bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Childhood Traumatization on Diabetes Mellitus Type 2 Risk in World War II Refugees and Their Offspring
Authors: Wildenberg Katharina S. , Zillich Lea , Streit Fabian , Maier Bernhard C. L. , Distel Daniela , Hammes Hans-Peter , Witt Stephanie H. , Deuschle Michael 
Published: May 2023

ABSTRACT

Objective
Type 2 diabetes mellitus (T2D) is a chronic disease that is influenced by different factors. The extent to which degree adverse childhood events (ACEs) can modify the potential to development of T2D is still not explored and therefore represents one of the central questions of the childhood escape–late life outcome (DRKS00012419) study. In addition, transgenerational effects were considered in the analyses.

Methods
The study analyzed the association of self-reported traumatic experiences and T2D disease of refugees from East Prussia, who were displaced from their former homeland at the end of the World War II. In addition, an independent sample consisting of participants of first-generation offspring of refugees was analyzed.

Results
Of the 242 refugees, all aged between 73 and 93 years, 17.36% reported T2D disease, whereas among the offspring (n = 272), aged between 47 and 73 years, it was 5.5%, meaning reduced T2D prevalence for both generations compared with the German population of comparable age. In the refugee generation, emotional neglect showed a negative association with development of T2D in later life. In women, separation from close caregivers in childhood showed a negative association with later T2D. In contrast, experiencing emotional abuse in childhood showed a positive association with later T2D. The offspring generation showed no associations of adverse childhood events and reported T2D diagnoses in later life.

Conclusions
Our results demonstrate that individual trauma in childhood is responded to with different mechanisms that can lead to both increased and decreased reported T2D diagnoses in adulthood and thus should by no means be considered in a generalized manner.
Adverse Childhood Experiences Predict Diurnal Cortisol Throughout Gestation
Authors: Panisch Lisa S. , Murphy Hannah R. , Wu Qiuyi , Brunner Jessica L. , Duberstein Zoe T. , Arnold Molly S. , Best Meghan , Barrett Emily S. , Miller Richard K. , Qiu Xing , O’Connor Thomas G. 
Published: May 2023

Abstract

Objective
Adverse childhood experiences (ACEs) are associated with negative prenatal and perinatal health outcomes and may, via these pathways, have intergenerational effects on child health and development. We examine the impact of ACEs on maternal salivary cortisol, a key measure of prenatal biology previously linked with pregnancy-related health outcomes.

Methods
Leveraging assessments across three trimesters, we used linear mixed effect models to analyze the influence of ACEs on maternal prenatal diurnal cortisol patterns in a diverse cohort of pregnant women (analytic sample n = 207). Covariates included comorbid prenatal depression, psychiatric medications, and socio-demographic factors.

Results
Maternal ACEs were significantly associated with flatter diurnal cortisol slopes (i.e., less steep decline), after adjusting for covariates, with effects consistent across gestation (estimate = 0.15 SE 0.06, p = 0.008).

Conclusions
ACEs experienced prior to pregnancy may have a robust and lasting influence on maternal prenatal hypothalamic-pituitary-adrenal activity throughout gestation, a key biological marker associated with perinatal and child health outcomes. The findings suggest one route of intergenerational transmission of early adverse experiences and underscore the potential value of assessing pre-pregnancy adverse experiences for promoting perinatal and maternal and child health.
Microbiota in the oral cavity of school-age children living with HIV who started antiretroviral therapy at young ages in South Africa
Authors: Kuhn Louise , Wang Tian , Li Fan , Strehlau Renate , Tobin Nicole H. , Violari Avy , Brooker Sarah , Patel Faeezah , Liberty Afaaf , Shiau Stephanie , Arpadi Stephen M. , Wadhwa Sunil , Yin Michael T. , Wang Shuang , Tiemessen Caroline T. , Aldrovandi Grace M. 
Published: May 2023

Background:
Infancy is an important developmental period when the microbiome is shaped. We hypothesized that earlier antiretroviral therapy (ART) initiation would attenuate HIV effects on microbiota in the mouth.

Methods:
Oral swabs were collected from 477 children living with HIV (CLWH) and 123 children without (controls) at two sites in Johannesburg, South Africa. CLWH had started ART <3 years of age; 63% <6 months of age. Most were well-controlled on ART at median age 11 years when the swab was collected. Controls were age-matched and recruited from the same communities. Sequencing of V4 amplicon of 16S rRNA was done. Differences in microbial diversity and relative abundances of taxa were compared between groups.

Results:
CLWH had lower alpha diversity than controls. Genus-level abundances of Granulicatella, Streptococcus and Gemella were greater and Neisseria and Haemophilus less abundant among CLWH than controls. Associations were stronger among boys. Associations were not attenuated with earlier ART initiation. Shifts in genus-level taxa abundances in CLWH relative to controls were most marked in children on lopinavir/ritonavir regimens; with fewer shifts seen if on efavirenz ART regimens.

Conclusions:
A distinct profile of less diverse oral bacterial taxa was observed in school-aged CLWH on ART compared to uninfected controls suggesting modulation of microbiota in the mouth by HIV and/or its treatments. Earlier ART initiation was not associated with microbiota profile. Proximal factors, including current ART regimen, were associated with contemporaneous profile of oral microbiota and may have masked associations with distal factors like age at ART initiation.
Bone and Renal Health in Infants With or Without Breastmilk Exposure to Tenofovir-Based Maternal Antiretroviral Treatment in the PROMISE Randomized Trial
Authors: Vhembo Tichaona , Baltrusaitis Kristin , Tierney Camlin , Owor Maxensia , Dadabhai Sufia , Violari Avy , Theron Gerhard , Moodley Dhayendre , Mukwasi-Kahari Cynthia , George Kathleen , Shepherd John , Siberry George K. , Browning Renee , Fowler Mary Glenn , Stranix-Chibanda Lynda ,   for the IMPAACT P1084s study team
Published: May 2023

Background:
We assessed bone and kidney outcomes in infants randomized postdelivery as mother–infant pairs within the IMPAACT PROMISE trial to maternal tenofovir disoproxil fumarate–based antiretroviral treatment (mART) or infant nevirapine prophylaxis (iNVP) to prevent breastfeeding HIV transmission.

Methods:
Infants were coenrolled in the P1084s substudy on randomization day and followed through Week 74. Lumbar spine bone mineral content (LS-BMC) was assessed at entry (6–21 age days) and Week 26 by dual-energy x-ray absorptiometry. Creatinine clearance (CrCl) was calculated at entry; Weeks 10, 26, and 74. Student t tests compared mean LS-BMC and CrCl at Week 26 and mean change from entry between arms.

Results:
Of 400 enrolled infants, the mean (SD; n) for entry LS-BMC was 1.68 g (0.35; n = 363) and CrCl was 64.2 mL/min/1.73 m2 (24.6; n = 357). At Week 26, 98% of infants were breastfeeding and 96% on their assigned HIV prevention strategy. The mean (SD) Week 26 LS-BMC was 2.64 g (0.48) for mART and 2.77 g (0.44) for iNVP; mean difference (95% confidence interval [CI]) −0.13 g (−0.22 to −0.04), P = 0.007, n = 375/398 (94%). Mean absolute (−0.14 g [−0.23 to −0.06]) and percent (−10.88% [−18.53 to −3.23]) increase in LS-BMC from entry was smaller for mART than iNVP. At Week 26, the mean (SD) CrCl was 130.0 mL/min/1.73 m2 (34.9) for mART vs. 126.1 mL/min/1.73 m2 (30.0) for iNVP; mean difference (95% CI) 3.8 (−3.0 to 10.7), P = 0.27, n = 349/398 (88%).

Conclusion:
Week 26 mean LS-BMC was lower in infants in the mART group compared with the iNVP group. However, this difference (∼0.23 g) was less than one-half SD, considered potentially clinically relevant. No infant renal safety concerns were observed.
FDG PET/CT Findings of Malignant Rhabdoid Tumor Arising From a Renal Allograft
Authors: Xiao Zhengguang , Lu Wenjie , Dong Aisheng , Wang Yang 
Published: May 2023

Abstract
Malignant rhabdoid tumor of the kidney is a rare aggressive malignancy with poor prognosis. We describe FDG PET/CT findings in a case of malignant rhabdoid tumor of the renal allograft with regional lymph node and pulmonary metastases. The primary renal tumor and lymph node metastases showed intense FDG uptake. The pulmonary metastases showed minimal FDG uptake due to small size. Posttreatment FDG PET/CT showed no evidence of residual disease. This case suggests that FDG PET/CT may be useful in the management of malignant rhabdoid tumor from the transplanted kidney.
3D-Ring CZT System With New Low- and Medium-Energy Range
Authors: Callaud Aurélien , Metrard Gilles , Bailly Matthieu 
Published: May 2023

Abstract
New 3D-ring CZT systems with low- and medium-energy-range detectors allow for simultaneous dual-isotope lung scintigraphy. We compared 10-, 7-, 5-, and 3-minute acquisitions for 99mTc and 81mKr performed simultaneously on StarGuide CZT-SPECT/CT and reframed in 50 patients. Ventilation/perfusion mismatches were calculated (mean, 15.6% ± 28%), and Spearman correlation coefficients of mismatches were 0.994, 0.994, and 0.984 between 10- and 7-, 5-, and 3-minute acquisitions, respectively. No visual difference in image quality or final diagnosis was found. 3D-ring CZT-SPECT with low and medium energy range detectors allows ultrafast dual-isotope lung scintigraphy up to 3 minutes.
Qualification of Ventricular Flow in Patients With Precapillary Pulmonary Hypertension With 4-dimensional Flow Magnetic Resonance Imaging
Authors: Xu Wenqing , Deng Mei , Zhang Ling , Zhang Peiyao , Gao Qian , Tao Xincao , Zhen Yanan , Liu Xiaopeng , Jin Ning , Chen Wenhui , Xie Wanmu , Liu Min 
Published: May 2023

Purpose:
Our goal was to study both right and left ventricular blood flow in patients with precapillary pulmonary hypertension (pre-PH) with 4-dimensional (4D) flow magnetic resonance imaging (MRI) and to analyze their correlation with cardiac functional metrics on cardiovascular magnetic resonance (CMR) and hemodynamics from right heart catheterization (RHC).

Materials and Methods:
129 patients (64 females, mean age 47 ± 13 y) including 105 patients with pre-PH (54 females, mean age 49 ± 13 y) and 24 patients without PH (10 females, mean age 40 ± 12 y) were retrospectively included. All patients underwent CMR and RHC within 48 hours. 4D flow MRI was acquired using a 3-dimensional retrospectively electrocardiograph-triggered, navigator-gated phase contrast sequence. Right and left ventricular flow components including the percentages of direct flow (PDF), retained inflow (PRI), delayed ejection flow (PDE), and residual volume (PRVo) were respectively quantified. The ventricular flow components between patients with pre-PH and non-PH were compared and correlations of flow components with CMR functional metrics and hemodynamics measured with RHC were analyzed. Biventricular flow components were compared between survivors and deceased patients during the perioperative period.

Results:
Right ventricular (RV) PDF and PDE significantly correlated with RVEDV and RV ejection fraction. RV PDF negatively correlated with pulmonary arterial pressure (PAP) and pulmonary vascular resistance. When the RV PDF was <11%, the sensitivity and specificity of RV PDF for predicting mean PAP ≥25 mm Hg were 88.6% and 98.7%, respectively, with an area under the curve value of 0.95 ± 0.02. When RV PRVo was more than 42%, the sensitivity and specificity of RV PRVo for predicting mean PAP ≥25 mm Hg were 85.7% and 98.5%, respectively, with an area under the curve value of 0.95 ± 0.01. Nine patients died during the perioperative period. Biventricular PDF, RV PDE, and PRI of survivors were higher than nonsurvivors whereas RV PRVo increased in deceased patients.

Conclusions:
Biventricular flow analysis with 4D flow MRI provides comprehensive information about the severity and cardiac remodeling of PH and may be a predictor of perioperative death of patients with pre-PH.
Comparison of hydroxocobalamin with other resuscitative fluids in volume-controlled and uncontrolled hemorrhage models in swine (Sus-scrofa)
Authors: Paredes R. Madelaine , Castaneda Maria , Mireles Allyson A. , Rodriguez Dylan , Maddry Joseph 
Published: May 2023

BACKGROUND
Traumatic hemorrhage is the leading cause of preventable death in military environments. Treatment with resuscitative fluids and blood components is based on availability, thus, frequently unavailable in the prehospital setting, due to lack of resources and costs. Hydroxocobalamin (HOC), increases blood pressure via nitric oxide scavenging. We evaluated HOC as a resuscitation fluid, in two swine hemorrhage models. Our objectives were to (1) evaluate whether HOC treatment following hemorrhagic shock improves hemodynamic parameters and (2) determine whether those effects are comparable to whole blood (WB) and lactated ringers (LR).

METHODS
Yorkshire swine (Sus scrofa) (n = 72) were used in models of controlled hemorrhage (CH) (n = 36) and uncontrolled hemorrhage (UH) (n = 36). Randomized animals received treatment with 500 mL of either WB, LR, HOC (150 mg/kg), followed by a six-hour observation (n = 6 each group). Survival, hemodynamics, blood gases (ABGs) and chemistries were collected. Data reported as mean ± standard error of the mean and statistical analysis by ANOVA (p < 0.05).

RESULTS
Blood loss for CH was 41% ± 0.02 versus 33% ± 0.07 for UH. For CH, HOC treatment maintained higher systolic blood pressure (sBP, mm Hg) compared with WB and LR (72 ± 1.1; 60 ± 0.8; 58 ± 1.6; respectively). Heart rate (HR), cardiac output (CO), Sp
o
2
and vascular resistance were comparable with WB and LR. The ABG values were comparable between HOC and WB. For UH, HOC treatment maintained sBP levels comparable to WB and higher than LR (70 ± 0.9; 73 ± 0.5; 56 ± 1.2). HR, CO, Sp
o
2
, and systemic vascular resistance were comparable between HOC and WB. Survival, hemodynamics, blood gases were comparable between HOC and WB. No survival differences were found between cohorts.

CONCLUSION
Hydroxocobalamin treatment improved hemodynamic parameters and Ca2+ levels compared with LR and equivalent to WB, in both models. Hydroxocobalamin may be a viable alternative when WB is not available.
Pediatric Intraoperative Neurophysiological Monitoring and Long-Term Outcomes in a Developing Country
Authors: San-Juan Daniel , Vanegas Jenny Angelica Vicuña , López Raúl Aguilar , Jiménez Christian Ramos , Reyes Luis Adrián de la Cruz 
Published: May 2023

Purpose:
Pediatric intraoperative neurophysiological monitoring (IONM) has been shown to be effective in preventing and reversing postoperative neurological deficits in developed countries. There are currently no published studies from developing countries that describe neurophysiological findings and postoperative outcomes. Our study aims to address these gaps in children undergoing neurosurgical procedures in a single center.

Methods:
We conducted a retrospective study of case series of children who underwent IONM (2014–2020) in the State of Mexico, Mexico. Sociodemographic characteristics, IONM modalities, changes during procedures, and short-term and long-term postoperative results were recorded. Descriptive statistics were used.

Results:
We included 35 patients (≤18 years of age), 57% (20/35) boys. A relative increase of up to 5 times in the use of IONM is observed from 2014 (5.7%) to 2020 (25.7%) in our center. The most frequent preoperative pathologies were located at the infratentorial cranium (40%), followed by the spine and spinal cord (37.1%). The IONM modalities were as follows: free-running EMG 94.3%, transcranial electrical stimulation motor-evoked potentials 91.4%, somatosensory-evoked potentials 85.7%, triggered EMG 28.6%, EEG 25.7%, and visual-evoked potentials 5.7%. Only in 8.3%, we did not obtain sufficient evoked potential baseline signals. At 24 hours postoperatively true negatives were 100%. Long-term follow-up was completed in 22/35 (63%) at 3 months, 12/35 (34.2%) at 6 months, and 5/35 (14.3%) at 12 months with progressive motor and sensory improvement.

Conclusions:
Pediatric multimodal IONM in neurosurgeries from a single center in a developing country is mainly used in pathologies of the posterior fossa, spine, and spinal cord, with true negatives in 100% of those monitored, preventing and avoiding postoperative sequelae.
Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors
Authors: Crawford McKenna C. , Tripu Deepika R. , Barritt Samuel A. , Jing Yihang , Gallimore Diamond , Kales Stephen C. , Bhanu Natarajan V. , Xiong Ying , Fang Yuhong , Butler Kamaria A. T. , LeClair Christopher A. , Coussens Nathan P. , Simeonov Anton , Garcia Benjamin A. , Dibble Christian C. , Meier Jordan L. 
Published: May 2023

AbstractThe human acetyltransferase paralogs EP300 and CREBBP are master regulators of lysine acetylation whose activity has been implicated in various cancers. In the half-decade since the first drug-like inhibitors of these proteins were reported, three unique molecular scaffolds have taken precedent: an indane spiro-oxazolidinedione (A-485), a spiro-hydantoin (iP300w), and an aminopyridine (CPI-1612). Despite increasing use of these molecules to study lysine acetylation, the dearth of data regarding their relative biochemical and biological potencies makes their application as chemical probes a challenge. To address this gap, here we present a comparative study of drug-like EP300/CREBBP acetyltransferase inhibitors. First, we determine the biochemical and biological potencies of A-485, iP300w, and CPI-1612, highlighting the increased potency of the latter two compounds at physiological acetyl-CoA concentrations. Cellular evaluation shows that inhibition of histone acetylation and cell growth closely aligns with the biochemical potencies of these molecules, consistent with an on-target mechanism. Finally, we demonstrate the utility of comparative pharmacology by using it to investigate the hypothesis that increased CoA synthesis caused by knockout of PANK4 can competitively antagonize binding of EP300/CREBBP inhibitors and demonstrate proof-of-concept photorelease of a potent inhibitor molecule. Overall, our study demonstrates how knowledge of relative inhibitor potency can guide the study of EP300/CREBBP-dependent mechanisms and suggests new approaches to target delivery, thus broadening the therapeutic window of these preclinical epigenetic drug candidates.
Beyond the Kidney: Extra-Renal Manifestations of Monogenic Nephrolithiasis and Their Significance
Authors: Badreddine Jad , Tay Kimberly , Lin Hsin-Ti Cindy , Rhodes Stephen , Schumacher Fredrick R. , Bodner Donald , Wu Chen-Han Wilfred 
Published: May 2023

AbstractObjectiveTo explore the frequency of occurrence of extra-renal manifestations associated with monogenic kidney stone diseases.MethodsA literature review was conducted to identify genes that are well-established monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) and Human Protein Atlas (HPA) databases were used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a single gene-associated phenotype (GAP) unit such that one GAP encompasses all related disease phenotypes for a specific gene. We measured the total number of GAPs involving each phenotype category and determined the median phenotype category. Phenotype categories were classified as overrepresented or underrepresented if the number of GAPs involving them was higher or lower than the median, respectively. A chi-square test was conducted to determine whether the number of GAPs affecting a given category significantly deviated from the median.ResultsFifty-five genes were identified as monogenic causes of nephrolithiasis. All GAPs comprised at least one extra-renal phenotype category. The median phenotype category was part of 10 (18%) unique GAPs. A total of 6 significantly overrepresented (growth, skeletal, neurologic, abdomen/gastrointestinal, muscle, metabolic features) and 5 significantly underrepresented (mouth, voice, neck, immunology, neoplasia) phenotype categories were identified among our group of monogenic kidney stone diseases (p<0.05) with impaired growth being the most common manifestation.ConclusionMonogenic nephrolithiasis is a multi-system disorder. Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal prognosis in patients.
Patient-derived xenografts and single-cell sequencing identifies three subtypes of tumor-reactive lymphocytes in uveal melanoma metastases
Authors: Karlsson Joakim , Sah Vasu R. , Olofsson Bagge Roger , Kuznetsova Irina , Iqbal Munir , Alsén Samuel , Stenqvist Sofia , Saxena Alka , Ny Lars , Nilsson Lisa M. , Nilsson Jonas A. 
Published: May 2023

AbstractUveal melanoma (UM) is a rare melanoma originating in the eye’s uvea, with 50% of patients experiencing metastasis predominantly in the liver. In contrast to cutaneous melanoma, there is only a limited effectiveness of combined immune checkpoint therapies, and half of patients succumb to recurrent disease after two years. This study aimed to provide a path towards enhancing immunotherapy efficacy by identifying and functionally validating tumor-reactive T cells in liver metastases of patients with UM. We employed single-cell RNA sequencing of biopsies and tumor-infiltrating lymphocytes (TILs) to identify potential tumor-reactive T cells. Patient-derived xenograft (PDX) models of UM metastases were created from patients, and tumor sphere cultures were generated from these models for co-culture with autologous or MART1-specific HLA-matched allogenic TILs. Activated T cells were subjected to TCR sequencing, and the TCRs were matched to those found in single-cell sequencing data from biopsies, expanded TILs and in livers or spleens of PDX models injected with TILs. Our findings revealed that tumor-reactive T cells resided not only among activated and exhausted subsets of T cells, but also in a subset of cytotoxic effector cells. In conclusion, combining single-cell sequencing and functional analysis provides valuable insights into which T cells in UM may be useful for cell therapy amplification and marker selection.
Design of multi-epitope vaccine candidate against Brucella type IV secretion system (T4SS)
Authors: Yin Zhengwei , Li Min , Niu Ce , Yu Mingkai , Xie Xinru , Haimiti Gulishati , Guo Wenhong , Shi Juan , He Yueyue , Ding Jianbing , Zhang Fengbo 
Published: May 2023

AbstractObjective the dominant epitopes of T and B cells of VirB8 and VirB10 of Brucella type IV. Secretory systems were predicted and analyzed by bioinformatics, and then multi-epitope vaccines were constructed by reverse vaccination. Methods The amino acid sequences of VirB8 and VirB10 were obtained from the UniProt database, T and B cell dominant epitopes were selected and supplemented with adjuvants to construct a multi-epitope vaccine, SOPMA and RoseTTAFold were applied to predict secondary and tertiary structures respectively for immune simulations. Finally, molecular dynamics simulations of iMEV-TLR4 were then performed. Results one cytotoxic T lymphocyte (CTL) epitope, five helper T lymphocyte (HTL) epitopes, two linear B cell epitopes and three conformational B cell epitopes were obtained in VirB8. 1 cytotoxic T lymphocyte (CTL) epitope, 4 helper T lymphocyte (HTL) epitopes, 4 linear B cell epitopes, and 3 conformational B cell epitopes were obtained in VirB10. The resulting multiepitope vaccine is a protein with good antigenicity, hydrophilicity, and stability. Conclusion a novel brucella multiepitope vaccine was designed by reverse vaccination, and this study provides a theoretical basis for further research.