University of Basel

Background Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott). Methods In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete. Findings Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33–48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138–630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2–38·7) and 30·7% (25·4–36·6) and specificities were 98·0% (97·1–98·6) and 90·4% (88·7–91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6–25·1), and 30·5% (26·4–34·9), and specificities were 99·1% (98·3–99·6) and 95·1% (93·5–96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants Interpretation Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment. Funding Global Health Innovative Technology Fund, KfW Development Bank, Commonwealth of Australia represented by the Department of Foreign Affairs and Trade, and the Netherlands Enterprise Agency.

We show the properness of the moduli stack of stable surfaces over $\mathbb{Z}\left[ {1/30} \right]$ , assuming the locally-stable reduction conjecture for stable surfaces. This relies on a local Kawamata–Viehweg vanishing theorem for 3-dimensional log canonical singularities at closed point of characteristic $p \ne 2,3$ and 5 , which are not log canonical centres.

General anesthesia (GA) earlier than recommended (as first‐ or second‐line treatment) was recently described to improve status epilepticus (SE) outcome. We aimed to assess the impact of early GA on outcome in matched groups. Data from a multicenter, prospective cohort of 1179 SE episodes in 1049 adults were retrospectively analyzed. Incident SE episodes were categorized as “early anesthesia” (eGA; GA as first‐ or second‐line treatment) or “non‐early anesthesia” (neGA; GA after second‐line treatment or not at all). Using propensity score matching, eGA episodes were paired 1:4 with neGA episodes. We assessed survival, functional outcomes at discharge (good: modified Rankin Scale = 0–2 or no worsening), SE cessation rate, SE duration, and hospital stay. Among 1049 SE episodes, 55 (5.2%) received eGA, and 994 constituted the neGA group; 220 represented the matched controls. Patients receiving eGA were younger (median = 63, interquartile range [IQR] = 56–76 vs. median = 70, IQR = 54–80 years, p = .004), had deeper consciousness impairment (80% vs. 40% stuporous/comatose, p < .001), and had more severe SE forms (89% vs. 54% generalized convulsive SE/nonconvulsive SE in coma, p < .001). Mortality, functional outcome, SE cessation rate, and duration of SE and hospital stay were similar between the eGA group and matched controls. We conclude that early anesthesia for SE treatment did not influence prognosis.

Background Opisthorchis viverrini (OV) and soil-transmitted helminths (STH) are two of the most common helminths contributing to the Neglected Tropical Disease (NTDs) burden in the Lower Mekong Basin. Although mass drug administration is the cornerstone of control programs to reduce morbidity caused by these infections, this approach has limitations in preventing re-infections. Elimination requires additional measures such as reservoir host treatment, improved hygiene and health education to reinforce MDA's impact. This study aims to examine the impact of a scalable multi-component One Health Helminth Elimination program in the Lower Mekong Basin (HELM) that combines human praziquantel (PZQ) and albendazole (ALB) treatment with a program that includes the “Magic Glasses” and the “Lawa Model” interventions with health promotion at their core. Methods This study will employ a cluster randomized controlled trial (cRCT) in 18 rural communities (with sub-district or villages as cluster units) across Cambodia, Laos and Thailand. The control arm will receive one round of PZQ/ALB treatment, while in the intervention arm, multi-component HELM program will be implemented, which includes PZQ/ALB treatment together with the Magic Glasses and Lawa Model interventions. OV and STH infections levels will be evaluated in individuals aged 5–75 years at baseline and will be repeated at follow-up (12 months after the HELM intervention), using modified formalin ethyl-acetate concentration technique and quantitative PCR. The primary outcome of the study will be cumulative incidence of human OV and STH infections. Outcomes between the study arms will be compared using generalized linear mixed models, accounting for clustering. Discussion Evidence from this trial will quantify the impact of a multi-component One Health control strategy in interrupting Ov and STH infections in the Lower Mekong Basin. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Prospectively registered 28 February 2022.

Background Use of serum procalcitonin (PCT), an inflammatory biomarker for bacterial infections, has shown promising results for early stopping antibiotic treatment among patients with respiratory infections and sepsis. There is need for additional data regarding effectiveness and safety of this concept among patients with cancer. Methods Individual data of patients with a documented diagnosis of cancer and proven or suspected respiratory infection and/or sepsis were extracted from previous trials where adult patients were randomized to receive antibiotic treatment based on a PCT protocol or usual care (control group). The primary efficacy and safety endpoints were antibiotic exposure and 28-day all-cause mortality. Results This individual-patient data meta-analysis included 777 patients with a diagnosis of cancer from 15 randomized-controlled trials. Regarding efficacy, there was a 18% reduction in antibiotic exposure in patients randomized to PCT-guided care compared to usual care ([days] 8.2 ± 6.6 vs. 9.8 ± 7.3; adjusted difference, − 1.77 [95% CI, − 2.74 to − 0.80]; p < 0.001). Regarding safety, there were 72 deaths in 379 patients in the PCT-guided group (19.0%) compared to 91 deaths in 398 participants in the usual care group (22.9%) resulting in an adjusted OR of 0.78 (95% CI, 0.60 to 1.02). A subgroup analysis showed a significant reduction in mortality in patients younger than 70 years (adjusted OR, 0.58 [95% CI, 0.40 to 0.86]). Conclusion Result of this individual patient meta-analysis from 15 previous trials suggests that among patients with cancer and suspected or proven respiratory infection or sepsis, use of PCT to guide antibiotic treatment decisions results in reduced antibiotic exposure with a possible reduction in mortality, particularly among younger patients.

Background The combination antimalarial artefenomel-piperaquine failed to achieve target efficacy in a phase 2b study in Africa and Vietnam. We retrospectively evaluated whether characterizing the pharmacological interaction of this antimalarial combination in a volunteer infection study (VIS) would have enabled prediction of the phase 2b study results. Methods Twenty-four healthy adults enrolled over three consecutive cohorts were inoculated with Plasmodium falciparum-infected erythrocytes on day 0. Participants were randomized within each cohort to one of seven dose combination groups and administered a single oral dose of artefenomel-piperaquine on day 8. Participants received definitive antimalarial treatment with artemether-lumefantrine upon parasite regrowth or on day 42 ± 2. The general pharmacodynamic interaction (GPDI) model implemented in the Bliss Independence additivity criterion was developed to characterize the pharmacological interaction between artefenomel and piperaquine. Simulations based on the model were performed to predict the outcomes of the phase 2b combination study. Results For a dose of 800 mg artefenomel administered with 640 mg, 960 mg, or 1440 mg piperaquine, the simulated adequate parasitological response at day 28 (APR28), incorporating actual patient pharmacokinetic (PK) data from the phase 2b trial, was 69.4%, 63.9%, and 74.8%, respectively. These results closely matched the observed APR28 in the phase 2b trial of 67.0%, 65.5%, and 75.4%, respectively. Conclusions These results indicate that VIS offer an efficient means for informing antimalarial combination trials conducted in the field, potentially expediting clinical development. Trial registration This study was registered on ClinicalTrials.gov on 11 May 2018 with registration number NCT03542149.

Staphylococcus aureus is a leading cause of nosocomial implant-associated infections, causing significant morbidity and mortality, underscoring the need for rapid, non-invasive, and cost-effective diagnostics. Here, we optimise the synthesis of renal-clearable gold nanoclusters (AuNCs) for enhanced catalytic activity with the aim of developing a sensitive colourimetric diagnostic for bacterial infection. All-atom molecular dynamics (MD) simulations confirm the stability of glutathione-coated AuNCs and surface access for peroxidase-like activity in complex physiological environments. We subsequently develop a biosensor by encapsulating these optimised AuNCs in bacterial toxin-responsive liposomes, which is extensively studied by various single-particle techniques. Upon exposure to S. aureus toxins, the liposomes rupture, releasing AuNCs that generate a colourimetric signal after kidney-mimetic filtration. The biosensor is further validated in vitro and in vivo using a hyaluronic acid (HA) hydrogel implant infection model. Urine samples collected from mice with bacteria-infected HA hydrogel implants turn blue upon substrate addition, confirming the suitability of the sensor for non-invasive detection of implant-associated infections. This platform has significant potential as a versatile, cost-effective diagnostic tool.

The review covering the development of capillary electrophoresis with capacitively coupled contactless conductivity detection from 2020 to 2024 is the latest in a series going back to 2004. The article considers applications employing conventional capillaries and planar lab‐on‐chip devices as well as fundamental and technical developments of the detector and complete electrophoresis instrumentation.

Objectives This study evaluates the advantages in diagnostic accuracy, confidence, and reading time of additional dual-energy CT-derived reconstructions for assessing acute bowel ischemia. Methods and materials This retrospective study includes 25 patients with surgically proven acute bowel ischemia and 25 gender- and age-matched controls who underwent biphasic abdominal dual-energy CT. Two fellowship-trained abdominal radiologists and two residents evaluated all cases with and without additional dual-energy CT-derived iodine maps and virtual non-contrast images. Diagnostic confidence was rated on a 10-point Likert scale. Reading time was recorded. The inter-reader agreement was assessed using Fleiss’ kappa. Sensitivity and specificity were compared using McNemar’s test, reader confidence, and reading times with the Wilcoxon signed-rank test. Results For conventional images alone, the inter-reader agreement was moderate ( κ = 0.58), with a sensitivity of 77% (95% CI: 67.5–84.8%) and specificity of 90% (95% CI: 82.4–95.1%). Adding dual-energy CT images, inter-reader agreement increased to substantial ( κ = 0.69), sensitivity increased significantly to 89% (95% CI: 81.2–94.4%, p = 0.02), while specificity increased non-significantly to 93% (95% CI: 86.1–97.1%, p = 0.51). Diagnostic confidence increased significantly from 8 (IQR: 6–8) to 9 (IQR: 8–9) ( p < 0.01). Equivalent diagnostic accuracy and confidence increases were observed for fellowship-trained and resident radiologists. A non-significant increase in mean reading time per case from 196 s to 201 s was observed ( p = 0.30). Conclusion Additional dual-energy CT reconstructions increase diagnostic accuracy and confidence without increasing reading time when evaluating suspected acute bowel ischemia. Both experienced and resident readers benefit from dual-energy CT images. Key Points Question There are too few clinical studies assessing the diagnostic accuracy of dual-energy CT (DECT) to recommend its use for evaluating suspected acute bowel ischemia . Findings Adding DECT-derived iodine maps and virtual-non-contrast images increase reader sensitivity and confidence while maintaining high specificity when evaluating for acute mesenteric ischemia . Clinical relevance Dual-energy CT should be used to investigate suspected acute bowel ischemia. Both diagnostic accuracy and confidence can be increased independent of reader experience without significantly increasing reading time .

Objective To evaluate the early and mid-term results of physician-modified candy-plug (pmCP) in patients with type-B or residual type-A aortic dissection (TBRAD). Methods All patients with TBRAD who received false lumen (FL) occlusion with pmCP between September 2018 and May 2024 were analyzed. Primary outcomes were technical and clinical success, and overall mortality. Secondary outcomes were postoperative aortic remodeling and aortic reintervention. Results Seventeen patients (88% male; mean age 69±12 years) underwent FL occlusion with a pmCP. Nine patients (53%) were emergently treated. The technical and clinical successes were 100% and 82%, respectively. One patient (6%) died postoperatively. Early complete FL occlusion was observed in 82% of the patients. One patient (6%) required an early pmCP-related reintervention. During a mean follow-up of 15±5 months, 75% of the patients had complete thoracic FL thrombosis while 13% of them aortic remodeling in the last computed tomography (CT) scan. Aneurysm size remained stable in 69% of the cases. There were no aortic-related re-interventions during follow-up. Conclusions The pmCP technique is a feasible and promising alternative technique, with high primary technical and clinical success rate. Stable aortic diameters can be expected during follow-up, thus reducing the need for further aortic reintervention. Clinical Impact Persistence of false lumen (FL) patency after thoracic endovascular aortic repair (TEVAR) for thoracic aortic dissection (TBAD) remains a significant challenge for physicians. Various strategies have been developed to address retrograde FL patency, including the candy-plug technique. This technique involves modifying thoracic stent grafts and placing an additional plug to occlude the reduced stent graft waist.Since its introduction, three generations of custom-made candy-plug devices (Cook Medical, Bloomington, IN, USA) have been developed. However, delivery times vary across countries and vascular surgery services, complicating procedural planning, particularly in symptomatic patients or cases of rapid FL diameter progression.In this study, we provide a step-by-step description of the physician-modified candy-plug technique and present our preliminary results.

Objectives To improve precision of secondary resection (SR) after positive surgical margin (PSM) detection by frozen section (FS) during nerve‐sparing (NS) robot‐assisted radical prostatectomy (RARP) by employing a personalised three‐dimensional (3D)‐printed prostate model derived from pelvic magnetic resonance imaging (MRI). This model was used to mark positive surgical margins (PSM) and guide intraoperative SR during NS‐RARP. Patients and Methods Prospective multicentre cohort study with 100 patients undergoing NS‐RARP between September 2018 and August 2021. Primary and secondary endpoints were the conversion rate of FS‐identified PSM to a tumour‐free margin and functional/oncological parameters within a 12‐month follow‐up, respectively. Results A PSM was identified in 23% of cases during FS, with a conversion to negative surgical margins (NSM) in 83% (19/23 cases) by model‐guided SR. The tumour detection rate in SR specimens was 39% (nine of 23 cases). Among the 19 patients with converted margins, 18 (95%) achieved undetectable prostate‐specific antigen levels 2 months postoperatively, with six (32%) having subsequent biochemical recurrence within 12 months. prostate‐specific‐membrane‐antigen positron emission tomography computed tomography found one local recurrence, and five cases of metastatic disease. In converted patients, the baseline median five‐item version of the International Index of Erectile Function score decreased by 16% after 1 year, with no significant difference compared to patients with primarily NSM. Limitations include the absence of a control group, the potential for false‐negative FS results and limited accuracy of MRI. Conclusion The integration of 3D‐printed prostate models into NS‐RARP has the potential to positively impact surgical outcomes by improving the precision of SR and optimising pathosurgical communication.

Introduction Cholangiocarcinoma (CCA) is a major contributor to hepatobiliary mortality in the Lao People’s Democratic Republic (Lao PDR). Infection with the carcinogenic trematode Opisthorchis viverrini (OV), acquired through consumption of insufficiently-cooked river fish, is a known risk factor for the development of CCA. Together with OV, other risk factors contribute to the pathogenesis of CCA. We conducted this study to identify the burden of CCA and identify risk factors in high-risk communities in Lao PDR. Method A cross-sectional study was performed in Champasack and Savannakhet provinces, southern Lao PDR, where OV infection is highly endemic. We assessed hepatobiliary morbidity with abdominal ultrasound (US). In addition, multiple risk factors known or suspected to be associated with CCA were assessed such as OV infection (examined by Kato-Katz technique for stool examination), lifestyle risks (e.g. smoking and alcohol consumption by face-to-face questionnaire), co-morbidity (e.g. diabetes mellitus) and hepatitis B infection status, both serologically tested. Results In 3,400 participants, the overall prevalence of suspected CCA was 7.2% (95% confidence interval [95% CI] 5.4−9.6). The suspected CCA prevalence increased with age, and was higher in men at all ages. Almost all participants (88.3%) were infected with OV. In the multivariate regression analysis, suspected CCA was positively associated with OV infection (adjusted odds ratio [aOR] 3.4, 95% CI 1.7−6.5), and a history of cholecystectomy (aOR 2.7, 95% CI 1.5−4.9). Conclusion Our CCA screening in high OV prevalence rural areas of Lao PDR uncovers a high public health burden, primarily driven by elevated OV infection rates. Urgent interventions are needed to curb OV infection in these communities. Age and gender disparities in suspected CCA prevalence highlight the need for targeted efforts. Beyond OV, notable factors like a history of cholecystectomy offer valuable insights for preventive strategies. This research enhances our understanding of hepatobiliary morbidity and informs public health initiatives in Lao PDR.

Background The locus coeruleus (LC) noradrenergic system may provide a potential new target for pharmacological insomnia treatment, particularly in patients suffering from elevated distress. The selective α2 noradrenergic agonist dexmedetomidine attenuates LC activity in sub-anesthetic doses, yet no adequate non-parental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oro-mucosal dexmedetomidine administration, we developed two distinct - one sublingual and one buccal - oro-mucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here we established their pharmacokinetic and pharmacodynamic (PK-PD) profiles. Methods In a pilot study (sublingual formulation; n=8 good sleepers) and a main study (buccal formulation; n=17 poor sleepers), each following a randomized, double-blind, placebo-controlled, cross-over design, we investigated sub-anesthetic doses (20 & 40 µg) of the two formulas. We complemented the PK assessments with all-night polysomnography, nocturnal cortisol and melatonin measurements, assessments of cardiovascular functions during and after sleep, cortisol awakening response, and post-awakening examination of subjective state and vigilance. Results Particularly buccal dexmedetomidine was rapidly absorbed and exhibited excellent dose-proportionality with minimal between-subject variation in exposure. In poor sleepers, 40 µg of buccal dexmedetomidine shortened the sleep latency by 11.5 min, increased the time spent in non-rapid-eye-movement (NREM) sleep by 37.2 min, and elevated NREM sleep electroencephalographic slow wave energy (0.75-4.0 Hz) in the first half of the night by roughly 23 %. REM sleep latency was dose-dependently prolonged (20 µg: 55.0 min; 40 µg: 115.3 min). Nocturnal cortisol, melatonin and heart rate, and morning cortisol were not significantly affected by dexmedetomidine, nor did post-awakening orthostatic regulation, subjective sleepiness and mood, and psychomotor vigilance differ among the conditions. Conclusions The favorable PK-PD profile of oro-mucosal dexmedetomidine delivery warrants further dose-finding and clinical studies, to establish the exact roles of α2 receptor agonism in pharmacological sleep enhancement and as possible novel mechanism to alleviate stress-related insomnia.

Background The rising prevalence of acute ischemic stroke (AIS) in young adults, particularly with undetermined pathogenesis, is a growing concern. This study assessed risk factors, treatments, and outcomes between young AIS patients with undetermined and determined pathogeneses. Methods and Results This was a retrospective cohort study including AIS patients aged 18 to 55 years in Switzerland, treated between 2014 and 2022. Stroke pathogeneses were classified using a modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification, with undetermined pathogenesis defined as no identified cause (including patent foramen ovale and cervical artery dissection). We examined vascular risk factors, acute treatments, 3‐month functional outcomes, and AIS recurrence within 3 months using logistic regression and Fine–Gray proportional hazards models. Of 3995 patients, 863 (22%) had undetermined pathogenesis. Compared with patients with determined pathogenesis, those with undetermined pathogenesis had a higher prevalence of dyslipidemia (54% versus 59%, P =0.007) and smoking (37% versus 43%, P =0.001), and were more likely to receive intravenous thrombolysis (27% versus 31%, P =0.046). Despite higher 3‐month AIS recurrence risk for the undetermined group (adjusted hazard ratio, 1.72 [95% CI, 1.01–2.94]), favorable functional outcomes at 3 months were more frequent (modified Rankin Scale score, 0–2: 90% versus 87%, P =0.033). Patients aged 46 to 55 years with undetermined pathogenesis had better outcomes than those with determined pathogenesis (modified Rankin Scale score, 0–1: 70% versus 64%, P =0.013; modified Rankin Scale score, 0–2: 89% versus 85%, P =0.023), while those aged 18 to 45 years showed higher recurrence rates (4.5% versus 1.8%, P <0.05) but similar functional outcomes. Conclusions Young adults with AIS exhibit a considerable vascular risk burden. Those with undetermined pathogenesis displayed age‐related outcome disparities, with better short‐term outcomes in older and higher recurrence rates in younger patients.

Eukaryotes must balance the need for gene transcription by RNA polymerase II (Pol II) against the danger of mutations caused by transposable element (TE) proliferation. In plants, these gene expression and TE silencing activities are divided between different RNA polymerases. Specifically, RNA polymerase IV (Pol IV), which evolved from Pol II, transcribes TEs to generate small interfering RNAs (siRNAs) that guide DNA methylation and block TE transcription by Pol II. While the Pol IV complex is recruited to TEs via SNF2-like CLASSY (CLSY) proteins, how Pol IV partners with the CLSYs remains unknown. Here, we identified a conserved CYC-YPMF motif that is specific to Pol IV and is positioned on the complex exterior. Furthermore, we found that this motif is essential for the co-purification of all four CLSYs with Pol IV, but that only one CLSY is present in any given Pol IV complex. These findings support a “one CLSY per Pol IV” model where the CYC-YPMF motif acts as a CLSY-docking site. Indeed, mutations in and around this motif phenocopy pol iv null and clsy quadruple mutants. Together, these findings provide structural and functional insights into a critical protein feature that distinguishes Pol IV from other RNA polymerases, allowing it to promote genome stability by targeting TEs for silencing.

Background The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis. Methods During the three annual intervention periods of the SchistoBreak study implemented in the north of Pemba from 2020 to 2024, malacological surveys were conducted up to four times per period in WBs of hotspot implementation units (IUs). Present freshwater snail species, vegetation, and WB characteristics were recorded. If Bulinus were found, the snails were inspected for Schistosoma infection and snail control with niclosamide was conducted. Results Across the three intervention periods, a total of 112 WBs were identified in 8 hotspots IUs. The spatial distribution of WBs with Bulinus per IU was heterogeneous, ranging from 0.0% (0/15) of WBs infested in one IU in 2022 to 80.0% (8/10) of WBs infested in one IU in 2021. Bulinus presence was significantly associated with lower pH values in WBs (odds ratio: 0.2, 95% confidence interval 0.1–0.4). A total of 0.2% (6/2360) of collected Bulinus were shedding Schistosoma cercariae. Following snail control, the number of Bulinus decreased or remained absent in 56.7% (38/67) of visits at WBs when compared with the previous visit in 2021, 54.9% (28/51) in 2022, and 33.3% (32/96) in 2023. In a total of 43.1% (22/55) of initially infested WBs, no Bulinus were found in the survey round conducted a few weeks after the first application of niclosamide. However, 25.4% (14/55) of WBs showed a pattern of recurring Bulinus presence. Conclusions The distribution of WBs containing Bulinus was very heterogeneous. The percentage of Bulinus with patent Schistosoma infection in our study area was extremely low. Repeated niclosamide application reduced the number of Bulinus in WBs, but snails often recurred after one or multiple treatments. While chemical mollusciciding can reduce snail numbers, to fully break the S. haematobium transmission cycle, timely diagnosis and treatment of infected humans, access to clean water, sanitation, and health communication remain of prime importance. Trial registration: ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493 Graphical Abstract

Trichuris trichiura , a soil-transmitted helminth (STH), often persists after a single dose of anthelminthic treatment. To overcome limited efficacy against T . trichiura of benzimidazoles (albendazole or mebendazole), the primary drugs used in mass drug administration (MDA) campaigns, the World Health Organization endorses the use of a combination of ivermectin and albendazole as a more effective treatment to be used for preventive chemotherapy. Given observed considerable differences in efficacy of the combination therapy over albendazole monotherapy, between different settings, it is necessary to evaluate the performance of the combination before introducing it on a larger scale. This open-label, randomized controlled superiority trial in two Ugandan primary schools enrolled eligible 6- to 12-year-olds positive for T . trichiura . Participants were randomized 1:1 to receive either a single dose of albendazole alone or co-administered albendazole and ivermectin. Adverse events were monitored at three and 24h post-treatment. Follow-up samples were collected 14 to 21 days post-treatment for efficacy assessment. The combination of albendazole with ivermectin showed superior efficacy against T . trichiura compared to albendazole alone, both in terms of cure rates (31.3% versus 12.3%, difference 18.9%-points, 95% CI 6.2–31.2, p < 0.004) and in terms of egg reduction rates (ERRs; 91.4% versus 52.7%). A higher cure rate against co-infecting Ascaris lumbricoides was observed in the combination compared to the albendazole monotherapy arm (100% versus 83.9%). Both therapies showed an excellent safety profile with few and only mild and transient treatment emergent adverse events observed in the albendazole monotherapy and albendazole plus ivermectin arm (total of 22 and 19 events, respectively). In conclusion, the efficacy of the combination therapy against T . trichiura in Uganda is superior to that of albendazole alone. Given the high ERRs observed albendazole-ivermectin might aid in eliminating morbidity, an important target of STH control programs. Trial registration (clinicaltrials.gov): NCT06037876 .

OBJECTIVES To develop and evaluate a deep learning (DL) model to reduce metal artefacts originating from the exomass in cone-beam computed tomography (CBCT) of the jaws. METHODS Five porcine mandibles, each featuring six tubes filled with a radiopaque solution, were scanned using four CBCT units before and after the incremental insertion of up to three titanium, titanium-zirconium, and zirconia dental implants in the exomass of a small field of view. A conditional denoising diffusion probabilistic model, using DL techniques, was employed to correct images from exomass-related metal artefacts across the CBCT units and implant scenarios. Three examiners independently scored the image quality of all datasets, including those without an implant (ground truth), with implants in the exomass (original), and DL-generated ones. Quantitative analysis compared contrast-to-noise ratio (CNR) to validate artefact reduction using repeated measures analysis of variance in a factorial design followed by Tukey test (α = 0.05). RESULTS The visualisation of the hard tissues and overall image quality was reduced in the original and increased in the DL-generated images. The score variation observed in the original images was not observed in the DL-generated images, which generally scored higher than the original images. DL-generated images revealed significantly greater CNR than both the ground truth and their corresponding original images, regardless of the material and quantity of dental implants and the CBCT unit (p < 0.05). Original images revealed significantly lower CNR than the ground truth (p < 0.05). CONCLUSIONS The developed DL model demonstrated promising performance in correcting exomass-related metal artefacts in CBCT of the jaws.