bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are comorbidities of patients with adrenal incidentaloma tied to sex?
Authors: Puglisi Soraya , Barač Nekić Anja , Morelli Valentina , Alessi Ylenia , Fosci Michele , Pani Angelo , Zibar Tomsic Karin , Palmieri Serena , Ferraù Francesco , Pia Anna , Chiodini Iacopo , Kastelan Darko , Reimondo Giuseppe , Terzolo Massimo 
Published: May 2024

BackgroundA recent cross-sectional study showed that both comorbidities and mortality in patients with adrenal incidentaloma (AI) are tied to sex. However, few longitudinal studies evaluated the development of arterial hypertension, hyperglycemia, dyslipidemia and bone impairment in patients with AI. The aim of this study is to analyze the impact of sex in the development of these comorbidities during long-term follow-up.MethodsWe retrospectively evaluated 189 patients (120 females, 69 males) with AI, from four referral centers in Italy and Croatia. Clinical characteristics, comorbidities and cortisol after 1-mg dexamethasone suppression test (1-mg DST) were assessed at baseline and at last follow-up visit (LFUV). Median follow-up was 52 (Interquartile Range 25-86) months.ResultsThe rates of arterial hypertension and hyperglycemia increased over time both in females (65.8% at baseline versus 77.8% at LFUV, p=0.002; 23.7% at baseline versus 39.6% at LFUV, p&lt;0.001; respectively) and males (58.0% at baseline versus 69.1% at LFUV, p=0.035; 33.8% at baseline versus 54.0% at LFUV, p&lt;0.001; respectively). Patients were stratified in two groups using 1.8 µg/dl as cut-off of cortisol following 1-mg DST: non-functional adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS). In the NFAT group (99 patients, females 62.6%), at baseline, we did not observe any difference in clinical characteristics and comorbidities between males and females. At LFUV, males showed a higher frequency of hyperglycemia than females (57.6% versus 33.9%, p=0.03). In the MACS group (89 patients, females 64.0%), at baseline, the prevalence of hypertension, hyperglycemia and dyslipidemia was similar between sexes, despite females were younger (60, IQR 55-69 versus 67.5, IQR 61-73, years; p=0.01). Moreover, females presented higher rates of bone impairment (89.3% versus 54.5%, p=0.02) than males. At LFUV, a similar sex-related pattern was observed.ConclusionPatients with AI frequently develop arterial hypertension and hyperglycemia and should be periodically checked for these comorbidities, regardless of sex. In patients with MACS, the lack of difference between sexes in the frequency of cardiometabolic comorbidities despite that females are younger, and the higher frequency of bone impairment in females, suggest a sex-specific effect of cortisol.
Two new and effective food-extracted immunomodulatory agents exhibit anti-inflammatory response activity in the hACE2 acute lung injury murine model of COVID-19
Authors: Liu Shasha , Wang Baiqiao , Chen Tianran , Wang Hui , Liu Jinbo , Zhao Xuan , Zhang Yi 
Published: May 2024

ObjectiveThe coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model.MethodsIn this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&amp;E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome.ResultsOur results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group.ConclusionHere, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.
Validating a theory of planned behavior questionnaire for assessing changes in professional behaviors of medical students
Authors: Guraya Shaista Salman , Clarke Eric , Sadeq Asil , Smith Mary , Hand Sinead , Doyle Frank , Kearney Grainne , Harbinson Mark , Ryan Aine , Boland Fiona , Bensaaud Abdelsalam , Guraya Salman Yousuf , Harkin Denis W. 
Published: May 2024

IntroductionTeaching professionalism is a fundamental aspect of medical undergraduate education, delivering important domains of professional attitudes, ethics, and behaviors. The effects of educational interventions can be assessed by measuring the change in such domains, but validated assessment tools for these professionalism domains are lacking. In this study, we constructed and conducted expert validation of a modified theory of planned behavior (TPB) questionnaire to assess changes in professional behaviors (PBs) in medical students.MethodsTo validate that, we modified an existing TPB questionnaire, and an 18-item questionnaire was subjected to expert panel evaluation using the content validation method. The clarity and relevance of items were assessed using a four-point rating scale (i.e., 1 = not relevant to 4 = highly relevant). Ratings of experts and free-text comments were analyzed. Quantitative evaluation of relevance and clarity was undertaken through analyses of the Item-level Content Validity Index (I-CVI) and Scale-level Content Validity Index (S-CVI). A qualitative assessment of the comments of experts was conducted to refine items, any disagreements were discussed, and a consensus decision was developed among authors for item changes.ResultsQuantitative evaluation of the Item-level Content Validity Index (I-CVI) scored 0.9–1 for relevance and 0.7–1 for clarity. Qualitative evaluation resulted in (i) changes to the wording of items (e.g., choices such as “worthless/worthwhile” were replaced with “not important/important”); and (ii) suggestion of the addition of social media in the construct of subjective norms.DiscussionThe proposed tool exhibits content validity and can assess TPB constructs in professionalism education. This study of content validity may help to ensure the modified TPB questionnaire accurately measures the TPB constructs, ensuring its effectiveness in accurately measuring the TPB constructs for PB in diversified educational medical institutions.
Nitrification inhibitor chlorate and nitrogen substrates differentially affect comammox Nitrospira in a grassland soil
Authors: Shah Anish S. , Hsu Pei-Chun , Chisholm Chris , Podolyan Andriy , Cameron Keith , Luo Jiafa , Stenger Roland , Carrick Sam , Hu Wei , Ferguson Scott A. , Wei Wenhua , Shen Jupei , Zhang Limei , Liu Hongbin , Zhao Tongke , Wei Wenxue , Ding Weixin , Pan Hong , Liu Yimeng , Li Bowen , Du Jianjun , Di Hong J. 
Published: May 2024

IntroductionThrough the combined use of two nitrification inhibitors, Dicyandiamide (DCD) and chlorate with nitrogen amendment, this study aimed to investigate the contribution of comammox Nitrospira clade B, ammonia oxidizing bacteria (AOB) and archaea (AOA) to nitrification in a high fertility grassland soil, in a 90-day incubation study.MethodsThe soil was treated with nitrogen (N) at three levels: 0 mg-N kg-1 soil, 50 mg-N kg-1 soil, and 700 mg-N kg-1 soil, with or without the two nitrification inhibitors. The abundance of comammox Nitrospira, AOA, AOB, and nitrite oxidising bacteria (NOB) was measured using qPCR. The comammox Nitrospira community structure was assessed using Illumina sequencing.Results and DiscussionThe results showed that the application of chlorate inhibited the oxidation of both NH4+ and NO2- in all three nitrogen treatments. The application of chlorate significantly reduced the abundance of comammox Nitrospira amoA and nxrB genes across the 90-day experimental period. Chlorate also had a significant effect on the beta diversity (Bray-Curtis dissimilarity) of the comammox Nitrospira clade B community. Whilst AOB grew in response to the N substrate additions and were inhibited by both inhibitors, AOA showed litle or no response to either the N substrate or inhibitor treatments. In contrast, comammox Nitrospira clade B were inhibited by the high ammonium concentrations released from the urine substrates. These results demonstrate the differential and niche responses of the three ammonia oxidising communities to N substrate additions and nitrification inhibitor treatments. Further research is needed to investigate the specificity of the two inhibitors on the different ammonia oxidising communities.
Sex differences in hippocampal β-adrenergic receptor subtypes drive retrieval, retention, and learning of cocaine-associated memories
Authors: Berry Melanie M. , Miller Beau , Kelsen Silvia , Cockrell Carlee , Kohtz Amy Stave 
Published: May 2024

BackgroundDrug seeking behavior occurs in response to environmental contexts and drug-associated cues. The presence of these pervasive stimuli impedes abstinence success. β-adrenergic receptors (β-ARs) have a long-standing historical implication in driving processes associated with contextual memories, including drug-associated memories in substance use disorders. However, sex differences in the role of β-adrenergic receptors in drug memories remain unknown.HypothesisPrior reports indicate a selective role for β2-ARs in retrieval and retention of contextual drug memories in males, and substantial sex differences exist in the expression of β-ARs of male and female rats. Therefore, we hypothesized that there are sex differences in selective recruitment of β-ARs during different stages of memory encoding and retrieval.MethodsThe role of β-ARs in driving retrieval and learning of contextual cocaine memories was investigated using cocaine conditioned place preference (CPP) in adult male and female Sprague–Dawley rats. Rats were infused directly to the dorsal hippocampus with Propranolol (β1 and β2) or ICI-118,551 (β1) and/or Betaxolol (β2), immediately prior to testing (retrieval), or paired to each cocaine (10 mg/kp, IP) conditioning session (learning).ResultsIn males, administration of either β1, β2, or combined β1 and β2-ARs before the initial CPP testing reduced the expression of a CPP compared to vehicle administration. In females, β2-ARs transiently decreased CPP memories, whereas β1 had long lasting but not immediate effects to decrease CPP memories. Additionally, β1 and combined β1 and β2-ARs had immediate and persistent effects to decrease CPP memory expression. DG Fos + neurons predicted cocaine CPP expression in males, whereas CA1 and CA3 Fos + neurons predicted cocaine CPP expression in females.ConclusionThere are significant sex differences in the role of dorsal hippocampus β-ARs in the encoding and expression of cocaine conditioned place preference. Furthermore, sub regions of the dorsal hippocampus appear to activate differently between male and female rats during CPP. Therefore DG, CA3, and CA1 may have separate region- and sex-specific impacts on driving drug- associated, or context-associated cues.
Wishes, beliefs, and jealousy: use of mental state terms in Cinderella retells after traumatic brain injury
Authors: Greenslade Kathryn J. , Honan Cynthia , Harrington Lauren , Kenealy Laura , Ramage Amy E. , Bogart Elise 
Published: May 2024

IntroductionTraumatic brain injury (TBI) negatively impacts social communication in part due to social cognitive difficulties, which may include reduced mental state term (MST) use in some discourse genres. As social cognitive difficulties can negatively impact relationships, employment, and meaningful everyday activities, assessing and treating these difficulties post-TBI is crucial. To address knowledge gaps, the present study examined MST use in the narrative retells of adults with and without severe TBI to compare between-group performance, evaluate changes over the first two years post-TBI, and investigate the impact of participant and injury-related variables.MethodsThe total number of MSTs, ratio of MSTs to total utterances, and diversity of MSTs were identified in the Cinderella narratives of 57 participants with no brain injury and 57 with TBI at 3, 6, 9, 12, and 24-months post-TBI.ResultsReduced MST use in participants with TBI was found at 3, 6, 9, and 12-months post-TBI, but these reductions disappeared when story length (total utterances) was accounted for. Further, MST diversity did not differ between groups. Similarly, although the total number of MSTs increased over time post-TBI, no changes were observed in the ratio of MSTs to total utterances or MST diversity over time. Injury severity (post-traumatic amnesia duration), years of education, and verbal reasoning abilities were all related to MST use.DiscussionOverall, although individuals used fewer MSTs in complex story retells across the first year following severe TBI, this reduction reflected impoverished story content, rather than the use of a lower ratio of MSTs. Further, key prognostic factors related to MST use included injury severity, educational attainment, and verbal reasoning ability. These findings have important implications for social communication assessment and treatment targeting social cognition post-TBI.
Differential transcriptional profiles of vagal sensory neurons in female and male mice
Authors: Jo Young-Hwan 
Published: May 2024

IntroductionDifferences in metabolic homeostasis, diabetes, and obesity between males and females are evident in rodents and humans. Vagal sensory neurons in the vagus nerve ganglia innervate a variety of visceral organs and use specialized nerve endings to sense interoceptive signals. This visceral organ-brain axis plays a role in relaying interoceptive signals to higher brain centers, as well as in regulating the vago-vagal reflex. I hypothesized that molecularly distinct populations of vagal sensory neurons would play a role in causing differences in metabolic homeostasis between the sexes.MethodsSnRNA-Seq was conducted on dissociated cells from the vagus nerve ganglia using the 10X Genomics Chromium platform.ResultsSingle-nucleus RNA sequencing analysis of vagal sensory neurons from female and male mice revealed differences in the transcriptional profiles of cells in the vagus nerve ganglia. These differences are linked to the expression of sex-specific genes such as Xist, Tsix, and Ddx3y. Among the 13 neuronal clusters, one-fourth of the neurons in male mice were located in the Ddx3y-enriched VN1 and VN8 clusters, which displayed higher enrichment of Trpv1, Piezo2, Htr3a, and Vip genes. In contrast, 70% of the neurons in females were found in Xist-enriched clusters VN4, 6, 7, 10, 11, and 13, which showed enriched genes such as Fgfr1, Lpar1, Cpe, Esr1, Nrg1, Egfr, and Oprm1. Two clusters of satellite cells were identified, one of which contained oligodendrocyte precursor cells in male mice. A small population of cells expressed Ucp1 and Plin1, indicating that they are epineural adipocytes.DiscussionUnderstanding the physiological implications of distinct transcriptomic profiles in vagal sensory neurons on energy balance and metabolic homeostasis would help develop sex-specific treatments for obesity and metabolic dysregulation.
Association of composite dietary antioxidant index with mortality in adults with hypertension: evidence from NHANES
Authors: Qin Huali , Shen Li , Xu Danyan 
Published: May 2024

ObjectiveThe objective of this study is to assess the correlation between composite dietary antioxidant index (CDAI) with all-cause mortality and cause-specific mortality in adults with hypertension.MethodsThe cohort study comprised adult participants with hypertension from the NHANES database, spanning 9 cycles from 2001 to 2018. Follow-up was conducted until December 31, 2019. Multi-variable Cox regression analysis was utilized to ascertain hazard ratios (HR) and their corresponding 95% confidence intervals, evaluating the relationship between CDAI and the risks of all-cause and cause-specific mortality. To further investigate the association between CDAI and mortality rates in adults with hypertension, Kaplan–Meier survival curves, restricted cubic splines (RCS), subgroup analyses and sensitivity analyses were employed.ResultsThe analysis included 16,713 adults with hypertension (mean age 56.93 ± 0.23 years, 8,327 [49.61%] male). During the mean follow-up time 102.11 ± 1.22 months, with 3,908 (18.08%) all-cause mortality occurred, 1,082 (4.84%) cardiovascular mortality and 833 (3.80%) cancer mortality. Compared to the lowest quartile of CDAI, the weighted multivariate hazard ratios of participants in the highest quartile was 0.77 (95% CI, 0.68–0.87) for all-cause mortality, 0.83 (95% CI, 0.67–1.04) for cardiovascular mortality, and 0.64 (95% CI, 0.50–0.82) for cancer mortality. RCS analysis demonstrated a nonlinear association of CDAI with all-cause and cancer mortality, and a linear association between CDAI and cardiovascular mortality. The results were robust in subgroup analyses and sensitivity analyses.ConclusionHigher CDAI is associated with reduced all-cause mortality, cardiovascular mortality, and cancer mortality in hypertensive adults. Our findings highlight the importance of an antioxidant diet in improving outcomes in adults with hypertension.
Complete remission of depression and anxiety using a ketogenic diet: case series
Authors: Calabrese Lori , Frase Rachel , Ghaloo Mariam 
Published: May 2024

BackgroundThere is little data that describe the use of ketogenic metabolic therapy to achieve full remission of major depression and generalized anxiety disorder in clinical practice. We present a retrospective case series of three adults with major depression and generalized anxiety disorder with complex comorbidity, treated with personalized ketogenic metabolic therapy, who achieved complete remission of major depression and generalized anxiety disorder and improvements in flourishing, self-compassion, and metabolic health.MethodsThree adults, ages 32–36, with major depression, generalized anxiety, other anxiety disorders, and comorbid psychiatric conditions were treated for 12–16 weeks with personalized whole food animal-based ketogenic metabolic therapy (1.5:1 ratio) in a specialized metabolic psychiatry practice. Interventions included twice-weekly visits with an experienced ketogenic registered dietitian; daily photo journaling and capillary blood BHB/glucose/GKI monitoring; virtual groups; family/friends support; nature walks and talks several times per week, and community building. Successful adoption of the ketogenic diet was defined as the achievement and maintenance of capillary BHB ≥ 0.8 mmol/L and GKI &lt; 6. Remission was assessed by GAD-7 and PHQ-9, and quality of life was assessed subjectively and with validated scales for flourishing and self-compassion. Metabolic health was assessed by laboratories/biometric measures.ResultsTwo patients achieved remission of major depression (PHQ-9 ≤ 4) and generalized anxiety (GAD-7 ≤ 4) within 7 weeks of therapeutic nutritional ketosis; one required 12 weeks. Anxiety responded and remitted more quickly than major depression. Flourishing and self-compassion increased steadily. Patients lost 10.9 to 14.8% of their initial body weight within 12 weeks and improved metabolically; one achieved optimal metabolic health.ConclusionComplete remission of major depression and generalized anxiety disorder occurred within 7–12 weeks of therapeutic nutritional ketosis during treatment with a personalized animal-based ketogenic diet (ratio 1.5:1) in adults with complex comorbid depression and anxiety engaged in a specialized metabolic psychiatry program.
Primary hepatic neuroendocrine neoplasms: imaging characteristics and misdiagnosis analysis
Authors: Yang Xiu-Rong , Li Ying-Li , Li Zi-Yan , Chai Xiao-Ming 
Published: May 2024

ObjectiveTo analyze the CT and MR features of Primary hepatic neuroendocrine neoplasms (PHNENs) in order to enhance the diagnostic accuracy of this disease.MethodsA retrospective analysis was conducted on patients diagnosed with hepatic neuroendocrine neoplasms, excluding other sites of origin through general examination and postoperative follow-up. The CT and MR signs were analyzed according to the 2018 version of Liver Imaging Reporting and Data System (LI-RADS), along with causes of misdiagnosis.ResultsTwelve patients, including 6 males and 6 females, were enrolled in this study. There was no significant increase in liver tumor markers among all cases. Most masses were multiple (9/12), exhibiting low attenuation on pre-contrast CT scans, T1-hypointense signal, T2-hyperintense signal, and restricted diffusion. The majority of these masses (7/10) demonstrated similar rim arterial phase hyper-enhancement as well as peripheral “washout” during venous portal phase and delayed phase imaging. Three cases had incomplete capsules while one case had a complete capsule. Cyst/necrosis was observed in 7 out of all cases following administration of contrast agent, with 5 mainly distributed in the periphery. All masses lacked fat, calcification, vascular or bile duct tumor thrombus formation.ConclusionThe imaging findings associated with PHNENs possess certain specificity, often presenting as multiple masses within the liver accompanied by peripheral cyst/necrosis, similar rim arterial phase hyper-enhancement during venous portal phase and delayed phase imaging.