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Traditional animal pose estimation techniques based on images face significant hurdles, including scarce training data, costly data annotation, and challenges posed by non-rigid deformation. Addressing these issues, we proposed dynamic conditional prompts for the prior knowledge of animal poses in language modalities. Then, we utilized a multimodal (language–image) collaborative training and contrastive learning model to estimate animal poses. Our method leverages text prompt templates and image feature conditional tokens to construct dynamic conditional prompts that integrate rich linguistic prior knowledge in depth. The text prompts highlight key points and relevant descriptions of animal poses, enhancing their representation in the learning process. Meanwhile, transformed via a fully connected non-linear network, image feature conditional tokens efficiently embed the image features into these prompts. The resultant context vector, derived from the fusion of the text prompt template and the image feature conditional token, generates a dynamic conditional prompt for each input sample. By utilizing a contrastive language–image pre-training model, our approach effectively synchronizes and strengthens the training interactions between image and text features, resulting in an improvement to the precision of key-point localization and overall animal pose estimation accuracy. The experimental results show that language–image contrastive learning based on dynamic conditional prompts enhances the average accuracy of animal pose estimation on the AP-10K and Animal Pose datasets.

Background Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN. Methods Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected. Results CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs. Conclusions CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.

Background Multiple myeloma (MM) in association with pregnancy is a rare event, and a consensus is lacking. It is urgent to increase the awareness of investigations required for a suspected diagnosis of MM during pregnancy and optimise its management. Methods A case of MM that occurred during pregnancy is presented with individual details, including clinical presentation, laboratory findings, diagnostic process, natural disease course, therapeutic approaches and outcomes. Afterwards, a literature search was conducted, and the available cases were descriptively reviewed. Results A 37-year-old pregnant woman was diagnosed with MM due to anaemia combined with other abnormalities, as revealed by laboratory tests performed during the second trimester. At 27 + 3 weeks gestation, the patient started chemotherapy with cyclophosphamide and methylprednisolone. She delivered a preterm infant via Caesarean section at 28 + 3 weeks gestation and continued to receive anti-myeloma therapy with standard induction postpartum, followed by autologous stem cell transplantation. Both the mother and her offspring achieved favourable outcomes. A total of 52 patients with MM associated with pregnancy aged between 21 and 44 years were identified from a literature review. Ten patients (19.2%) were diagnosed prior to pregnancy, 38 patients (73.1%) were diagnosed during pregnancy, and 4 patients (7.7%) were diagnosed postpartum. The most common initial complaint included bodily pain (53.8%), which was mostly attributed to bone lesions. Among the 48 patients diagnosed with MM before or during pregnancy, 25 patients (52.0%) received chemotherapy during pregnancy. Forty-seven patients (90.4%) delivered healthy infants, and all of them remained symptom-free up to the publication date. Forty-one women (78.8%) remained alive, whereas 10 women (19.2%) died. Conclusion Pregnant patients with MM exhibited a broad spectrum of manifestations. Clinicians should raise concerns and be aware of which investigations to request for a suspected diagnosis of MM. Prompt diagnosis in our patient ensured targeted monitoring, and an individualised strategy formulated by a multidisciplinary team allowed for acceptable maternal and foetal outcomes. Currently, multidisciplinary team work-up is preferable for management. The number of agents deemed to be safe for treating MM during pregnancy is fairly limited. Corticosteroids were observed to be the mainstay temporising treatment. Further research should focus on collaborative studies and be designed to assess novel therapies.

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer. The advent of immunotherapy has revolutionised cancer therapeutics, but its application in the context of pancreatic ductal adenocarcinoma has been limited. Here authors explore the effect of innate trained responses to fungal β-glucan and assess its effect in a murine model of pancreatic ductal adenocarcinoma where they observe reduced tumour burden and enhanced survival.

To evaluate and identify reports of adverse events related to hearing impairment with drugs approved in the past 20 years, to identify new adverse reaction signals related to hearing impairment that have not yet been reported, and to improve the safety of drug treatments. The adverse event report data from the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were retrieved. \"Hearing disorders\" was used as the keyword to screen for drugs related to the adverse event. After standardizing the drug name and the adverse drug event name, the adverse event reports with hearing disorders as the main suspect were collected, and the proportional imbalance algorithm was used to detect the potential adverse event signals to drug-related hearing impairment. The top five drugs with the highest number of reported adverse events to hearing impairment were sacubitril/valsartan (2,674), adalimumab (2,479), etanercept (1,834), tofacitinib (1,812), and apixaban (1,600). Except for adalimumab, the risk of hearing impairment is not mentioned in the instructions. The top five drugs for new signal strength are pancuronium ( = 13, ROR 67.57, PRR 53.61, IC5.74, EBGM 53.06), paromomycin ( = 6, ROR 46.3, PRR 39.33, IC5.30, EBGM 39.33), tafamidis ( = 300, ROR 14.90, PRR 14.13, IC3.82, EBGM 14.07), vildagliptin/metformin ( = 83, ROR 11.47, PRR 11.02, IC3.46, EBGM 11.01), and atorvastatin calcium/ezetimibe ( = 6, ROR 10.76, PRR 10.36, IC3.37, EBGM 10.36). Our study covered 20 years of real-world data on reports of adverse events related to hearing impairment in the FAERS database, validating previous reports and studies, as well as identifying drugs that signal new adverse events of hearing impairment, especially some drugs commonly used for the treatment of chronic diseases (a combination of hypoglycemic drugs, antihypertensive drugs, and lipid modulators) and some new drugs in the 5-year post-market period.

N 6 -methyladenosine (m 6 A) maintains maternal RNA stability in oocytes. One regulator of m 6 A, ALKBH5, reverses m 6 A deposition and is essential in RNA metabolism. However, the specific role of ALKBH5 in oocyte maturation remains elusive. Here, we show that Alkbh5 depletion causes a wide range of defects in oocyte meiosis and results in female infertility. Temporal profiling of the maternal transcriptomes revealed striking RNA accumulation in Alkbh5 −/− oocytes during meiotic maturation. Analysis of m 6 A dynamics demonstrated that ALKBH5-mediated m 6 A demethylation ensures the timely degradation of maternal RNAs, which is severely disrupted following Alkbh5 −/− depletion. A distinct subset of transcripts with persistent m 6 A peaks are recognized by the m 6 A reader IGF2BP2 and thus remain stabilized, resulting in impaired RNA clearance. Additionally, reducing IGF2BP2 in Alkbh5 -depleted oocytes partially rescued these defects. Overall, this work identifies ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m 6 A removal in maternal RNA decay. N6-methyladenosine (m6A) maintains maternal RNA stability in oocytes. Here, the authors identify demethylase ALKBH5 as a key determinant of oocyte quality and unveil the facilitating role of ALKBH5-mediated m6A removal in maternal RNA decay.

Background Mild cognitive impairment (MCI) is an intermediate stage between normal cognitive aging and dementia. People with MCI have a higher risk of developing dementia than normal healthy people. Improving their cognitive functions may delay dementia onset. The aim of this project is to conduct a randomized controlled trial to assess the effects of transcranial direct current stimulation (tDCS) on cognition in adults with mild cognitive impairment. Methods/design Forty-eight MCI participants will be recruited from four local day centers for the elderly and assigned to experimental or control groups randomly in a 1:1 ratio. Participants and assessors are blinded to their group assignment. The experiment will consist of pre- and post-assessments and a 1-month follow-up assessment. Participants will receive 8 sessions (2×/week for 4 weeks) of tDCS intervention (either real or sham, 20 min per session). Primary outcome measures will include digit span test, color trail test, verbal fluency, Chinese version of the Verbal Learning Test, and the Hong Kong version of Montreal Cognitive Assessment. Participants will also have their brain waves recorded while completing a computer memory task at each assessment point. The task will require them to study and memorize certain Chinese characters and take a recognition memory test. Secondary outcomes include scores from the Geriatric Depression Scale and the Modified Barthel Index. Discussion The study addresses the shortcomings in previous studies and investigates multiple domains of cognition (e.g., attention, memory, executive function), the sustainability of the effects, and includes electroencephalography as an outcome measure with application to people with MCI. The results of this proposed project are expected to have an impact on the long-term care and rehabilitation of older and clinical populations and to increase general knowledge about tDCS and related cognitive enhancement in MCI. Trial registration ClinicalTrials.gov NCT05584748 ( https://clinicaltrials.gov/study/NCT05584748 ). Registered on October 10, 2022.

Background Robotic-assisted rehabilitation has been used to release the labor burden in manual practice for early stroke rehabilitation. However, its broader application is constrained by high costs, limited accessibility, and high dependence on professional operation. This study aimed to investigate the feasibility and effectiveness of semi-independent, bedside upper limb rehabilitation assisted by a wrist-hand exoneuromusculoskeleton (WH-ENMS) for individuals with subacute stroke via a randomized controlled trial compared with the outcomes achieved by conventional therapy and training programs assisted by an interlimb-coordinated (IC) robot. Methods Fifty-four participants with subacute stroke were randomized into three groups: ENMS, IC, or conventional therapy. All groups underwent 21 rehabilitation sessions (60 min/day for 21 consecutive days), each including 30 min of standardized Bobath therapy. During the additional 30 min of training, the ENMS group engaged in semi-independent bedside training with minimal supervision, the IC group received supervised IC cycling, and the conventional group received proprioceptive neuromuscular facilitation. The rehabilitative effects were evaluated via clinical scores. The primary outcome was the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), and the secondary outcomes included the action research arm test (ARAT), modified Ashworth scale (MAS), and modified Barthel index (MBI). The manpower consumption was quantified on the basis of the professional hours required during training. Results The ENMS group required significantly less total occupational therapist (OT) involvement (11.6 h) compared with the IC (22.9 h) and conventional (21.0 h) groups, representing a 49.4% reduction in professional manpower demand. All groups showed significant improvements in FMA-UE, ARAT, and MBI scores. Compared with the other groups, the ENMS group achieved superior gains in voluntary motor function (FMA-UE and ARAT, P  < 0.05). The ENMS group also obtained significant reductions in muscle spasticity across multiple joints (MAS, P  < 0.05). The IC group demonstrated the largest MBI improvements, while the conventional group showed greater gains in hand function than the IC group ( P  < 0.05). Conclusions Semi-independent bedside rehabilitation with WH-ENMS is feasible, safe, and effective for inpatients with subacute stroke. It reduced the demand for professional manpower while promoting upper limb recovery, particularly wrist–hand function, during the critical subacute neuroplasticity window. This approach could optimize rehabilitation resource allocation and facilitate more personalized interventions. Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR2300074469. Registered on 2023/08/08.

Background Over 2.5 million cycles in vitro fertilization (IVF) are conducted annually, and numbers are expected to rise with the aging population. The controlled ovarian stimulation (COS) process, key to IVF success, is inherently complex. Given advances in artificial intelligence (AI), this study investigated whether a series of AI models can outperform traditional clinical practices in predictive accuracy and COS optimization. Methods This retrospective cohort study analyzed first-cycle ovarian stimulation patients (Oct 2017–Dec 2020) and was validated using an independent cohort (Jan 2018–Jan 2022). Six AI algorithms and 73 variables were screened. A four-submodel strategy included risk prediction models for low and hyper ovarian response (LORRM, HORRM) and strategy deployment models (LORSM, HORSM) for managing critical COS components. Feature importance was assessed using Shapley additive explanations, with sensitivity analyses performed for robustness. The ability to propose effective COS strategies was also retrospectively assessed. Results A four-submodel system prototype using extreme gradient boosting trees was developed. All submodels showed superior discrimination compared to conventional ovarian reserve markers (AUC, 95% CI: LORSM, 0.95 [0.94–0.96]; LORRM, 0.93 [0.92–0.94]; HORSM, 0.90 [0.88–0.91]; HORRM, 0.89 [0.87–0.91]. DeLong P  < 0.001 for all). They demonstrated adequate calibration (Brier scores of four submodels ranged from 0.064 to 0.072), promising performance in external validation (AUCs ranging from 0.84 to 0.88) and sensitivity analyses. Among COS components, COS protocol and recombinant follicle-stimulating hormone (FSH) use had the largest impact on low and hyper response risks, respectively, with FSH starting dose ranking third. Diastolic blood pressure, alanine aminotransferase, and white blood cell count predicted low response, while basal luteinizing hormone (LH) levels and platelet count were key for hyper response. Several were newly identified potential biomarkers. LORSM and HORSM identified effective strategies with precision of 95.5% (95% CI, 94.6–96.4%) and 98.4% (95% CI, 98.0–98.9%), respectively. Conclusions The AI-based system demonstrated superior detection of abnormal ovarian responses and effective individualized COS design compared to conventional clinical practice while maintaining transparency. The system identified potential biomarkers beyond conventional ovarian reserve markers and offered new insights for optimizing IVF, showing promise for advancing personalized reproductive medicine.

The precise evaluation of sensory perceptions during fabric-skin interactions is still poorly understood in neuroscience. This study aims to investigate the cortical sensory response to fabric stimuli with different textiles by Electroencephalographic (EEG) spectral intensities, and evaluate the relationships between EEG frequency bands, traditional subjective questionnaires, and the materials' physical properties. Twelve healthy adult participants were recruited to test three fabrics with different textile compositions of 1) cotton, 2) nylon, and 3) polyester and wool. The physical properties of the fabrics were quantitatively evaluated by a Fabric Touch Tester (FTT). Subjects were invited to rate the sensory perception of the fabric samples via a subjective questionnaire and objective EEG recording. Significant differences in the EEG relative spectral power of Theta and Gamma bands were acquired in response to the different fabric stimuli (P<0.05). The Theta and Gamma powers demonstrated a significant correlation with the most of the subjective sensations evaluated by questionnaire and the fabrics' physical properties by FTT (P<0.05). The EEG spectral analysis could feasibly be used for the discrimination of fabric stimuli with different textile compositions and further indicates sensory perceptions during fabric stimulation. This finding may provide evidence for further exploratory research of sensory perceptions via EEG spectral analysis, which could be applied to the study of brain generators of skin tactility in future prostheses and the automatic detection of sensory perception in industries.