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Journal articleJebreel WMA, Abdel Hamid MM, Mustafa SA, et al., 2026,
Characterisation of malaria and glucose-6-phosphate dehydrogenase deficiency in conflict-affected zones of southern and eastern Sudan
, BMC Infectious Diseases, Vol: 26, ISSN: 1471-2334BackgroundMalaria causes high morbidity and mortality in Sudan. Malaria control efforts have been disrupted by conflict and displacement, which affected the whole health system. This study aimed to characterize malaria and glucose-6-phosphate dehydrogenase deficiency in conflict-affected zones of southern and eastern Sudan.MethodsThis cross-sectional study was conducted between 2023 and 2024, enrolling 717 patients with clinical symptoms suggestive of malaria in Kosti (southern Sudan, n = 252) and Kassala (Eastern Sudan, n = 465). Malaria infection was confirmed by light microscopy as a standard test, and qPCR was used as a reference method. Haematological indices were analysed on automated analysers, and PCR-RFLP was used to determine G6PD genotypes.ResultsMalaria prevalence was 62.6% (291/465; 95% CI 58.2–67.0%) in Kassala and 52% (133/252; 95% CI 46.6–59.0%) in Kosti using PCR. In Kassala, 157 cases (54%; 95% CI: 48.2–59.7%) were Plasmodium vivax (P.v), 99 (34%; 95% CI: 28.6–39.8%) were Plasmodium falciparum (P. f), and 35 (12%; 95% CI: 8.6–16.2%) were P. f/P. v infections. In Kosti, P. f was detected in 130 (97.7%) subjects, and P. v was detected in 3 (2.7%; all were negative by microscopy). There were 37 (8.7%) subjects not detected by microscopy but positive by PCR (submicroscopic), 20 (15%) in Kosti and 17 (5.8%) in Kassala. The G6PD B variant predominated in Kassala (438/94.2%) and Kosti (200/79.4%). The African A− variant was detected in 9 (3.5%) individuals in Kosti (7 males, 2 females). In Kosti females, BA, BA−, AA, and AA− were observed in 11 (7%), 4 (2.5%), 4 (2.5%), and 9 (5.7%), respectively, compared to 10 (4.1%), 4 (1.6%), and 7 (3%) BA, BA−, and AA cases in Kassala females. No significant association was observed between G6PD genotype and parasite density. Malaria prevalence did not differ significantly between Internally Displaced Persons (IDPs) and residents.Conclu
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Journal articleWan Y, Wong JLC, Sanchez-Garrido J, et al., 2026,
Genomic and molecular characterisation of a KPC-producing Klebsiella pneumoniae clinical isolate resistant to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam
, BMC Genomic Data, Vol: 27, ISSN: 2730-6844Background Resistance to carbapenems and third-generation cephalosporins is increasing in Klebsiella pneumoniae globally, restricting therapeutic options. The β-lactam/β-lactamase inhibitor combinations are widely used to circumvent β-lactamase-mediated resistance. In 2021, an unusual K. pneumoniae clinical isolate, KpMVR1, was recovered from a hospitalised patient in England, exhibiting resistance to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam. To investigate this phenomenon, we characterised the genome and antimicrobial susceptibility of KpMVR1 alongside two clonally related isolates susceptible to all three β-lactam/β-lactamase inhibitor combinations: KpMVS1, collected from the same patient 42 days earlier, and KpMVS2, from another patient in the same hospital. Methods Illumina and MinION whole-genome sequencing were conducted for these three isolates, followed by hybrid genome assembly. Annotated genome assemblies were compared to identify genetic variation. Mutagenesis experiments were performed to verify predicted functional alterations. Results All isolates belonged to clone ST8134 and carried blaKPC-2 alleles (KpMVR1: blaKPC-157; KpMVS1 and KpMVS2: blaKPC-2) in plasmids predicted to be conjugative. Insertion sequence ISEc68 caused a frameshift mutation in KpMVR1’s ompK36 gene, reducing susceptibility to meropenem-vaborbactam and imipenem-relebactam. KPC-157 demonstrated decreased hydrolysis of imipenem and ceftazidime when compared with KPC-2. KpMVR1 also encoded a disrupted transcriptional repressor MarR and a destabilising mutation in AcrB, a component of the AcrAB-TolC multidrug efflux pump. An intact, iron-transporting fec operon was identified on a novel IncFII(pKP91)/IncFIB(K) plasmid unique to KpMVS2, possibly accounting for the cefiderocol resistance observed in this isolate. ConclusionsKpMVR1 carried multiple resistance-associated genetic alterations and likely developed its resistance profile
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Journal articleCelsa C, Pressiani T, Nishida N, et al., 2026,
Reproducible safety and efficacy of durvalumab with or without tremelimumab for hepatocellular carcinoma in clinical practice: Results of the DT-real study
, JHEP Reports, Vol: 8, ISSN: 2589-5559Background & AimsDurvalumab plus tremelimumab (STRIDE) has emerged as a first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC). This international multicentre study aimed to evaluate the efficacy and tolerability of STRIDE or durvalumab monotherapy in routine clinical practice, comparing outcomes between patients within and outside key eligibility criteria for the HIMALAYA trial.MethodsFrom a database of 1,423 patients with advanced/unresectable HCC treated with immunotherapy across 35 centres, we analysed 233 patients receiving STRIDE or durvalumab monotherapy. Patients were categorized as HIMALAYA-IN or HIMALAYA-OUT based on key trial eligibility criteria (no prior systemic therapy, ECOG-PS 0–1, Child-Pugh class A, no Vp4 thrombosis). Baseline characteristics were assessed for overall survival (OS) and hepatic decompensation using a multivariable Cox model and competing-risk analysis, respectively. Objective response rates and treatment-related adverse events were recorded.ResultsOf the 233 patients, 123 (53%) were HIMALAYA-IN and 110 (47%) were HIMALAYA-OUT. STRIDE was given in 95% of HIMALAYA-IN patients. After median follow-up of 6.0 months, median OS was 20.4 months (95% CI 11.7-NR) in the overall population. HIMALAYA-IN patients achieved significantly longer OS than HIMALAYA-OUT patients (23.0 vs. 12.2 months; hazard ratio 0.61; 95% CI 0.39-0.96; p = 0.03). Macrovascular invasion and hepatic decompensation were independent negative prognostic factors in the whole cohort. Hepatic decompensation occurred in 10.5% of patients within 12 months from treatment start. Objective response rate was 23.7% and 17.8% of HIMALAYA-IN and -OUT patients, respectively. Patients achieving disease control (whole cohort: 59.4%) demonstrated 24-month OS of 58.2% in HIMALAYA-IN and 44.8% in HIMALAYA-OUT groups. Grade 3-4 treatment-related adverse events occurred in 16.3% of patients.ConclusionsSTRIDE shows reproducible effectiveness and an ac
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Journal articleWade J, Thomas DC, Pickering MC, et al., 2026,
Complement and kidney diseases: unlocking the opportunity of targeted treatments for glomerular diseases, including IgA nephropathy.
, Pediatr Nephrol, Vol: 41, Pages: 3231-3246The imminent availability of multiple therapeutic complement inhibitors, which target different complement pathway components, could revolutionise treatment for a broad range of kidney diseases. However, the complexity of complement activity within and between kidney diseases, for which IgA nephropathy is an illustrative example, and the possible adverse effects of complement inhibition mean robust patient selection and stratification to appropriately targeted inhibitors will be needed to maximise this therapeutic opportunity. Despite promising candidates, novel biomarkers that stratify patients to targeted complement inhibition have not yet been validated for clinical practice.
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Journal articleWu HLA, Le Floch P, Duverdier A, et al., 2026,
Current research landscape and future prospects of in silico modeling approaches for atopic dermatitis
, JID Innovations, Vol: 6, ISSN: 2667-0267Atopic dermatitis (AD) is a chronic, multifactorial inflammatory skin disease with a complex, heterogeneous pathogenesis. Understanding its mechanisms, stratifying patients into biologically relevant endotypes, and predicting treatment responses remain challenging if we use empirical approaches alone. In silico approaches, including mathematical modeling, statistical and machine learning methods, enable the dissection of molecular and cellular interactions, the identification of key clinical and biological drivers, and the extraction of meaningful insights from high-dimensional, noisy datasets, while preserving a systems-level perspective. This review summarizes recent advancements in in silico approaches for AD and outlines strategies to enhance their translational and clinical utility in AD research.
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Journal articleCorbaux P, You B, McNeish I, et al., 2026,
Differences in first-line chemosensitivity assessed by ELIMination rate constant K in advanced serous ovarian cancer: evidence from Western and Japanese Trials in a Gynecologic Cancer InterGroup meta-analysis
, International Journal of Gynecological Cancer, Vol: 36, ISSN: 1048-891XObjective: Growing evidence suggests potential ethnic and geographical variations in chemotherapy efficacy. The CA125 ELIMination rate constant K score is a pragmatic and reproducible indicator of tumor chemosensitivity in newly diagnosed ovarian cancer. We compared ELIMination rate constant K distributions and prognostic performances between patients enrolled in Japanese and Western trials who had stage III/IV serous ovarian cancer from the Gynecologic Cancer InterGroup individual-patient-data Meta-Analysis in OVarian cancer. Methods: The ELIMination rate constant K values were previously estimated for 5884 women receiving first-line chemotherapy for ovarian cancer. Data from 246 women enrolled in the Japanese JGOG-3016 trial were compared to 2561 patients from Western trials. ELIMination rate constant K was analyzed as a binary variable (favorable ≥1.0 vs unfavorable <1.0). Prognostic value for progression-free survival and overall survival was assessed using univariable and multi-variable models. A standardization cut-off specific to patients enrolled in the Japanese trial was explored using maximally selected rank statistics. Results: KELIM was significantly higher in patients enrolled in the Japanese trial (median 0.071 day<sup>-1</sup> vs 0.056 day<sup>-1</sup>; p <.0001). Using the standard cut-off, favorable ELIMination rate constant K was independently associated with improved progression-free survival (hazard ratio 0.59, 95% confidence interval 0.43 to 0.83) and overall survival (hazard ratio 0.53, 95% confidence interval 0.36 to 0.79) in patients from the Japanese trial. Applying the exploratory cut-off of 0.07 day<sup>-1</sup> strengthened prognostic discrimination (progression-free survival: hazard ratio 0.35, 95% confidence interval 0.25 to 0.49, p <.0001; overall survival: hazard ratio 0.40, 95% confidence interval 0.26 to 0.61, p <.0001). Conclusions: Potential higher ELIMination rate constant K-asse
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Journal articleGrant B, Kean J, de Silva NL, et al., 2026,
Clinical features of androgen abuse withdrawal in men during the first year of cessation: a community dwelling study
, Journal of Clinical Endocrinology and Metabolism (JCEM), Vol: 111, Pages: 2649-2663, ISSN: 0021-972XContextAndrogen abuse is an increasing public health concern, particularly among young men seeking muscular or image enhancement. Although most achieve biochemical recovery within 12 months of cessation, mood disturbances, sexual dysfunction, and fatigue is widely reported for years afterward.ObjectiveTo examine symptom severity the relationship to biochemical recovery during the first year after androgen abuse cessation.MethodsWe conducted a cross-sectional study of community-dwelling men grouped as non-users, current users, or past users who had ceased within the last 12 months. Participants completed questionnaires on androgen and substance use and four validated instruments assessing mood (BDI-II), anxiety (GAD-7), sexual function (IIEF-15), and quality-of-life (SF-36). Morning fasted serum hormonal analysis and screening to exclude undisclosed androgen use were performed.Results247 men were included: 50 non-users, 125 current users, 72 past users. Self-reported psychiatric diagnoses were 2.5-fold higher among current and past users than non-users. Total testosterone was highest in current users (p<0.001) with no difference between past and non-users. Past users reported significantly worse mood, anxiety, sexual function, and quality of life versus non-users. Multivariable analyses showed psychiatric comorbidity was independently associated with depression (p=0.001), anxiety (p<0.001), and poorer quality-of-life (p<0.05). Older age and higher LH were associated with reduced sexual function (p<0.05), while lower testosterone showed only a modest association with depressive symptoms (p=0.03).ConclusionAmong men in the first year after stopping androgen abuse, psychological symptoms and reduced quality-of-life were most strongly associated with psychiatric comorbidity than biochemical recovery. These findings challenge the assumption that androgen withdrawal symptoms are predominantly driven by hypogonadism, and supports developing psychological and beh
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Journal articleEvans TRJ, Cook N, El-Khoueiry A, et al., 2026,
A first-in-human, open-label multicentre Phase 1 study of the orally administered E7386 in patients with selected advanced neoplasms.
, Br J Cancer, Vol: 135, Pages: 736-746BACKGROUND: We present data from the Phase 1 open-label Study 101 of E7386, an oral protein-protein interaction inhibitor reported to block the CBP/β-catenin interaction, in patients with solid tumours. METHODS: Eligible patients (across the UK and US) aged ≥18 years had advanced/recurrent solid tumours (dose-escalation) or CTNNB1-mutated hepatocellular carcinoma (dose-expansion). Primary objectives were to assess safety/tolerability and determine the recommended Phase 2 dose (RP2D) of E7386. RESULTS: Thirty-eight patients received study drug (dose-escalation: n = 32; expansion: n = 6; dose-range: 5-120 mg twice daily [BID]); 60.5% received ≥3 prior anticancer medications. Dose-limiting toxicities (grade-2 lethargy and grade-2 decreased appetite) occurred in 1 patient (20 mg BID cohort). The RP2D was determined as 120 mg BID. Most (94.7%) patients experienced treatment-related adverse events (TRAEs), most frequently nausea (65.8%) and vomiting (60.5%), which were primarily grade 1/2 and well-managed with antiemetics. No grade 4/5 TRAEs were noted. Pharmacokinetic exposure increased with increasing dose, although large intersubject variability was observed. No objective responses were noted; stable disease (SD) was observed in 36.8% of patients, including SD ≥ 23 weeks in 18.8% of patients (dose-escalation). CONCLUSIONS: E7386 demonstrated a manageable safety profile, a dose-dependent pharmacokinetic profile, and some disease stabilisation in heavily pretreated patients with advanced solid tumours. TRIAL REGISTRATION: NCT03264664 https://clinicaltrials.gov/study/NCT03264664 .
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Journal articleYounossi ZM, Papatheodoridis G, Tsochatzis E, et al., 2026,
Hepatology: Emerging Paradigms in MASLD, Viral Hepatitis, Cholestatic Liver Disease, Portal Hypertension and Hepatocellular Carcinoma: Summary of the First Annual Paris International Liver Meeting 2026.
, Liver Int, Vol: 46The Paris International Liver Meeting (January 19-21, 2026) brought together leading hepatology experts to discuss transformative advances in chronic liver disease management. The meeting highlighted pivotal developments reflecting the field's evolution from disease characterisation toward precision, mechanism-based therapeutics. Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), were highlighted, marking the transition to an era of approved disease-modifying therapies. Resmetirom and semaglutide are now approved for MASH with F2-F3 fibrosis, with a robust pipeline generating anti-fibrotic signals through FGF21 analogs, pan-peroxisome proliferator-activated receptor (PPAR) agonists, and incretin-based dual and triple agonists. Non-invasive tests have evolved beyond their original diagnostic role to enable prognostic stratification, screening of at-risk populations, treatment selection, and monitoring of therapeutic response. This evolution is not limited to MASLD, but extends to other chronic liver diseases, including primary biliary cholangitis (PBC) and portal hypertension, as highlighted by the recommendations of the Baveno Consensus Workshops. Hepatitis B and D are moving toward functional cure strategies, with simplified HBV treatment algorithms based on fibrosis and viral load, supported by biomarkers for risk stratification and safe treatment discontinuation. In parallel, HDV management is transitioning from a severe disease to one with emerging suppressive and potential curative l through bulevirtide and novel HBsAg-targeting and RNA-silencing therapies, respectively. Management of PBC has advanced with novel PPAR agonists that improve cholestatic biochemistry and pruritus, supported by individualised risk stratification. However, significant treatment gaps persist, with fewer than half of eligible PBC patients receiving second-line therapy, and fatigue remains a
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Journal articlePawa R, Derecichei I, Klein K, et al., 2026,
The genomic sequence of packaged viral ribonucleic acid predicts mucosal HIV-1 transmission fitness.
, iScience, Vol: 29RNA viruses are responsible for many zoonotic disease transmission events, and remain a global health challenge. To evade immune detection, RNA viruses suppress the numbers of immunostimulatory oligonucleotide motifs (INMs) present in their genomes. Although this is thought to occur in human immunodeficiency virus-1 (HIV-1), our bioinformatic analysis on well characterized clinical datasets, along with in vitro studies, demonstrate that HIV-1 is enriched for INMs within its transmitted/founder (T/F) population relative to non-transmitting variants. Importantly, our data suggests that within the host, there is an evolutionary genetic replacement of T/F viruses that otherwise exhibit high transmission fitness and low replicative fitness, with variants having low transmission fitness but high replicative fitness. These findings provide insights into HIV-1 transmission by studying within-host and between-host evolutionary dynamics, enabling us to identify a framework for HIV infection biology, with viral RNA playing a role in transmission and replication processes.
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