bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep patterns, genetic susceptibility, and digestive diseases: a large-scale longitudinal cohort study
Authors: Ma Yuying , Yu Shiyi , Li Qinming , Zhang Haifeng , Zeng Ruijie , Luo Ruibang , Lian Qizhou , Leung Felix W. , Duan Chongyang , Sha Weihong , Chen Hao 
Published: May 2024

Background:
Sleep problems are prevalent. However, the impact of sleep patterns on digestive diseases remains uncertain. Moreover, the interaction between sleep patterns and genetic predisposition with digestive diseases has not been comprehensively explored.

Methods:
Four hundred ten thousand five hundred eighty-six participants from UK Biobank with complete sleep information were included in the analysis. Sleep patterns were measured by sleep scores as the primary exposure, based on five healthy sleep behaviors. Individual sleep behaviors were secondary exposures. Genetic risk of the digestive diseases was characterized by polygenic risk score. Primary outcome was incidence of 16 digestive diseases.

Results:
Healthy sleep scores showed dose-response associations with reduced risks of digestive diseases. Compared to participants scoring 0–1, those scoring 5 showed a 28% reduced risk of any digestive disease, including a 50% decrease in irritable bowel syndrome, 37% in non-alcoholic fatty liver disease, 35% in peptic ulcer, 34% in dyspepsia, 32% in gastroesophageal reflux disease, 28% in constipation, 25% in diverticulosis, 24% in severe liver disease, and 18% in gallbladder disease, whereas no correlation was observed with inflammatory bowel disease and pancreatic disease. Participants with poor sleep and high genetic risk exhibited approximately a 60% increase in the risk of digestive diseases. A healthy sleep pattern is linked to lower digestive disease risk in participants of all genetic risk levels.

Conclusions:
In this large population-based cohort, a healthy sleep pattern was associated with a reduced risk of digestive diseases, regardless of genetic susceptibility. The authors’ findings underscore the potential impact of healthy sleep traits in mitigating the risk of digestive diseases.
99mTc-DTPA dynamic SPECT/CT renogram in adults: feasibility and diagnostic benefit
Authors: Spiliotopoulou Maria , Papathanasiou Nikolaos , Łabieniec Łukasz , Papachristou Evangelos , Fokaefs Eleftherios , Spyridonidis Trifon , Fotopoulos Andreas , Apostolopoulos Dimitrios J. 
Published: May 2024

Objective
The objective of this study is to investigate the feasibility and potential advantages of 99mTc-DTPA dynamic single photon emission computed tomography/computed tomography (SPECT/CT) renogram in adults.

Methods
Fifty-five patients aged 19–80 years (mean 56.3) were enrolled. The imaging protocol included: day 1: 99mTc-DTPA planar renogram, followed by planar 99mTc-DMSA scan. Day 3: attenuation-corrected dynamic 99mTc-DTPA SPECT renogram [DSPECT(AC)] and Cr-51 ethylenediamine tetraacetic acid (EDTA) glomerular filtration rate (GFR) calculation. DSPECT(AC) included an initial CT scan followed by 12 consecutive SPECT sessions acquired via continuous-mode acquisition for a total of 24 min. Fast SPECT sequences (1–2 s/projection, 60 projections, every 6°) were obtained for the first 8 min, followed by slower acquisitions (3–4 s/projection) during the rest of the study. Renal activity was measured in the total kidney volume by regions of interest drawn on consecutive transaxial slices of the third SPECT, which were then copied on the whole 12-SPECT series. Corresponding time-activity curves were created. DSPECT(AC) parameters were compared with those of planar renogram. The reference method for split renal function was 99mTc-DMSA (geometrical mean of anterior and posterior projection counts) and for GFR the Cr-51 EDTA 2-blood sample clearance method.

Results
DSPECT(AC) images were of good quality. There was good correlation between renogram parameters (time to peak activity and NORA20) comparing the two techniques (r = 0.959 and 0.933, respectively). In 21 cases with >30% absolute difference between the two kidneys, spilt renal function calculation by DSPECT(AC) correlated perfectly (r = 0.968) with the reference method, whereas planar renogram was less accurate (r = 0.843). Anatomic information provided by nonenhanced CT offered an integrated structural-functional view valuable for final diagnosis. DSPECT(AC) early kidney uptake as a fraction of injected dose correlated better with reference GFR (r = 0.789) than the Gates’ method (r = 0.642).

Conclusion

99mTc-DTPA dynamic SPECT/CT renogram is feasible with conventional SPECT/CT systems. It allows accurate split renal function measurement, offers additional anatomical information and can be used for closer approximation of GFR compared with Gates’ method.
New Morbidities During Critical Illness and Associated Risk of ICU Readmission: Virtual Pediatric Systems Cohort, 2017–2020*
Authors: Heneghan Julia A. , Akande Manzilat Y. , Ramgopal Sriram , Evans Michael D. , Hallman Madhura , Goodman Denise M. 
Published: May 2024

OBJECTIVES:
To describe change in Functional Status Scale (FSS) associated with critical illness and assess associated development of new morbidities with PICU readmission.

DESIGN:
Retrospective, cross-sectional cohort study using the Virtual Pediatric Systems (VPS; Los Angeles, CA) database.

SETTING:
One hundred twenty-six U.S. PICUs participating in VPS.

SUBJECTS:
Children younger than 21 years old admitted 2017–2020 and followed to December 2022.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Among 40,654 patients, 86.2% were classified as having good function or mild dysfunction before illness. Most patients did not have a change in their FSS category during hospitalization. Survival with new morbidity occurred most in children with baseline good/mild dysfunction (8.7%). Hospital mortality increased across categories of baseline dysfunction. Of 39,701 survivors, 14.2% were readmitted within 1 year. Median time to readmission was 159 days. In multivariable, mixed-effects Cox modeling, time to readmission was most associated with discharge functional status (hazard ratio [HR], 5.3 [95% CI, 4.6–6.1] for those with very severe dysfunction), and associated with lower hazard in those who survived with new morbidity (HR, 0.7 [95% CI, 0.6–0.7]).

CONCLUSIONS:
Development of new morbidities occurs commonly in pediatric critical illness, but we failed to find an association with greater hazard of PICU readmission. Instead, patient functional status is associated with hazard of PICU readmission.
Finding Perforator “Freeway” for Design Optimization of Expanded Flaps by Indocyanine Green Angiography
Authors: Xie Tingjun , Liu Yuanbo , Zhu Shan , Li Shanshan , Chen Zixiang , Han Tinglu , Jin Shengyang , Wang Miao , Zang Mengqing 
Published: May 2024

Summary:
Indocyanine green angiography (ICGA) is a useful tool for the visual assessment of superficial blood flow. The authors used ICGA to visualize perforator branches and linking vessels to provide a road map for flap design of an expanded flap. Twenty-eight expansions were planned to use the back-cut technique in 26 patients. ICGA was used to visualize the perforator branching pattern with the linking vessels and the venous network in the expanded flap before expander explantation. The appropriate perforator was selected, and the flap was designed following the axiality of its branch linked by true anastomoses. The vein running closely was chosen as the axial vein. The back cut was designed to avoid transection of the axial artery and vein. Patient characteristics, defect characteristics, and reconstructive outcomes were assessed. ICGA clearly visualized the perforator branches and the linking vessels in the expanded flap at 4the head and neck, trunk, and extremity. The back-cut flap containing the axial artery and vein was raised successfully in 27 expansions. The arterial perforator and superficial vein separated greatly and resulted in design modification from back-cut to advancement flap in one expansion. All expanded flaps met the reconstructive needs and exhibited complete survival. ICGA allowed the visualization of the preoperative topography of the vascular network in the expanded flap and helped surgeons locate the vascular axis and perform an appropriate back-cut design for efficient and safe flap transfer.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Photometric Comparison of Skin Color Match between Abdominal and Thigh-Based Free Flaps for Breast Reconstruction in White Patients
Authors: Mahrhofer Maximilian , Reichert Raphael , Fierdel Frederic , Gu Xinchen , Grabenwöger Johannes , Russe Elisabeth , Schoeller Thomas , Weitgasser Laurenz 
Published: May 2024

Background:
With the increasing demand for autologous breast reconstruction, different surgical techniques have emerged to provide patients with the best possible result tailored to their individual needs. The upper thigh provides an alternative tissue resource in patients where abdominal based flaps are not feasible. Although surgical outcomes and donor-site morbidity demonstrate favorable results using abdominal and thigh-based free flaps for autologous breast reconstruction, the differences in skin constitution and color between the two flap donor sites have not been investigated.

Methods:
From the authors’ flap database, 60 patients who underwent unilateral secondary breast reconstruction with free deep inferior epigastric perforator (DIEP) or transverse myocutaneous gracilis (TMG) flaps where randomly selected. In both cohorts, postoperative pictures were used for photometric color evaluation of the reconstructed breast using the delta E (ΔE) 2000 score at time A (1.5 to 3 months), time B (6 to 8 months), and time C (12 to 20 months). Standard univariate descriptive statistics and group comparisons were performed.

Results:
The DIEP flap demonstrated a better skin color match at time A (P < 0.001), time B (P = 0.003), and time C (P = 0.009). Over time, both flaps showed improved ΔE 2000 values, and patient age was only associated with higher ΔE 2000 values in TMG flaps after 1.5 to 3 months (P = 0.021).

Conclusions:
The study provides the first objective analysis of skin color match in secondary autologous breast reconstruction. The DIEP flap reconstruction shows a preferable color match compared with the TMG flap. Both free flaps demonstrate an improved skin color match 12 to 20 months after secondary breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Estimated Fetal Radiation Dose From 18F-FDG PET/CT During the Second and Third Trimesters of Pregnancy
Authors: Al Mansour Laure , Tylski Perrine , Chene Gautier , Plaisant Franck , Janier Marc , Bolze Pierre Adrien , You Benoit , Defez Didier , Tordo Jérémie , Flaus Anthime 
Published: May 2024

Purpose
Data published in the literature concerning the doses received by fetuses exposed to a 18F-FDG PET are reassuring but were obtained from small and heterogeneous cohorts, and very few data are available concerning the fetal dose received after exposure to both PET and CT. The present study aimed to estimate the fetal dose received following a PET/CT exposure using methods that include anthropomorphic phantoms of pregnant women applied on a large cohort.

Patients and Methods
This retrospective multicenter study included 18 pregnant patients in the second and third trimesters. For PET exposure, the fetal volume and mean concentration of radioactivity in the fetus were measured by manually drawing regions of interest. Those data, combined with the time-integrated activities of the fetus and the mother’s organs, were entered into the OLINDA/EXM software 2.0 to assess the fetal dose due to PET exposure. To estimate the fetal dose received due to CT exposure, 2 softwares were used: CT-Expo (based on geometric phantom models of nonpregnant patients) and VirtualDose (using pregnant patient phantoms).

Results
The fetal dose exposure for PET/CT examination in the second trimester ranged from 5.7 to 15.8 mGy using CT-Expo (mean, 11.6 mGy) and from 5.1 to 11.6 mGy using VirtualDose (mean, 8.6 mGy). In the third trimester, it ranged from 7.9 to 16.6 mGy using CT-Expo (mean, 10.7 mGy) and from 6.1 to 10.7 mGy using VirtualDose (mean, 7.6 mGy).

Conclusions
The estimated fetal doses were in the same range of those previously published and are well below the threshold for deterministic effects. Pregnancy does not constitute an absolute contraindication for a clinically justified hybrid 18F-FDG PET/CT.
Triple Tumors (Neuroendocrine Tumor, Schwannoma, and Papillary Thyroid Carcinoma) With Brain Lesions in a Single Patient Demonstrating Avidity on 68Ga-DOTATATE PET/CT and Their Characterization With FDG-PET/CT and Brain MRI
Authors: Parghane Rahul V. , Basu Sandip 
Published: May 2024

Abstract
Neuroendocrine tumor (NET) typically spreads to the liver, lymph nodes, lungs, and skeleton. Brain metastasis in NET is uncommon. Therefore, each case of detected brain metastases in NET is crucial for the development of treatment guidelines for these types of tumors. We present a unique case of triple tumors (NET, papillary thyroid carcinoma, and schwannoma) in a single patient who presented with neurological symptoms and somatostatin receptor–avid T2 hyperintense multiple metastatic brain lesions from NET on 68Ga-DOTATATE-PET/CT scan and brain MRI. Despite the rarity of brain metastases in NET, we conclude that the presence of neurological sign or symptoms and/or the detection of somatostatin receptor–avid brain lesions in patients with NET should raise suspicion of brain metastases.
Levodopa infusion therapies for Parkinson disease
Authors: Dean Marissa N. , Standaert David G. 
Published: May 2024

Purpose of review
to review recent progress in the development and use of continuous levodopa therapies in Parkinson disease (PD).

Recent findings
Levodopa/Carbidopa intestinal gel (LCIG) is a continuous levodopa therapy which is widely used in the United States, Europe and other countries and is effective at reducing ‘off’ time. Recent work has shown that LCIG can be useful in managing dyskinesias and can improve nonmotor symptoms and quality of life. Several studies have shown good long-term effectiveness of LCIG. Recent data support the cost-effectiveness of this treatment strategy. Subcutaneous (SC) delivery of levodopa is a newer strategy that avoids the need for a surgically placed gastric tube. Two different products enabling SC delivery of levodopa are in development: ND0612 and foslevodopa/foscarbidopa. Both have recently been shown to reduce ‘off’ time in randomized, double-blind trials. Adverse effects of SC levodopa are primarily related to skin reactions at the infusion site.

Summary
Continuous levodopa therapies can be used to treat Parkinson disease motor fluctuations that cannot be managed with standard oral therapies. They may also improve nonmotor symptoms, and improve overall quality of life in patients with advanced PD.
Spatial Dissection of the Distinct Cellular Responses to Normal Aging and Alzheimer’s Disease in Human Prefrontal Cortex at Single-Nucleus Resolution
Authors: Gong Yun , Haeri Mohammad , Zhang Xiao , Li Yisu , Liu Anqi , Wu Di , Zhang Qilei , Jazwinski S. Michal , Zhou Xiang , Wang Xiaoying , Jiang Lindong , Chen Yi-Ping , Yan Xiaoxin , Swerdlow Russell H. , Shen Hui , Deng Hong-Wen 
Published: May 2024

ABSTRACTAging significantly elevates the risk for Alzheimer’s disease (AD), contributing to the accumulation of AD pathologies, such as amyloid-β (Aβ), inflammation, and oxidative stress. The human prefrontal cortex (PFC) is highly vulnerable to the impacts of both aging and AD. Unveiling and understanding the molecular alterations in PFC associated with normal aging (NA) and AD is essential for elucidating the mechanisms of AD progression and developing novel therapeutics for this devastating disease. In this study, for the first time, we employed a cutting-edge spatial transcriptome platform, STOmics® SpaTial Enhanced Resolution Omics-sequencing (Stereo-seq), to generate the first comprehensive, subcellular resolution spatial transcriptome atlas of the human PFC from six AD cases at various neuropathological stages and six age, sex, and ethnicity matched controls. Our analyses revealed distinct transcriptional alterations across six neocortex layers, highlighted the AD-associated disruptions in laminar architecture, and identified changes in layer-to-layer interactions as AD progresses. Further, throughout the progression from NA to various stages of AD, we discovered specific genes that were significantly upregulated in neurons experiencing high stress and in nearby non-neuronal cells, compared to cells distant from the source of stress. Notably, the cell-cell interactions between the neurons under the high stress and adjacent glial cells that promote Aβ clearance and neuroprotection were diminished in AD in response to stressors compared to NA. Through cell-type specific gene co-expression analysis, we identified three modules in excitatory and inhibitory neurons associated with neuronal protection, protein dephosphorylation, and negative regulation of Aβ plaque formation. These modules negatively correlated with AD progression, indicating a reduced capacity for toxic substance clearance in AD subject samples. Moreover, we have discovered a novel transcription factor, ZNF460, that regulates all three modules, establishing it as a potential new therapeutic target for AD. Overall, utilizing the latest spatial transcriptome platform, our study developed the first transcriptome-wide atlas with subcellular resolution for assessing the molecular alterations in the human PFC due to AD. This atlas sheds light on the potential mechanisms underlying the progression from NA to AD.
Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Downie Carolina G. , Highland Heather M. , Alotaibi Mona , Welch Barrett M. , Howard Annie Green , Cheng Susan , Miller Nick , Jain Mohit , Kaplan Robert C. , Lilly Adam G. , Long Tao , Sofer Tamar , Thyagarajan Bharat , Yu Bing , North Kari E. , Avery Christy L. 
Published: May 2024

AbstractBioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years, standard deviation = 13.8 years). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom joint tests. Heritability estimates ranged from 0% to 47.9%, and 48 of the 81oxylipins and fatty acids were significantly heritable. Moreover, 40 (49.4%) of the 81 oxylipins and fatty acids had at least one genome-wide significant (p< 6.94E-11) variant resulting in 19 independent genetic loci involved in fatty acid and oxylipin synthesis, as well as downstream pathways. Four loci (lead variant minor allele frequency [MAF] range: 0.08-0.50), including the desaturase-encodingFADSand the OATP1B1 transporter protein-encodingSLCO1B1, exhibited associations with four or more fatty acids and oxylipins. The majority of the 15 remaining loci (87.5%) (lead variant MAF range = 0.03-0.45, mean = 0.23) were only associated with one oxylipin or fatty acid, demonstrating evidence of distinct genetic effects. Finally, while most loci identified in two-degree-of-freedom tests were previously identified in our main effects analyses, we also identified an additional rare variant (MAF = 0.002) nearCARS2, a locus previously implicated in inflammation. Our analyses revealed shared and distinct genetic architecture underlying fatty acids and oxylipins, providing insights into genetic factors and motivating future multi-omics work to characterize these compounds and elucidate their roles in disease pathways.
Frequency-Dependent Inter-Brain Synchrony is Modulated by Social Interaction in Freely Moving Mice
Authors: Scaglione Alessandro , Lucchesi Jessica , Mascaro Anna Letizia Allegra , Pavone Francesco Saverio 
Published: May 2024

ABSTRACTSocial interaction, a pivotal aspect of human and animal behavior, involves a dynamic exchange of information that shapes behavioral responses, emotional states, and cognitive processes. To gain insights into the neural mechanisms underlying these processes, it is necessary to simultaneously investigate the brain activity of socially interacting subjects. Commonly, the simultaneous study of behavior and brain activity during the execution of social tasks is conducted through Hyperscanning in humans which limits the availability of interventions. Here we describe a new experimental platform that combines the development of a new miniaturized optical system, the “MiCe-μScope”, to monitor neural activity across the entire cortical mantle with a behavioral paradigm to perform a Hyperscanning study in freely moving mice engaged in social interaction. Our results revealed inter-brain synchrony across different frequency bands widespread over the entire cortical mantle, modulated by social behavior. This finding suggests that synchronization reflects the mutual prediction performed by the entire cortex in mice of interacting dyads. The presence of different synchronization maps in these frequency bands suggests a multiscale nature of interaction, extending the predictive nature of interaction to cortical areas beyond the medial prefrontal cortex. Our work provides an experimental framework to conduct Hyperscanning studies in an animal model that mirrors findings from human studies.
Functional MRI reveals that subcortical auditory push-pull interactions rely on intercollicular integrity
Authors: Severo Frederico , Valente Mafalda , Shemesh Noam 
Published: May 2024

AbstractThe role of subcortical structures in binaural integration is of great interest for auditory processing. The inferior colliculus (IC) is the main auditory midbrain center where ascending and descending auditory projections converge, which was suggested to encode auditory information via a push-pull mechanism between the two ICs. However, the origin of this push-pull mechanism in the brain and how it interacts with other upstream/downstream subcortical areas is still a matter of great debate. Here, we harness functional MRI (fMRI) in combination with IC lesions in the rat to dissect the push-pull interaction from a pathway-wide perspective. We find evidence for the push-pull mechanism in IC through negative/positive fMRI signals in the ipsilateral/contralateral ICs upon monaural stimulation. By unilaterally lesioning the corresponding contralateral IC, we demonstrate the necessity of collicular integrity and intercollicular interactions for the push-pull interaction. Using binaural stimulation and IC lesions, we show that the push-pull interaction is exerted also in binaural processing. Finally, we demonstrate that, at least at the population level revealed by fMRI, the main push-pull interactions occur first at the IC level, and not earlier, and that the outcome of the push-pull “calculation” is relayed downstream to MGB. This dissection of the push-pull interaction sheds light into subcortical auditory function.