bluuebunny/crossref_metadata_2025_split huggingface dataset:
Petrogenesis and geological implications of the qiyishan triassic granitoids in east Beishan orogen, inner Mongolia, NW China: evidence from geochronology, geochemistry and Nd-Hf isotopes
Authors: Liu Ruiqin , Chen Chao , Lv Xinbiao , Zhang Zhongcheng , Ruan Banxiao , Zhang Shanming , Hu Erhong 
Published: October 2023

The Qiyishan deposit is a large-scale Rb polymetallic deposit in the Beishan orogen. However, there remain debates regarding its metallogenic age and tectonic setting. In addition, studies of Triassic tectono-magmatic events in the Beishan orogen are still insufficient, and conducting genesis studies on the Qiyishan Triassic granitoids will help to enhance the understanding of Triassic magmatism and tectonic evolution in the Beishan orogen. In this contribution, we report new data for the ore-forming granitoids of Qiyishan deposit, including zircon U-Pb ages, major and trace element concentrations and Nd-Hf isotope compositions to define the ages and genesis of the Qiyishan granitoids and discuss their origin and geodynamic implications. Zircon U-Pb dating of the Qiyishan ore-forming granitoids yielded three ages of 217.5 ± 1.3 Ma, 217.2 ±0.8 Ma, and 207.5 ± 2.0 Ma, respectively. The age of Rb mineralization can be constrained to 207.5± 2.0 Ma, while the age of W-Sn-Mo mineralization is considered to be slightly younger than approximately 217 Ma. The Characteristics of major and trace elements of the rock samples indicate that the Qiyishan granites can be classified to highly fractionated I-type granite, and characterised by a transition to A-type like granite to some extent. The granites were not only affected by fractional crystallisation, but also underwent magmatic-hydrothermal interaction. The zircon εHf(t) values of the Qiyishan granitoids ranged from 3.28 to 16.07 and the Hf model age (TDMc) ranged from 0.216 to 1.042 Ga, revealing that the Qiyishan granitoids originated from the partial melting of both mantle and crustal sources. εNd(t) values ranged from −0.52 to −0.25, with Nd model ages of 0.998 Ga to 1.007 Ga. These results indicate that the granitoids originated from the mantle-derived magmas intruding into the lower crust within an intracontinental extensional environment. Combining the previous studies of Triassic granites in the Beishan orogen and this work, the Triassic granites exhibit a transition from I-type to A-type along the northeast direction, indicating a decrease in the contribution of ancient crustal to the magma source. We propose that the Qiyishan granitoids formed in a transitional tectonic environment, signifying the shift from post-orogenic to intracontinental extensional settings in beishan orogen during late Triassic.
Pathological mechanisms of type 1 diabetes in children: investigation of the exosomal protein expression profile
Authors: Bai Baoling , Gao Kang , Zhang Kexin , Liu Lingyun , Chen Xiaobo , Zhang Qin 
Published: October 2023

IntroductionType 1 diabetes (T1D) is a serious autoimmune disease with high morbidity and mortality. Early diagnosis and treatment remain unsatisfactory. While the potential for development of T1D biomarkers in circulating exosomes has attracted interest, progress has been limited. This study endeavors to explore the molecular dynamics of plasma exosome proteins in pediatric T1D patients and potential mechanisms correlated with T1D progressionMethodsLiquid chromatography-tandem mass spectrometry with tandem mass tag (TMT)6 labeling was used to quantify exosomal protein expression profiles in 12 healthy controls and 24 T1D patients stratified by age (≤ 6 years old and &gt; 6 years old) and glycated hemoglobin (HbA1c) levels (&gt; 7% or &gt; 7%). Integrated bioinformatics analysis was employed to decipher the functions of differentially expressed proteins, and Western blotting was used for validation of selected proteins' expression levels. ResultsWe identified 1035 differentially expressed proteins (fold change &gt; 1.3) between the T1D patients and healthy controls: 558 in those ≤ 6-year-old and 588 in those &gt; 6-year-old. In those who reached an HbA1c level &lt; 7% following 3 or more months of insulin therapy, the expression levels of most altered proteins in both T1D age groups returned to levels comparable to those in the healthy control group. Bioinformatics analysis revealed that differentially expressed exosome proteins are primarily related to immune function, hemostasis, cellular stress responses, and matrix organization. Western blotting confirmed the alterations in RAB40A, SEMA6D, COL6A5, and TTR proteins. DiscussionThis study delivers valuable insights into the fundamental molecular mechanisms contributing to T1D pathology. Moreover, it proposes potential therapeutic targets for improved T1D management.
Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy
Authors: Gubbi Sriram , Al-Jundi Mohammad , Auh Sungyoung , Jha Abhishek , Zou Joy , Shamis Inna , Meuter Leah , Knue Marianne , Turkbey Baris , Lindenberg Liza , Mena Esther , Carrasquillo Jorge A. , Teng Yating , Pacak Karel , Klubo-Gwiezdzinska Joanna , Del Rivero Jaydira , Lin Frank I. 
Published: October 2023

PurposeWhile there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.MethodsThe study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 – 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed.ResultsAmong the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours.Conclusions[177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&amp;draw=2&amp;rank=1, identifier NCT03206060.
Cytometry profiling of ex vivo recall responses to Coxiella burnetii in previously naturally exposed individuals reveals long-term changes in both adaptive and innate immune cellular compartments
Authors: Raju Paul Susan , Scholzen Anja , Reeves Patrick M. , Shepard Robert , Hess Joshua M. , Dzeng Richard K. , Korek Skylar , Garritsen Anja , Poznansky Mark C. , Sluder Ann E. 
Published: October 2023

IntroductionQ fever, caused by the intracellular bacterium Coxiella burnetii, is considered an occupational and biodefense hazard and can result in debilitating long-term complications. While natural infection and vaccination induce humoral and cellular immune responses, the exact nature of cellular immune responses to C. burnetii is incompletely understood. The current study seeks to investigate more deeply the nature of long-term cellular recall responses in naturally exposed individuals by both cytokine release assessment and cytometry profiling.MethodsIndividuals exposed during the 2007-2010 Dutch Q fever outbreak were grouped in 2015, based on a C. burnetii-specific IFNγ release assay (IGRA), serological status, and self-reported clinical symptoms during initial infection, into asymptomatic IGRA-negative/seronegative controls, and three IGRA-positive groups (seronegative/asymptomatic; seropositive/asymptomatic and seropositive/symptomatic). Recall responses following in vitro re-stimulation with heat-inactivated C. burnetii in whole blood, were assessed in 2016/2017 by cytokine release assays (n=55) and flow cytometry (n=36), and in blood mononuclear cells by mass cytometry (n=36).ResultsCytokine release analysis showed significantly elevated IL-2 responses in all seropositive individuals and elevated IL-1β responses in those recovered from symptomatic infection. Comparative flow cytometry analysis revealed significantly increased IFNγ, TNFα and IL-2 recall responses by CD4 T cells and higher IL-6 production by monocytes from symptomatic, IGRA-positive/seropositive individuals compared to controls. Mass cytometry profiling and unsupervised clustering analysis confirmed recall responses in seropositive individuals by two activated CD4 T cell subsets, one characterized by a strong Th1 cytokine profile (IFNγ+IL-2+TNFα+), and identified C. burnetii-specific activation of CD8 T cells in all IGRA-positive groups. Remarkably, increased C. burnetii-specific responses in IGRA-positive individuals were also observed in three innate cell subpopulations: one characterized by an IFNγ+IL-2+TNFα+ Th1 cytokine profile and lack of canonical marker expression, and two IL-1β-, IL-6- and IL-8-producing CD14+ monocyte subsets that could be the drivers of elevated secretion of innate cytokines in pre-exposed individuals.DiscussionThese data highlight that there are long-term increased responses to C. burnetii in both adaptive and innate cellular compartments, the latter being indicative of trained immunity. These findings warrant future studies into the protective role of these innate responses and may inform future Q fever vaccine design.
Acute abdominal pain as the first symptom of Chlamydia psittaci pneumonia complicated by acute pancreatitis: a case report
Authors: Fang Changquan , Xie Yanjun , Mai Hui , Xu Limin 
Published: October 2023

BackgroundChlamydia psittaci infections primarily cause damage to the lungs but may also affect the cardiovascular system, gastrointestinal tract, liver, kidney, and brain, resulting in a variety of extrapulmonary complications. However, reports regarding C. psittaci infection-associated pancreatitis are rare. In this report, a patient with C. psittaci pneumonia complicated by acute pancreatitis is presented.Case descriptionThe patient presented with acute upper abdominal pain and developed severe pyrexia and dyspnoea one day later. A chest computed tomography image revealed patchy consolidation in the left lung. The disease progressed rapidly, and the patient exhibited liver and kidney damage and type 1 respiratory failure within a short period of time. Metagenomic next-generation sequencing of alveolar lavage fluid revealed the presence of C. psittaci. The patient was administered doxycycline and moxifloxacin, after which the patient’s abdominal pain and lung infection significantly resolved.ConclusionThis case report demonstrates that extrapulmonary C. psittaci infections due to secondary acute pancreatitis can manifest as abdominal pain, although the exact mechanisms of C. psittaci caused by acute pancreatitis remain unclear. Timely diagnoses and treatments of such infections are necessary to achieve favorable clinical outcomes.
A cohort study on anxiety and perceived recovery 3 and 12 months after mild to moderate stroke
Authors: Nelsone Linda , Rafsten Lena , Abzhandadze Tamar , Sunnerhagen Katharina S. 
Published: October 2023

BackgroundAnxiety is a common complication of stroke, affecting one in every three stroke survivors. Stroke recovery is a dynamic process, with most recovery occurring within the first 3 months. However, how anxiety affects this dynamic remains unknown. Therefore, this study aimed to investigate how anxiety affects perceived recovery at 3 and 12 months after stroke. Additionally we also examined the change in perceived stroke recovery from 3 to 12 months and its relationship with anxiety.MethodsIn this longitudinal study patients with stroke were enrolled at Sahlgrenska University Hospital, Gothenburg, Sweden. The Hospital Anxiety and Depression Scale was used to assess anxiety, and the Stroke Impact Scale was used to assess perceived recovery 3 and 12 months after the stroke. The difference in perceived stroke recovery between the anxiety and no-anxiety groups at 3 and 12 months was analyzed. Changes in perceived stroke recovery were calculated and trichotomized from 3 to 12 months based on clinically significant positive changes (+10 points or more), clinically important negative changes (−10 points or less), or no changes (±9). At 3 and 12 months after the stroke, negative and positive recovery was compared to no change in recovery regarding anxiety scores.ResultsThis study included 99 patients (44.4% female, median age, 77 years). At 3 and 12 months after the stroke, the median recovery score was 80 out of 100. At 3- and 12-months 17.6 and 15.7% of the patients experienced anxiety, respectively. At both time points, there was a significant association between anxiety and lower perceived stroke recovery (at 3 months: p &lt; 0.001; and 12 months p = 0.002). Among participants with anxiety at 3 or 12 months after stroke, a positive change in recovery from 3 to 12 months was identified (3 months, p = 0.004 and 12 months, p = 0.0014).ConclusionAnxiety symptoms following a stroke are associated with lower levels of perceived stroke recovery for at least 1 year after the stroke. Identifying patients with anxiety early after stroke may be beneficial for identifying those at risk of lower recovery.Clinical trial registration:ClinicalTrials.gov, identifier [NCT01622205]. Registered on June 19, 2012 (retrospectively registered).
Planned drug holidays during treatment with lenvatinib for radioiodine-refractory differentiated thyroid cancer: a retrospective study
Authors: Matsuyama Chihiro , Enokida Tomohiro , Ueda Yuri , Suzuki Shinya , Fujisawa Takao , Ito Kazue , Okano Susumu , Tahara Makoto 
Published: October 2023

BackgroundIn the phase 3 SELECT study, lenvatinib significantly improved prognostic outcomes vs. placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, toxicity of lenvatinib is sometimes considerable and requires frequent dose interruptions and modifications. Recently, planned drug holidays have been proposed as a means of avoiding severe adverse events (AEs).MethodsWe retrospectively reviewed medical records to compare the efficacy and safety of lenvatinib in RR-DTC patients who underwent planned drug holidays (planned holiday group) vs. those who received conventional daily oral administration (daily group).ResultsThe subjects were 25 patients in the planned holiday group and 21 in the daily group. Median age was 73 years (range 43-84) and 62 years (range 42-75), and histologic subtype of papillary/follicular was 21/4 cases and 15/6 cases, respectively. Time to treatment failure (TTF) and overall survival (OS) were significantly longer in the planned holiday group than the daily group (not reached [NR] vs. 14.9 months, hazard ratio [HR] 0.25, 95% confidence interval [Cl] 0.11-0.58, p&lt;0.001; NR vs. 26.6 months, HR 0.20, 95% CI 0.073-0.58, p=0.001, respectively). Median progression-free survival (PFS) was NR in the planned holiday group vs. 15.1 months in the daily group (HR 0.31, 95% CI 0.14-0.68, p=0.002). Duration of the period with lenvatinib dose ≥10 mg was significantly longer in the planned holiday group (NR vs. 6.5 months, HR 0.22, 95% CI 0.10-0.49, p&lt;0.001), and the frequency of drug interruption due to intolerable AEs was lower (68.0% vs. 95.2%, p=0.027).ConclusionPlanned drug holidays for lenvatinib demonstrated significantly longer PFS, TTF, and OS than daily oral administration, and less intolerable toxicity leading to further unplanned treatment interruption. These benefits were apparently associated with a more extended period of lenvatinib administration at ≥10 mg. These findings might contribute to a favorable patient prognosis and safer toxicity profile.
Role of mu opioid receptor (MOR) agonist efficacy as a determinant of opioid antinociception in a novel assay of pain-depressed behavior in female and male mice
Authors: Negus S. Stevens , Akbarali Hamid I. , Kang Minho , Lee Young K. , Marsh Samuel A. , Santos Edna J. , Zhang Yan 
Published: October 2023

IntroductionIntermediate efficacy mu opioid receptor (MOR) agonists have potential to retain analgesic effectiveness while improving safety, but the optimal MOR efficacy for effective and safe opioid analgesia is unknown. Preclinical assays of pain-depressed behavior can assess effects of opioids and other candidate analgesics on pain-related behavioral depression, which is a common manifestation of clinically relevant pain and target of pain treatment. Accordingly, the present study goal was to validate a novel assay of pain-depressed locomotor behavior in mice and evaluate the role of MOR efficacy as a determinant of opioid analgesic effects and related safety measures.MethodsMale and female ICR mice were tested in a locomotor chamber consisting of 2 compartments connected by a doorway that contained a 1-inch-tall barrier. Dependent measures during 15-min behavioral sessions included crosses between compartments (which required vertical activity to surmount the barrier) and total movement counts (which required horizontal activity to break photobeams in each compartment).Results and DiscussionIntraperitoneal injection of lactic acid (IP acid) produced a concentration- and time-dependent depression of both endpoints. Optimal blockade of IP acid-induced behavioral depression with minimal motor impairment was achieved with intermediate-efficacy MOR treatments that also produced less gastrointestinal-transit inhibition and respiratory depression than the high-efficacy MOR agonist fentanyl. Sex differences in treatment effects were rare. Overall, these findings validate a novel procedure for evaluating opioids and other candidate analgesic effects on pain-related behavioral depression in mice and support continued research with intermediate-efficacy MOR agonists as a strategy to retain opioid analgesic effectiveness with improved safety.
Neonatal cholestasis as the onset symptom of McCune–Albright syndrome: case reports and a literature review
Authors: Fang Weiyuan , Zhang Yanhui , Chen Lian , Xie Xinbao 
Published: October 2023

AimThis study aimed to summarize and show the characteristics and evolutionary process of neonatal cholestasis caused by McCune–Albright syndrome (MAS), as neonatal cholestasis may be the initial manifestation of MAS before other classic clinical features appear.MethodsThe clinical characteristics, treatment methods, and outcomes of three neonatal cholestasis cases caused by MAS in our center were retrospectively studied. In addition, all the reported cases of MAS combined with cholestasis were reviewed and summarized to show the cholestatic features in them.ResultsWe have confirmed three MAS cases in our center, presenting onset symptoms of jaundice, pale stool, and neonatal cholestasis soon after birth. The cholestasis subsided spontaneously at around the sixth month. The literature review showed that the levels of total bilirubin, conjugated bilirubin, ALT, AST, and GGT in neonatal MAS cholestasis cases were 207 μmol/L (range 65–445 μmol/L), 162 μmol/L (range 46–412 μmol/L), 821 U/L (range 85–3,597 U/L), 532 U/L (range 127–3,633 U/L), and 244 U/L (range 79–3,800 U/L), respectively. Liver histology showed canalicular and hepatocellular cholestasis, giant hepatic cell transformation, and bile paucity. Extrahepatic manifestations such as café-au-lait pigmented skin lesions, Cushing's syndrome, hyperthyroidism, renal tubular dysfunction, and skeletal abnormalities could occur simultaneously when jaundice occurred. GNAS mutations had a high positive rate (83.3%–100%) in liver tissue with cholestasis. Neonatal cholestasis caused by MAS could be self-resolved, but hepatic lesions persist and have malignant potential.ConclusionMAS can be one of the causes of neonatal cholestasis, which may be the first manifestation of the disease. Extrahepatic coexisting symptoms of MAS and liver histology can help to distinguish MAS from other etiology of cholestasis. Detecting GNAS mutations in liver tissue may shorten diagnostic time and is of particular interest in the partial and atypical forms of MAS with neonatal cholestasis. Neonatal cholestasis in children with MAS can self-resolve, but liver dysfunction and malignant lesions persist.