bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aptamer-associated colorimetric reverse transcription loop-mediated isothermal amplification assay for detection of dengue virus
Authors: Arruda Vitória de Oliveira , Filho Luiz Ricardo Goulart , Neves Adriana Freitas 
Published: July 2024

ABSTRACT

Current diagnostic methods for dengue, such as serological tests, have limitations in terms of cross-reactivity with other viruses. To address this issue, we explored the potential of combining the loop-mediated isothermal amplification (LAMP) technique with the affinity of aptamers to develop point-of-care testing. In this study, we utilized 60 serum samples. An aptamer capable of binding to the dengue virus was employed as a platform for capturing genetic material, and its performance was compared to a commercial kit. Dengue virus was detected through RT-PCR and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP), allowing visual observation of the results without the need for equipment. In the context of the aptamer LAMP assay, our analysis revealed the detection of the dengue virus in 38 out of 60 samples, with 95% sensitivity and 100% specificity compared to RT-PCR and/or APTA-RT-PCR. Importantly, we observed no cross-reaction when assessing samples positive for the zika virus, underscoring the assay’s selectivity. This innovative aptameric capture of the viral RNA in combination with the RT-LAMP (APTA-RT-LAMP) method has the potential to offer valuable molecular insights into neglected infectious diseases in a simpler and faster manner.

IMPORTANCE
Dengue is a neglected tropical disease of significant epidemiological importance in tropical and subtropical countries. Current diagnostics for this infection present challenges, such as cross-reactivity in serological tests. Finding ways to enhance the diagnosis of this disease is crucial, given the absence of specific treatments. An accurate, simple, and effective diagnosis contributes to the improved management of infected individuals. In this context, our work combines molecular biology techniques, such as isothermal loop amplification, with aptamers to detect the dengue virus in biological samples. Our method produces colorimetric results based on a color change, with outcomes available in less than 2 hours. Moreover, it requires simpler equipment compared to molecular PCR tests.
Parkinson’s disease psychosis associated with accelerated multidomain cognitive decline
Authors: Pisani Sara , Gosse Luca , Aarsland Dag , Ray Chaudhuri K , Ballard Clive , Ffytche Dominic , Velayudhan Latha , Bhattacharyya Sagnik 
Published: July 2024

BackgroundCognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson’s disease (PD) psychosis. The trajectory of cognitive decline in PD psychosis remains however unclear.ObjectiveWe examined this using data from the Parkinson’s Progression Markers Initiative study.MethodsWe analysed data from patients with drug-naïve PD (n=676) and healthy controls (HC, n=187) over 5 years, and examined all cognitive measures assessed at each time point. We classified patients with PD into those who developed psychosis over the course of the study (PDP) and those without psychosis throughout (PDnP) using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale part I hallucinations/psychosis item. We used linear mixed-effect models with restricted maximum likelihood. Age, sex, ethnicity, education and neuropsychiatric and PD-specific symptoms were entered as covariates of interest.FindingsThere were no baseline cognitive differences between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments.Patients with PDP exhibited greater cognitive decline over 5 years compared with PDnP across most domains even after controlling for sociodemographics, depression, sleepiness, rapid eye movement sleep behaviour disorder and motor symptom severity (immediate recall, b=−0.288, p=0.003; delayed recall, b=−0.146, p=0.003; global cognition, Montreal Cognitive Assessment, b=−0.206, p<0.001; visuospatial, b=−0.178, p=0.012; semantic fluency, b=−0.704, p=0.002; processing speed, b=−0.337, p=0.029).ConclusionsPatients with PD psychosis exhibited decline in semantic aspects of language, processing speed, global cognition, visuospatial abilities and memory, regardless of sociodemographic characteristics, neuropsychiatric and motor symptoms. These cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation.Trial registration numberNCT01141023.
Perceptions of advice for acute low back pain: a content analysis of qualitative data collected in a randomised experiment
Authors: Augustine Lidiya , Zadro Joshua , Maher Christopher , Traeger Adrian C , Jones Caitlin , West Courtney A , Yang Jingjing , O'Keeffe Mary , Jenkins Hazel , McAuley James H , Ferreira Giovanni E 
Published: July 2024

ObjectivesTo explore how people perceive three different forms of advice for acute low back pain (LBP).DesignContent analysis of qualitative data collected in a three-arm randomised experiment.Participants2200 participants with acute LBP (ie, pain duration for ≤6 weeks) were randomly assigned to receive three types of advice: guideline advice and guideline advice with the addition of either brief pain science or ergonomics messages.Primary and secondary outcomesAfter receiving the advice, participants answered two questions: ‘If your health professional gave you this advice, how would it make you feel?’ and ‘If your health professional gave you this advice, what treatments (if any) do you think you would need?’ Two researchers coded responses using deductive content analysis.ResultsWe analysed 4400 free-text responses from 2200 participants. There were little to no differences in participants’ feelings, thoughts and expectations after receiving three types of advice for acute LBP. Participants most commonly expressed feeling positive about the advice (38%–35%), reassured (23%–22%) and empowered (10%–8%). Some expressed being unhappy or being frustrated with the advice (4%–3%). Participants most commonly thought they needed no treatment apart from staying active, followed by exercise and medication.ConclusionsGuideline advice with or without the addition of brief pain science or ergonomics messages generated positive feelings, reassurance or a sense of empowerment in many people with acute LBP, with no difference between types of advice.Trial registration numberACTRN12623000364673.
Feasibility and efficacy of virtual reality rehabilitation compared with conventional physiotherapy for upper extremity impairment due to ischaemic stroke: protocol for a randomised controlled trial
Authors: Paul Rinta , Elango Sundari , Chakravarthy Srinivasa , Sinha Aniruddha , P R Srijithesh , Raju Bapi , C Kesavadas , Sarma P Sankara , Hafsath Shabeera , Francis Amal Jude Ashwin , Darshini Divya , Sylaja Padmavathy Narayanapillai 
Published: July 2024

IntroductionApproximately half of all stroke survivors have persistent upper extremity functional impairment, leading to reduced self-care, independence and quality of life. High-intensity, task-oriented virtual reality rehabilitation improves motor recovery. However, its clinical efficacy over standard rehabilitation remains uncertain. This study aims to evaluate the feasibility and efficacy of a virtual reality-based comprehensive rehabilitation gaming system (VR-cRGS) in stroke survivors with upper extremity impairment and to characterise the structural and functional plasticity of the affected regions in the brain due to the proposed rehabilitation.Methods and analysisThis study is a multicentric, open-label, randomised controlled trial with an intention-to-treat analysis. A total of 162 patients will be enrolled in two academic institutes in India that specialise in stroke care. Patients with a first-ever ischaemic stroke (18–70 years and 1–6 months of stroke onset) with upper extremity impairment with 1 and 1+ grades of spasticity as per the modified Ashworth Scale and 3, 4 or 5 stages on Brunnstrom recovery staging will be enrolled. They will be randomised (1:1) into two treatment groups to receive 12 weeks of training either on VR-cRGS or on conventional physiotherapy. The primary feasibility outcome is compliance with the treatment. The primary efficacy outcome is the functional recovery of the upper extremity assessed by the Fugl-Meyer Assessment-Upper Extremity and Wolf Motor Function Test. The secondary outcomes are the Barthel Index and the 36-item Short-Form Health Survey. Multimodal brain imaging will be done in all enrolled patients at baseline and post-treatment to evaluate the structural and functional connectivity changes. The outcome measures will be analysed using paired t-tests or non-parametric tests.Ethics and disseminationThe study has been approved by the Institutional Ethics Review Board of the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India (SCT/IEC/1415/AUGUST-2019) and the National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India (NIMHANS/IEC (BS and NS DIV.)/32nd Meeting/21). All participants will sign an informed consent form prior to participation. The study results will be disseminated through scholarly publication.Trial registration numberCTRI/2021/11/038339.
Primary caregiver employment status is associated with traumatic brain injury in children in the USA
Authors: Tian Emma , O'Guinn MaKayla L. , Chen Stephanie Y. , Ourshalimian Shadassa , Chaudhari Pradip P. , Spurrier Ryan G. 
Published: July 2024

BackgroundTraumatic brain injury (TBI) is a common injury in children. Previous literature has demonstrated that TBI may be associated with supervision level. We hypothesised that primary caregiver employment would be associated with child TBI.MethodsA retrospective cross-sectional study was performed for children aged 0–17 using the National Survey of Children’s Health (NSCH) 2018–2019. The NSCH contains survey data on children’s health completed by adult caregivers from randomly selected households across the USA. We compared current TBI prevalence between children from households of different employment statuses. Current TBI was defined by survey responses indicating a healthcare provider diagnosed TBI or concussion for the child and the condition was present at the time of survey completion. Household employment status was categorised as two caregivers employed, two caregivers unemployed, one of two caregivers unemployed, single caregiver employed and single caregiver unemployed. Multivariable logistic regression was performed, controlling for sociodemographic factors.ResultsOf 56 865 children, median age was 10 years (IQR: 5–14), and 0.6% (n=332) had a current TBI. Children with TBI were older than children without TBI (median 12 years vs 10 years, p<0.001). On multivariable regression, children with at least one caregiver unemployed had increased odds of current TBI compared with children with both caregivers employed.ConclusionsChildren with at least one caregiver unemployed had increased TBI odds compared with children with both caregivers employed. These findings highlight a population of families that may benefit from injury prevention education and intervention.
rhIL-7-hyFc, a long-acting interleukin-7, improves efficacy of CAR-T cell therapy in solid tumors
Authors: Li Dan , Liang Tianyuzhou , Hutchins Laura E , Wolfarth Alexandra A , Ferrando-Martinez Sara , Lee Byung Ha , Ho Mitchell 
Published: July 2024

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable remission in patients with B-cell malignancies. However, its efficacy in treating solid tumors remains limited. Here, we investigated a combination therapy approach using an engineered long-acting interleukin (IL)-7 (rhIL-7-hyFc or NT-I7) and CAR-T cells targeting three antigens, glypican-2 (GPC2), glypican-3 (GPC3), and mesothelin (MSLN), against multiple solid tumor types including liver cancer, neuroblastoma, ovarian cancer, and pancreatic cancer in mice.MethodsCAR-T cells targeting GPC2, GPC3, and MSLN were used in combination with NT-I7 to assess the anticancer activity. Xenograft tumor models, including the liver cancer orthotopic model, were established using NOD scid gamma mice engrafted with cell lines derived from hepatocellular carcinoma, neuroblastoma, ovarian cancer, and pancreatic cancer. The mice were monitored by bioluminescence in vivo tumor imaging and tumor volume measurement using a caliper. Immunophenotyping of CAR-T cells on NT-I7 stimulation was evaluated for memory markers, exhaust markers, and T-cell signaling molecules by flow cytometry and western blotting.ResultsCompared with the IL-2 combination, preclinical evaluation of NT-I7 exhibited regression of solid tumors via enhanced occupancy of CD4+CAR-T, improved T-cell expansion, reduced exhaustion markers (programmed cell death protein 1 or PD-1 and lymphocyte-activation gene 3 or LAG-3) expression, and increased generation of stem cell-like memory CAR-T cells. The STAT5 pathway was demonstrated to be downstream of NT-I7 signaling, mediated by increased expression of the IL-7 receptor expression in CAR-T cells. Furthermore, CAR-T cells improved efficacy against tumors with low antigen density when combined with NT-I7 in mice, presenting an avenue for patients with heterogeneous antigenic profiles.ConclusionThis study provides a rationale for NT-I7 plus CAR-T cell combination therapy for solid tumors in humans.
Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma
Authors: Yoshida Takashi , Nakamoto Takahiro , Atsumi Naho , Ohe Chisato , Sano Takeshi , Yasukochi Yoshiki , Tsuta Koji , Kinoshita Hidefumi 
Published: July 2024

BackgroundAnti-programmed death-1 (PD-1)/anti-PD-ligand-1 (PD-L1) pathway inhibition is a standard regimen for advanced urothelial carcinoma (UC); however, its limited efficacy has been reflected in reported medium response rates. This study explored the role of next-generation coinhibitory receptors (IRs; lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain 3 (TIM-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT)) and their ligands (LGs) in the response to PD-(L)1 blockade therapy and the oncological outcomes in patients with UC.MethodsWe investigated metastatic UC cases who underwent PD-(L)1 therapy (cohort 1: n=348, cohort 2: n=89, and cohort 4: n=29) or advanced UC cases involving surgery (cohort 3: n=293 and cohort 5: n=90). We assessed the mRNA expression profiles and corresponding clinical information regarding IRs and LGs using cohorts 1, 2, and 3. Additionally, we elucidated the spatial features of these targeted markers using multiplex immunohistochemistry (mIHC) on formalin-fixed paraffin-embedded samples from cohorts 4 and 5. Survival, differential expressed gene, and Gene Set Enrichment analyses were performed. For mIHC, quantitative analyses were also performed to correlate immune and tumor cell densities with patient survival.ResultsLAG-3expression was strongly associated with the responsiveness of PD-(L)1 blockade compared with the expression ofTIM-3andTIGIT. In tumors with highLAG-3levels, the increased expression offibrinogen-like protein 1(FGL1) had a significantly negative effect on the response to PD-(L)1 blockade and overall survival. Moreover, highFGL1levels were associated with elevated CD4+regulatory T-cell gene signatures and the upregulation ofCD39andneuropilin-1, with both indicating CD8+T-cell exhaustion. mIHC analyses revealed that patients with stromal CD8+LAG-3+cellshigh–tumor FGL1+cellshighexhibited a significant negative correlation with survival rates compared with those with stromal CD8+LAG-3+cellshigh–tumor FGL1+cellslow.ConclusionsLAG-3 expression and high FGL1 coexpression are important predictive factors of adverse oncological outcomes related to the presence of immunosuppressive contextures. These findings are hypothesis-generating, warranting further mechanistic and clinical studies aimed to evaluate LAG-3/FGL1 blockade in UC.
When is the right time to change therapy? An observational study of the time to response to immunosuppressive drugs in systemic lupus erythematosus
Authors: Tani Chiara , Maffi Michele , Cascarano Giancarlo , Signorini Viola , Zucchi Dina , Menchini Marina , Stagnaro Chiara , Carli Linda , Elefante Elena , Ferro Francesco , Cardelli Chiara , Manca Maria Laura , Mosca Marta 
Published: July 2024

ObjectivesTo analyse the response to immunosuppressants (IS) in extrarenal flares of SLE to determine the most appropriate timing during follow-up for a change in therapeutic strategy.MethodsObservational cohort study including a total of 81 patients with SLE with extrarenal flares requiring a change in IS over the period 2015–2022. Baseline clinical variables were described, and follow-up data at 1, 3, 6 and 12 months time-points were collected.ResultsAmong patients flaring that achieved lupus low disease activity state (LLDAS5) at 12 months of follow-up, we identified two subgroups (‘late responders’ and ‘early responders’), which showed no significant differences in demographic characteristics, baseline clinical data, cumulative dosage of glucocorticoids or type of IS. Cox model analysis revealed a significant association of a change in IS (p=0.019) and achieving LLDAS5. Contingency table analysis indicated a significant relationship (p=0.004) between IS change at 6 months and individuals achieving LLDAS5 and remission at 12 months.ConclusionsOur findings suggest that clinical improvement of extrarenal flares typically occurs within 6 months of initiating IS. This timeframe could represent an appropriate timing to evaluate the response in a treat-to-target approach in SLE.
Sex-based differences in hematological values after normalization to body mass or fat-free mass in adults matched for aerobic fitness
Authors: Kontro Hilkka , Caswell Allison M. , Tripp Thomas R. , Ajayi Oluwatimilehin O. , MacInnis Martin J. 
Published: July 2024

Blood properties influence aerobic exercise performance. While vascular volumes and hemoglobin mass (Hbmass) are elevated in trained individuals, evidence of sex differences in vascular volumes is equivocal due to inadequate matching of aerobic fitness between males and females. This cross-sectional study aimed to compare hematological values normalized to body mass (BM) and fat-free mass (FFM) between males ( n = 45) and females ( n = 34) matched for aerobic fitness (V̇O2max) normalized to FFM (mL∙kg FFM−1∙min− 1). Data included body composition measured by dual-energy X-ray absorptiometry (DXA), V̇O2max from an incremental test, and hematological values derived from a CO rebreathe test. Fat mass was unrelated to blood volume (BV; R2 = 0.02, P = 0.26) and Hbmass ( R2 = 0.03, P = 0.16), while FFM was the strongest predictor of both ( R2 = 0.75 and R2 = 0.83, respectively, P < 0.001). Females exhibited higher FFM-normalized BV (+4%, P < 0.05) and plasma volume (PV) (+14%, P < 0.001) and lower red blood cell volume (RBCV) (−8%, P < 0.001) and Hbmass (−8%, P < 0.001) compared to males. Positive correlations between aerobic fitness and relative Hbmass and BV were observed in both sexes when normalized to BM and FFM (0.48 < r < 0.71; P < 0.003). Stepwise multiple regression models, including FFM, V̇O2max, height, and [Hb], provided accurate predictions of Hbmass ( R2 = 0.91) and BV ( R2 = 0.85). Overall, sex differences persist in relative Hbmass, BV, PV, and RBCV after matching of aerobic fitness, though relative BV and PV were greater in females. These findings suggest sex-specific strategies in oxygen delivery and/or extraction, and they underscore the importance of carefully selecting normalization practices when assessing sex-based differences in hematological variables.
m6A-Mediated Induction of 7-Dehydrocholesterol Reductase Stimulates Cholesterol Synthesis and cAMP Signaling to Promote Bladder Cancer Metastasis
Authors: Zeng Youmiao , Luo Yongbo , Zhao Keyuan , Liu Sheng , Wu Kaiwen , Wu Yudong , Du Kaixuan , Pan Wenbang , Dai Yiheng , Liu Yuanhao , Ren Mengda , Tian Fengyan , Zhou Lijie , Gu Chaohui 
Published: July 2024

Abstract
Dysregulation of cholesterol homeostasis occurs in multiple types of tumors and promotes cancer progression. Investigating the specific processes that induce abnormal cholesterol metabolism could identify therapeutic targets to improve cancer treatment. In this investigation, we observed upregulation of 7-dehydrocholesterol reductase (DHCR7), a vital enzyme involved in the synthesis of cholesterol, within bladder cancer tissues in comparison to normal tissues, which was correlated with increased bladder cancer metastasis. Increased expression of DHCR7 in bladder cancer was attributed to decreased mRNA degradation mediated by YTHDF2. Loss or inhibition of DHCR7 reduced bladder cancer cell invasion in vitro and metastasis in vivo. Mechanistically, DHCR7 promoted bladder cancer metastasis by activating the cAMP/protein kinase A/FAK pathway. Specifically, DHCR7 increased cAMP levels by elevating cholesterol content in lipid rafts, thereby facilitating the transduction of signaling pathways mediated by cAMP receptors. DHCR7 additionally enhanced the cAMP signaling pathway by reducing the concentration of 7-dehydrocholesterol and promoting the transcription of the G protein–coupled receptor, namely gastric inhibitory polypeptide receptor. Overall, these findings demonstrate that DHCR7 plays an important role in bladder cancer invasion and metastasis by modulating cholesterol synthesis and cAMP signaling. Furthermore, inhibition of DHCR7 shows promise as a viable therapeutic strategy for suppressing bladder cancer invasion and metastasis.
Significance: Inhibiting DHCR7 induces cholesterol metabolism reprogramming and lipid raft remodeling to inactivate the cAMP/protein kinase A/FAK axis and suppress bladder cancer metastasis, indicating the therapeutic potential of targeting DHCR7.
The Difficulty in Defining the True High-Risk Smoldering Myeloma
Authors: Weinhold Niels , Rasche Leo 
Published: July 2024

SummaryEarly intervention trials have been initiated for the precursor disease smoldering myeloma (SMM). A recent study showed that genomic complexity varies widely among patients treated for high-risk SMM and is associated with response to triplet therapy, suggesting that established clinical risk scores often fail to discriminate between stable and aggressive disease.See related article by Kazandjian et al., p. 4482
Assessment of Waste Management Awareness and Practices among Par-ents: A Sequential Explanatory Study
Authors: Sambat Lanah Maria D. , Bulaun Cassandra M. , Soliman Rachel Ann D. , Muñoz Ezequel R. , Hu Anabel S. , Deang Mark Anthony C. , Dominado Noel L. 
Published: July 2024

This study explores parents’ awareness and practices on solid waste management. It shows the significance of solid waste segregation for parental involvement and how it influences parents' attitudes and behaviors in a barangay in Magalang, Pampanga. The parents benefit from this study by learning more about the practices and appropriate segregation within their community. In this study, which involved 100 parents, a mixed-method sequential explanatory technique was employed. The results indicate that parents are not aware of the relevant laws about solid waste management and the sources of information about it. In terms of practices, parents are productive at disposing of, reducing, and recycling solid waste, but they don't reuse and segregate the solid waste that much. Overall, the results highlight how crucial proper waste sorting, awareness-building, community involvement, resourcefulness, and sustainability are to improve waste management. Although there are challenges, such as a lack of awareness and inconsistent efforts, recycling and waste removal are mentioned as sources of satisfaction. Parents also emphasize the need for proper segregation, solid waste management regulations, and providing incentives to promote sustainable behaviors in the barangay.