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We present a case of a staged "double switch" complex biventricular repair in a newborn with heterotaxy, dextrocardia, [S, L, L] double outlet right ventricle, double outlet left atrium, with right-dominant unbalanced complete atrioventricular canal, L-transposition of the great arteries, and aortic arch hypoplasia. A staged "double switch" approach allowed safe biventricular correction of a rare complex cardiac defect without residual lesions before one year of age.
Burkina Faso is experiencing a rapid nutritional transition, yet evidence on the double burden of malnutrition (DBM) at household and individual levels remains limited. This study aimed to estimate the national prevalence of DBMs and identify associated factors with a particular focus on the most common type of DBM. We used data from the 2021 Burkina Faso Demographic Health Survey, a nationally representative cross-sectional survey. The analysis included 4119 households with 5146 women of reproductive age (15-49 years) and 4114 mother-child pair. Eleven (11) potential combinations of maternal and child nutritional status indicators, defined according to WHO standards (anemia, stunting, wasting, underweight, and overweight/obesity) were assessed. Weighted descriptive and bivariate analyses were conducted to identify the most prevalent double burden of malnutrition (DBM) combination, which was selected as the primary outcome. Factors associated with this outcome were examined using multivariate logistic regression with four nested models incorporating household, maternal, and child level characteristics. Overall, 72% of children were affected by anemia, 23% by stunting, and 17% were in underweight condition. Among women, 53% were living with anemia, 17.9% with underweight, and 7.6% with obesity. The predominant DBM form was children with anemia combined with overweight/obesity in women, affecting 14.3% of households. The individual prevalence of anemia and overweight/obesity in women was 9.47%, while stunting paired with overweight in children affected 3.6% of households. Multivariate analysis identified several independent of the predominant form of DBM: region (aOR = 1.94, 95% CI = 1.09-3.45 for Sahel region vs. Boucle du Mouhoun), household wealth (aOR = 3.1, 95% CI = 1.74-5.53 for richest vs. poorest), place of residence (aOR = 0.6, 95% CI = 0.45-0.79 for rural vs. urban), women's age (aOR = 6.48, 95% CI = 2.53-16.61 for 35-39 years compared to 15-19), and women's occupation (aOR = 2.71, 95% CI = 1.5-4.87 for professional manager vs. not working). The most common DBM, child with anemia and maternal overweight/obese women affect more than one in seven households in Burkina Faso, with a higher risk in urban and wealthier settings. Integrated "double duty" interventions are urgently needed to address both mother with overweight/obesity and child with anemia while addressing the structural drivers of nutrition transition and broader social determinants of health.
Dry eye disease (DED) commonly impairs quality of life. This phase 3, randomized, double-masked, multicenter, vehicle-controlled trial evaluated the efficacy of 5.0% lifitegrast ophthalmic solution (KH732) in improving signs and symptoms of DED. Adults with moderate-to-severe DED and corneal staining score ≥2.0 in any corneal region were randomized 1:1 to lifitegrast (KH732) or vehicle twice daily for 84 days after a 3-7-day vehicle washout. The primary endpoint was change from baseline in inferior corneal staining score (ICSS) at Day 84. Secondary endpoints included changes in total corneal staining score, Eye Dryness Score (EDS), Ocular Surface Disease Index (OSDI), 7-item visual analogue scale, and Ocular Discomfort Score. At Day 84, lifitegrast (n=309) significantly reduced ICSS versus vehicle (n=306) (P=0.027). In a post hoc analysis, the effect was more pronounced in participants with the highest baseline staining in the inferior region (P=0.046). Lifitegrast also significantly improved EDS (adjusted P=0.006), ocular discomfort (adjusted P=0.010), photophobia (adjusted P=0.004), and OSDI (adjusted P=0.014) versus vehicle. Post hoc analyses showed significant between-group differences in EDS, photophobia, and OSDI as early as Day 14. No serious ocular adverse events were reported. Lifitegrast (KH732) improved both signs and symptoms of DED and was generally well tolerated, with potentially greater benefit in patients with prominent inferior corneal staining.
When androgen receptor (AR) signaling is suppressed, prostate cancer progression is inhibited; however, many patients eventually relapse, developing castration-resistant prostate cancer (CRPC). Recently, the incidence of double-negative CRPC (DNPC)-which lacks AR and neuroendocrine activity-has increased, yet effective treatments remain unavailable. Our research demonstrated that KRAS has minimal influence during the AR-dependent stages of prostate cancer but significantly activates cancer cells when AR signaling is suppressed. Further investigation revealed that AR inhibition modifies fibroblast growth factor receptor expression in prostate cancer cells. Additionally, CCL2, secreted by AR-inhibited prostate cancer cells, induces FGF8b secretion from stromal cells within the tumor microenvironment, which in turn enhances KRAS activation. A pan-KRAS inhibitor effectively suppressed AR-independent prostate cancer cells by disrupting KRAS-mediated cell survival signaling. This inhibition led to the significant induction of programmed cell death, characterized by the downregulation of the anti-apoptotic protein BCL-xL and the promotion of apoptosis as evidenced by increased cleaved caspase-3 in vivo. These findings highlight KRAS activation, driven by the CRPC microenvironment, as a critical factor in DNPC progression and identify the induction of KRAS-targeted cell death as a promising therapeutic strategy for DNPC.
Recent reports indicate that sustained interaction with conversational artificial intelligence (AI) systems can, in a small subset of users, contribute to the emergence or stabilisation of delusional experience. Existing accounts typically attribute such cases either to individual vulnerability or to failures of safety engineering. These explanations are incomplete. Drawing on phenomenology, psychiatry, and cognitive neuroscience, this paper argues that the risk arises from the relational and ontological structure of the interaction itself. Conversational AI generates ontological dissonance: a conflict between the appearance of relational presence and the absence of any subject capable of sustaining it. Maintained through a communicative double bind and amplified by attentional asymmetries, this dissonance tends, under conditions of affective vulnerability, to stabilise into a technologically mediated analogue of folie à deux. This account explains why explicit disclaimers often fail to disrupt delusional involvement and clarifies the ethical and clinical implications for the design and use of conversational AI.
Strain engineering is a useful way for modifying semiconductor functioning, allowing for alteration in the material's physical characteristics that can be used for specific optoelectronic device applications. In this manuscript, ab initio calculations are performed to investigate the effects of compressional strain on the physical traits of A-site double perovskite oxide BaLaSrBiO6. The compressional strain till 30% is applied with the step size selected as 10%. The obtained ground state energy, negative value of the formation enthalpy and minimum distortions in the crystal structure signify that the studied oxide is completely stable. The compliance matrix is utilized to obtain the mechanical properties of BaLaSrBiO6. With compressional strain application, elastic constants of the studied oxide report a declining trend, implying that the material's tendency to withstand external forces decreases as strain enhances. BaLaSrBiO6's ductility is also enhanced as the compressional strain is increased. Thermo-dynamical characteristics report that the atomic bonding in the lattice weakens and the stiffness of the oxide reduces as the compressional strain is increased. The electronic properties reveal the narrowing of the bandgap as compressional strain is enhanced. With strain application, a significant shift in the optical traits is noticed for BaLaSrBiO6. A significant shift is noticed in absorption, reflectivity, polarization, dispersion, and conductivity from the UV to visible range, making it appropriate for optoelectronics, such as visible-light photodetectors and solar cells.
Mudan granules are Chinese patented medicines approved by the National Medical Product Administration, used to treat diabetic peripheral neuropathy (DPN) with Qi deficiency and collateral obstruction syndrome. However, placebo-controlled studies definitively establishing efficacy and safety are lacking. To evaluate the efficacy and safety of Mudan granules as an adjunct treatment for DPN with qi deficiency and collateral obstruction syndrome. This multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial recruited patients from 13 clinical centers in mainland China. 400 participants were randomly assigned in a 1:1 ratio to either the Mudan (Mudan granules + mecobalamin) or control group (placebo + mecobalamin), and were reassessed after the 24-week intervention. The primary outcome was the Michigan Diabetic Neuropathy Score (MDNS). The complete analysis set comprised 357 participants. The mean baseline MDNS of the Mudan and control groups were 9.69 and 9.43, respectively. The mean change in MDNS from baseline to week 24 was -4.80 in the Mudan and -2.66 in the control group. Using a covariate-adjusted analysis of covariance model, the least squares mean for the Mudan and control groups were -4.74 (-5.33 to -4.15) and -2.72 (-3.33 to -2.11), respectively. There was a statistically significant difference between the two groups. After 24 weeks of follow-up, the Mudan group showed a significant improvement in MDNS compared to the control group. These findings suggest that Mudan granules may improve the clinical symptoms of DPN. Given this, Mudan granules may be helpful in the management of DPN.
This described the Double Lumen Technique (DLT) - an endotracheal tube-guided Levin tube insertion technique, which was originally introduced in 1987. It is designed for patients who have repeatedly failed due to kinking of the Levin tube in their oropharyngeal cavity, caused by incooperation of swallowing a Levin tube, particularly in those with stupor or comatose mentality. The main concept of the DLT is to reinforce the flexibility of a Levin tube by inserting it into a more elastic tube, the endotracheal tube (E-tube). The combination of the Levin tube and the E-tube allow it to pass through the oropharyngeal cavity into the esophagus successfully. For stuporous or comatose patients who have repeatedly failed Levin tube insertion, if passage through an oropharyngeal cavity to the esophagus is difficult, the novel technique, DLT, may be a worthwhile option to try at the bedside.
This study addresses critical limitations of conventional hemostatic materials-such as significant swelling and inadequate adhesion to wet tissues-by developing an injectable and photocurable hydrogel (OPP-HAMA). The hydrogel is constructed through a rational molecular design: phenylalanine is grafted onto an oxidized chitosan backbone via a Schiff base reaction, thereby introducing hydrophobic domains and active hemostatic sites. Subsequently, polyethylene glycol is conjugated to enhance structural flexibility, followed by crosslinking with methacrylated hyaluronic acid to form a stable dual-network architecture. This engineered structure enables excellent injectability and rapid photopolymerization within 30 s, facilitating the effective sealing of irregularly shaped wounds. The synergistic contribution of the positively charged chitosan moiety and hydrophobic interactions from phenylalanine promotes erythrocyte aggregation and platelet activation, enabling rapid hemostasis in clinically relevant models, including liver resection and cardiac puncture. The densely crosslinked network, reinforced by hydrophobic regions, exhibits outstanding anti-swelling properties (swelling ratio < 50%), thereby preventing tissue compression and maintaining robust adhesion under wet conditions (∼20 kPa). Moreover, the hydrogel demonstrates notable antioxidant and antibacterial activities, significantly accelerating wound repair in full-thickness skin injury models. This work presents a novel and integrated strategy for designing carbohydrate-based hydrogel adhesives with combined anti-swelling capabilities and highly efficient hemostatic performance.
Determining which posterolateral elbow dislocations require surgery is challenging as major ligament tears often occur regardless of clinical stability. This study aimed to identify specific MRI patterns that represent the functional threshold for persistent mechanical instability. We retrospectively reviewed MRIs of 186 elbows following acute posterolateral dislocation. The unstable group (n=24, 12.9%) showed gross mechanical instability or redislocation. We evaluated single-structure effects and a "Core-4" model comprising the flexor-pronator mass (FPM), posterior medial collateral ligament (pMCL), common extensor origin (CEO), and posterolateral ligament (PLL), representing the principal pillars of stability. Complete tears of the lateral collateral ligament complex (LCLC) and anterior bundle of the medial collateral ligament (aMCL) were highly prevalent in both stable and unstable groups, offering low specificity. In contrast, the concurrent disruption of the FPM and PLL, termed the "Double Hit" pattern, was the most powerful predictor, yielding a specificity of 98.8% and positive predictive value (PPV) of 91.7%. The Core-4 model showed excellent diagnostic accuracy (Area Under the Curve [AUC]: 0.979). While Score 2 elbows showed low instability (4.8%), Score 3 elbows exhibited a divergence: those with the Double Hit pattern had a 75% instability rate, while those without it remained stable (0%). All Score 4 elbows were unstable. Mechanical instability following posterolateral elbow dislocation is a threshold-driven phenomenon resulting from the cumulative failure of critical stabilizers. The Double Hit pattern (concurrent failure of the FPM and PLL) represents the critical functional threshold for mechanical failure. By identifying high-risk subsets (Score 4 and Double Hit Score 3) with high specificity, the Core-4 model provides a definitive objective criterion for early surgical intervention while supporting functional rehabilitation for most stable dislocations.
To evaluate whether the number of sutures used during transvaginal cervical cerclage influences obstetric and neonatal outcomes when surgical technique, suture material, and perioperative management are standardized. This retrospective cohort study included 125 women who underwent transvaginal cervical cerclage using identical monofilament suture material. Cerclage was performed with either a single suture (n = 23) or a double suture (n = 102) in this non-randomized observational cohort. The primary outcome was term delivery (≥ 37 weeks' gestation). Secondary outcomes included gestational age at delivery and selected neonatal outcomes. To address non-random allocation and baseline group imbalance, propensity scores were estimated using pre-treatment maternal, obstetric, and clinical severity variables. Stabilized inverse probability of treatment weighting (IPTW) with truncation was applied, and doubly robust outcome models were used to estimate adjusted associations. Neonatal outcomes were analyzed at the pregnancy level to account for clustering in twin gestations. Women receiving double-suture cerclage presented at earlier gestational ages and with greater markers of cervical severity at baseline; however, after IPTW and doubly robust adjustment accounting for these baseline differences, no statistically significant difference in term delivery was observed. Secondary obstetric outcomes, including gestational age at delivery, were also comparable between groups after adjustment. Pregnancy-level neonatal outcomes, including NICU admission and neonatal mortality, did not differ meaningfully by suture number. Sensitivity analysis restricted to singleton pregnancies and stratified by cerclage indication yielded consistent results. After accounting for baseline cervical severity and clinical indication, single- and double-suture transvaginal cerclage was associated with comparable obstetric and neonatal outcomes under standardized surgical conditions. These findings suggest that cervical status at the time of cerclage placement, rather than the number of sutures applied, is the primary determinant of outcome.
Oxidative stress can cause double-strand breaks in DNA in patients with preeclampsia (PE), but whether the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is involved in PE remains unclear. Here, we show that glutathione (GSH) metabolism is disrupted in placentas from PE patients, leading to increased oxidative stress and activation of the cGAS-STING pathway. Using metabolomics and and CRISPR-Cas9 generated cGAS/STING knockout human trophoblast cells, we found that GSH depletion elevate reactive oxygen species (ROS) levels in HTR-8/SVneo cells, leading to cellular DNA damage and the release of double-stranded DNA (dsDNA) into the cytosol. This activates the cGAS-STING signalling, promoting NF-κB-mediated inflammatory and type I interferon responses. This mechanism highlights the critical role of ROS-mediated DNA damage and cGAS-STING-dependent inflammation in PE development, suggesting potential therapeutic targets for its intervention.
The therapeutic management of thrombotic antiphospholipid syndrome (APS) is based on indefinite anticoagulation. Vitamin K antagonists (VKA) remain the standard of care, particularly in patients with triple antiphospholipid antibody positivity or a history of arterial thrombosis. In low-risk patients, defined as those with single or double antiphospholipid antibody positivity and no prior arterial thrombosis, recent data suggest that direct oral anticoagulants (DOAC) may provide efficacy comparable to VKA. However, the quality of the available evidence is moderate to low. This study aims to compare the effectiveness of DOAC versus VKA in preventing thrombotic recurrence in low-risk patients with APS. This is a multicentre, ambispective, observational, analytical study conducted in Internal Medicine departments across Spanish hospitals. Adult patients with low-risk thrombotic APS treated with DOAC or VKA will be included and followed for a minimum of two years. The primary effectiveness outcome will be venous thrombotic recurrence. The DOACS-APS study will provide clinically relevant real-world evidence on the effectiveness of DOAC in a selected subgroup of patients with APS, thereby improving therapeutic decision-making in routine clinical practice. The study is registered at ClinicalTrials.gov (NCT07372170).
Ketamine may alleviate treatment-resistant depression (TRD) primarily through glutamatergic modulation, with downstream dopaminergic activation. Iron plays an important role in monoaminergic metabolism, that is also implicated in the pathophysiology of TRD. Both Quantitative Susceptibility Mapping (QSM) and Effective Transverse Relaxation Rate (R2*) mapping can determine the extent of iron deposition in the brain. Given that abnormal iron accumulation may reflect dopamine dysfunction, we hypothesized that baseline magnetic substances could predict ketamine's antidepressant effects in patients with TRD. We used data from a double-blind, randomized placebo-controlled trial followed by an extended single-arm open-label study to assess the efficacy of repeated intravenous ketamine in Japanese patients with TRD (jRCTs031210124). This study analyzed the data from the participants who underwent QSM and R2* mapping before receiving ketamine in either phase. Multivariable regression analyses were conducted to explore the association between baseline magnetic susceptibility and R2* with change in MADRS total and subdomain scores. This study included 17 patients with TRD (7 women; mean ± standard deviation age, 42.9 ± 10.6 years). Baseline magnetic susceptibility in the right nucleus accumbens negatively correlated with the change in MADRS retardation symptom scores (β = -0.73, p = 0.003). Moreover, baseline R2* in the left amygdala was negatively associated with the change in MADRS vegetative symptom scores (β = -0.71, p = 0.004). Baseline magnetic substances in the right nucleus accumbens and the left amygdala may be biomarkers to predict the effect of repeated ketamine infusions in patients with TRD.
Chronic kidney disease (CKD) attributable to type 2 diabetes mellitus (T2DM) represents a growing global health concern. However, comprehensive long-term epidemiological trends and projections, stratified by sociodemographic and geographic variables, remain inadequately delineated. To evaluate the global, regional, and national burden of CKD due to T2DM from 1990 to 2021, and to forecast its trends through 2035 using Bayesian age-period-cohort (BAPC) modeling. This population-based observational study used data from the Global Burden of Disease Study 2021 (GBD 2021), which includes 204 countries and territories across five sociodemographic index (SDI) quintiles and 21 GBD regions. The study covers the period 1990-2021 with projections to 2035. Diagnosis of T2DM mellitus as an underlying cause for CKD. Incident and prevalent cases, mortality, and disability-adjusted life-years (DALYs) attributable to T2DM-related CKD. Age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASDR), and DALY (ASR) rates were computed, alongside estimated annual percentage changes (EAPC). From 1990 to 2021, the global number of incident CKD cases due to T2DM increased by 167.2%, while the ASIR rose by 21.0% (EAPC: 0.61). Prevalent cases nearly doubled (+85.1%), although ASPR declined slightly (-5.1%, EAPC: -0.17). Deaths surged by 222.6%, and ASDR increased by 37.8% (EAPC: 1.17). DALYs rose by 173.6%, with a 24.0% increase in ASR (EAPC: 0.81). Males and older adults consistently exhibited higher burden across all indicators. Low- and middle-SDI nations experienced the most pronounced burden growth, yet high-SDI regions also registered substantial increases in mortality and DALYs. Projections to 2035 suggest a continued escalation, with incident cases exceeding 2.6 million and deaths surpassing 700,000 annually by mid-century. These findings highlight the importance of targeted prevention, early detection, and improved management strategies, particularly in high-growth regions and vulnerable populations.
A sensitive analytical protocol was developed to quantify trace levels of three azole fungicides-ketoconazole (KZ), miconazole (MZ), and clotrimazole (CZ)-in cosmetic matrices. This method integrates fiber-in-tube solid-phase microextraction (FIT-SPME) with high-performance liquid chromatography and ultraviolet detection (HPLC-UV). The extraction medium utilized magnesium-aluminum layered double hydroxides (LDHs) intercalated with sodium dodecyl sulfate (SDS), prepared via urea hydrolysis. To fabricate the sorbent, this modified LDH was embedded within a polyvinyl alcohol (PVA) solution-chosen for its green chemistry attributes-and electrospun onto stainless steel substrates. To prevent dissolution in aqueous samples, the coating was thermally cross-linked using citric acid, ensuring robust mechanical stability. The device consisted of these coated fibers housed within a steel capillary, through which samples were circulated for equilibrium adsorption, followed by solvent desorption. A rigorous optimization process was conducted to determine ideal conditions for pH, ionic strength, flow rates, and timing variables. Performance metrics revealed low limits of detection (0.3-0.6 µg L-1) and high precision, with inter-day relative standard deviations (RSDs) not exceeding 6.2%. The technique displayed a broad linear dynamic range (up to 750.0 µg L-1) and satisfactory determination coefficients (R2 > 0.9913). Finally, the analysis of real samples, including shampoos, creams, and lotions, yielded relative recoveries ranging from 82% to 115%, confirming the method's reliability for complex formulations.
The aim of this study was to conduct a randomized, double-blind, split-mouth comparative clinical trial to clinically assess and compare different bi-layer biomimetic strategies of composite resin in large class I cavities over an 18-month period. A total of 160 posterior composite restorations in 40 participants of age 35-45 years old were enrolled in the study based on inclusion criteria. Each patient received four different bilayer biomimetic bases in four equal groups (n = 40) as follows: Group I: short-fiber reinforced composite (everX Posterior, GC Corporation, Tokyo, Japan); Group II: long-fiber reinforced composite (polyethylene fibers, Ribbond Inc., USA); Group III: Resin-Modified Glass Ionomer Cement (RMGIC) (Riva SDI, Bayswater, VIC, Australia); and Group IV: flowable composite (G-aenial universal Flo, GC Corp., Tokyo, Japan). A 2 mm surface layer of nanohybrid composite resin (Tetric Evo Ceram, Ivoclar Vivadent) was applied to cover the biomimetic base in all groups. Occlusal Class I cavities were prepared according to caries extension with a cavity depth of 4-5 mm. No bevels were prepared. Clinical assessment was carried out according to the World Dental Federation (FDI) by two calibrated evaluators at baseline and at 6, 12, and 18 months for aesthetic properties (surface and marginal staining), functional properties (fracture and retention, marginal adaptation), and biological properties (postoperative sensitivity, secondary caries). Statistical analysis employed Friedman and Kruskal-Wallis tests. The level of significance was established at α = 0.05 across all tests. Forty patients with a total of 160 restorations were evaluated in line with FDI at the end of the study with 100% recall rates. No fracture or secondary caries was reported over an 18-month evaluation period. The intragroup (Friedman test) and intergroup (Kruskal-Wallis test) comparisons revealed no statistically significant differences among short fiber reinforced composite, long fiber reinforced composite, resin-modified glass ionomer cement, and flowable composite for the assessed criteria over time (p > 0.05). All tested bilayer biomimetic composite resins have comparable excellent short-term clinical performance by the end of the study period. The protocol of the current study was approved by the Research Ethics Committee of the Faculty of Dentistry, Tanta University, Egypt, with approval number #R-RD-03-25-3194. This study was registered at www. gov with the identification number NCT07285772 on 15/12/2025-'retrospectively registered.'
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that significantly predisposes individuals to delirium and dementia through multifaceted neurobiological pathways. The essence of this neurocognitive decline involves mechanisms such as central insulin resistance, chronic low-grade inflammation, and mitochondrial dysfunction. While metformin remains the cornerstone of T2DM management, its impact on the central nervous system exhibits a "double-edged sword" nature, balancing intrinsic neuroprotective properties against the potential neurotoxicity associated with vitamin B12 deficiency. This review aims to systematically synthesize epidemiological and clinical evidence linking metformin to neurocognitive outcomes, contrasting its efficacy with newer glucose-lowering agents such as GLP-1 receptor agonists and SGLT2 inhibitors. In addition, it sheds light on the reciprocal connectivity between systemic metabolic regulation and direct CNS modulation, specifically elucidating AMPK activation, the autophagy-lysosome axis, and the gut-brain and liver-brain axes. We review these molecular mechanisms to delineate the delicate trade-off between neuroprotection and risk, providing a framework for precision pharmacotherapy and biomarker-guided stratification in high-risk T2DM populations.
South Africa is often viewed as a safe refuge for LGBTQ+ individuals, yet the reality for queer African migrants is marked by insecurity and exclusion. Despite strong constitutional protections, migrants from highly homophobic contexts continue to face discrimination and marginalisation. This article examines how gay Zimbabwean migrants experience and navigate violence, discrimination and marginalisation across their move to South Africa. As part of a larger study, in-depth interviews took place with five men, with a focus on legal precarity, economic exclusion and institutional bias, including housing insecurity, barriers to healthcare and reliance on survival strategies such as sex work. Participants reported sex work as a survival strategy amidst limited economic opportunities and widespread stigma. Participants' experiences reflected a process of double displacement, as they fled persecution at home only to face prejudice and exclusion in South Africa. The findings challenge narratives that position South Africa as a safe haven and instead highlight the gap between formal legal protections and lived realities. Intersectional, trauma-informed, rights-based programmes are needed to improve healthcare access and promote community support for queer African migrants.
Root nodules host nitrogen-fixing bacteria and likely evolved through modifications of the lateral root program. Members of the NOOT-BOP-COCH-LIKE transcriptional coregulator family suppress root identity in nodules and plant hormones play key roles in nodule organogenesis, but the interaction between these pathways is unclear. In this study, we investigate how COCH regulates nodule identity through crosstalk with plant hormones, using the Pisum sativum cochleata (Pscoch) mutant - which forms root-nodule hybrids - in combination with hormone biosensors, double mutants, hormone quantification, and RNA-seq analysis. We found that COCH suppresses cytokinin levels and response during nodule formation. By contrast, PsCOCH promotes auxin accumulation and precise auxin response patterning in nodules. Mutant coch developing nodules have gene expression profiles more similar to that of root primordia, with increased expression of defence and auxin response genes and reduced expression of cytokinin biosynthesis genes compared to wild-type. We found gibberellin is unlikely to act downstream of PsCOCH. Constitutive expression of PsCOCH also produces root-nodule hybrids and we found intriguing links between the autoregulation of nodulation pathway and PsCOCH. We show that PsCOCH is required for spatial tight regulation of auxin and cytokinin during nodule organogenesis and identify key hormone and signalling genes that act downstream of COCH.