bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brainstem anesthesia during awake craniotomy: illustrative case
Authors: Chen Yun , Sun Mei , Bai Hongmin , Yang Ruixin , He Huan 
Published: February 2024

BACKGROUND
Awake craniotomy (AC) is performed to remove the lesions near or in eloquent areas, during which the patients are alert and without any airway instrument. Apnea is a severe complication in AC. Here, the authors describe a case of sudden apnea induced by unexpected local anesthesia of the brainstem during AC.

OBSERVATIONS
A 42-year-old male underwent AC for a large, recurrent, bilateral frontal lobe mass and experienced transient apnea and loss of brainstem reflexes during the surgery. The patient recovered spontaneous breath rhythm just a few minutes after the removal of a lidocaine cotton pledget, which was found near the patient’s midbrain. Then the patient awoke and cooperated to finish the surgery.

LESSONS
The administration of a local anesthetic subdurally in AC is common but risky. The scouring action of cerebral spinal fluid can spread those agents and cause unexpected brainstem anesthesia. A lower concentration of the anesthetic and keeping away from the cistern can make it safer.
Dimethyl Fumarate Exerts a Neuroprotective Effect by Enhancing Mitophagy via the NRF2/BNIP3/PINK1 Axis in the MPP+ Iodide-Induced Parkinson’s Disease Mice Model
Authors: Pinjala Poojitha , Tryphena Kamatham Pushpa , Kulkarni Amrita , Goswami Prince Giri , Khatri Dharmendra Kumar 
Published: February 2024

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder linked to the loss of dopaminergic neurons in the substantia nigra. Mitophagy, mitochondrial selective autophagy, is critical in maintaining mitochondrial and subsequently neuronal homeostasis. Its impairment is strongly implicated in PD and is associated with accelerated neurodegeneration. Objective: To study the positive effect of dimethyl fumarate (DMF) on mitophagy via the NRF2/BNIP3/PINK1 axis activation in PD disease models. Methods: The neuroprotective effect of DMF was explored in in vitro and in vivo PD models. MTT assay was performed to determine the DMF dose followed by JC-1 assay to study its mitoprotective effect in MPP+ exposed SHSY5Y cells. For the in vivo study, C57BL/6 mice were divided into six groups: Normal Control (NC), Disease Control (DC), Sham (Saline i.c.v.), Low Dose (MPP+ iodide+DMF 15 mg/kg), Mid Dose (MPP+ iodide+DMF 30 mg/kg), and High Dose (MPP+ iodide+DMF 60 mg/kg). The neuroprotective effect of DMF was assessed by performing rotarod, open field test, and pole test, and biochemical parameter analysis using immunofluorescence, western blot, and RT-PCR. Results: DMF treatment significantly alleviated the loss of TH positive dopaminergic neurons and enhanced mitophagy by increasing PINK1, Parkin, BNIP3, and LC3 levels in the MPP+ iodide-induced PD mice model. DMF treatment groups showed good locomotor activity and rearing time when compared to the DC group. Conclusions: DMF confers neuroprotection by activating the BNIP3/PINK1/Parkin pathway, enhancing the autophagosome formation via LC3, and improving mitophagy in PD models, and could be a potential therapeutic option in PD.
Rancang Bangun Game Edukasi Pengenalan Huruf Hijaiyah Menggunakan Construct 2
Authors: Sholehah Fitri Amalia , Windiarti Ika Safitri , Qamaruzzaman Muhammad Haris 
Published: February 2024

Pengenalan dan pembiasaan Huruf Hijaiyah pada anak usia dini menjadi cara penting dalam kemampuan belajar Al-Qur’an. Permasalahan yang sering terjadi diantaranya anak sering tertukar melafalkan Huruf Hijaiyah terutama huruf yang sama bentuknya tetapi berbeda titiknya, sehingga akan membuat anak menjadi malas untuk mengaji, perkembangan teknologi juga berpengaruh kepada psikologi anak usia dini yang dapat menjadikan anak-anak jauh dari media pembalajaran berbentuk teks. Dari permasalahan tersebut, fokus penelitian ini adalah bagaimana membuat sebuah Game Edukasi Pengenalan Huruf Hijaiyah. Game ini merupakan game yang berbasis mobile yang dibuat menggunakan Construct 2, dengan tujuan mampu memberikan pembelajaran pengenalan Huruf Hijaiyah pada anak usia dini. model waterfall adalah model klasik yang bersifat sistematis, berurutan dalam membangun software.. Penelitian dilakukan di PAUD Islam HASANKA Palangka Raya yang menerapkan kurikulum Pendidikan Islam dan pengupayaan penerapan media teknologi. Hasil dari penelitian ini adalah game edukasi pengenalan Huruf Hijaiyah untuk anak usia dini dengan visialisasi audio dan gambar yang menarik.
Measuring the Impact of Incorporating Case Study Presentations Into Applied Biomedical Science Placement Workshops for Trainee Biomedical Scientists
Authors: Bashir Amreen , Dudley Kathryn , Rana Karan Singh , Wilkins Kayleigh , Pallett Ross 
Published: February 2024

Introduction: Successfully completing the Institute of Biomedical Science (IBMS) registration portfolio is essential to becoming a Health and Care Professions Council (HCPC) registered Biomedical Scientist. In the West Midlands, a unique collaboration between four universities (Aston, Wolverhampton, Coventry, and Keele) and local NHS Trusts supports student placements and portfolio development. The universities support Training Officers in delivering components of the registration portfolio through the delivery of eight combined placement workshops. These have been designed to align to the IBMS registration portfolio and help students meet the HCPC Standards of Proficiency. This study aimed to evaluate the effectiveness of a redesigned workshop where students generated and presented medical case studies to peers, academics, and training leads.Materials and Methods: The three phases of the case study intervention included a pre-intervention survey, academic-led sessions focussing on medical case presentations and delivery of the presentation followed by a post-intervention survey.Results: Analysing survey responses pre- and post-intervention, students demonstrated enhanced confidence in their understanding of clinical conditions (p&lt;0.0001), connecting lab findings to diseases, and in delivering a case presentation to their peers (p&lt;0.001). Students reported an increased confidence in structuring case presentations and their critical thinking ability (p&lt;0.0001). All students agreed engaging with the case study workshop improved their ability to communicate knowledge of scientific concepts orally. Thematic analysis revealed that the case presentation deepened students' understanding of multidisciplinary teams. 98% of respondents agreed patient communication should be integrated into Biomedical Sciences courses and 85% would like to see case study presentations embedded into the curriculum.Discussion: Combined placement workshops are an integral part of the Applied Biomedical Science placement journey. Case study presentations are clearly a valuable teaching and learning tool to nurture and develop key transferable skills and competencies in conjunction with Biomedical Science expertise. The collaborative approach in the West Midlands effectively prepares graduates with essential pathology knowledge, skills, and a completed IBMS registration portfolio. This study highlights a successful framework for a collaborative partnership with local NHS trusts that has allowed the completion of numerous pathology placements and could be adopted by other universities delivering accredited Biomedical Science courses.
Biomimetic dual sensing polymer nanocomposite for biomedical applications
Authors: Omar Abdalla M. , Hassan Mohamed H. , Daskalakis Evangelos , Smith Albert , Donoghue Jack , Mirihanage Wajira , Bartolo Paulo J. D. S. 
Published: February 2024

There is a growing need for sensing materials that can provide multiple sensing capabilities for wearable devices, implantable sensors, and diagnostics tools. As complex human physiology requires materials that can simultaneously detect and respond to slow and fast pressure fluctuations. Mimicking the slow adaptive (SA) and fast adaptive (FA) mechanoreceptors in skin can lead to the development of dual sensing electrospun polymer nanocomposites for biomedical applications. These dual sensing nanocomposites can provide simultaneous sensing of both slow and fast pressure fluctuations, making them ideal for applications such as monitoring vital signs, detecting a wider range of movements and pressures. Here we develop a novel dual sensing PVDF-HFP-based nanocomposite that combines the advantages of capacitive and piezoelectric properties through controling electrospinning environment and processing parameters, polymer solution composition, and addition of nucleating agents such as Carbon Black (CB) to enhance the crystalline development of β-phase, fibre thickness, and morphology. The developed PVDF-HFP/CB nanocomposite presents and response to both slow and fast pressure fluctuations with high capacitance (5.37 nF) and output voltage (1.51 V) allowing for accurate and reliable measurements.
Association between liver enzymes and type 2 diabetes: a real-world study
Authors: Bi Yaru , Yang Yang , Yuan Xiaojie , Wang Jiping , Wang Tuo , Liu Zhiyuan , Tian Suyan , Sun Chenglin 
Published: February 2024

AimThis study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship.MethodsThis cross-sectional study enrolled participants aged &gt;20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences.ResultsA total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (Pnon-linear &lt; 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, &lt;50 IU/L) and then plateaued when ALT and GGT levels were &gt;50 IU/L. Elevated AST within a certain range (range, &lt;35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (&gt;35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence.ConclusionLiver enzymes were non–linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.
Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps
Authors: Huang George X. , Mandanas Michael V. , Djeddi Sarah , Fernandez-Salinas Daniela , Gutierrez-Arcelus Maria , Barrett Nora A. 
Published: February 2024

IntroductionChronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa with distinct endotypes including type 2 (T2) high eosinophilic CRS with nasal polyps (eCRSwNP), T2 low non-eosinophilic CRS with nasal polyps (neCRSwNP), and CRS without nasal polyps (CRSsNP).MethodsGiven the heterogeneity of disease, we hypothesized that assessment of single cell RNA sequencing (scRNA-seq) across this spectrum of disease would reveal connections between infiltrating and activated immune cells and the epithelial and stromal populations that reside in sinonasal tissue.ResultsHere we find increased expression of genes encoding glycolytic enzymes in epithelial cells (EpCs), stromal cells, and memory T-cell subsets from patients with eCRSwNP, as compared to healthy controls. In basal EpCs, this is associated with a program of cell motility and Rho GTPase effector expression. Across both stromal and immune subsets, glycolytic programming was associated with extracellular matrix interactions, proteoglycan generation, and collagen formation. Furthermore, we report increased cell-cell interactions between EpCs and stromal/immune cells in eCRSwNP compared to healthy control tissue, and we nominate candidate receptor-ligand pairs that may drive tissue remodeling.DiscussionThese findings support a role for glycolytic reprograming in T2-elicited tissue remodeling and implicate increased cellular crosstalk in eCRSwNP.
Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART
Authors: Gärtner Kathleen , Domínguez-Rodríguez Sara , Heaney Judith , Gkouleli Triantafylia , Grant Paul , Dorgham Karim , Sauce Delphine , Soulie Cathia , Busby Eloise J. , O’Sullivan Denise M. , Spyer Moira , Botha Johannes C. , Muñoz-Fernandez Maria Angeles , Tagarro Alfredo , Cotugno Nicola , Huggett Jim F. , Klein Nigel , Palma Paolo , Rojo Conejo Pablo , Foster Caroline , Giaquinto Carlo , Rossi Paolo , Persaud Deborah , De Rossi Anita , Marcelin Anne-Geneviève , Nastouli Eleni 
Published: February 2024

IntroductionInitiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population.MethodsForty adolescents perinatally infected with HIV on suppressive ART for &gt;5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested.ResultsCA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-α was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study.ConclusionsLow CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.
Mitf regulates gene expression networks implicated in B cell homeostasis, germinal center responses, and tolerance
Authors: Amarnani Abhimanyu , Lopez-Ocasio Maria , Dilshat Ramile , Anumukonda Kamala , Davila Jonathan , Malakhov Nikita , Huan Chongmin , Magnusdottir Erna , Steingrimsson Eirikur , Roman Christopher A. 
Published: February 2024

IntroductionThe microphthalmia transcription factor Mitf has been shown to regulate B cell activation and tolerance. However, the underlying B cell-specific mechanisms responsible, and those that distinguish Mitf from closely related Mitf/TFE (MiT) transcription factors Tfe3, Tfeb, and Tfec, remain obscure.MethodsTwo complementary mouse models of Mitf and MiT deficiency were used: the Mitfmi-vga9/mi-vga9 systemic loss-of-function mutation, and B-cell specific MiT family inactivation via transgenic expression of a trans-dominant negative (TDN) protein (TDN-B). These models were employed to identify MiT family candidate target genes and pathways.ResultsBoth models displayed spontaneous splenomegaly coincident with elevated plasma cell numbers, autoantibody titers, and proteinuria. These abnormalities appeared dependent on T helper cells, but independent of other non-B cell intrinsic effects of systemic Mitf inactivation. MiT inactivation in B cells augmented aspects of lupus-like autoimmune disease on the C57BL/6-Faslpr/lpr background. In both models, RNAseq of ex vivo resting B cells showed transcriptional upregulation of genes that control cell cycle, germinal center responses, and plasma cell differentiation. Among the genes strongly upregulated in both models were Socs6, Isp53 (Baiap1), S1pR2, and IgG2b/c. Mitf null B cells, but not TDN-B cells, showed evidence of type I interferon dysregulation.DiscussionThese studies clarify Mitf’s role as 1) a key regulator of a B cell intrinsic germinal center program that influences self-tolerance through novel target genes, and 2) a regulator of systemic inflammatory processes that can impact the B cell microenvironment. This distinction of Mitf's function from that of related MiT transcription factors advances our understanding of B cell regulation and autoimmunity.
Limb asymmetries persist 6 months after anterior cruciate ligament reconstruction according to the results of a jump test battery
Authors: Legnani Claudio , Del Re Matteo , Peretti Giuseppe M. , Borgo Enrico , Macchi Vittorio , Ventura Alberto 
Published: February 2024

ObjectivesTest batteries used to assess a patient’s return-to-sports (RTS) following anterior cruciate ligament reconstruction (ACLR) are currently undergoing continual development, although no consensus exist on tests to be administered to athletes before allowing return to play. A simple standardized jump test battery was developed to objectively evaluate knee function following ACLR, thereby aiding in RTS decision-making.MethodsThirty-three patients who underwent ACLR were prospectively assessed pre-operatively, 6, and 12 months after surgery. Knee function was assessed using a device for optical detection using a test battery consisting of three jump tests: monopodalic countermovement jump (CMJ), drop jump, and monopodalic side-hop. Limb symmetry index (LSI) was reported for all tests at all time points. LSI ≥90% was defined as RTS criteria.ResultsAt 12-month evaluation, mean LSI significantly improved compared to 6-month follow up (p &lt; 0.01), and also compared to baseline (p &lt; 0.01), reporting a mean value of 92.6% for CMJ, 90.6 for drop jump and 96.9% for side hop test. Most patients fulfilled the RTS criteria 12 months after surgery (LSI ≥90%). The percentages of patients demonstrating LSI ≥90% at 6 months was 7/33 (21.2%) for CMJ, 12/33 (36.4%) for drop jump, and 11/33 (33.3%) for side-hop test. One year after surgery, percentages grew up to 66.6% (22/33), 63.6% (21/33), and 81.8% (27/33) respectively.ConclusionSix months after ACLR, knee functional performance was unsatisfactory in most patients, whereas a significantly higher percentage of patients met RTS criteria 1 year after surgery. The results of the jump test battery proposed in this study support the idea that timing for resumption of cutting and pivoting sports should be delayed later than 6 months, as still limb asymmetries persist at this time point.
Multimodal imaging shows acute multilayered retinal hemorrhages in heatstroke–a rare case report
Authors: Zhang Yi , Lei Chunyan , Huang Xi , Zhang Meixia 
Published: February 2024

BackgroundHeatstroke is a life-threatening disease clinically characterized by central nervous system dysfunction, multiorgan failure, and extreme hyperthermia. There are no reports about eye involvement in heat stroke. Here, we report a rare case of multilayered retinal hemorrhages in a patient with heatstroke.Case presentationA 55-year-old male with a one-month history of blurry vision in both eyes presented at our department after suffering from heatstroke. His visual acuity was 5/20 OD and 10/20 OS. Fundus examination revealed retinal hemorrhages in both eyes. Fundus autofluorescence images and near-infrared reflectance images revealed well-defined retinal lesions. Optical coherence tomography helped to accurately locate the different layers of the lesions, including the nerve fiber layer, sub-inner limiting membrane, outer plexiform layer, ellipsoid zone and Henle fiber layer hemorrhages. We followed up with the patient for 8 months. At the last follow-up, his visual acuity was 20/20 in both eyes, and fundus examination showed that retinal hemorrhages were almost completely absorbed.ConclusionTo our knowledge, this is the first report on multilayered retinal hemorrhages secondary to heat stroke. Intraretinal and preretinal hemorrhages can gradually resolve, and the patient’s vision will improve with the absorption of the retinal hemorrhages. Multimodal imaging may help to reveal additional details about retinal lesions and monitor the course of the disease.
Real world evidence of epidemiological trends, clinical presentation, and prognostic outcomes of multiple myeloma (2007-2021)
Authors: Elsabah Hesham , El Omri Halima , Habas Elmukhtar , Taha Ruba Y. , ElKourashy Sarah A. , Ibrahim Feryal , Nashwan Abdulqadir J. , Kassem Nancy , Ojha Laxmi , Singh Rajvir , Ghasoub Rola , El Omri Abdelfatteh 
Published: February 2024

BackgroundMultiple myeloma (MM) is one of the most common hematological malignancies globally, and it is projected to increase in the coming years. It occurs more frequently in males and affects older individuals. Presenting symptoms can range from being asymptomatic to severely debilitating. The objective of this study was to determine the epidemiology, clinical features, and prognostic outcomes of patients with MM in the only tertiary cancer hospital in Qatar.MethodsPatients with symptomatic myeloma diagnosed at the National Center for Cancer Care and Research in Qatar between 2007 and 2021 were included. Data on demographics, laboratory work, bone marrow analysis, radiology, and given treatment were collected. Descriptive statistics, survival curves, and multivariable cox regression were used to identify independent mortality risk factors.ResultsDuring the study period of 15 years, a total of 192 patients were diagnosed with MM. The incident rate of myeloma cases in 2021 was 8 patients per million. The median age of patients was 57 years [range 22–88], with 68% being above the age of 50 years at diagnosis. The majority of patients were male (71%) and (85%) were expats. At the time of diagnosis, most patients [n = 169 (88%)] had bone lesions, and 27% had extramedullary plasmacytoma. Anemia, hypercalcemia, and spinal cord compression were reported in 53%, 28%, and 7% of patients, respectively, at presentation. The monoclonal immunoglobulin subtypes were IgG, IgA, and free light chain in 52%, 16%, and 26% of patients, respectively. The overall median survival was 103 months (95% CI 71–135 months). In a multivariate cox-regression analysis for risk factors, only high serum calcium (≥ 2.7 mmol/L) was associated with increased mortality (HR: 2.54, 95% C.I.: 1.40–4.63, p = 0.002). Patients who received an autologous stem cell transplant (ASCT) had significantly better overall survival.ConclusionIn this comprehensive study of patients with MM treated in a country with a small and young general population, centralized hematology care, and free cancer care, we found a low but increasing incidence of MM and a good overall survival. Hypercalcemia was confirmed as a negative risk factor. ASCT had a significant positive impact on survival and should be provided to all patients eligible for this treatment, even in the era of novel agents.