Future Interventions Research Articles

A Number of the N-terminal RASSF Family: RASSF7

The Ras association domain family 7 (RASSF7, also named HRC1), a potential tumor-related gene, located on human chromosome 11p15, has been identified as an important member of the N-terminal RASSF family. Whereas, the molecular biological mechanisms of RASSF7 in tumorigenesis remain to be further established. We perform a systematic review of the literature and assessment from PUBMED and MEDLINE databases in this article. RASSF7 plays a significant role in mitosis, microtubule growth, apoptosis, proliferation and differentiation. Many research literature shows that the RASSF7 could promote the occurrence and advance of human tumors by regulating Aurora B, MKK4, MKK7, JNK, YAP, MEK, and ERK, whereas, it might inhibit c-Myc and thus lead to the suppression of tumorigenesis. The pregulation of RASSF7 often occurs in various malignancies such as lung cancer, neuroblastoma, thyroid neoplasm, hepatocellular cancer, breast cancer and gastric cancer. The expression stage of RASSF7 is positively correlated with the tumor TNM stage. In this review, we primarily elaborate on the acknowledged structure and progress in the various biomechanisms and research advances of RASSF7, especially the potential relevant signaling pathways. We hope that RASSF7 , a prospective therapeutic target for human malignancies, could play an available role in future anti-cancer treatment.

Visual Pathway Recovery Post Pituitary Adenoma Surgery: Insights from Retinal Structure, Vascular Density, and Neural Conduction Analysis.

This study investigates how surgery for pituitary adenoma (PA) affects the visual pathway, examining changes in the retina, blood vessel density, and nerve function. Since PAs often impair vision as a result of their location near visual structures, this research is key to understanding and improving vision recovery after surgery. Our study is based on a retrospective analysis of the historical data of 28 patients diagnosed with pituitary adenomas. We conducted assessments by reviewing preoperative and postoperative imaging records. These included optical coherence tomography (OCT) for retinal structure analysis, diffusion tensor imaging (DTI) for neural transmission evaluation, and optical coherence tomography angiography for assessing blood vessel density. These tools allowed for a detailed understanding of the structural and functional changes within the visual pathway following PA surgery. OCT findings show postoperative changes in the eye: thinning in average and nasal circumpapillary retinal nerve fiber layer, thickening in macular central 1mm inner plexus layer, ganglion cell complex, and nasal retinal nerve fiber layer. DTI reveals increased fractional anisotropy (FA) in the left optic chiasm and posterior optic nerve, decreased mid-segment optic nerve FA, and increased apparent diffusion coefficient (ADC) in the right optic chiasm and nerve segments. Early postoperative reduction in radial peripapillary capillaries plexus density is noted. Preoperative ganglion cell layer (GCL) thickness correlates with postoperative visual radiation FA and ADC values, especially in the inferior quadrant. A negative correlation exists between preoperative GCL thickness and postoperative visual field mean defect values, particularly on the temporal side and superior inner ring. All changes are statistically significant (P < 0.05). The study finds that surgery for PA has varied effects on vision. Early post surgery, there are changes in the retina and nerve signals. Macular GCL thickness before surgery might predict early visual recovery, influencing future research and treatment for vision issues related to PA.

Evaluation of a psychoeducation group for children presenting with functional tic-like behaviours.

We describe the implementation and evaluation of an online psychoeducation group for young people experiencing functional tic-like behaviours (FTLBs) - a type of functional neurological disorder (FND). Across six groups, 50 participants completed pre- and post-group goal-based outcomes (GBOs) and 36 participants completed service-user feedback, which gathered qualitative and quantitative data about participants experiences of the group. Young people and their parents reported significant improvement in their GBOs following the group and increased knowledge and confidence in managing FTLBs. The findings highlight that virtual psychoeducation group intervention is an acceptable and effective first step in treatment of young people with FTLBs. We discuss implications for future intervention development.

Investigating Stem Cell Therapy for Alzheimer's Disease: A Promising Approach

Alzheimer's disease (AD) is a neurodegenerative disorder, a form of dementia commonly affecting people 40-65. Growing more prevalent in society, approximately 6.2 million Americans aged 65 and older live with AD. AD is a progressive, long-term neurological disorder that worsens cognitive skills, memory, and communication abilities leading to a performative decline in daily tasks. Characterized by the accumulation of extracellular amyloid beta (Aβ) plaque and neurofibrillary tangles (NFTs) of tau in the central nervous system, these account for synapse loss and neuronal death in the brain. Unfortunately, even with its detrimental impacts, clinical trials of therapeutic drugs are still to be tested and not available to the public. Current research on stem cell transplantation has been shown to alleviate neuropathologies and is explored as a prospective treatment for AD. This literature review assesses the important uses of stem cell therapy for AD patients to provide a new clinical approach for future treatment. Further clinical research should be conducted on the long-term outcomes of stem cell therapy for deeper analysis of its therapeutic effects for AD.

Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges

Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges

Evaluation of WHO catalog of mutations and five WGS analysis tools for drug resistance prediction of Mycobacterium tuberculosis isolates from China.

The continuous advancement of molecular diagnostic techniques, particularly whole-genome sequencing (WGS), has greatly facilitated the early diagnosis of drug-resistant tuberculosis patients. Nonetheless, the interpretation of results from various types of mutations in drug-resistant-associated genes has become the primary challenge in the field of molecular drug-resistance diagnostics. In this study, our primary objective is to evaluate the diagnosis accuracy of the World Health Organization (WHO) catalog of mutations and five WGS analysis tools (PhyResSE, Mykrobe, TB Profiler, Gen-TB, and SAM-TB) in drug resistance to 10 anti-Mycobacterium tuberculosis (MTB) drugs. We utilized the data of WGS collected between 2014 and 2017 in Zhejiang Province, consisting of 110 MTB isolates as detailed in our previous study. Based on phenotypic drug susceptibility testing (DST) results using the proportion method on Löwenstein-Jensen medium with antibiotics, we evaluated the predictive accuracy of genotypic DST obtained by these tools. The results revealed that the WHO catalog of mutations and five WGS analysis tools exhibit robust predictive capabilities concerning resistance to isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, and capreomycin. Notably, Mykrobe, SAM-TB, and TB Profiler demonstrate the most accurate predictions for resistance to pyrazinamide, prothionamide, and para-aminosalicylic acid, respectively. These findings are poised to significantly guide and influence future clinical treatment strategies and resistance monitoring protocols.IMPORTANCEWhole-genome sequencing (WGS) has the potential for the early diagnosis of drug-resistant tuberculosis. However, the interpretation of mutations of drug-resistant-associated genes represents a significant challenge as the amount and complexity of WGS data. We evaluated the accuracy of the World Health Organization catalog of mutations and five WGS analysis tools in predicting drug resistance to first-line and second-line anti-TB drugs. Our results offer clinicians guidance on selecting appropriate WGS analysis tools for predicting resistance to specific anti-TB drugs.

Approved AI-based fluid monitoring to identify morphological and functional treatment outcomes in neovascular age-related macular degeneration in real-world routine

AimTo predict antivascular endothelial growth factor (VEGF) treatment requirements, visual acuity and morphological outcomes in neovascular age-related macular degeneration (nAMD) using fluid quantification by artificial intelligence (AI) in a real-world...

BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.

This study aims to find whether the proliferation and migration of triple negative breast cancer (TNBC) cell lines can be reduced by treatment with bromodomain and extra-terminal domain (BET) inhibitor JQ1 and BET protein targeting chimeras (PROTACs) ARV-771 and MZ1. Cytotoxicity tests, scratch migration assays and western blot proteome profiler arrays for protein expression of cancer-related proteins were used to evaluate the impact of a BET-inhibitor and two BET-directed PROTACs on cell viability, migration and on protein expression. JQ1 and the PROTACs MZ1 and ARV-771 significantly inhibited the growth and migration of the KRAS G13D-mutated MDA-MB-231 cells. In this cell line, the PROTACs suppressed the residual expression of ERBB2/HER2, 3 and 4 that are essential for the proliferation of breast cancer cells and this cell line proved sensitive to HER2 inhibitors. In contrast, the effects of the PROTACs on the protein expression of MDA-MB-436 cells mostly affected cytokines and their cognate receptors. The degradation of BET-protein by PROTACs demonstrated significant anti-proliferative effects. The KRAS-mutated MDA-MB-231 cells belong to the low-HER2 expressing tumors that have a poorer prognosis compared to HER2-null patients. Since first oral PROTACs against tumor hormone receptors are in clinical trials, this mode of tumor therapy is expected to become an important therapeutic strategyin the future treatment of TNBC.

Investigation of the adsorption performance and mechanism of multi-source mineral composite calcination materials on heavy metal ions

To address the challenges of plume generation and the release of heavy metal ions caused by deep-sea mining operations, this study utilized multi-source minerals, including steel slag (SS), oceanic manganese nodules (OMN), attapulgite (AT), and sawdust (SD), to fabricate a multi-source mineral composite calcination material (MMCCM) through a sintering process, and then the preliminary heavy metal ion adsorption experiment was carried out. The results indicated that both Langmuir and Freundlich models can describe the adsorption behavior of Cu2+ in a single system, while the Freundlich model was more applicable in competitive systems. The adsorption of Co2+ and Ni2+ consistently aligned with the Langmuir model across all systems. The adsorptive behavior conformed to pseudo-second-order kinetics, indicating that chemisorption played a leading role. The intraparticle diffusion was the principal rate-limiting step, and the adsorption process was spontaneous. BET, TG-DTG, SEM-EDS, XRD, FT-IR and XPS elucidated that surface physical adsorption, ion exchange, complexation with functional groups, electrostatic attraction, and co-precipitation, which were the predominant adsorption mechanisms for MMCCM. Evaluations of regenerability, economy, security, and suitability demonstrated that MMCCM is an eco-friendly adsorbent, which provides materials and data support for future heavy metal marine sewage treatment, especially for immobilizing heavy metal in deep-sea sediments.

EE460 Theoretical Exploration of the Inclusion of Non-Traditional Multiple Sclerosis Measurement Variables on the Cost-Effectiveness of Future Treatments

EE460 Theoretical Exploration of the Inclusion of Non-Traditional Multiple Sclerosis Measurement Variables on the Cost-Effectiveness of Future Treatments

Subcutaneous edema as a potential cause of catheter failure in older inpatients receiving peripheral parenteral nutrition.

Malnutrition is a common problem among hospitalized older patients. Peripheral parenteral nutrition (PN) can improve patient outcomes but can also lead to complications that affect future treatment. Older inpatients, in particular, are expected to be prone to these catheter-related complications. However, the impact of peripheral PN on older inpatients has been rarely investigated. In the current study, the impact of PN on short peripheral catheters (SPCs) was evaluated by comparing signs and symptoms at the time of catheter removal between 22 patients with PN and 27 without. In addition to external clinical assessment, sonographic investigations of the SPC site were performed. The prevalence of external signs and symptoms of complications was similar between the patients (all P > 0.05). However, subcutaneous edema was found by ultrasound in > 80% of patients with PN, compared with 55.6% of those without PN (P = 0.051). Unlike cases without PN, all patients with PN who presented with external signs and symptoms developed subcutaneous edema (P = 0.022). Multivariate analysis demonstrated that administration of PN was independently associated with subcutaneous edema (adjusted odds ratio = 6.88, 95% confidence interval = 1.083-75.486, P = 0.040). For several decades, phlebitis has been the primary focus of complications related to peripheral PN in clinical settings. However, our results imply that peripheral PN causes subcutaneous edema, which can lead to catheter failure in older inpatients. This study contributes to understanding the etiology of catheter failure during peripheral PN in this population.

The susceptibility of shi drum juveniles to betanodavirus increases with rearing densities in a process mediated by neuroactive ligand-receptor interaction.

Nervous necrosis virus (NNV) is one of the greatest threats to Mediterranean aquaculture, infecting more than 170 fish species and causing mortalities up to 100% in larvae and juveniles of susceptible species. Intensive aquaculture implies stressed conditions that affect the welfare of fish and their ability to fight against infections. In fact, a higher susceptibility to NNV has been related to poor welfare conditions. In order to analyze the physiological link between stressed conditions and increased susceptibility to NNV, as well as its possible role in the pathogenesis of this disease, we reared shi drum (Umbrina cirrosa) juveniles (30.7 ± 3.10 g body weight), which are expected to be asymptomatic upon NNV infection, at three stocking densities (2, 15, and 30 kg/m3) for 27 days and subsequently challenged them with NNV. We firstly characterized the stressed conditions of the specimens before and after infection and recorded the mortalities, demonstrating that stressed specimens reared at 30 kg/m3 suffered mortalities. However, the viral loads in different tissues were similar in all experimental groups, allowing horizontal and vertical transmission of the virus from asymptomatic specimens. All of these data suggest that shi drum tolerates wide ranges of culture densities, although high densities might be a setback for controlling NNV outbreaks in this species. In an attempt to understand the molecular pathways orchestrating this susceptibility change in stressed conditions, we performed a transcriptomic analysis of four tissues under mock- and NNV-infected conditions. In addition to the modification of the exceptive pathways such as cell adhesion, leukocyte migration, cytokine interaction, cell proliferation and survival, and autophagy, we also observed a heavy alteration of the neuroactive ligand-receptor pathway in three of the four tissues analyzed. Our data also point to some of the receptors of this pathway as potential candidates for future pharmacological treatment to avoid the exacerbated immune response that could trigger fish mortalities upon NNV infection.

Isotretinoin‐associated intracranial hypertension: A concise report

AbstractWe present a case of a 24‐year‐old preobese female undergoing isotretinoin treatment for acne vulgaris, who experienced drug‐induced intracranial hypertension (DIIH). Recognizing and addressing this potentially serious adverse effect is essential to prevent severe outcomes, particularly irreversible vision impairment. When suspected, immediate discontinuation of isotretinoin, neuroradiological imaging and urgent ophthalmologic evaluation to rule out papilloedema is imperative. Formulation of alternative treatment strategies, caution while prescribing DIIH‐causing drugs in future patient treatments and proactive reporting of adverse events are integral aspects of its comprehensive management.

Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1.

The naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates. Drug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay's Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism. WG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: <0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates. Our data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.

Genotypes and phenotypes of motor neuron disease: an update of the genetic landscape in Scotland

Abstract Background Using the Clinical Audit Research and Evaluation of Motor Neuron Disease (CARE-MND) database and the Scottish Regenerative Neurology Tissue Bank, we aimed to outline the genetic epidemiology and phenotypes of an incident cohort of people with MND (pwMND) to gain a realistic impression of the genetic landscape and genotype–phenotype associations. Methods Phenotypic markers were identified from the CARE-MND platform. Sequence analysis of 48 genes was undertaken. Variants were classified using a structured evidence-based approach. Samples were also tested for C9orf72 hexanucleotide expansions using repeat-prime PCR methodology. Results 339 pwMND donated a DNA sample: 44 (13.0%) fulfilled criteria for having a pathogenic variant/repeat expansion, 53.5% of those with a family history of MND and 9.3% of those without. The majority (30 (8.8%)) had a pathogenic C9orf72 repeat expansion, including two with intermediate expansions. Having a C9orf72 expansion was associated with a significantly lower Edinburgh Cognitive and Behavioural ALS Screen ALS-Specific score (p = 0.0005). The known pathogenic SOD1 variant p.(Ile114Thr), frequently observed in the Scottish population, was detected in 9 (2.7%) of total cases but in 17.9% of familial cases. Rare variants were detected in FUS and NEK1. One individual carried both a C9orf72 expansion and SOD1 variant. Conclusions Our results provide an accurate summary of MND demographics and genetic epidemiology. We recommend early genetic testing of people with cognitive impairment to ensure that C9orf72 carriers are given the best opportunity for informed treatment planning. Scotland is enriched for the SOD1 p.(Ile114Thr) variant and this has significant implications with regards to future genetically-targeted treatments.

Role of FFAR3 in ketone body regulated glucagon-like peptide 1 secretion

BackgroundRoux-en-Y gastric bypass (RYGB) is an effective treatment for obesity, resulting in long-term weight loss and rapid remission of type 2 diabetes mellitus. Improved glucagon-like peptide 1 (GLP-1) levels is one factor that contributes to the positive effects. Prior to RYGB, GLP-1 response is blunted which can be attributed to intestinal ketogenesis. Intestinal produced ketone bodies inhibit GLP-1 secretion in enteroendocrine cells via an unidentified G-protein coupled receptors (GPCRs). A possible class of GPCRs through which ketone bodies may reach are the free fatty acid receptors (FFARs) located at the basolateral membrane of enteroendocrine cells. AimTo evaluate FFAR3 expression in enteroendocrine cells of the small intestine under different circumstances, such as diet and bariatric surgery, as well as explore the link between ketone bodies and GLP-1 secretion. Materials and methodsFFAR3 and enteroendocrine cell expression was analyzed using Western blot and immunohistochemistry in biopsies from healthy volunteers, obese patients undergoing RYGB and mice. GLUTag cells were used to study GLP-1 secretion and FFAR3 signaling pathways. ResultsThe expression of FFAR3 is markedly influenced by diet, especially high fat diet, which increased FFAR3 protein expression. Lack of substrate such as free fatty acids in the alimentary limb after RYGB, downregulate FFAR3 expression. The number of enteroendocrine cells was affected by diet in the normal weight individuals but not in the subjects with obesity. In GLUTag cells, we show that the ketone bodies exert its blocking effect on GLP-1 secretion via the FFAR3, and the Gαi/o signaling pathway. ConclusionOur findings that ketone bodies via FFAR3 inhibits GLP-1 secretion bring important insight into the pathophysiology of T2D. This highlights the role of FFAR3 as a possible target for future anti-diabetic drugs and treatments.

Upregulation of caveolae-associated structural proteins in the hair follicle bulge of lichen planopilaris and frontal fibrosing alopecia.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary cicatricial alopecia that cause a major impact on quality of life due to irreversible hair loss and symptoms as itching, burning and pain. They are characterized by permanent loss of hair follicle stem cells (HFSCs) by pathomechanisms still poorly understood, resulting in poor efficacy of currently available treatments. Caveolae are flask-shaped lipid rafts invaginated within the plasma membrane of multiple cell types. Although their role in the HF physiology and pathophysiology is relatively unknown, we have previously demonstrated that the primary structural component of caveolae (caveolin-1 or Cav1) is upregulated in FFA. Thus, we propose to investigate the expression and localization of caveolae-associated structural proteins (Cav1, Cav2, and Cavin-1) and HFSCs (identified by K15) in both LPP and FFA. We analyzed 4 patients with LPP biopsied in affected and non-affected (NA) scalp, 4 patients with FFA biopsied in affected scalp and 4 healthy controls. Affected scalp of LPP and FFA demonstrated increased levels of Cav1 and Cavin-1 compared with HC and LPP-NA. Moreover, Cav1, Cav2 and Cavin1 all exhibit high colocalization with K15 and their expression appears to be negatively correlated, supporting the hypothesis that these proteins are important players in LPP/FFA and may serve as therapeutic targets in future treatments.

Treatment experience for different risk groups of Kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging. The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE. Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data. In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge. Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Resting State Functional Networks in Gliomas: Validation With Direct Electric Stimulation of a New Tool for Planning Brain Resections.

Precise mapping of functional networks in patients with brain tumor is essential for tailoring personalized treatment strategies. Resting-state functional MRI (rs-fMRI) offers an alternative to task-based fMRI, capable of capturing multiple networks within a single acquisition, without necessitating task engagement. This study demonstrates a strong concordance between preoperative rs-fMRI maps and the gold standard intraoperative direct electric stimulation (DES) mapping during awake surgery. We conducted an analysis involving 28 patients with glioma who underwent awake surgery with DES mapping. A total of 100 DES recordings were collected to map sensorimotor (SMN), language (LANG), visual (VIS), and speech articulation cognitive domains. Preoperative rs-fMRI maps were generated using an updated version of the ReStNeuMap software, specifically designed for rs-fMRI data preprocessing and automatic detection of 7 resting-state networks (SMN, LANG, VIS, speech articulation, default mode, frontoparietal, and visuospatial). To evaluate the agreement between these networks and those mapped with invasive cortical mapping, we computed patient-specific distances between them and intraoperative DES recordings. Automatically detected preoperative functional networks exhibited excellent agreement with intraoperative DES recordings. When we spatially compared DES points with their corresponding networks, we found that SMN, VIS, and speech articulatory DES points fell within the corresponding network (median distance = 0 mm), whereas for LANG a median distance of 1.6 mm was reported. Our findings show the remarkable consistency between key functional networks mapped noninvasively using presurgical rs-fMRI and invasive cortical mapping. This evidence highlights the utility of rs-fMRI for personalized presurgical planning, particularly in scenarios where awake surgery with DES is not feasible to protect eloquent areas during tumor resection. We have made the updated tool for automated functional network estimation publicly available, facilitating broader utilization of rs-fMRI mapping in various clinical contexts, including presurgical planning, functional reorganization over follow-up periods, and informing future treatments such as radiotherapy.

Prevalence and Characteristics of Plasmodium vivax Gametocytes in Duffy-Positive and Duffy-Negative Populations across Ethiopia.

Plasmodium parasites replicate asexually in human hosts. The proportion of infections that carries gametocytes is a proxy for human-to-mosquito transmissibility. It is unclear which proportion of Plasmodium vivax infections in Duffy-negative populations carries gametocytes. We determined the prevalence and characteristics of P. vivax gametocytes in Duffy-positive and -negative populations across broad regions of Ethiopia. Finger-prick blood samples were collected for microscopic and molecular screening of Plasmodium parasites and Duffy status of individuals. Molecular screening of Plasmodium species and Duffy blood group genotyping was done using SYBR green and the Taqman quantitative polymerase chain reaction method. Of the 447 febrile patients who were shown to be P. vivax smear positive, 414 (92.6%) were confirmed by molecular screening as P. vivax and 16 (3.9%) of them were from Duffy-negative individuals. Of these, 5 of 16 (31.3%) Duffy-negative P. vivax-infected samples were detected with gametocytes. Of the 398 Duffy-positive P. vivax-infected samples, 150 (37.7%) were detected with gametocytes, slightly greater than that in Duffy-negative samples. This study highlights the presence of P. vivax gametocytes in Duffy-negative infections, suggestive of human-to-mosquito transmissibility. Although P. vivax infections in Duffy-negative individuals were commonly associated with low parasitemia, some of these infections were shown to have relatively high parasitemia and may represent a prominent erythrocyte invasion capability of P. vivax, and hidden reservoirs that can contribute to transmission. A better understanding of P. vivax transmission biology and gametocyte function particularly in Duffy-negative populations would aid future treatment and management of P. vivax malaria in Africa.