bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of gestational diabetes and proton density fat fraction of vertebral bone marrow and paraspinal musculature in premenopausal women
Authors: Harada Saori , Gersing Alexandra S. , Stohldreier Yannick , Dietrich Olaf , Lechner Andreas , Seissler Jochen , Ferrari Uta , Pappa Eleni , Hesse Nina 
Published: January 2024

Background and objectiveFat content in bones and muscles, quantified by magnetic resonance imaging (MRI) as a proton density fat fraction (PDFF) value, is an emerging non-invasive biomarker. PDFF has been proposed to indicate bone and metabolic health among postmenopausal women. Premenopausal women with a history of gestational diabetes (GDM) carry an increased risk of developing type 2 diabetes and an increased risk of fractures. However, no studies have investigated the associations between a history of GDM and PDFF of bone or of paraspinal musculature (PSM), composed of autochthonous muscle (AM) and psoas muscle, which are responsible for moving and stabilizing the spine. This study aims to investigate whether PDFF of vertebral bone marrow and of PSM are associated with a history of GDM in premenopausal women.MethodsA total of 37 women (mean age 36.3 ± 3.8 years) who were 6 to 15 months postpartum with (n=19) and without (n=18) a history of GDM underwent whole-body 3T MRI, including a chemical shift encoding-based water-fat separation. The PDFF maps were calculated for the vertebral bodies and PSM. The cross-sectional area (CSA) of PSM was obtained. Associations between a history of GDM and PDFF were assessed using multivariable linear and logistic regression models.ResultsThe PDFF of the vertebral bodies was significantly higher in women with a history of GDM (GDM group) than in women without (thoracic: median 41.55 (interquartile range 32.21-49.48)% vs. 31.75 (30.03-34.97)%; p=0.02, lumbar: 47.84 (39.19-57.58)% vs. 36.93 (33.36-41.31)%; p=0.02). The results remained significant after adjustment for age and body mass index (BMI) (p=0.01-0.02). The receiver operating characteristic curves showed optimal thoracic and lumbar vertebral PDFF cutoffs at 38.10% and 44.18%, respectively, to differentiate GDM (AUC 0.72 and 0.73, respectively, sensitivity 0.58, specificity 0.89). The PDFF of the AM was significantly higher in the GDM group (12.99 (12.18-15.90)% vs. 10.83 (9.39-14.71)%; p=0.04) without adjustments, while the CSA was similar between the groups (p=0.34).ConclusionA history of GDM is significantly associated with a higher PDFF of the vertebral bone marrow, independent of age and BMI. This statistical association between GDM and increased PDFF highlights vertebral bone marrow PDFF as a potential biomarker for the assessment of bone health in premenopausal women at risk of diabetes.
Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata
Authors: Zheng Xue-Yong , Ma Yan-Ping , Zhang Bo , Chen Yan-Xin , Tang Lei , Tai Xiao-Hua , Cao Jia-Hao 
Published: January 2024

BackgroundAlthough observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.ObjectivesThis study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata.Methodsgenome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein–protein interaction networks.ResultUtilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12–1.75, p = 3.03×10−3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein–protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3.ConclusionThis study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.
Beyond mere respect: new perspectives on dignity for healthcare workplace learning
Authors: Klinner Christiane , Dario Amabile Borges , Bell Amani , Nisbet Gillian , Penman Merrolee , Monrouxe Lynn V. 
Published: January 2024

IntroductionAlthough dignity in workplace learning in healthcare is gathering interest, we know little about stakeholders’ conceptualizations in this area across professional groups. Dignity breaches in workplace learning are common, often with serious and long-lasting consequences for the affected. Conceptualizations shape behaviours and experiences. To prevent dignity violations in students’ learning, it is thus important to understand stakeholders’ understandings of the topic. This study therefore explores the dignity conceptualizations around workplace learning that students, placement educators and university staff hold across seven allied health professional groups.MethodsUsing a social constructionist perspective, we conducted individual and group narrative interviews (n = 51) with students, placement educators and university workplace learning staff from seven allied health professional groups. We used the 5-step Framework Analysis to explore and develop themes, identifying differences and similarities across stakeholder groups.ResultsWe identified eight distinct, yet interrelated, dimensions of dignity from participants’ narratives: dignity as respect, dignity as self-x (the various relationships we have with ourselves), dignity as feeling safe, dignity as understanding otherness, dignity as supporting others, dignity as equality, dignity as professionalism, and dignity as belonging. Dignity as respect was identified across all participants, although mutual respect and a culture of respect were only present in academic participants’ talk. The remaining seven dimensions all present important factors extending our understanding of the construct of dignity.DiscussionIn line with existing research, our study identifies the absence of an unambiguous, positive conceptualization of dignity in workplace learning among stakeholders. It adds novelty in two ways: by identifying dignity dimensions that require informed action beyond respecting others, and by revealing a tension between dignity as professionalism and dignity as equality. We suggest revising existing dignity concepts in workplace learning to address this tension and to reinforce that active care, team integration and skilled support are all non-negotiable elements of dignified behaviour within workplace learning.
Effects of STN-DBS on cognition and mood in young-onset Parkinson’s disease: a two-year follow-up
Authors: Hong Jun , Xie Huimin , Chen Yuhua , Liu Di , Wang Tianyu , Xiong Kun , Mao Zhiqi 
Published: January 2024

BackgroundThe effects of subthalamic nucleus deep brain stimulation (STN-DBS) on the cognition and mood of patients with PD are still not uniformly concluded, and young-onset Parkinson’s disease (YOPD) is even less explored.ObjectiveTo observe the effectiveness of STN-DBS on the cognition and mood of YOPD patients.MethodsA total of 27 subjects, with a mean age at onset of 39.48 ± 6.24 and age at surgery for STN-DBS of 48.44 ± 4.85, were followed up preoperatively and for 2 years postoperatively. Using the Unified Parkinson disease rating scale (UPDRS), H&amp;Y(Hoehn and Yahr stage), 39-Item Parkinson’s Disease Questionnaire (PDQ-39), Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) to assess motor, cognition, and mood.ResultsAt the 2-year follow-up after STN-DBS, YOPD patients showed significant improvements in motor and quality of life (UPDRS III: p &lt; 0.001, PDQ-39: p &lt; 0.001); overall cognition was not significantly different from preoperative (MMSE: p = 0.275, MoCA: p = 0.913), although language function was significantly impaired compared to preoperative (MMSE: p = 0.004, MoCA: p = 0.009); depression and anxiety symptoms also improved significantly (HAMD: p &lt; 0.001, HAMA: p &lt; 0.001) and the depression score correlated significantly with motor (preoperative: r = 0.493, p = 0.009), disease duration (preoperative: r = 0.519, p = 0.006; postoperative: r = 0.406, p = 0.036) and H&amp;Y (preoperative: r = 0.430, p = 0.025; postoperative: r = 0.387, p = 0.046); total anxiety scores were also significantly correlated with motor (preoperative: r = 0.553, p = 0.003; postoperative: r = 0.444, p = 0.020), disease duration (preoperative: r = 0.417, p = 0.031), PDQ-39 (preoperative: r = 0.464, p = 0.015) and H&amp;Y (preoperative: r = 0.440, p = 0.022; postoperative: r = 0.526, p = 0.005).ConclusionSTN-DBS is a safe and effective treatment for YOPD. The mood improved significantly, and overall cognition was not impaired, were only verbal fluency decreased but did not affect the improvement in quality of life.
Estradiol reduction through aromatase inhibition impairs cocaine seeking in male rats
Authors: Alvarado-Torres John K. , Morales-Silva Roberto , Sanabria Ponce de Leon Alexia , Rodriguez-Torres Genesis , Perez-Torres Joshua , Perez-Perez Yobet , Mueller Devin , Sepulveda-Orengo Marian T. 
Published: January 2024

IntroductionClinical and preclinical research on cocaine use disorder (CUD) has shown that sex differences in drug seeking are influenced by hormonal fluctuations. Estradiol (E2), a sex steroid hormone, has been linked to female drug effects, vulnerability to use/abuse, and psychosocial factors. Preclinical studies show that estradiol in females facilitates the extinction of cocaine-seeking behavior indicating a possible role in regulating extinction learning. Similar to females, males’ brains contain the aromatase enzyme which converts testosterone to estradiol. However, it is unclear whether estradiol plays a role in male extinction learning as it does in females. Furthermore, how endogenously aromatized estradiol affects drug addiction in males is unknown. Therefore, this study investigated whether endogenous estradiol regulates cocaine seeking in male rats. We hypothesized that decreased aromatase enzyme activity, resulting in decreased estradiol synthesis in male brains, will impair extinction learning leading to increased cocaine-seeking behavior.MethodsThis hypothesis was tested using cocaine-conditioned place preference (CPP), and short access self-administration (SA), followed by extinction and reinstatement. Before each extinction session for CPP or SA, male rats received an injection of either 1 (low dose) or 2.5 mg/kg (high dose) of the aromatase inhibitor Fadrozole (FAD), or vehicle.ResultsFAD groups showed dose-dependent effects on cocaine-seeking behavior compared to the vehicle group during CPP extinction. Specifically, low dose FAD facilitated extinction of cocaine CPP, whereas high dose FAD impaired it. In contrast, neither dose of FAD had any effects on the extinction of cocaine SA. Interestingly, only the low dose FAD group had decreased active lever pressing during cue- and cocaine-primed reinstatement compared to the vehicle group. Neither dose of FAD had an effect on sucrose extinction or reinstatement of sucrose seeking.DiscussionThese results from CPP experiments suggest that estradiol may impact extinction learning, as a low dose of FAD may strengthen the formation of cocaine extinction memory. Additionally, in male rats undergoing cocaine SA, the same low dose of aromatase inhibitor effectively reduced reinstatement of cocaine-seeking behavior. Thus, estradiol impacts cocaine seeking and extinction in both males and females, and it may also influence the development of sex-specific treatment strategies for CUD.
Serum GFAP, NfL, and tau concentrations are associated with worse neurobehavioral functioning following mild, moderate, and severe TBI: a cross-sectional multiple-cohort study
Authors: Edwards Katie A. , Lange Rael T. , Lippa Sara M. , Brickell Tracey A. , Gill Jessica M. , French Louis M. 
Published: January 2024

IntroductionThe purpose of this study was to examine whether blood-based biomarkers associate with neurobehavioral functioning at three time points following traumatic brain injury (TBI).Materials and methodsParticipants were 328 United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence (DVBIC-TBICoE) 15-Year Longitudinal TBI Study, recruited into three groups: uncomplicated mild TBI (MTBI, n = 155); complicated mild, moderate, severe TBI combined (STBI, n = 97); non-injured controls (NIC, n = 76). Participants were further divided into three cohorts based on time since injury (≤12 months, 3–5 years, and 8–10 years). Participants completed the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF) and underwent blood draw to measure serum concentrations of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau. A total of 11 MMPI-2-RF scales were examined (e.g., depression, anxiety, anger, somatic, cognitive symptoms). Stepwise hierarchical regression models were conducted within each group.ResultsSignificant associations were found between biomarkers and MMPI-2-RF scales (all p &lt; 0.05; R2Δ &gt; 0.10). GFAP was inversely related to (a) neurological complaints in the MTBI group at ≤12 months, (b) demoralization, anger proneness in the STBI group at ≤12 months, and (c) head pain complaints in the STBI group at 8–10 years. NfL was (a) related to low positive emotions in the NIC group; and inversely related to (b) demoralization, somatic complaints, neurological complaints, cognitive complaints in the MTBI group at ≤12 months, (c) demoralization in the STBI group at ≤12 months, and (d) demoralization, head pain complaints, stress/worry in the STBI group at 3–5 years. In the STBI group, there were meaningful findings (R2Δ &gt; 0.10) for tau, NFL, and GFAP that did not reach statistical significance.DiscussionResults indicate worse scores on some MMPI-2-RF scales (e.g., depression, stress/worry, neurological and head pain complaints) were associated with lower concentrations of serum GFAP, NfL, and tau in the sub-acute and chronic phase of the recovery trajectory up to 5 years post-injury, with a reverse trend observed at 8–10 years. Longitudinal studies are needed to help elucidate any patterns of association between blood-based biomarkers and neurobehavioral outcome over the recovery trajectory following TBI.
Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis
Authors: Howard James F. , Bril Vera , Vu Tuan , Karam Chafic , Peric Stojan , De Bleecker Jan L. , Murai Hiroyuki , Meisel Andreas , Beydoun Said R. , Pasnoor Mamatha , Guglietta Antonio , Van Hoorick Benjamin , Steeland Sophie , T’joen Caroline , Utsugisawa Kimiaki , Verschuuren Jan , Mantegazza Renato ,   the ADAPT+ Study Group
Published: January 2024

ObjectiveADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).MethodsADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.ResultsAs of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received ≥1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Ab−. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported ≥1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Ab− participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of ≥2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of ≥3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with ≥1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5–7.6]).ConclusionResults of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403.
Efficacy and safety of neoadjuvant immunotherapy protocols and cycles for non-small cell lung cancer: a systematic review and meta-analysis
Authors: Wang Huaiyong , Liang Song , Yu Yue , Han Yun 
Published: January 2024

ObjectivesThis study evaluated the use of different neoadjuvant immunotherapy cycles and regimens for non-small cell lung cancer.Materials and methodsDatabases were searched for articles published up until December 2023. Data on the major pathologic response (MPR), complete pathologic response (pCR), radiological response, treatment-related adverse events (TRAEs), serious adverse events (SAEs), surgical resection, surgical complications, R0 resection, and conversion to thoracotomy were collected. A subgroup analysis was performed according to the treatment regimens and cycles. Stata/MP software was used for statistical analyses.ResultsIn total, 2430 individuals were assessed from 44 studies. Compared with those following neoadjuvant immunotherapy alone (MPR/pCR/TRAEs/SAEs: ES=0.26/0.07/0.43/0.08, 95% CI: 0.18-0.34/0.04-0.10/0.28-0.58/0.04-0.14), the MPR and pCR rates, incidence of TRAEs and SAEs following neoadjuvant chemoimmunotherapy increased significantly (MPR/pCR/TRAEs/SAEs: ES=0.55/0.34/0.81/0.22, 95% CI: 0.48-0.63/0.28-0.41/0.69-0.90/0.13-0.33, P=0.001/0.002/0.009/0.034). No significant differences were found in the surgical resection, surgical complications, R0 resection, or conversion to thoracotomy. In the chemoimmunotherapy group, no statistically significant differences were found in the MPR and pCR rates, incidence of TRAEs and SAEs in the two-cycle, three-cycle and four-cycle groups (MPR/pCR/TRAEs/SAEs: ES=0.50;0.70;0.36/0.32;0.49;0.18/0.95;0.85;0.95/0.34;0.27;0.37, P=0.255/0.215/0.253/0.848). In the ICIs group, there was little change in the MPR and pCR rates, incidence of TRAEs and SAEs in the two-cycle group compared to the three-cycle group. (MPR/pCR/TRAEs/SAEs: ES=0.28;0.20/0.06;0.08/0.45;0.35/0.10;0.02, P=0.696/0.993/0.436/0.638). The neoadjuvant treatment cycle had no significant effect on surgical resection, surgical complications, R0 resection, or conversion to thoracotomy in both regimens.ConclusionNeoadjuvant chemoimmunotherapy significantly increased the rate of tumor pathological remission compared to neoadjuvant immunotherapy alone but also increased the incidence of TRAEs and SAEs. The efficacy and safety of neoadjuvant chemoimmunotherapy are found to be favorable when administered for a duration of three cycles, in comparison to both two and four cycles.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023407415.
Distinctive physiological and molecular responses of foxtail millet and maize to nicosulfuron
Authors: Lu Boyu , Meng Ru , Wang Yiru , Xiong Wei , Ma Yuchao , Gao Peng , Ren Jianhong , Zhang Liguang , Zhao Zhihai , Fan Guangyu , Wen Yinyuan , Yuan Xiangyang 
Published: January 2024

IntroductionNicosulfuron is the leading acetolactate synthase inhibitor herbicide product, and widely used to control gramineous weeds. Here, we investigated the metabolic process of nicosulfuron into foxtail millet and maize, in order to clarify the mechanism of the difference in sensitivity of foxtail millet and maize to nicosulfuron from the perspective of physiological metabolism and provide a theoretical basis for the breeding of nicosulfuron-resistant foxtail millet varieties.MethodsWe treated foxtail millet (Zhangzagu 10, Jingu 21) and maize (Nongda 108, Ditian 8) with various doses of nicosulfuron in both pot and field experiments. The malonaldehyde (MDA) content, target enzymes, detoxification enzymes, and antioxidant enzymes, as well as related gene expression levels in the leaf tissues of foxtail millet and maize were measured, and the yield was determined after maturity.ResultsThe results showed that the recommended dose of nicosulfuron caused Zhangzagu 10 and Jingu 21 to fail to harvest; the yield of the sensitive maize variety (Ditian 8) decreased by 37.09%, whereas that of the resistant maize variety (Nongda 108) did not decrease. Nicosulfuron stress increased the CYP450 enzyme activity, MDA content, and antioxidant enzyme activity of foxtail millet and maize, reduced the acetolactate synthase (ALS) activity and ALS gene expression of foxtail millet and Ditian 8, and reduced the glutathione S-transferase (GST) activity and GST gene expression of foxtail millet. In conclusion, target enzymes, detoxification enzymes, and antioxidant enzymes were involved in the detoxification metabolism of nicosulfuron in plants. ALS and GST are the main factors responsible for the metabolic differences among foxtail millet, sensitive maize varieties, and resistant maize varieties.DiscussionThese findings offer valuable insights for exploring the target resistance (TSR) and non-target resistance (NTSR) mechanisms in foxtail millet under herbicide stress and provides theoretical basis for future research of develop foxtail millet germplasm with diverse herbicide resistance traits.