Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

Inhibition of Rho-associated protein kinase activity enhances oxidative phosphorylation to support corneal endothelial cell migration.

Corneal endothelial cell (CEC) dysfunction causes corneal edema and severe visual impairment that require transplantation to restore vision. To address the unmet need of organ shortage, descemetorhexis without endothelial keratoplasty has been specifically employed to treat early stage Fuchs endothelial corneal dystrophy, which is pathophysiologically related to oxidative stress and exhibits centrally located corneal guttae. After stripping off central Descemet's membrane, rho-associated protein kinase (ROCK) inhibitor has been found to facilitate CEC migration, an energy-demanding task, thereby achieving wound closure. However, the correlation between ROCK inhibition and the change in bioenergetic status of CECs remained to be elucidated. Through transcriptomic profiling, we found that the inhibition of ROCK activity by the selective inhibitor, ripasudil or Y27632, promoted enrichment of oxidative phosphorylation (OXPHOS) gene set in bovine CECs (BCECs). Functional analysis revealed that ripasudil, a clinically approved anti-glaucoma agent, enhanced mitochondrial respiration, increased spare respiratory capacity, and induced overexpression of electron transport chain components through upregulation of AMP-activated protein kinase (AMPK) pathway. Accelerated BCEC migration and in vitro wound healing by ripasudil were diminished by OXPHOS and AMPK inhibition, but not by glycolysis inhibition. Correspondingly, lamellipodial protrusion and actin assembly that were augmented by ripasudil became reduced with additional OXPHOS or AMPK inhibition. These results indicate that ROCK inhibition induces metabolic reprogramming toward OXPHOS to support migration of CECs.

Automated Age-Related Macular Degeneration Detector on Optical Coherence Tomography Images Using Slice-Sum Local Binary Patterns and Support Vector Machine.

Artificial intelligence has revolutionised smart medicine, resulting in enhanced medical care. This study presents an automated detector chip for age-related macular degeneration (AMD) using a support vector machine (SVM) and three-dimensional (3D) optical coherence tomography (OCT) volume. The aim is to assist ophthalmologists by reducing the time-consuming AMD medical examination. Using the property of 3D OCT volume, a modified feature vector connected method called slice-sum is proposed, reducing computational complexity while maintaining high detection accuracy. Compared to previous methods, this method significantly reduces computational complexity by at least a hundredfold. Image adjustment and noise removal steps are excluded for classification accuracy, and the feature extraction algorithm of local binary patterns is determined based on hardware consumption considerations. Through optimisation of the feature vector connection method after feature extraction, the computational complexity of SVM detection is significantly reduced, making it applicable to similar 3D datasets. Additionally, the design supports model replacement, allowing users to train and update classification models as needed. Using TSMC 40 nm CMOS technology, the proposed detector achieves a core area of 0.12 mm2 while demonstrating a classification throughput of 8.87 decisions/s at a maximum operating frequency of 454.54 MHz. The detector achieves a final testing classification accuracy of 92.31%.

Ranibizumab reimbursement and treatment patterns for neovascular age-related macular degeneration in Taiwan - Results from the 12-month, observational RENOWNED study.

BACKGROUND: The RENOWNED study investigated the treatment patterns, real-world effectiveness and safety of ranibizumab in Taiwanese patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg in accordance with the first reimbursement scheme effective from 2012 to 2014. METHODS: This study was a Phase IV, 12-month, open-label, prospective, observational study conducted in Taiwan. Patients with visual impairment due to nAMD initiating treatment with ranibizumab 0.5 mg were included. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from Baseline at Month 3. RESULTS: Overall, 202 patients with nAMD were included. Mean (standard deviation [SD]) BCVA Early Treatment Diabetic Retinopathy Study letters improved from Baseline (49.6 [21.5] letters) at Month 3 (+4.9 [11.8], P < 0.0001), and at Month 12 (+3.5 [14.1], P = 0.0043). The proportion of patients with nAMD who lost ≥5 letters at Months 3 and 12 was 13.6% (n = 27) and 26.6% (n = 37), respectively. Mean (SD) central retinal thickness decreased from Baseline (320.1 [127.2] µm) with a mean reduction of 49.1 (107.3) µm at Month 3 (P < 0.0001), but was not significant at Month 12 with a mean reduction of 11.6 (115.6) µm (P = 0.2861). Mean (SD) number of ranibizumab injections over 12 months was 3.1 (1.0). A mean treatment interval of 109.5 days was observed between the third and fourth injections. After limited reimbursed ranibizumab injections, 43.8% patients received other treatments. The safety findings are consistent with previous studies. CONCLUSION: Ranibizumab 0.5 mg treatment for 12 months under real-world settings improved visual outcomes in Taiwanese patients with nAMD.

Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system characterized by relapses and autoimmunity caused by antibodies against the astrocyte water channel protein aquaporin-4. Over the past decade, there have been significant advances in the biologic knowledge of NMOSD, which resulted in the IDENTIFICATION of variable disease phenotypes, biomarkers, and complex inflammatory cascades involved in disease pathogenesis. Ongoing clinical trials are looking at new treatments targeting NMOSD relapses. This review aims to provide an update on recent studies regarding issues related to NMOSD, including the pathophysiology of the disease, the potential use of serum and cerebrospinal fluid cytokines as disease biomarkers, the clinical utilization of ocular coherence tomography, and the comparison of different animal models of NMOSD.

Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing.

BACKGROUND: Circulating cell-free DNA (cfDNA) methylation has been demonstrated to be a promising approach for non-invasive cancer diagnosis. However, the high cost of whole genome bisulfite sequencing (WGBS) hinders the clinical implementation of a methylation-based cfDNA early detection biomarker. We proposed a novel strategy in low-pass WGBS (~ 5 million reads) to detect methylation changes in circulating cell-free DNA (cfDNA) from patients with liver diseases and hepatocellular carcinoma (HCC). METHODS: The effective small sequencing depth were determined by 5 pilot cfDNA samples with relative high-depth WGBS. CfDNA of 51 patients with hepatitis, cirrhosis, and HCC were conducted using low-pass WGBS. The strategy was validated in an independent WGBS cohort of 32 healthy individuals and 26 early-stage HCC patients. Fifteen paired tumor tissue and buffy coat samples were used to characterize the methylation of hepatitis B virus (HBV) integration regions and genome distribution of cfDNA. RESULTS: A significant enrichment of cfDNA in intergenic and repeat regions, especially in previously reported HBV integration sites were observed, as a feature of cfDNA and the bias of cfDNA release. Methylation profiles nearby HBV integration sites were a better indicator for hypomethylation of tumor genome comparing to Alu and LINE (long interspersed nuclear element) repeats, and were able to facilitate the cfDNA-based HCC prediction. Hypomethylation nearby HBV integration sites (5 kb flanking) was detected in HCC patients, but not in patients with hepatitis and cirrhosis (MethylHBV5k, median:0.61 vs 0.72, P = 0.0003). Methylation levels of integration sites certain candidate regions exhibited an area under the receiver operation curve (AUC) value > 0.85 to discriminate HCC from non-HCC samples. The validation cohort achieved the prediction performance with an AUC of 0.954. CONCLUSIONS: Hypomethylation around viral integration sites aids low-pass cfDNA WGBS to serve as a non-invasive approach for early HCC detection, and inspire future efforts on tumor surveillance for oncovirus with integration activity.

Algae Oil Treatment Protects Retinal Ganglion Cells (RGCs) via ERK Signaling Pathway in Experimental Optic Nerve Ischemia.

BACKGROUND: We investigated the therapeutic effects and related mechanisms of algae oil (ALG) to protect retinal ganglion cells (RGCs) in a rat model of anterior ischemic optic neuropathy (rAION). METHODS: Rats were daily gavaged with ALG after rAION induction for seven days. The therapeutic effects of ALG on rAION were evaluated using flash visual evoked potentials (FVEPs), retrograde labeling of RGCs, TUNEL assay of the retina, and ED1 staining of optic nerves (ONs). The levels of inducible nitric oxide synthase (iNOS), IL-1ß, TNF-α, Cl-caspase-3, ciliary neurotrophic factor (CNTF), and p-ERK were analyzed by using western blots. RESULTS: Protection of visual function in FVEPs amplitude was noted, with a better preservation of the P1-N2 amplitude in the ALG-treated group (p = 0.032) than in the rAION group. The density of RGCs was 2.4-fold higher in the ALG-treated group compared to that in the rAION group (p < 0.0001). The number of ED1-positive cells in ONs was significantly reduced 4.1-fold in the ALG-treated group compared to those in the rAION group (p = 0.029). The number of apoptotic RGCs was 3.2-fold lower in number in the ALG-treated group (p = 0.001) than that in the rAION group. The ALG treatment inhibited ERK activation to reduce the levels of iNOS, IL-1ß, TNF-α, and Cl-caspase-3 and to increase the level of CNTF in the rAION model. CONCLUSION: The treatment with ALG after rAION induction inhibits ERK activation to provide both anti-inflammatory and antiapoptotic effects in rAION.

Effect of dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes of Taiwanese patients with treatment-naïve diabetic macular edema.

BACKGROUND/PURPOSE: Vitrectomy may affect intravitreal drug clearance and efficacy for treating diabetic macular edema (DME). This study aimed to evaluate functional and anatomical outcomes of intravitreal dexamethasone (DEX) implant for vitrectomized and nonvitrectomized eyes with treatment-naïve DME in Taiwanese patients. METHODS: In this retrospective single-center study, we reviewed treatment-naïve patients who received DEX implant monotherapy for center-involved DME from January 2015 to May 2017. Retreatments were provided at least 4 months apart as needed. The primary outcomes included changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at Month 6. Adverse events were recorded. RESULTS: Twenty-seven eyes in 27 patients had prior vitrectomy and 43 eyes in 41 patients without vitrectomy. Baseline data were comparable. Overall, the improvements in BCVA and CFT were significant by 1 month post-treatment and sustained throughout the study (all p < 0.05). At Month 6, BCVA improved by 16.5 and 12.1 letters, and CFT reduced by 138.0 and 121.9 µm in vitrectomized and nonvitrectomized eyes, respectively, with a mean of 1.5 DEX implant injection. No significant differences in clinical outcomes were seen between the two groups (all p > 0.05). DEX implant injection was well tolerated. About 30% of patients had post-injection intraocular pressure value > 20 mmHg, and all were manageable with topical hypotensive agents, and no serious ocular complication was observed. CONCLUSION: In this 6-month retrospective study, intravitreal DEX implant was effective in Taiwanese patients with treatment-naïve DME regardless of vitrectomy status.

Comparison of efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema.

PURPOSE: To compare the efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema (DME). STUDY DESIGN: A retrospective, nonrandomized, and comparative study. METHODS: From May 2013 to March 2016, 148 eyes of 148 patients with treatment-naïve center-involving DME were reviewed in one institution. Forty-six eyes underwent prior vitrectomy at least 3 months ago, and 102 eyes did not receive any vitrectomy. Three monthly then PRN intravitreal ranibizumab treatments were performed in all the patients with monthly follow-up for 6 months. Primary outcome measures included change in central foveal thickness (CFT) and best-corrected visual acuity (BCVA) at month 6. RESULTS: The CFT significantly reduced, and the BCVA significantly improved 6 months after ranibizumab injections in either vitrectomized or non-vitrectomized groups (p < 0.05). There was no difference between vitrectomized and non-vitrectomized eyes in baseline characteristics. Significantly better final BCVA and visual gain were found in non-vitrectomized eyes than in vitrectomized eyes (p = 0.01 and 0.03, respectively). Final CFT and CFT decrease were significantly greater in non-vitrectomized group than in vitrectomized group (p = 0.02 and 0.006, respectively). Injection number of ranibizumab was 4.12 ± 0.58 in non-vitrectomized eyes, significantly less than that in vitrectomized eyes (5.05 ± 0.71) during 6-month period (p < 0.001). There were no severe systemic/ocular adverse effects in both groups. CONCLUSIONS: Intravitreal ranibizumab was helpful for either vitrectomized or non-vitrectomized eyes with DME in short-term follow-up. Anatomical and functional improvements were greater in non-vitrectomized patients than in vitrectomized cases.

Surgical approach affects intraocular lens decentration.

BACKGROUND/PURPOSE: This study aims to quantify and identify risk factors for intraocular lens (IOL) tilt and decentration early after surgery using Scheimpflug imaging. METHODS: We prospectively included 268 eyes of 253 patients who underwent uneventful cataract surgery and one-piece IOL implantation using a superior or temporal approach. Scheimpflug imaging was used to evaluate the tilt and decentration of IOLs at 1 week, 1 month, and 3 months postoperatively. Differences in IOL tilt and decentration between the approaches were examined. Correlations of age and axial length with the magnitudes of IOL decentration and tilt were also examined. RESULTS: In total, 139 right and 129 left eyes were included. IOL displacement averaged 150 µm upward and 150 µm to the nasal side of the pupil. Over 50% of the eyes were tilted upward and approximately 90% to the temporal side. The surgical approach was significantly associated with horizontal decentration in both eyes, but significantly associated with only vertical decentration in the right eye 1 week postoperatively. In the left eyes, IOLs were shifted to the nasal side in 57.1% and 36.8% of the eyes that received the temporal and the superior approach, respectively, compared with 75.8% and 50% in the right eyes. The differences were significant only at 1-week follow-up (p = 0.035 and p = 0.003, respectively). Age or axial length was not associated with IOL tilt or decentration in either eye. CONCLUSION: Scheimpflug imaging can be used as a quantitative tool to evaluate IOL position. The incision site affected the IOL position, this finding was significant at 1 week postoperatively only.

Refractive results of phacoemulsification in vitrectomized patients.

The aim of this study was to compare the refractive errors after uneventful phacoemulsification and intraocular lens implantation in the cases of vitrectomized eyes and non-vitrectomized eyes. Vitrectomized eyes were divided into 2 groups: vitrectomy alone as Group 1, vitrectomy with gas tamponade as Group 2. Normal-controlled eyes were categorized as Group 3. Intraocular lens (IOL) power calculation and the measurements of axial length (AL) and keratometric value (K) were performed using the IOLMaster and the Haigis and SRK/T formula as subgroup A and B. The measurements of AL, K, and IOL power calculation were also performed by the applanation ultrasound and the SRK/T formula as comparison subgroup C. The mean numeric error (MNE) and median absolute error (MedAE) were compared between Groups and subgroups. The MedAE was not significantly different in Group 1A, 2A, and 3A, respectively (p > 0.05). The MNE was significantly different in Group 1A, 2A, and 3A (p = 0.04). Post hoc test showed an insignificant difference between Group 1A and 3A (p = 0.36), but significantly a higher MNE in Group 2A than that in Group 3A (p = 0.03). A significantly longer AL was noted in Group 1B and 2B, comparing with Group 1C and 2C (p < 0.01). Refractive outcomes after phacoemulsification sequential to vitrectomy alone were comparable to those in normal control. Hyperopic shift was found following phacoemulsification sequential to vitrectomy with gas tamponade comparing to normal eyes. A significantly longer AL was found using optical biometry compared to applanation ultrasound in vitrectomized eyes, but not in normal eyes.

Involvement of CKS1B in the anti-inflammatory effects of cannabidiol in experimental stroke models.

We have previously demonstrated that treatment with cannabidiol (CBD) ameliorates mitochondrial dysfunction and attenuates neuronal injury in rats following cerebral ischemia. However, the role of CBD in the progression of ischemic stroke-induced inflammation and the molecules involved remain unclear. Here, we found that CBD suppressed the production of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), reduced the activation of microglia, ameliorated mitochondrial deficits, and decreased the phosphorylation of nuclear factor κ-B (NF-κB) in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cyclin-dependent kinase regulatory subunit 1B (CKS1B) expression was decreased in BV-2 cells following OGD/R and this reduction was blocked by treatment with CBD. Knockdown of CKS1B increased the activation of microglia and enhanced the production of IL-1ß and TNF-α in BV-2 cells treated with CBD. Moreover, CKS1B knockdown exacerbated mitochondrial deficits and increased NF-κB phosphorylation. CBD treatment also ameliorated brain injury, reduced neuroinflammation, and enhanced the protein levels of mitochondrial transcription factor A and CKS1B in rats following middle cerebral artery occlusion/reperfusion. These data identify CKS1B as a novel regulator of neuroinflammation; and reveals its involvement in the anti-inflammatory effects of CBD. Interventions targeting CKS1B expression are potentially promising for treating in ischemic stroke.

Posterior subtenon injection of triamcinolone acetonide after phacoemulsification in a patient with X-linked retinoschisis.

PURPOSE: To describe a case of X-linked retinoschisis with pseudophakic cystoid macular edema treated by posterior subtenon injection of triamcinolone acetonide. CASE REPORT: The patient was a 60-year-old man. His best-corrected visual acuity (BCVA) was counting fingers in the right eye. Senile cataract was found with grade II nuclear sclerosis. Optical coherence tomography revealed foveoschisis with a central foveal thickness (CFT) of 545 µm. The patient underwent uneventful phacoemulsification and in-the-bag implantation of intraocular lens. Postoperative persistent cystoid macular edema was found, with CFT increased to 787 µm. The macular edema did not respond to topical corticosteroids and nonsteroidal anti-inflammatory drugs. Triamcinolone acetonide 20 mg was injected into the posterior subtenon space 10 weeks after the surgery. Macular cystic lesions dramatically disappeared 2 months after the injection, and CFT decreased to 171 µm, with accompanying inner/outer segment disruption. His BCVA also improved to 20/100. Macular edema or foveoschisis did not recur, and BCVA remained stable 1 year after the cataract operation. CONCLUSIONS: Foveoschisis and pseudophakic cystoid macular edema disappeared after posterior subtenon injection of triamcinolone acetonide without recurrence during the 15-month follow-up period.

Computed Tomography Morphology of Affected versus Unaffected Sides in Patients with Unilateral Primary Acquired Nasolacrimal Duct Obstruction.

BACKGROUND: This study aimed to describe the anatomical details of the bony nasolacrimal duct (BNLD) and adjacent nasal structures by analyzing computed tomography (CT) images, and to investigate their effects on the development of primary acquired nasolacrimal duct obstruction (PANDO). METHODS: A total of 50 patients with unilateral PANDO who underwent dacryocystorhinostomy, with a mean age of 57.96 years, were included. The preoperative CT images were reviewed to measure the anteroposterior and transverse diameters of the BNLD at the entrance and exit levels, as well as the minimum transverse diameter along the tract. The sagittal CT images were analyzed to classify the shape of the bony canals into columnar, funnel, flare, and hourglass. The associated paranasal abnormalities, including nasal septum deviation (NSD), sinusitis, angle between the bony inferior turbinate and medial wall of the maxillary sinus, and mucosal thickness of the inferior turbinate, were investigated. RESULTS: Fifty CT images were analyzed, and all parameters measured on both sides of the BNLD were not significantly different between the PANDO and non-PANDO sides, except for the minimum transverse diameter, which was significantly smaller on the PANDO side (p = 0.002). Columnar-shaped BNLD was the most common on both sides. No significant difference was observed in the incidence of paranasal abnormalities between sides; however, deviation of the septum toward the non-PANDO side was more common (67.9%). CONCLUSIONS: A small minimum transverse diameter of the BNLD may be a risk factor for PANDO. The association between nasal abnormalities and PANDO was not remarkable.

Bilateral Retinal Artery Occlusions and Uveitis as the First Manifestation of Crohn's Disease.

PURPOSE: To present a case of newly diagnosed Crohn's disease, in which retinal artery occlusion (RAO) with uveitis was the first clinical manifestation. CASE DESCRIPTION: A 55-year-old man presented with bilateral blurred vision, with decreased best corrected visual acuity (BCVA) to light perception (right eye, RE) and 20/40 (left eye, LE). Ophthalmological examination revealed bilateral iritis, vitritis, disc edema, and retinal vascular occlusions. Because of concurrent fever and leukocytosis, a systemic infection was highly suspected. However, whole-body imaging was unrevealing. Subsequently, the patient presented with massive bloody stool. Histopathological specimen from emergent hemicolectomy confirmed transmural granulomatous inflammation. Crohn's disease was finally diagnosed. Following treatment, the BCVA recovered to 20/40 (RE) and 20/22 (LE). The systemic condition remained stable after a 3-year follow-up. CONCLUSION: RAO with uveitis is a possible manifestation of Crohn's disease. In complex uveitis cases, clinicians should be aware of inflammatory bowel diseases as an important differential diagnosis.

Adherence to visual field examination in glaucoma patients during the Coronavirus disease 2019 outbreak.

We described the proportion of adherence to the scheduled visual field (VF) examination and the associated factors in glaucoma patients in a tertiary referral center during the Coronavirus disease 2019 (COVID-19) outbreak in Taiwan. Patients with scheduled VF examinations during May 25th to July 12th, 2021, were retrospectively evaluated. Clinical characteristics including type of glaucoma, intraocular pressure (IOP) at the day of arranging VF examinations, prescriptions of anti-glaucoma medications, non-medical glaucoma treatment, length of glaucoma history, mean deviation (MD) of VF defect, and announcement of glaucoma progression were recorded. The associations between the adherence and the clinical factors were analyzed by univariate and multivariate logistic regression. There were 204 patients included, of which 37 patients (18.14%) adhered to VF examinations. A total of 161 patients (78.9%) were diagnosed with open-angle glaucoma (OAG), 27 patients (13.2%) with angle closure glaucoma, and 16 patients (7.8%) with glaucoma suspect. Most of the participants (41.2%) had mild VF defect and had been prescribed with no more than 1 bottle of anti-glaucoma medication. In the multivariate analysis, diagnosis of glaucoma suspect (P = .02) and history of SLT (P = .04) were significantly associated with better adherence. Glaucoma severity and the announcement of glaucoma progression were not significantly associated with adherence to VF examination. The COVID-19 pandemic had greatly influenced the adherence to VF examination in glaucoma patients. This study demonstrated that patients with the diagnosis of glaucoma suspect and history of SLT were more likely to adhere to VF examinations even during the COVID-19 pandemic.

Integrating multi-modal information to detect spatial domains of spatial transcriptomics by graph attention network.

Recent advances in spatially resolved transcriptomic technologies have enabled unprecedented opportunities to elucidate tissue architecture and function in situ. Spatial transcriptomics can provide multimodal and complementary information simultaneously, including gene expression profiles, spatial locations, and histology images. However, most existing methods have limitations in efficiently utilizing spatial information and matched high-resolution histology images. To fully leverage the multi-modal information, we propose a SPAtially embedded Deep Attentional graph Clustering (SpaDAC) method to identify spatial domains while reconstructing denoised gene expression profiles. This method can efficiently learn the low-dimensional embeddings for spatial transcriptomics data by constructing multi-view graph modules to capture both spatial location connectives and morphological connectives. Benchmark results demonstrate that SpaDAC outperforms other algorithms on several recent spatial transcriptomics datasets. SpaDAC is a valuable tool for spatial domain detection, facilitating the comprehension of tissue architecture and cellular microenvironment. The source code of SpaDAC is freely available at Github (https://github.com/huoyuying/SpaDAC.git).

SPIRAL: integrating and aligning spatially resolved transcriptomics data across different experiments, conditions, and technologies.

Properly integrating spatially resolved transcriptomics (SRT) generated from different batches into a unified gene-spatial coordinate system could enable the construction of a comprehensive spatial transcriptome atlas. Here, we propose SPIRAL, consisting of two consecutive modules: SPIRAL-integration, with graph domain adaptation-based data integration, and SPIRAL-alignment, with cluster-aware optimal transport-based coordination alignment. We verify SPIRAL with both synthetic and real SRT datasets. By encoding spatial correlations to gene expressions, SPIRAL-integration surpasses state-of-the-art methods in both batch effect removal and joint spatial domain identification. By aligning spots cluster-wise, SPIRAL-alignment achieves more accurate coordinate alignments than existing methods.

Whole-genome DNA methylation profiling reveals epigenetic signatures in developing muscle in Tan and Hu sheep and their offspring.

Introduction: The Tan sheep is a popular local breed in China because of its tenderness and flavor. The Hu sheep breed is also famous for its high litter size, and its muscle growth rate is faster than that of Tan sheep. However, the epigenetic mechanism behind these muscle-related phenotypes is unknown. Methods: In this study, the longissimus dorsi tissue from 18 6 month-old Tan sheep, Hu sheep, and Tan-Hu F2 generation (6 sheep per population) were collected. After genomic DNA extraction, whole-genome bisulfite sequencing (WGBS) and bioinformatics analysis were performed to construct genome-wide DNA methylome maps for the Tan sheep, Hu sheep and their Tan-Hu F2 generation. Results: Distinct genome-wide DNA methylation patterns were observed between Tan sheep and Hu sheep. Moreover, DNA methylated regions were significantly increased in the skeletal muscle from Tan sheep vs. the F2 generation compared to the Hu sheep vs. F2 generation and the Tan sheep vs. Hu sheep. Compared with Hu sheep, the methylation levels of actin alpha 1 (ACTA1), myosin heavy chain 11 (MYH11), Wiskott-Aldrich syndrome protein (WAS), vav guanine nucleotide exchange factor 1 (VAV1), fibronectin 1 (FN1) and Rho-associated protein kinase 2 (ROCK2) genes were markedly distinct in the Tan sheep. Furthermore, Gene Ontology analysis indicated that these genes were involved in myotube differentiation, myotube cell development, smooth muscle cell differentiation and striated muscle cell differentiation. Conclusion: The findings from this study, in addition to data from previous research, demonstrated that the ACTA1, MYH11, WAS, VAV1, FN1, and ROCK2 genes may exert regulatory effects on muscle development.