Everolimus and peptide receptor radionuclide therapy (PRRT, 177Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d\'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 mo (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 mo (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations.

Nontyphoidal Salmonella enterica serovars are foodborne pathogens commonly transmitted through poultry products. Draft genome sequences of three Salmonella enterica subsp. enterica serovar Shamba isolates which were obtained from poultry house dust in South Africa are reported herein.

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda\'s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies.

Daily experiences often involve the processing of multiple sequences, yet storing them challenges the limited capacity of working memory (WM). To achieve efficient memory storage, relational structures shared by sequences would be leveraged to reorganize and compress information. Here, participants memorized a sequence of items with different colors and spatial locations and later reproduced the full color and location sequences one after another. Crucially, we manipulated the consistency between location and color sequence trajectories. First, sequences with consistent trajectories demonstrate improved memory performance and a trajectory correlation between reproduced color and location sequences. Second, sequences with consistent trajectories show neural reactivation of common trajectories, and display spontaneous replay of color sequences when recalling locations. Finally, neural reactivation correlates with WM behavior. Our findings suggest that a shared common structure is leveraged for the storage of multiple sequences through compressed encoding and neural replay, together facilitating efficient information organization in WM.
When we memorize a grocery list before heading into the store, we make use of our working memory. This type of neural process allows us to temporarily store the knowledge needed for a task, yet its capacity is limited. Having to recall more than one type of information at the same time, in particular, can quickly create challenges. Exactly how the brain maximizes the use of this limited working memory space remains unclear. One possible strategy would be to take advantage of the patterns or connections that exist between seemingly unrelated pieces of information – for example, by remembering to buy apples, oranges and bananas under one broader ‘fruit’ category. To explore if this may be the case, Qiaoli Huang and Huan Luo designed a memory task in which two types of information were either connected through an underlying pattern (aligned trajectory condition) or completely independent (misaligned trajectory condition). Participants watched three colored dots appearing on screen one after the other, in such a way that they seemed to ‘travel’ around an imaginary circle. The volunteers were then asked to recall, in order, the location and color of each dot. Performance increased when color and location information were structured in the same way – that is, when both emerged from the three dots traveling around a circle or a color wheel with the same trajectory. Recording the brain activity of the participants ‘live’ as they performed the task indicates that, in the aligned trajectory condition, the brain ‘compresses’ both types of information and extracts their common structure. Even when participants were asked to recall only the location of the dots, their brain also spontaneously replayed the related color information. Taken together, these findings provide new insights into how working memory aids in multitasking, a crucial aspect of our daily lives, and lay the groundwork for further exploration of this capability.

Melioidosis is a potentially severe disease caused by the gram-negative soil-dwelling bacterium called Burkholderia pseudomallei. The true breadth of the distribution of this tropical pathogen is starting to emerge with environmental and clinical isolates frequently characterized in new countries and regions. Even so, isolates, clinical cases, and genetic data from the continent of Africa remain scant. We previously confirmed the presence of B. pseudomallei in the environment of Ghana, unmasking a new area of endemicity for this pathogen. Here, we describe the genetic characteristics of isolates obtained from that environmental survey. Twenty-one isolates were subjected to whole genome sequencing and found to represent three discrete sequence types (ST), one of which was novel, and designated ST2058. Phylogenetic analysis places this novel isolate within a B. pseudomallei clade that includes genomes derived from the Americas, although it is closely related to a sub-clade that includes isolates from Africa. Importantly, phenotypic characterization demonstrates common features including API 20NE profiles and B. pseudomallei CPS to support existing diagnostics, and susceptibility to standard of care antibiotics often used in the clinical management of melioidosis. These findings add to our knowledge about the presence and distribution of B. pseudomallei in Africa and represent the first published genomes out of Ghana.

A comprehensive and systematic examination of dengue virus (DENV) evolution is essential in Pakistan, where the virus poses a significant public health challenge due to its ability to adapt and evolve. To shed light on the intricate evolutionary patterns of all four DENV serotypes, we analyzed complete genome sequences (n = 43) and Envelope (E) gene sequences (n = 44) of all four DENV serotypes collected in Pakistan from 1994 to 2023, providing a holistic view of their genetic evolution. Our findings revealed that all four serotypes of DENV co-circulate in Pakistan with a close evolutionary relationship between DENV-1 and DENV-3. Among the genetically distinct serotypes DENV-2 and DENV-4, DENV-4 stands out as the most genetically different, while DENV-2 exhibits greater complexity due to the presence of multiple genotypes and the possibility of temporal fluctuations in genotype prevalence. Selective pressure analysis of the Envelope (E) gene revealed heterogeneity among sequences (n = 44), highlighting 46 codons in the genome experiencing selective pressure, characterized by a bias toward balancing selection, indicating genetic stability of the virus. Furthermore, our study suggested an intriguing evolutionary shift of DENV-4 toward the DENV-2 clade, potentially influenced by antibodies with cross-reactivity to multiple serotypes, providing a critical insight into the complex factors, shaping DENV evolution and contributing to the emergence of new serotypes.

Increasing SNP density by incorporating sequence information only marginally increases prediction accuracies of breeding values in livestock. To find out why, we used statistical models and simulations to investigate the shape of distribution of estimated SNP effects (a profile) around quantitative trait nucleotides (QTNs) in populations with a small effective population size (Ne). A QTN profile created by averaging SNP effects around each QTN was similar to the shape of expected pairwise linkage disequilibrium (PLD) based on Ne and genetic distance between SNP, with a distinct peak for the QTN. Populations with smaller Ne showed lower but wider QTN profiles. However, adding more genotyped individuals with phenotypes dragged the profile closer to the QTN. The QTN profile was higher and narrower for populations with larger compared to smaller Ne. Assuming the PLD curve for the QTN profile, 80% of the additive genetic variance explained by each QTN was contained in ± 1/Ne Morgan interval around the QTN, corresponding to 2 Mb in cattle and 5 Mb in pigs and chickens. With such large intervals, identifying QTN is difficult even if all of them are in the data and the assumed genetic architecture is simplistic. Additional complexity in QTN detection arises from confounding of QTN profiles with signals due to relationships, overlapping profiles with closely spaced QTN, and spurious signals. However, small Ne allows for accurate predictions with large data even without QTN identification because QTNs are accounted for by QTN profiles if SNP density is sufficient to saturate the segments.

BACKGROUND: Physiological motion of the lumbar spine is a topic of interest for musculoskeletal health care professionals since abnormal motion is believed to be related to lumbar complaints. Many researchers have described ranges of motion for the lumbar spine, but only few have mentioned specific motion patterns of each individual segment during flexion and extension, mostly comprising the sequence of segmental initiation in sagittal rotation. However, an adequate definition of physiological motion is still lacking. For the lower cervical spine, a consistent pattern of segmental contributions in a flexion-extension movement in young healthy individuals was described, resulting in a definition of physiological motion of the cervical spine.
OBJECTIVE: This study aimed to define the lumbar spines\' physiological motion pattern by determining the sequence of segmental contribution in sagittal rotation of each vertebra during maximum flexion and extension in healthy male participants.
METHODS: Cinematographic recordings were performed twice in 11 healthy male participants, aged 18-25 years, without a history of spine problems, with a 2-week interval (time point T1 and T2). Image recognition software was used to identify specific patterns in the sequence of segmental contributions per individual by plotting segmental rotation of each individual segment against the cumulative rotation of segments L1 to S1. Intraindividual variability was determined by testing T1 against T2. Intraclass correlation coefficients were tested by reevaluation of 30 intervertebral sequences by a second researcher.
RESULTS: No consistent pattern was found when studying the graphs of the cinematographic recordings during flexion. A much more consistent pattern was found during extension, especially in the last phase. It consisted of a peak in rotation in L3L4, followed by a peak in L2L3, and finally, in L1L2. This pattern was present in 71% (15/21) of all recordings; 64% (7/11) of the participants had a consistent pattern at both time points. Sequence of segmental contribution was less consistent in the lumbar spine than the cervical spine, possibly caused by differences in facet orientation, intervertebral discs, overprojection of the pelvis, and muscle recruitment.
CONCLUSIONS: In 64% (7/11) of the recordings, a consistent motion pattern was found in the upper lumbar spine during the last phase of extension in asymptomatic young male participants. Physiological motion of the lumbar spine is a broad concept, influenced by multiple factors, which cannot be captured in a firm definition yet.
BACKGROUND: ClinicalTrials.gov NCT03737227; https://clinicaltrials.gov/ct2/show/NCT03737227.
UNASSIGNED: RR2-10.2196/14741.

In severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab is unclear. We utilised a novel overlapping strategy in three patients with very-high fracture risk despite long-term denosumab which led to greater bone density improvements than previously reported with standard approaches. Larger confirmatory prospective studies are needed.
OBJECTIVE: In patients with severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab has not been established. The ideal strategy would maximise gains in bone mineral density (BMD) with romosozumab and effectively mitigate the risk of rebound increased bone turnover when sequencing from denosumab. Limited studies exploring the sequence from denosumab to romosozumab report only modest-to-no improvement in BMD and inadequate suppression of rebound bone turnover.
METHODS: We describe three patients with severe osteoporosis and multiple fragility fractures despite long-term denosumab. A novel overlapping sequential treatment approach was utilised to maximise therapeutic benefit given these patients had a very high fracture risk. Romosozumab was commenced 3 months after the last denosumab dose. Instead of waiting until completion of romosozumab, denosumab was recommenced 6 months after commencing romosozumab in response to rising bone turnover markers.
RESULTS: Patients experienced a ~ 5-22% increase in lumbar spine BMD, and one patient had an 8% increase in total hip BMD after 12 months romosozumab. Serum bone turnover markers demonstrated an anabolic effect of romosozumab occurred despite overlapping treatment with denosumab. Recommencement of denosumab suppressed an increase in bone resorption in all cases. No new vertebral fractures occurred during this treatment.
CONCLUSIONS: A novel overlapping sequential treatment approach between denosumab and romosozumab produced greater improvements in lumbar spine and hip BMD than previously reported with standard approaches. Larger prospective controlled studies are needed to confirm these findings and establish the optimal use of romosozumab in patients pre-treated with denosumab to maximise BMD gains and minimise fracture risk.

UNASSIGNED: To evaluate and compare magnetic resonance imaging (MRI) sequences that could potentially be used in the diagnosis of coronavirus disease 2019 (COVID-19).
UNASSIGNED: Included in the study were 42 patient who underwent thorax computed tomography (CT) for COVID-19 pneumonia and thorax MRI for any reason within 24 h after CT. The T2-weighted fast spin echo periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) (T2W-FSE-P), fast imaging employing steady-state acquisition, T2 fat-saturated FSE, axial T1 liver acquisition with volume acceleration (LAVA) and single-shot FSE images were compared in terms of their ability to show COVID-19 findings.
UNASSIGNED: The mean age of the patients was 47.2 ± 24 years. Of the patients, 22 were male (52.4%) and 20 (47.6%) were female. The interobserver intraclass coefficient (ICC) for the image quality score was the highest in the T2W-FSE-P sequence and lowest in the T1 LAVA sequence. All of the lesion-based evaluations of the interobserver agreement were statistically significant, with the kappa value varying between 0.798 and 0.998.
UNASSIGNED: All 5 sequences evaluated in the study were successful in showing the parenchymal findings of COVID-19. Since the T2W-FSE-P sequence had the best scores in both interobserver agreement and ICC for the image quality score, it was considered that it can be included in thorax MRI examinations to assist the diagnosis of COVID-19.