bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target
Authors: Sasso Etianne Martini , Muraki Katsuhiko , Eaton-Fitch Natalie , Smith Peter , Jeremijenko Andrew , Griffin Paul , Marshall-Gradisnik Sonya 
Published: May 2024

IntroductionRecently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.MethodsWhole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (N = 9; 40.56 ± 11.26 years), ME/CFS (N = 9; 39.33 ± 9.80 years) and healthy controls (HC) (N = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition (N = 9; 40.56 ± 11.26 years) and HC (N = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol. ResultsThis investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.DiscussionOur findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after in vitro treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca2+) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.
Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding
Authors: Bauernfeind Clarissa , Zettl Ines , Ivanova Tatiana , Goryainova Oksana , Weijler Anna Marianne , Pranz Barbara , Drescher Anja , Focke-Tejkl Margarete , Pavkov-Keller Tea , Eckl-Dorna Julia , Tillib Sergei V. , Flicker Sabine 
Published: May 2024

BackgroundAround 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients´ IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergen-induced basophil degranulation.MethodsNanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients’ IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated.ResultsTrimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release.ConclusionWe generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives.
Prefrontal cortical activity during uneven terrain walking in younger and older adults
Authors: Hwang Jungyun , Liu Chang , Winesett Steven P. , Chatterjee Sudeshna A. , Gruber Anthony D. , Swanson Clayton W. , Manini Todd M. , Hass Chris J. , Seidler Rachael D. , Ferris Daniel P. , Roy Arkaprava , Clark David J. 
Published: May 2024

IntroductionWalking in complex environments increases the cognitive demand of locomotor control; however, our understanding of the neural mechanisms contributing to walking on uneven terrain is limited. We used a novel method for altering terrain unevenness on a treadmill to investigate the association between terrain unevenness and cortical activity in the prefrontal cortex, a region known to be involved in various cognitive functions.MethodsPrefrontal cortical activity was measured with functional near infrared spectroscopy while participants walked on a novel custom-made terrain treadmill surface across four different terrains: flat, low, medium, and high levels of unevenness. The assessments were conducted in younger adults, older adults with better mobility function and older adults with worse mobility function. Mobility function was assessed using the Short Physical Performance Battery. The primary hypothesis was that increasing the unevenness of the terrain would result in greater prefrontal cortical activation in all groups. Secondary hypotheses were that heightened prefrontal cortical activation would be observed in the older groups relative to the younger group, and that prefrontal cortical activation would plateau at higher levels of terrain unevenness for the older adults with worse mobility function, as predicted by the Compensation Related Utilization of Neural Circuits Hypothesis.ResultsThe results revealed a significant main effect of terrain, indicating a significant increase in prefrontal cortical activation with increasing terrain unevenness during walking in all groups. A significant main effect of group revealed that prefrontal cortical activation was higher in older adults with better mobility function compared to younger adults and older adults with worse mobility function in all pooled terrains, but there was no significant difference in prefrontal cortical activation between older adults with worse mobility function and younger adults. Contrary to our hypothesis, the older group with better mobility function displayed a sustained increase in activation but the other groups did not, suggestive of neural compensation. Additional findings were that task-related increases in prefrontal cortical activation during walking were lateralized to the right hemisphere in older adults with better mobility function but were bilateral in older adults with worse mobility function and younger adults.DiscussionThese findings support that compared to walking on a flat surface, walking on uneven terrain surfaces increases demand on cognitive control resources as measured by prefrontal cortical activation.
Cerebral hemodynamics and optic nerve sheath diameter acquired via neurosonology in critical patients with severe coronavirus disease: experience of a national referral hospital in Peru
Authors: Heredia-Orbegoso Omar , Vences Miguel A. , Failoc-Rojas Virgilio E. , Fernández-Merjildo Diana , Lainez-Chacon Richard H. , Villamonte Renán 
Published: May 2024

AimWe aimed to describe the neurosonological findings related to cerebral hemodynamics acquired using transcranial Doppler and to determine the frequency of elevated ICP by optic nerve sheath diameter (ONSD) measurement in patients with severe coronavirus disease (COVID-19) hospitalized in the intensive care unit of a national referral hospital in Peru.MethodsWe included a retrospective cohort of adult patients hospitalized with severe COVID-19 and acute respiratory failure within the first 7 days of mechanical ventilation under deep sedoanalgesia, with or without neuromuscular blockade who underwent ocular ultrasound and transcranial Doppler. We determine the frequency of elevated ICP by measuring the diameter of the optic nerve sheath, choosing as best cut-off value a diameter equal to or &gt;5.8 mm. We also determine the frequency of sonographic patterns obtained by transcranial Doppler. Through insonation of the middle cerebral artery. Likewise, we evaluated the associations of clinical, mechanical ventilator, and arterial blood gas variables with ONSD ≥5.8 mm and pulsatility index (PI) ≥1.1. We also evaluated the associations of hemodynamic findings and ONSD with mortality the effect size was estimated using Poisson regression models with robust variance.ResultsThis study included 142 patients. The mean age was 51.39 ± 13.3 years, and 78.9% of patients were male. Vasopressors were used in 45.1% of patients, and mean arterial pressure was 81.87 ± 10.64 mmHg. The mean partial pressure of carbon dioxide (PaCO2) was elevated (54.08 ± 16.01 mmHg). Elevated intracranial pressure was seen in 83.1% of patients, as estimated based on ONSD ≥5.8 mm. A mortality rate of 16.2% was reported. In the multivariate analysis, age was associated with elevated ONSD (risk ratio [RR] = 1.07). PaCO2 was a protective factor (RR = 0.64) in the cases of PI ≥ 1.1. In the mortality analysis, the mean velocity was a risk factor for mortality (RR = 1.15).ConclusionsA high rate of intracranial hypertension was reported, with ONSD measurement being the most reliable method for estimation. The increase in ICP measured by ONSD in patients with severe COVID-19 on mechanical ventilation is not associated to hypercapnia or elevated intrathoracic pressures derived from protective mechanical ventilation.
Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study
Authors: Shao Fengling , Yao Yingling , Weng Dunchu , Wang Runzhi , Liu Ruiling , Zhang Yongjia , Li Erhan , Wang Mengdi , Tang Yuewu , Ding Yubin , Xie Yajun 
Published: May 2024

BackgroundNephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few have harnessed genetic methodologies to establish causal relationships.MethodsThrough Mendelian randomization (MR) in two substantial cohorts, spanning large sample sizes, we evaluated over 100 plasma circulating metabolites and 263 drugs to discern their causal effects on nephritis risk. The primary analytical tool was the inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny of GSE115857 (IgA nephropathy, 86 samples) and GSE72326 (lupus nephritis, 238 samples) unveiled anomalies in lipid metabolism and immunological characteristics in nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken to verify the instrumental variables’ (IVs) assumptions.ResultsUnique lipoprotein-related molecules established causal links with diverse nephritis subtypes. Notably, docosahexaenoic acid (DHA) emerged as a protective factor for acute tubulointerstitial nephritis (ATIN) (OR1 = 0.84, [95% CI 0.78–0.90], p1 = 0.013; OR2 = 0.89, [95% CI 0.82–0.97], p2 = 0.007). Conversely, multivitamin supplementation minus minerals notably increased the risk of ATIN (OR = 31.25, [95% CI 9.23–105.85], p = 0.004). Reduced α-linolenic acid (ALA) levels due to lipid-lowering drugs were linked to both ATIN (OR = 4.88, [95% CI 3.52–6.77], p &lt; 0.001) and tubulointerstitial nephritis (TIN) (OR = 7.52, [95% CI 2.78–20.30], p = 0.042). While the non-renal drug indivina showed promise for TIN treatment, the use of digoxin, hydroxocobalamin, and liothyronine elevated the risk of chronic tubulointerstitial nephritis (CTIN). Transcriptome analysis affirmed that anomalous lipid metabolism and immune infiltration are characteristic of IgA nephropathy and lupus nephritis. The robustness of these causal links was reinforced by sensitivity analyses and leave-one-out tests, indicating no signs of pleiotropy.ConclusionDyslipidemia significantly contributes to nephritis development. Strategies aimed at reducing plasma low-density lipoprotein levels or ALA supplementation may enhance the efficacy of existing lipid-lowering drug regimens for nephritis treatment. Renal functional status should also be judiciously considered with regard to the use of nonrenal medications.
Association between homocysteine and blood pressure in the NHANES 2003–2006: the mediating role of Vitamin C
Authors: Wu Peng , Ma Juan , Yang Shaobin , Wu Hailiang , Ma Xueping , Chen Dapeng , Jia Shaobin , Yan Ning 
Published: May 2024

BackgroundThe yearly escalation in hypertension prevalence signifies a noteworthy public health challenge. Adhering to a nutritious diet is crucial for enhancing the quality of life among individuals managing hypertension. However, the relationship between vitamin C and hypertension, as well as homocysteine, remains unclear.ObjectiveThe primary aim of this investigation was to scrutinize the potential mediating role of Vitamin C in the association between homocysteine levels and blood pressure, utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES) database.MethodsA total of 7,327 participants from the NHANES 2003–2006 were enrolled in this cross-sectional survey. The main information was obtained using homocysteine, Vitamin C, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Correlation analysis was used to assess the correlation between homocysteine, SBP, DBP and vitamin C. Linear regression analysis was utilized to determine the β value (β) along with its 95% confidence intervals (CIs). Mediation analysis was performed to investigate whether the relationship between homocysteine and blood pressure was mediated by Vitamin C, and to quantify the extent to which Vitamin C contributed to this association.ResultsThe results manifested that the homocysteine was positively associated with SBP (r = 0.24, p &lt; 0.001) and DBP (r = 0.03, p &lt; 0.05), while negatively correlated with Vitamin C (r = −0.008, p &lt; 0.001). Vitamin C was found to be negatively associated with SBP (r = −0.03, p &lt; 0.05) and DBP (r = 0.11, p &lt; 0.001). Mediation effect analysis revealed that a partial mediation (indirect effect: 0.0247[0.0108–0.0455], p &lt; 0.001) role accounting for 11.5% of total effect, among homocysteine and SBP. However, the mediating effect of Vitamin C between homocysteine and DBP was not statistically significant.ConclusionHypertension patients should pay attention to homocysteine and Vitamin C level. What is more, hypertension patients ought to formulate interventions for Vitamin C supplementation as well as homocysteine reduce strategies to lower blood pressure.
Case report: ‘Atypical Richter transformation from CLL-type monoclonal B-cell lymphocytosis into Burkitt lymphoma in a treatment naïve patient’
Authors: Jauch Annaïse J. , Alborelli Ilaria , Reusser Andreas , Baschong Albert , Rütsche Cyrill , Bignucolo Olivier , Passweg Jakob , Dirnhofer Stefan , Krasniqi Fatime 
Published: May 2024

BackgroundRichter transformation refers to the progression of an initially slow-growing small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) into an aggressive lymphoma, typically diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma.Case presentationThe patient presented with a rapid onset of localized cervical swelling, accompanied by monoclonal B-cell lymphocytosis displaying a CLL immunophenotype. The histopathological analysis identified a Burkitt lymphoma (BL) located in the submandibular gland and adjacent lymph node. The patient’s bone marrow displayed a minor infiltration of monoclonal B-cells with a CLL immunophenotype (&lt; 10%). Molecular analysis demonstrated the presence of the same monoclonal rearrangement in the framework region (FR3 region) of the immunoglobulin heavy chain (IGH) locus. High-throughput sequencing of the immunoglobulin heavy and light chains also confirmed the presence of the same rearrangement in SLL/CLL and in the Burkitt lymphoma sample, but also highlighted the presence of a second rearrangement in the Burkitt lymphoma cells, not shared with the SLL/CLL cells in the bone marrow. The patient was treated with DA-EPOCH-R, which lead to a complete metabolic response.ConclusionThis report provides an exceptionally rare description of a CLL-type monoclonal B-cell lymphocytosis transforming into a very aggressive Burkitt lymphoma in a treatment naïve patient.
Health service providers experience of psycho-emotional violence and associated factors among urban hospitals in Eastern Ethiopia
Authors: Tolera Abebe , Weldesenbet Adisu Birhanu , Regassa Lemma Demissie , Tusa Biruk Shalmeno , Merga Bedasa Taye , Tariku Mandaras , Cheru Abera , Enyew Daniel Birhanie , Gemeda Assefa Tola 
Published: May 2024

BackgroundPsycho-emotional violence, a type of workplace violence targeting healthcare workers, varies across countries, occasions, and professions in the healthcare sector. Unfortunately, there is a scarcity of comprehensive studies focusing on violence against healthcare workers in Ethiopia, which may also encompass psycho-gender-based emotional violence against healthcare workers. Therefore, there is a compelling need for in-depth research to address this gap and develop effective strategies to mitigate psycho-emotional violence in the healthcare sector in Ethiopia, especially in the eastern region. Hence, we aimed to identify the prevalence of and factors associated with workplace psycho-emotional violence against healthcare providers in eastern Ethiopia.MethodsThis institution-based cross-sectional study was conducted among 744 health professionals working in urban public hospitals in eastern Ethiopia. Multistage stratified random sampling was used, and data were collected using a standardized structured tool adopted from the WHO workplace violence assessment tool. Binary and multivariable logistic regression analyses were employed to identify factors associated with psycho-emotional workplace violence. Adjusted odds ratio (OR) with 95% confidence interval (CI) was reported, and a p-value of 0.05 was used as the cut-off point to declare significance.ResultsWorkplace psycho-emotional violence was reported by 57.39% of the healthcare workers. The absence of guidelines for gender-based abuse [AOR = 35.62, 95% CI:17.47, 72.64], presence of measures that improve surroundings (class lighting and privacy) [AOR = 0.58, 95% CI: 0.35, 0.98], training on workplace violence coping mechanism [AOR = 0.16, 95%CI: 0.26, 0.98], spending more than 50% of their time with HIV/AIDS patients [AOR = 1.96, 95%CI:1.05, 3.72], and spending more than 50% of their time with psychiatric patients [AOR = 1.92, 95%CI:1.08, 3.43] were factors significantly associated with workplace violence against health professionals.ConclusionThe prevalence of workplace psycho-emotional violence against health professionals in eastern Ethiopia was relatively high. Improving the working environment decreases the chance of workplace violence; however, there is a lack of guidelines for gender-based violence, the absence of training on coping mechanisms, and spending more time with psychiatric and HIV/AIDS patients’ increases workplace violence. We recommend that health institutions develop gender abuse mitigation guidelines and provide training on coping mechanisms.
A cross-sectional mental-health survey of Chinese postgraduate students majoring in stomatology post COVID-19 restrictions
Authors: Zhang Yuwei , Jia Yue , MuLaTiHaJi MaErWa , Mi Yiying , Mei Yukun , Sun Tianxiang , Shi Haibo , Zhang Yifei , Zhang Yikun , Zou Rui , Niu Lin , Dong Shaojie 
Published: May 2024

BackgroundThe psychological status of Chinese postgraduate students majoring in stomatology after the COVID-19 restrictions still remains unclear. The objective of this study is to evaluate the mental status through a cross-sectional survey and gather related theoretical evidence for psychological intervention on postgraduate students majoring in stomatology.MethodsAn online survey was administered, and subjective well-being, anxiety, stress and depression symptoms were assessed using the 5-item World Health Organization Well-Being Index (WHO-5), item Generalized Anxiety Disorder Scale (GAD-7), 10-item Perceived Stress Scale (PSS-10), and Patient Health Questionnaire-9 (PHQ-9), respectively, wherein suicidal ideation and sleep-related problems were measured with PHQ-9 and Insomnia Severity Index (ISI).ResultsA total of 208 participants who completed one questionnaire were considered as valid. It was found that female respondents generally exhibited significantly higher levels of PSS-10, PHQ-9, and GAD-7 scores and shorter physical activity hours than male students. Students from rural areas demonstrated significantly higher levels of PHQ-9, suicidal ideation, and less portion of good or fair family economic support. Additionally, individuals from only-child families reported increased levels of activity hours (1.78 ± 2.07, p = 0.045) and a higher portion (55.10%, p = 0.007) of having clear future plan as compared with multiple-child families. The risk factors for anxiety symptoms (GAD-7 score) were higher scores of PSS-10 (OR = 1.15, 95% CI = 1.09–1.22), PHQ-9 (OR = 1.35, 95% CI = 1.22–1.49), and ISI-7 (OR = 1.14, 95% CI = 1.06–1.23), while owning a clear graduation plan was the protective factor (OR = 0.55, 95% CI = 0.31–0.98). Moreover, the risk factors for depressive symptoms (PHQ-9) included PSS-10 (OR = 1.10, 95% CI = 1.04–1.16), GAD-7 (OR = 1.38, 95% CI = 1.25–1.52), suicidal ideation (OR = 5.66, 95% CI = 3.37–9.51), and ISI-7 (OR = 1.17, 95% CI = 1.09–1.25). Approximately 98.08% of Chinese postgraduates studying stomatology reported experiencing at least moderate stress after the COVID-19 restrictions.ConclusionWithin the limitations of this study, senior students were more inclined to stress, while anxiety symptoms were related to severer levels of stress, depression, and insomnia. Depressive symptoms were associated with higher levels of stress, anxiety, insomnia, suicidal ideation, and lower levels of self-reported well-being. Thus, psychological interventions for postgraduates should be timely and appropriately implemented by strengthening well-being, reasonably planning for the future, and good physique, thereby mitigating the psychological issues after COVID-19 restrictions.