bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tezepelumab for refractory eosinophilic granulomatosis with polyangiitis-related asthma
Authors: Vincent-Galtié Nina , Marquant Quentin , Catherinot Emilie , Ackermann Felix , Magnan Antoine , Tcherakian Colas , Groh Matthieu 
Published: July 2024

AbstractConventional immunosuppressants are ineffective for the management of EGPA-related asthma. Tezepelumab is a human monoclonal antibody that inhibits thymic stromal lymphopoietin (TLSP) that has proven efficacy in several phase 3 studies for the treatment of asthma. We treated with off-label tezepelumab the first two patients with severe refractory EPGA-related asthma. These preliminary findings suggest that targeting upstream signaling of the T2 inflammatory pathway can improve symptoms, reduce BVAS and increase Asthma Control Test scores, even in patients with refractory asthma who have failed several previous lines of treatment. Nevertheless, by analogy with dupilumab-induced IL-4/13 blockade, the persistence of sputum eosinophilia (reported in both patients) raises questions as to whether TSLP inhibition could lead to a rebound of eosinophilia and potentially to eosinophil-related symptoms in patients with EGPA.
Targeting CSF1R in myeloid-derived suppressor cells: insights into its immunomodulatory functions in colorectal cancer and therapeutic implications
Authors: Tong Xin , Qiao Shifeng , Dong Zhe , Zhao Xiaohui , Du Xiaxia , Niu Wei 
Published: July 2024

Abstract
Objective
This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination.

Methods
Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses.

Results
CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors.

Conclusion
CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.
Ultrasound-responsive Bi2MoO6-MXene heterojunction as ferroptosis inducers for stimulating immunogenic cell death against ovarian cancer
Authors: Cheng Shuangshuang , Zhou Ting , Luo Yue , Zhang Jun , Dong Kejun , Zhang Qi , Shu Wan , Zhang Tangansu , Zhang Qian , Shi Rui , Yao Yuwei , Wang Hongbo 
Published: July 2024

Abstract
Background
Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis.

Results
In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi2MoO6-MXene) to induce ferroptosis. A Schottky heterojunction between Bi2MoO6 (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron–hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity.

Conclusion
We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway.

Graphical Abstract
Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration
Authors: Lei Haoqi , Sun Jiwei , Dai Zhiyin , Wo Keqi , Zhang Junyuan , Wang Yifan , Zhao Baoying , Fan Wenjie , Wang Jinyu , Shi Yunsong , Yang Cheng , Su Bin , Luo Zhiqiang , Wu Junjie , Chen Lili , Chu Yingying 
Published: July 2024

AbstractRecapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.
Graphical Abstract
Assessing knowledge of hypertension and diabetes mellitus among informal healthcare providers in urban slums in southeastern Nigeria
Authors: Mbachu Chinyere Ojiugo , Arize Ifeyinwa , Obi Chinelo , Ebenso Bassey , Elsey Helen , Onwujekwe Obinna 
Published: July 2024

AbstractInformal healthcare providers (IHPs) often serve as the first point of contact for healthcare services for non-communicable diseases in urban slums and their ability to identify risk factors and symptoms of the diseases is crucial for early detection and management. This paper assesses level of knowledge of hypertension and diabetes mellitus (DM) among IHPs. A cross-sectional survey was conducted in eight slums in Enugu and Onitsha cities in south-eastern Nigeria. Data was collected from 238 IHPs including patent medicine vendors, traditional birth attendants, traditional bonesetters, and herbalists. Knowledge scores were computed for each respondent. Adequate knowledge was set at ≥ 50% score and inadequate knowledge at < 50%. Binary logistic regression analysis was used to identify factors/independent variables associated with adequate knowledge among IHPs. Independent variables in the regression model were seven items that describe the profile of IHPs and can influence their access to information on non-communicable diseases. Knowledge of risk factors and symptoms of hypertension and DM among IHPs was low since only 21 (8.82%) and 19 (7.98%) of them had adequate knowledge of hypertension and DM, respectively. In regression analysis, IHPs who had received formal training in the past demonstrated significantly higher levels of knowledge, with odds of adequate knowledge in hypertension being 14.62 times greater for trained providers, and the odds of adequate knowledge of both non-communicable diseases being 21.34 times greater for trained providers. Training of IHPs is needed to address the critical knowledge deficit of risk factors and symptoms of hypertension and DM. This would contribute to better health outcomes and reduced disease burden in urban slums.
Designing and expression of novel recombinant fusion protein for efficient antigen screening of SARS-CoV-2
Authors: Vidyasagar G. Vinaya Chandu , Reddy P. V. Janardhan , Ghouse M. Md. , Venkateswarulu T. C. , Kishor P. B. Kavi , Suravajhala Prashanth , Polavarapu Rathnagiri 
Published: July 2024

AbstractCorona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), claimed millions globally. After the report of the first incidence of the virus, variants emerged with each posing a unique threat than its predecessors. Though many advanced diagnostic assays like real-time PCR are available for screening of SARS-CoV-2, their applications are being hindered because of accessibility and cost. With the advent of rapid assays for antigenic screening of SARS-CoV-2 made diagnostics far easy as the assays are rapid, cost-effective and can be used at point-of-care settings. In the present study, a fusion construct was made utilising highly immunogenic B cell epitopes from the three important structural proteins of SARS-CoV-2. The protein was expressed; purified capture mAbs generated and rapid antigen assay was developed. Eight hundred and forty nasopharyngeal swab samples were screened for the evaluation of the developed assay which showed 37.14% positivity, 96.51% and 100% sensitivity and specificity respectively. The assay developed was supposed to identify SARS-CoV-2 wild-type as well as variants of concern and variants of importance in real-time conditions.
The influence of PER3 VNTR genotypes on the age of onset in a group of bipolar I disorder patients: an exploratory study
Authors: Barlattani Tommaso , Soltmann Bettina , D’Amelio Chiara , Socci Valentina , Pacitti Francesca , Pompili Maurizio , Ritter Philipp 
Published: July 2024

Abstract
Background
PER3 is a circadian gene that contains a variable number of tandem repeats (VNTR) which codifies for three genotypes: 4/4; 4/5; and 5/5 and is involved in non-visual response to light, a critical process associated with bipolar disorder onset. Benedetti et al. (Neurosci Lett 445(2):184–7) related this VNTR with bipolar disorder age of onset and linked genotype 5/5 with an earlier onset. In this study, we aimed to investigate these associations of PER3 VNTR genotypes with age of onset in a homogenous sample of German patients with bipolar I disorder through Kaplan-Meier curves.

Methods
45 patients were enrolled and divided into three groups according to PER3 VNTR genotypes. Recognizing common biological features, we built a combined group of -5 allele carriers (4/5 + 5/5). As a primary outcome, Kaplan-Meier analysis was conducted to delineate the three genotypes’ influence on age of onset. The secondary Kaplan-Meier analysis aimed to evaluate the relation between the 4/4 homozygotes group and the combined group (4/5 + 5/5) with age of onset. Finally, we proceeded to compare groups through a Log Rank Test and performed an analysis of covariance (ANCOVA).

Results
The Kaplan-Meier analysis with three separate genotypes didn’t replicate the findings of Benedetti’s study. The analysis comparing genotype 4/4 with the combined group showed the influence of PER3 VNTR variants on the age of onset and relates genotype 4/4 to an earlier onset. ANCOVA between the combined and the 4/4 genotype groups, correlated genotype 4/4 with an increased number of depressive episodes.

Conclusion
This study showed no significant effect of PER3 VNTR genotypes on the age of onset and in linking genotype 5/5 with an earlier onset age. Contrasting results may arise from intrinsic differences between the two studies but also shed light on hypothetically different levels of functioning of PER3 VNTR genotypes in the context of bipolar pathology. Further studies will require bigger and more homogeneous clinical samples.
Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential
Authors: Ho Ming Yao , Liu Songhan , Xing Bengang 
Published: July 2024

AbstractBacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals’ development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided.
Graphical Abstract
Employing technology-enhanced feedback and scaffolding to support the development of deep science understanding using computer simulations
Authors: Kaldaras Leonora , Wang Karen D. , Nardo Jocelyn E. , Price Argenta , Perkins Katherine , Wieman Carl , Salehi Shima 
Published: July 2024

AbstractConstructivist learning theories consider deep understanding of the content to be the result of engagement in relevant learning activities with appropriate scaffolding that provides the learner with timely and substantive feedback. However, any group of students has a variety of levels of knowledge and cognitive development, which makes providing appropriate individual-level scaffolding and feedback challenging in the classroom. Computer simulations can help meet this challenge by providing technology-enhanced embedded scaffolding and feedback via specific simulation design. The use of computer simulations does not, however, guarantee development of deep science understanding. Careful research-driven design of the simulation and the accompanying teaching structure both play critical roles in achieving the desired learning outcomes. In this paper, we discuss the capabilities of computer simulations and the issues that can impact the learning outcomes when combining technology-enhanced scaffolding and feedback with external teaching structures. We conclude with suggestions of promising research avenues on simulation design and their use in the classroom to help students achieve deep science understanding.
Simultaneous cannabis and psychedelic use among festival and concert attendees in Colorado: characterizing enhancement and adverse reactions using mixed methods
Authors: Piercey Cianna J. , Hetelekides Eleftherios , Karoly Hollis C. 
Published: July 2024

Abstract
Background
Most studies examining the simultaneous use of cannabis with other drugs have focused on cannabis and alcohol, with fewer studies examining simultaneous use of cannabis with other drugs. The United States is currently experiencing an upward trend in psychedelic use and there is an increasing need to characterize cannabis and psychedelic drug interactions to best inform public health recommendations.

Materials and Methods
A mixed methods field study design was used to survey participants (N = 128) on their lifetime co-use of cannabis with other drugs. Participants who reported lifetime co-use of cannabis and psychedelics (N = 63) were then asked open-ended questions about their most recent simultaneous co-use experience (i.e., how cannabis enhanced their psychedelic experience and whether they experienced any adverse reactions). We conducted a thematic analysis of responses describing how cannabis enhanced the psychedelic experience (N = 54). However, due to low response rate for participants reporting an adverse reaction (N = 7, 11.1%), responses to this question were not analyzed thematically and are instead presented individually.

Results
Themes included tension reduction and balancing of drug effects (N = 27, 50%), enhancement to psychological processes (N = 11, 20.4%), intensified psychedelic drug effects (N = 12, 22.2%), enhanced psychedelic come-down experience (N = 8, 14.8%), and overall ambiguous enhancement (N = 7, 13%). Among participants reporting an adverse reaction, individual responses included increased anxiety and intensity of the experience, decreased sociability, increased negative affect, sleepiness, disassociation, and confusion.

Conclusion
Additional research is warranted to better characterize cannabis and psychedelic drug interactions to best inform public health recommendations.
Misconceptions about trigger finger: a scoping review. Definition, pathophysiology, site of lesion, etiology. Trigger finger solving a maze
Authors: Shohda Eslam , Sheta Reda Ali 
Published: July 2024

AbstractTrigger finger (TF) is a disorder characterized by snapping or locking a finger. It has a prevalence of greater than 3% in the general population; however, this estimate could be increased to 5% up to 20% in diabetic patients. Some unreal ambiguity about definition, pathophysiology, site of lesion, and etiology are found among researchers and clinicians, leading to a lack of understanding of all aspects of the disease and improper management as many clinicians proceed to anti-inflammatory medications or steroids injection without in-depth patient evaluation. Original articles cited up to 2022, found through a Google search using the specified keywords, have been used in this review. Close-access articles were accessed through our researcher account with the Egyptian Knowledge Bank. In this review, we will focus on pathophysiology to present all possible findings and etiology to represent all risk factors and associated diseases to assess and confirm a diagnosis and the exact location of pathology hence better treatment modalities and reducing the recurrence of the pathology.
Risk assessment models for development of carpal tunnel syndrome: clinical, anthropometric, and neuromuscular ultrasound predictors
Authors: El-Sherif Sherine Mahmoud , Hassan Nermin Muhammad , Eltantawi Gihan A. Younis , Abdelfattah Yousra Hisham 
Published: July 2024

Abstract
Background
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy with multifactorial etiologies. We intended in this case–control study to identify, out of a comprehensive set of risk factors, the relatively important ones and develop a quantitative risk assessment model for this disorder. It was also legitimate to define the hazard of those factors in a dose-related manner and the acceptable safe limit especially for work-related stresses.

Results
Age and female predominance were comparable between the 60 patients (89 hands with electrophysiologically confirmed CTS) and 50 controls (100 hands). Occupation of the studied sample varied between housewives only, employed housewives, and manual workers with a distribution that differed significantly between patients and controls. Significantly higher body mass index (BMI) and mean wrist depth were found in patients than controls. Wrist ratio (clinically or sonographically) was significantly squarer in patients than controls. Overall workload and number of hours spent daily performing work with repeated hand movements or awkward hand position were significantly higher among patients than controls.
ROC curves were constructed for wrist measurements and occupational stresses. Cut-off points of wrist ratio and internal carpal tunnel ratio (by ultrasound) to discriminate subjects with CTS were > 0.68 and ≤ 1.854, respectively. The best cut-off value for number of hours spent daily performing work with repeated hand movements was 3 h/ day. As for working with awkward hand position or cold exposure, cut-off value was 0.6 h/day for both.
Two logistic regression models were conducted to investigate nonoccupational and occupational predictors of CTS. The independent predictors concluded from the first model were BMI, positive family history of CTS, wrist ratio, and decrease grip strength. As for the occupational model, predictors were tasks requiring awkward hand position and cold exposure.

Conclusion
Occupational risk assessment by clinical, anthropometric, and ultrasonographic measurement should be used in professions requiring repetitive or awkward hand movements, so that in overweight persons with square wrists appropriate workplace setup measures or assistive technology at work or home could be taken to prevent or decrease the impact of work hazards or help choose individuals with low risk for appropriate jobs.