The cocaine- and amphetamine-regulated transcript (CART) peptide is widely expressed throughout the mammalian central nervous system. CART was first identified during sequencing of a hypothalamic peptide whose biological function was unknown at the time. Subsequent studies used immunohistochemistry to detect CART peptides and in situ hybridization to localize the corresponding messenger ribonucleic acid (mRNA) in several species, including rats, mice, non-human primates, and humans. Additional investigations have examined the neurotransmitters that are co-localized with CART peptides. Accumulated evidence indicates that CART peptides participate in diverse physiological processes, including addiction, reward, pain modulation, memory, sleep, hormonal regulation and the energy homeostasis. A clearer understanding of the widespread distribution of CART peptides is therefore essential for elucidating their functional roles. Accordingly, this review summarizes recent findings on the distribution of CART peptides in the aim of this review is to summarize recent findings regarding the distribution of CART peptides within the central nervous system of rodents, non-human primates, and humans, with particular emphasis on interspecies differences as abasis for identifying future research priorities. Accordingly, this review summarizes recent findings on the distribution of CART peptides within the central nervous system of rodents, non-human primates, and humans, with particular emphasis on interspecies differences as a basis for identifying future research priorities.
Milk oligosaccharides (MOs) are essential for the development of mammalian offspring, yet their fine-scale structural evolutionary divergence remains unelucidated, largely due to isomeric complexity and the limitations of analytical methods. Here, we present GlycoBond X, an online platform that couples high-resolution separation with parallel structural characterization of glycan isomers through multi-stage chemical derivatization and RP-HPLC-MS/MS. By applying this strategy to four evolutionarily distinct mammals, we uncovered a conserved transition from acidic MO dominance (>75% in mouse and tree shrew) to predominantly fucosylated neutral MOs (>62% in macaque and human). GlycoBond X unveiled unprecedented structural diversity, including 22 unique fucosylation motifs and 66 previously undescribed human MOs. Notably, tree shrew MOs exhibited human-like structures and shared over 69% FUT2 sequence homology with primates. This study established a high-throughput, high-sensitivity platform, elucidated the adaptive structural evolution of oligosaccharides via evolutionary glycomics, and provided a foundation for exploring their biosynthetic pathways.
In a previous study, retrospective predictions of human serum concentration-time profiles for three therapeutic monoclonal antibodies (mAbs) with linear pharmacokinetics were performed using allometric scaling in common marmosets and achieved favorable predictability. To generalize this method, in the present study, golimumab and ustekinumab, which exhibit linear pharmacokinetics, were repeatedly administered to marmosets. Additionally, the immunogenicity of these mAbs in common marmosets was evaluated. Golimumab and ustekinumab were administered in four repeated doses. Following the initial administration, the scaling exponents of the two mAbs were calculated, and the average scaling exponents of the five mAbs were used for the predictions. Furthermore, serum anti-ustekinumab and anti-golimumab antibodies were evaluated following the repeated-dose administration. Human serum concentration-time curves of golimumab and ustekinumab were predicted using the average scaling exponents of the five mAbs. Although the predictability of the golimumab elimination rate was slightly inferior, ustekinumab showed excellent prediction performance. Low levels of anti-ustekinumab antibodies were detected in the serum when the serum ustekinumab levels were considered to have completely diminished. Furthermore, serum anti-golimumab antibodies were negligible during the experimental period. We identified provisional optimal scaling exponents for predicting human PK and found minimal anti-drug antibody formation. As the cost of acquiring and maintaining cynomolgus monkeys is increasing, pharmacokinetic data of marmosets is expected to encourage the potential use of these small non-human primates as an alternative model.
The intricate cortical folds of large primates physically restrict access to substantial portions of neural information via interface devices. Here, we develop a bioelectronic system, sFlex-Fold, with switchable flexibility, representing the neural interface capable of nondestructive three-dimensional (3D) access to both cortical gyri and sulci, providing large-area, nonpenetrative deep tissue coverage. sFlex-Fold is based on an artificial intelligence (AI)-designed liquid metal alloy (LM-alloy), leveraging the phase change of the tailor-made LM-alloy to create neural interfacing electronics with tunable mechanical response to temperatures ranging from 25° to 37°C. The LM-alloy can be patterned into arbitrary circuit layouts with an ~10-micrometer resolution. The flexibility switching happens at the LM melting point, fine-tuned to 36.2°C, upon in vivo tissue contact, causing a three-order-of-magnitude reduction in the effective modulus of the implanted device. As a result, sFlex-Fold has the unique advantages of both a rigid and flexible state and can be morphed into complex, folded, 3D shapes. This enables nondestructive in vivo implantation into deep cortical sulci while maintaining large coverage (>80 square centimeters) over curved brain surfaces with tissue-matching mechanical compliance. Such 3D structural and mechanical mimicking enables high-quality electrical interfacing as quantitatively assessed using rodent and porcine models.
Expression of calbindin D28k (CB) and parvalbumin (PV) distinguishes matrix and core type thalamic neurons, respectively, in primates. Whether the nice correspondence of intracellular calcium binding proteins and matrix/core neuron types translates to mouse remains unknown. Sixty reconstructed 3D mediodorsal thalamic nuclear neurons (MDCalb1 neurons), defined by calb1, the gene encoding CB in mouse MD, were mapped onto Allen Mouse Brain Common Coordinate Framework (CCFv3). Most MDCalb1 neurons (54/60) were isocortex-projecting ones, possessing collateral connections with caudate putamen (CP). Collectively, MDCalb1 neuron ensemble linked 93 anatomically-defined brain structures/regions with their axons; and of these 93 axon-connected structures/regions, the single MDCalb1 neurons had projection areas (receiving ≥ 2 axon terminals) ranging from 3 to 34 in number. Distinct projectomic profiles defined roughly 8 neuron subgroups, which differed from each other in composition of axon targets involving cortical and subcortical regions. Isocortical areas in prefrontal and sensorimotor cortices such as agranular insular cortex (AI), secondary motor cortex (MOs) and orbital cortex (ORB) etc., as well as structures of striatopallidal and olfactory systems such as CP, nucleus accumbens (ACB) and main olfactory bulb (MOB), among others, constituted the main axonal projection targets. Intriguingly, some proximal axon branches from over a dozen MDCalb1 neurons (14/60) were seen to be spatially confined to MD, most frequently within dendritic territories of their source neurons, suggesting intra-MD innervation. For thalamocortical connectivity, most neurons (49/54, i.e., about 91%) had widespread, tangentially distributed axons terminating in layers 1-3 (L1-3) of multiple cortical areas. Thus, these neurons were of thalamic matrix type, per core-matrix-intralaminar classifying framework. Our morphometric data support the role of MDCalb1 neurons for coordinated signal processing in networks integrating broad cortical areas, as well as subcortical structures, to fulfil emotion/cognition-related executive behaviors.
Biodiversity in Southeast Asia is currently facing a significant decline, with primate species particularly impacted due to deforestation, poaching, global warming, and various other challenges. All 20 recognized gibbon species are considered at risk of extinction due to rapidly decreasing population sizes. The northern white-cheeked gibbon (Nomascus leucogenys) is among six gibbon species belonging to the genus Nomascus documented in Vietnam. This gibbon has been recorded in several protected areas, but significant populations persist only in a few locations, potentially including Vu Quang National Park (52.733 km2). In our study, we utilized the auditory point count method to collect data in the field and applied a distance sampling method to estimate the abundance of northern white-cheeked gibbons in Vu Quang National Park. A total of 27 gibbon groups were documented during our field survey. The estimated gibbon group density was approximately 0.48 groups/km², leading us to estimate the gibbon population size in Vu Quang National Park at about 155 groups. Vu Quang National Park therefore has the largest documented population of northern white-cheeked gibbons in Vietnam, highlighting the urgent need for prioritizing the conservation of this species.
Polymerase template switching is an essential mechanism in coronaviruses (CoVs) enabling both subgenomic RNA synthesis and increasing genomic diversity via recombination. Despite its importance, the CoV polymerase template-switching molecular mechanism remains unclear. Using magnetic tweezers, we show that the CoV nonstructural protein (nsp) 13-helicase drives intramolecular polymerase template switching, followed by copy-back RNA synthesis. This activity requires nsp13-helicase adenosine triphosphatase activity and a duplex RNA downstream of the CoV polymerase. Remdesivir and molnupiravir are antiviral nucleotide analogs reported to stall the viral polymerase and induce mutations in genome, respectively. Unexpectedly, we show that their incorporation in the nascent strand increases copy-back RNA synthesis in vitro and decreases recombination events in infected cells. We propose a mechanism of action where these analogs' incorporation traps replication complex in a recombination intermediate, preventing viral RNA utilization. Our study highlights the importance of investigating nucleotide analog mechanisms in replication complexes beyond the polymerase.
Catheterisation laboratories (Cath labs) are vital for diagnosing and treating cardiovascular and other vascular conditions. In Ghana, there is limited national-level data on the distribution and capacity of Cath labs. This study provides a nationwide overview of existing Cath labs, their equipment, and their functional scope. A descriptive cross-sectional survey of Cath labs in Ghana was conducted in September 2025. Data was collected on the number, location, equipment type (monoplane/biplane), and functional specialities (interventional cardiology [IC], interventional radiology [IR]). Information was verified through institutional sources and facility representatives. A total of 10 Cath labs were identified in Ghana across nine facilities. Euracare hosts two Cath labs (one monoplane, one biplane). Of the total, nine (90%) are located in Accra and one (10%) in Kumasi. Eight facilities use monoplane systems, and Euracare is the only centre with a biplane system. Four facilities (Euracare, Korle Bu Teaching Hospital, Spectra, and Bank Hospital) offer both IC and IR services, while others are limited to IC. Cath lab services in Ghana are predominantly centred in Accra, with merely one facility located outside the capital. Euracare offers advanced imaging capabilities with two Cath labs, featuring the sole biplane system. Strategic planning is essential to enhance the availability of Cath labs nationwide and to improve access to advanced cardiovascular and interventional care.
To develop and validate an MRI-clinical nomogram predicting surgical difficulty in extraperitoneal single-site robot-assisted radical prostatectomy (ssRARP). We retrospectively evaluated 252 patients undergoing extraperitoneal ssRARP. High difficulty was defined using cohort-specific ≥ 75th percentiles for console time (≥ 107.75 min) or estimated blood loss (≥ 50 mL). A nomogram was constructed via multivariable logistic regression and assessed using AUC, calibration plots, bootstrap validation, and decision curve analysis (DCA). High difficulty occurred in 124 patients (49.2%). Independent predictors included higher body mass index (OR = 1.122, P = 0.012), neoadjuvant therapy (OR = 1.972, P = 0.019), larger prostate volume (OR = 1.020, P = 0.003), narrower intertuberous distance (OR = 0.971, P = 0.043), and greater symphysis pubis height (OR = 1.071, P = 0.017). The nomogram showed acceptable discrimination (AUC = 0.675; optimism-corrected C-index = 0.650), good calibration, and positive DCA net benefit (13-92% thresholds). This novel nomogram optimizes patient selection and mitigates perioperative risks. However, because the difficulty thresholds were calibrated to our institution's specific cohort, recalibration is required before direct application to other centers.
Retinoic acid (RA), a bioactive metabolite of vitamin A, plays roles in early embryogenesis and hematopoietic development. However, its precise function in directing the hematopoietic lineage outcomes of human pluripotent stem cells (hPSCs) remains unclear. Here, we uncovered a distinct, stage-specific role for RA as a lineage-specifying modulator during late-stage hematopoietic differentiation, rather than as a promoter of hematopoietic progenitor generation. Using a stepwise hPSC differentiation system, we demonstrated that RA exerted minimal or inhibitory effects when applied during early mesoderm or hemogenic endothelial stages. In contrast, RA treatment during days 13-15 significantly enhanced progenitor maturation, proliferation, and functional output. Notably, RA acted cooperatively with external cytokines to modulate lineage fate. In the presence of erythropoietin (EPO), RA strongly promoted erythroid differentiation by activating EPOR signaling and upregulating erythroid transcriptional programs, including GATA1, KLF1, and globin gene expression. Conversely, under GM-CSF/M-CSF stimulation, RA biased progenitor differentiation toward macrophages, consistent with its role as an amplifier of the prevailing cytokine-directed lineage fate rather than an independent suppressor of erythropoiesis. These effects were highly dose- and context-dependent, with low-dose RA optimally enhancing lineage bias without cytotoxicity. Importantly, RA modulated the transcriptional and proliferative dynamics of committed progenitors. Taken together, our findings reveal a previously unrecognized role of RA as a versatile and tunable modulator of hematopoietic lineage fate that offers a novel strategy for in vitro blood cell engineering. This study advances approaches for lineage-specific blood production relevant to disease modeling, drug screening, and regenerative medicine.
Focal spinal cord lesions occur across a variety of neurological diseases including non-traumatic cervical myelopathies which can lead to neuropathic pain. Currently, the degree to which signs and symptoms of neuropathic pain correlate with functional impairments and/or anatomical deficits remains unclear. This study aimed to identify structural and functional determinants associated with neuropathic pain in individuals with focal spinal lesions. Individuals fulfilling the diagnostic criteria of neuropathic pain were identified among individuals with cervical myelopathy presenting with focal spinal lesions. Lesion volume and the extent of structural damage affecting the spinothalamic tract, dorsal columns, dorsal horn, and ventral horn were evaluated with tract-specific MRI of the cervical spinal cord. Quantitative sensory testing (QST) (i.e., thermal/mechanical thresholds) was performed at the most affected skin area. Additionally, contact heat-evoked potentials (CHEPs) were acquired following stimulation at the most affected skin area to objectively assess the functional integrity of the spinothalamic tract. MRI-derived structural damage was similar for individuals with (n=8) and without (n=8) neuropathic pain in all regions of interest (p>0.05). Mechanical hyperalgesia upon QST was observed in both groups. However, functional preservation of the spinothalamic system, measured by CHEPs, was present in 87 % of individuals with neuropathic pain, compared to 38 % of pain-free individuals (p=0.039). These observations suggest that segmental hyperexcitability resulting from structural spinal cord damage, in combination with residual sparing of spinothalamic afferents, may represent a key pathophysiological constellation contributing to central neuropathic pain following focal spinal lesions.
Hepatitis B virus-infected pregnant women often develop liver dysfunction. Although the NLRP3 inflammasome drives HBV-related liver injury, its predictive role in this group remains unclear. Participants were categorized into normal liver function (NLF, N = 73), abnormal liver function (ALF, N = 66) and control (N = 40) groups. Reverse transcription quantitative polymerase chain reaction was used to measure NLRP3 mRNA expression in peripheral blood mononuclear cells, and serum levels of interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) were detected using enzyme-linked immunosorbent assay. Correlations between inflammatory markers and liver function parameters were analysed, and multivariate logistic regression and receiver operating characteristic curve analyses were performed to evaluate predictive performance. The ALF group showed significantly elevated NLRP3 mRNA expression and higher serum levels of IL-1β and IL-18 compared to the NLF and control groups (all P < 0.001). These inflammatory markers were positively correlated with ALT, AST and HBV-DNA levels (all P < 0.001). Multivariate analysis identified NLRP3, IL-1β, IL-18, ALT and HBV-DNA as independent risk factors for liver dysfunction. The combined model of NLRP3, IL-1β, IL-18 and HBV-DNA demonstrated superior predictive performance (AUC = 0.954) compared to any single indicator. This research shows that elevated NLRP3 expression and increased levels of IL-1β and IL-18 in early pregnancy are associated with liver dysfunction in HBV-infected pregnant women. The combination of these inflammatory markers with HBV-DNA provides a highly accurate diagnostic model for early identification of high-risk individuals, offering a potential strategy for early intervention and improved management.
The differentiation of primary ischemic from secondary nonischemic T-wave inversion (TWI) on electrocardiograms (ECGs) presents a critical and pervasive diagnostic challenge in emergency cardiology. Historical clinical literature reports that clinician-led visual interpretation of isolated TWI yields a positive predictive value of only approximately 50% due to profound morphological ambiguity. This high degree of uncertainty frequently leads to high false-positive rates, resulting in unnecessary, costly, and potentially risky invasive angiographic procedures for patients. Furthermore, although existing deep learning models have attempted to address this clinical bottleneck, they are frequently limited to single-modality, "black box" architectures. Their inability to process complex multimodal data or provide transparent reasoning traces fundamentally limits clinical trust and real-world adoption. The objective of this study was to develop a novel diagnostic framework designed to address the critical clinical challenge of accurately differentiating ischemic from nonischemic TWI. By using a multimodal vision-language model trained with a reinforcement learning (RL) paradigm, this study aimed to improve diagnostic accuracy and provide interpretable reasoning. We developed ECG-R1, a multimodal framework using the Qwen2-VL-2B vision-language model, to analyze ECG waveform images and associated clinical text. Instead of supervised fine-tuning (SFT), the model was trained using an RL paradigm with the group relative policy optimization algorithm. The model was trained to generate a structured output containing an explicit reasoning trace and a final "yes" or "no" answer. A 2-component, rule-based reward function was designed to assess format adherence and diagnostic accuracy. Performance was compared against strong SFT baselines. Evaluated on a large-scale multimodal dataset of 12,917 TWI cases, our ECG-R1 model achieved a state-of-the-art in-domain accuracy of 75.21%, a sensitivity of 82.55%, and an area under the receiver operating characteristic curve of 84.18%. The model demonstrated robust cross-hospital generalization, maintaining a 72.93% out-of-domain accuracy and an 81.56% area under the receiver operating characteristic curve. When controlling for model scale, the RL paradigm yielded substantial absolute improvements of 6.69% in in-domain performance and a substantial 11.48% improvement in out-of-domain performance over the capacity-matched Qwen2-VL-2B full-FT baseline. These results suggested that the RL approach was superior for learning invariant physiological features rather than overfitting to source-domain artifacts. The RL-based ECG-R1 framework significantly outperformed capacity-matched SFT baselines in both diagnostic accuracy and cross-domain robustness. By explicitly modeling interpretable clinical reasoning and using probabilistic diagnostic language to prevent premature cognitive closure, ECG-R1 may serve as a highly transparent clinical decision support system. It was structurally designed to safely assist cardiologists within a strict human-in-the-loop paradigm, establishing a robust foundation for prospective clinical trials.
Cephaeline (CPL), a bioactive compound derived from the medicinal plant Ipecacuanha, has demonstrated inhibitory effects on several tumor types. Nevertheless, its role in breast cancer and the underlying molecular mechanisms remain largely unexplored. This research aimed to investigate the anti-cancer potential of CPL in breast cancer cells. The IC50 of CPL was determined using the CCK-8 assay. Subsequently, the effects of CPL on cell migration and proliferation were assessed through wound healing (scratch) and colony formation assays, respectively. Additionally, MDA and GSH levels were quantified using ELISA, while ROS production was visualized via DHE staining. Intracellular iron content was measured using an iron assay kit. Furthermore, the expression levels of p53, SLC7A11, and GPX4 were evaluated using Western blot. All experiments were performed in triplicate and independently repeated at least three times, and data were analyzed using Student's t-test or one-way ANOVA, as appropriate. CPL significantly inhibited the proliferation and viability of 4T1 and MDA-MB-231 breast cancer cells in a dose-dependent manner, with IC50 values of 38.89 nM and 50.29 nM, respectively, and concomitantly suppressed cell migration and colony formation at higher concentrations. It also increased intracellular MDA and ROS and downregulated GSH, SLC7A11 and GPX4, inducing ferroptosis. siRNA knockdown of p53 attenuated CPL's effects, indicating p53's key role in CPL's anti-cancer activity. This study provides evidence that CPL exerts anti-breast cancer effects by promoting ferroptosis through the p53/SLC7A11/GPX4 axis, highlighting its therapeutic potential as a novel agent for cancer treatment.
Recently under the European Society of Cardiology (ESC) EURObservational Research Programme (EORP) PPCM registry the first predictive score was derived. This study sought to test the validity of this predictive score in a cohort of women with PPCM in Uganda. 80 PPCM cases enrolled had a 12-lead electrocardiography, echocardiography at baseline and at 6-months follow-up. Core clinical data included LVEF, LVEDD, duration of symptoms, QRS duration and pre-eclampsia were captured. Recovered participants' scores included one case who scored ≤ 1 and one of 2, six cases had a score of 3, fifteen cases had a score of 4, six cases had a score of 5, two cases had a score of 6 and only five cases had the highest score of 7. The discrimination analysis achieved a c-statistic of 0.67. The ESC EORP PPCM LV predictive recovery score under performed in predicting LV recovery in our Ugandan PPCM cohort.
Compression therapy is the primary treatment for venous ulcers (VU). Topical treatments are used as an adjunct to accelerate healing, but they can be costly, and there is currently no standard medication. To evaluate reduction in venous ulcer area in patients treated with 5% aqueous extract of Rhizophora mangle L. leaves in cream form. Patients were randomized into 2 groups: the experimental group (EG) (55 ulcers) received 5% Rhizophora mangle cream, and the control group (CG) (45 ulcers) received medium chain triglyceride oil. Ulcers were evaluated using the MEASURE (measurement, exudate, appearance, suffering, weakening, reassess, edge) methodology, and area was measured using software on day 1, 4 weeks, 8 weeks, and 12 weeks. At 12 weeks, the EG showed a mean 51.69% reduction in ulcer area (mean [SD] 3.97 [6.18] cm²), whereas the CG exhibited lesion worsening, with a mean increase in ulcer area corresponding to a -187.82% variation (mean [SD], 12.17 [20.17] cm²). Complete healing was observed in 34.5% of ulcers in the EG compared with 15.6% in the CG (P = .002). Furthermore, the EG demonstrated greater improvement across all clinical ulcer parameters than the CG. The 5% Rhizophora mangle cream was effective in venous ulcer area reduction and clinical healing, which suggests that it may be an effective an alternative treatment for venous ulcers in the lower limbs.
The skin serves as a critical barrier against infection and external damage. Effective wound management demands prompt hemostasis and infection control. Inspired by the hierarchical "epidermis-dermis" architecture of human skin, this work introduces a biomimetic bilayer hydrogel dressing. The hydrogel (named Fe@S/C) combines a dermis-mimetic layer of a double-crosslinked network of silk fibroin (Silk-GMA) and oxidized carboxymethyl cellulose (OXCMC-MA) with an in situ-formed epidermis-mimetic "Armor" antimicrobial protective layer via Fe3+ coordination. The hydrogel exhibits favorable mechanical flexibility and wet adhesion. It demonstrates excellent hemostatic efficacy, achieving rapid blood coagulation in vitro and in vivo. The hydrogel achieves a 96% bacterial reduction at 0.1 M Fe3+, as confirmed through in vitro assays and in vivo infection models. The hydrogel's electrical conductivity (0.566 S/m) and sensitivity (gauge factor = 1.17) enable real-time monitoring of physiological movements. Histological analysis reveals accelerated wound healing with reduced inflammation and organized collagen deposition. This strategy addresses key limitations of traditional dressings by integrating multiple functionalities, enhancing therapeutic outcomes, and offering a promising solution for advanced wound management.
The use of pharmacotherapies with weight loss properties for the management of obesity and chronic disease are now routinely prescribed. We investigated the evidence from randomised-controlled trials for the effects on lean body mass of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) in humans. PubMed, MEDLINE, the Cochrane Library and CINAHL were searched from inception to October 2022. The primary outcome was change in body composition focused on measures of lean body mass (LBM). Thirty-six studies in population groups with obesity (n = 8), type 2 diabetes mellitus (n = 20), type 1 diabetes mellitus (n = 5) and polycystic ovary syndrome (n = 3) receiving a GLP-1RA or SGLT2i therapy versus placebo or active comparator satisfied our inclusion criteria, including 21 for GLP-1RA and 15 for SGLT2i. Meta-analysis showed an overall loss of LBM in the direction of the intervention groups prescribed GLP-1RA (MD: -1.51 kg [95% CI: -2.00 to -1.01]) and SGLT2i (MD: -1.04 kg [95% CI: -1.45 to -0.64]) with sub-group analysis showing largely consistent results when stratified by type of body composition outcome, type of body composition measurement technique and disease status. Results were not modified by sex. Further meta-analysis found that lean mass accounted for 28% (95% CI: 22%-34%) of overall weight loss induced by GLP-1RA and SGLT2i. GLP-1RA and SGLT2i are associated with a loss of LBM that appears congruent with overall weight loss. Monitoring of body composition and provision of combined therapy to preserve lean mass during weight loss should be considered.
Poor health is strongly linked to reduced employment, lower earnings, and long-term labour market disengagement. While elective inpatient treatments may improve health, their broader economic impact is not well understood. This study aimed to estimate the long-term relationship between elective inpatient treatment and labour market outcomes across a wide range of specialties in England. We conducted a retrospective, longitudinal study using linked administrative data, combining Hospital Episode Statistics, the 2011 Census, death registrations, and HMRC Pay As You Earn records. Adults aged 25-64 who received elective inpatient care between April 2015 and March 2023 across 32 specialties were included. Monthly earnings and employment status were measured before and after treatment and standardized for age. Interrupted timeseries models with data-driven breakpoints were used to estimate counterfactual labour market trajectories had treatment not occurred. Treatment effects were calculated as the difference between observed and modelled outcomes. Among 4.9 million patients, elective treatment was associated with improved earnings and employment relative to a counterfactual of continued health deterioration. At 60 months after treatment, the largest effects were observed in haematology, oncology, and renal medicine. Across all specialties, cumulative 5-year treatment effects ranged from £47.2 billion to £73.7 billion in additional earnings and from 198 918 to 745 262 person-years of employment. Elective inpatient treatment is associated with substantial and sustained labour market benefits. Receiving treatment may improve individuals' ability to participate in work, with benefits persisting for many years after treatment, relative to the counterfactual.
Osteoporotic fractures (OPF) represent a substantial share of all fracture types, seriously affecting the quality of life. Therefore, it is essential to find a biomarker for early diagnosis and prevention of OPF. Detection of mRNA expression was performed using RT-qPCR. The diagnostic value of miR-335-3p in OPF was examined by the ROC curve. Pearson's correlation analysis was employed to explore the correlation. The rat model of OPF was established by bilateral oophorectomy (OVX) and creation of a fracture in the middle of the left femur. Then, bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the rats. MiR-335-3p was over-expressed or inhibited by transfection in BMSCs. Adipogenic factors, inflammatory factors, osteogenic markers and cell metabolic activity were detected in BMSCs. MiR-335-3p expression was markedly reduced in patients with OPF, and this molecule exhibited favorable diagnostic efficacy for OPF. In OPF, miR-335-3p was positively correlated with bone mineral density. In BMSCOPF, miR-335-3p reduced inflammatory factors and increased cell metabolic activity. In addition, the over-expression of miR-335-3p reduced adipogenic factors and increased osteogenic markers. In conclusion, miR-335-3p was decreased in OPF and may have high diagnostic potential in OPF. In BMSCOPF, miR-335-3p is downregulated in OPF and possesses promising diagnostic value. It can inhibit adipogenic differentiation and inflammatory responses while promoting osteogenic differentiation in BMSCs. These findings suggest that miR-335-3p may participate in the pathogenesis of OPF and be associated with fracture healing.