:00 h: 23 lx (12–37 lx); morning 7:00–11:00 h: 81 lx (19–201 lx); midday 11:00–15:00 h: 68 lx (19–164 lx); afternoon 15:00–19:00 h: 22 lx (6–58 lx), resulting in only 36 min > 500 lx per day. Timing of daytime light intensity was significantly associated with subsequent sleep: lower midday illuminance with shorter REM latency (Rho = 0.817; p = 0.049) and earlier REM polarity (less prevalence of REM at end‐of‐sleep; Rho = 0.817; p = 0.049). Humans, living in an urban environment, appear to be exposed to extremely low light levels, which we named as ‘Living in Biological Darkness’. Most fascinating, physiology seems to adapt and responds to variation in light intensity on such low levels. Interestingly, the observed changes in sleep architecture with low light levels are reminiscent of those suspected to constitute biological markers of depression some 40–50 years ago.
Causal Relationship Between Intestinal Microbiota, Inflammatory Cytokines, Peripheral Immune Cells, Plasma Metabolome and Parkinson's Disease: A Mediation Mendelian Randomization Study
Authors: Wang Chengcheng , Tang Yuhang , Yang Tao , Wang Yuhao , Niu Zihui , Zhang Kang , Lin Ning , Li Qun
Published: January 2025

Parkinson's disease (PD) is a neurodegenerative disease involving multiple factors. We explored the connection between intestinal microbiome levels and PD by examining inflammatory cytokines, peripheral immune cell counts and plasma metabolomics as potential factors. By obtaining the Genome‐Wide Association Study (GWAS) data needed for this study from GWAS Catalog, including summary data for 473 intestinal microbiota traits (N = 5959), 91 inflammatory cytokine traits (N = 14,824), 118 peripheral immune cell count traits (N = 3757), 1400 plasma metabolite traits (N = 8299) and PD traits (N = 482,730). We used two‐step Mendelian randomization (MR) mediated analysis to investigate possible pathways from intestinal microbiota to PD mediated by inflammatory cytokines, peripheral immune cells and plasma metabolites. MR has revealed the causal effects of 19 intestinal microbiota, 1 inflammatory cytokine and 12 plasma metabolites on PD, whereas there is no significant causal relationship between immune cell count characteristics and the occurrence of PD. Mediation analysis showed that the associations between the genus Demequina and PD were mediated by tryptophan with mediated proportions of 17.51% (p = 0.0393). Our study demonstrates that genus Demequina may promote the occurrence of PD by reducing the levels of tryptophan.
Hemispheric Asymmetry of Intracortical Myelin Orientation in the Mouse Auditory Cortex
Authors: Ruthig Philip , Müller Gesine Fiona , Fink Marion , Scherf Nico , Morawski Markus , Schönwiesner Marc
Published: January 2025

Communication sound processing in mouse AC is lateralized. Both left and right AC are highly specialised and differ in auditory stimulus representation, functional connectivity and field topography. Previous studies have highlighted intracortical functional circuits that explain hemispheric stimulus preference. However, the underlying microstructure remains poorly understood. In this study, we examine structural lateralization of AC on the basis of immunohistochemically stained and tissue‐cleared adult mouse brains (n = 11). We found hemispheric asymmetries of intracortical myelination, most prominently in layer 2/3, which featured more intercolumnar connections in the right AC. Furthermore, we found a larger structural asymmetry in the right AC. We also investigated sex differences. In male mice, myelination direction in the right AC is tilted to the anterior side. This pattern is inverted in female mice. However, the spatial distribution of neuronal cell bodies in the left and right AC along the laminar axis of the cortex was remarkably symmetric in all samples. These results suggest that basic developmentally defined structures such as cortical columns remain untouched by lateral specialisation, but more plastic myelinated axons show diverse hemispheric asymmetries. These asymmetries may contribute to specialisation on lateralized tasks such as vocal communication processing or specialisation on spectral or temporal complexity of stimuli.
Relationship Between Structural and Functional Network Connectivity Changes for Patients With Traumatic Brain Injury and Chronic Health Symptoms
Authors: Kang Xiaojian , Grossner Emily , Yoon Byung C. , Adamson Maheen M.
Published: January 2025

Combination of structural and functional brain connectivity methods provides a more complete and effective avenue into the investigation of cortical network responses to traumatic brain injury (TBI) and subtle alterations in brain connectivity associated with TBI. Structural connectivity (SC) can be measured using diffusion tensor imaging to evaluate white matter integrity, whereas functional connectivity (FC) can be studied by examining functional correlations within or between functional networks. In this study, the alterations of SC and FC were assessed for TBI patients, with and without chronic symptoms (TBIcs/TBIncs), compared with a healthy control group (CG). The correlation between global SC and FC was significantly increased for both TBI groups compared with CG. SC was significantly lower in the TBIcs group compared with CG, and FC changes were seen in the TBIncs group compared with CG. When comparing TBI groups, FC differences were observed in the TBIcs group compared with the TBIncs group. These observations show that the presence of chronic symptoms is associated with a distinct pattern of SC and FC changes including the atrophy of the SC and a mixture of functional hypoconnectivity and hyperconnectivity, as well as loss of segregation of functional networks.
The impact of radiofrequency thermocoagulation on brain connectivity in drug‐resistant epilepsy: Insights from stereo‐electroencephalography and cortico‐cortical evoked potentials
Authors: Gula Justyna , Slegers Rutger J. , Van Hoof Raf H. M. , Krishnan Balu , Mischi Massimo , van Kranen‐Mastenbroek Vivianne H. J. M. , Van Straaten Ilse E. C. W. , Hilkman Danny , Wagner Louis , Colon Albert , Schijns Olaf E. M. G. , Hunyadi Borbála , Jansen Jacobus F. A. , Tousseyn Simon ,   The ACE Epilepsy Surgery group
Published: January 2025

Objective

To investigate whether local lesions created by stereo‐electroencephalography (SEEG)–guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug‐resistant epilepsy (DRE).

Methods

Ten patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico‐cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post‐stimulation with baseline correction. Contact pairs were categorized as both coagulated, hybrid, or both non‐coagulated. The data were divided into nine categories based on the stimulating and recording contact pair combinations. RMS of CCEPs was compared before and after (<12 h) RFTC using a two‐sample t test (Hochberg corrected, p < 0.05) for each patient. Boost score, indicating power increase during seizures before RFTC relative to baseline, was analyzed in 4 s windows with 1 s overlap during seizure duration.

Results

RFTC altered connectivity across all categories. Of interest, decreases and increases in RMS were observed in connections between non‐coagulated contacts distant from coagulation site (range: 1.09–85 mm, median = 17.7 mm, interquartile range [IQR] 10.1–32.3). Contact pairs involved in significantly altered non‐coagulated connections showed a higher boost score correlation in the theta, beta, and gamma bands, as well as a stronger maximum correlation with coagulated sites in the delta band than contacts for which connectivity did not change after RFTC.

Significance

This study highlights how local lesions alter distant brain connectivity, providing insights for future research on epilepsy network changes and seizure outcomes following RFTC.
Co‐production of smart eldercare between technology and service‐oriented companies in China
Authors: Yu Yi
Published: January 2025

Smart eldercare is promoted as a potential solution to the urgent healthcare crisis stemming from an ageing population and a shortage of staff. The exact meaning of smart eldercare varies among stakeholders, including government bodies, eldercare firms, and the elderly. This study investigates the differing strategies of technology‐focused and service‐focused companies within smart care. Emphasising the political elements of intelligent eldercare, it highlights the importance of co‐production. Using thematic analysis, the study demonstrates that technology‐focused firms at a 2024 smart eldercare summit in Shanghai prioritise innovation and market prospects of emerging technologies, based on ethnographic research. In contrast, service‐oriented firms focus on the pragmatic utilisation of technology in their eldercare services. This study contributes to the understanding of smart eldercare technology adoption and co‐production by revealing the complexities and discussions associated with real‐world implementation.
Association of trajectories of physical frailty status and incident disability in community‐dwelling older adults: A longitudinal study
Authors: Kiuchi Yuto , Tsutsumimoto Kota , Nishimoto Kazuhei , Misu Yuka , Nosaka Shinnosuke , Ohata Tomoka , Makizako Hyuma , Shimada Hiroyuki
Published: January 2025

Aim

Frailty is a mediator between robustness and functional disability. This study examined the association between remission of frailty and incident disability.

Methods

The present study analyzed longitudinal data from 2601 community‐dwelling older adults who were aged ≥65 years (mean age 70.8 ± 4.5 years, 1307 women [50.2%]) using the Cardiovascular Health Study criteria. Next, examining changes in status from wave 1 (2011) to wave 2 (2015), participants were categorized into a frailty group (those who remained or became frail), a remission of frailty group (those who were frail and became robust) and a robust group (those who remained robust). Cox proportional hazard modeling was used to determine the change of frailty status from wave 1 to wave 2, as well as incident disability at wave 2 (median duration 35 months).

Results

Of those participants who started in the frailty or prefrailty groups at wave 1, 15.8% had an improved frailty status at the 47‐month follow up. After adjusting for covariates at baseline, the Cox proportional hazard regression models showed that the hazard ratio of disability among participants who remained robust was significantly less than for those who were in the frailty group (hazard ratio 0.515; 95% confidence interval 0.333–0.796).

Conclusion

Our data confirm that among those whose frailty status improved, the risk of disability was lower than for those who remained frail. Geriatr Gerontol Int 2025; 25: 220–225.
Quality of life of older adult patients with heart failure with different somatic symptom profiles: The mediating role of depressive symptoms
Authors: Fang Wenjie , Zhang Xiuting , Zhang Yilin , Li Ximiao , Li Jinliang , Fan Xiuzhen
Published: January 2025

Aim

With an increasingly aging population, the management of heart failure (HF) in older adult patients warrants greater attention. This study aimed to identify somatic symptom profiles by using the person‐oriented approach, explore the association between somatic symptom profiles and quality of life (QoL) and examine the mediating effect of depressive symptoms on this association among older adult patients with HF.

Methods

This cross‐sectional study involved a convenience sample of 445 older adult patients with HF from two tertiary hospitals in China. Patients' somatic symptoms, depressive symptoms and QoL were measured using self‐reported questionnaires. Latent profile analysis, linear regression analysis and mediation analysis were used to analyze the data.

Results

Among the 445 patients (71.84 ± 7.61 years, 49.7% women), four somatic symptom profiles were identified: mild symptoms, high dyspnea symptoms, high difficulty sleeping symptoms and severe symptoms. Considering the mild symptoms profile as a reference, the high difficulty sleeping symptoms and severe symptoms profiles were associated with reduced physical and mental QoL (β = −0.277 to −0.179, all P < 0.001), whereas the high dyspnea symptoms profile was associated with reduced mental QoL (β = −0.105, P = 0.041). Furthermore, both the high difficulty sleeping symptoms and severe symptoms profiles had significantly indirect effects on physical and mental QoL through depressive symptoms.

Conclusions

Our findings showed that older adult patients with different HF somatic symptom profiles experience varying levels of QoL. Tailored interventions that facilitate somatic symptom management and alleviate depressive symptoms might improve older adult patients' physical and mental QoL. Geriatr Gerontol Int 2025; 25: 251–259.
Association of liver fibrosis progression with non–liver‐related mortality in metabolic dysfunction‐associated steatotic liver disease
Authors: Tada Toshifumi , Kumada Takashi , Toyoda Hidenori , Yasuda Satoshi , Koshiyama Yuichi , Akita Tomoyuki , Kodama Yuzo , Tanaka Junko
Published: January 2025

Aim

In patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), the prognosis and outcomes, particularly non–liver‐related mortality, remain insufficiently elucidated. We investigated all‐cause mortality in patients with MASLD to elucidate the association of the severity of liver fibrosis with liver‐related and non–liver‐related mortality in MASLD.

Methods

Among 4528 participants with MASLD, we examined the causes of death and analyzed liver‐related and non–liver‐related mortality, stratified by the degree of fibrosis using the competing risk method. Fibrosis severity was assessed using the Fibrosis‐4 (FIB‐4) and FIB‐3 indices.

Results

The median follow‐up period was 11.7 years. Of the 4528 participants, 551 died during the follow‐up period, with only 37 (6.7%) deaths attributable to liver‐related diseases and 514 (93.3%) to non–liver‐related causes. For the risk of hepatocellular carcinoma, the hazard ratios (HRs; 95% confidence interval [CI]) for FIB‐4 were 5.67 (2.20–14.59) and 32.14 (12.40–83.35) and for FIB‐3 were 5.43 (2.73–10.79) and 19.96 (10.50–37.93). For liver‐related mortality, the HRs (95% CI) for FIB‐4 were 6.32 (2.23–17.85) and 27.62 (9.74–78.37) and for FIB‐3 were 7.15 (2.62–19.50) and 19.86 (8.12–48.55), respectively. In contrast, intermediate and high FIB‐4 and FIB‐3 indices were unassociated with non–liver‐related mortality: HRs (95% CI) for FIB‐4 were 0.85 (0.70–1.04) and 0.87 (0.64–1.18), and for FIB‐3 were 0.96 (0.77–1.20) and 0.92 (95% CI, 0.64–1.31), respectively.

Conclusions

The progression of liver fibrosis was unassociated with mortality from non–liver‐related causes in patients with MASLD.