bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Clinical Characteristics and Survival in Patients With Functional Neuroendocrine Tumors of Gastrointestinal Origin
Authors: Kaur Anahat , Wang Shuai , Herbert Joshua , Steinberg Lewis , Kumar Abhishek 
Published: April 2023

Objectives
Functional neuroendocrine tumors (FNETs) are characterized by excess secretion of disease-specific hormones. In this study, we attempted to define survival trends in patients with some of these uncommon tumors.

Methods
Using the Surveillance, Epidemiology, and End Results database, 529 patients with FNETs (gastrinoma, insulinoma, glucagonoma, VIPoma, and somatostatinoma) were identified. We analyzed patient and tumor characteristics, overall survival, and cancer-specific survival.

Results
Functional neuroendocrine tumors were found to be more predominant in White patients older than 50 years. Most common FNETs were gastrinoma (56.3%) and insulinoma (23.8%). Most FNETs were found in the pancreas, with the second most common location being the small bowel. Surgery was the primary modality of treatment, used in 55.8% of the cases. Median overall survival was 9.8 years (95% confidence interval [CI], 7.9–11.8) with a median cancer-specific survival of 18.5 years (95% CI, 12.8–24.2). In multivariate analysis, age >50 years (hazard ratio [HR], 2.7; 95% CI, 2.02–3.64), no surgical resection (HR, 1.88; 95% CI, 1.43–2.46), metastasis (HR, 3.0; 95% CI, 2.0–4.5), and poor differentiation were associated with poor survival. Site and histology did not have a significant impact on survival (P = 0.82 and 0.57 respectively).

Conclusions
Our study highlights the most important prognostic factors for gastrointestinal FNETs.
Therapeutic Targets and Prognostic Biomarkers Among CXC Chemokines in Pancreatic Ductal Adenocarcinoma Microenvironment
Authors: Yin Zi , Chen Sheng 
Published: April 2023

Objectives
Pancreatic ductal adenocarcinoma (PDAC) is characterized by occult onset, rapid progression, and poor prognosis. CXC chemokines play an important role in tumor microenvironment and development. However, the potential mechanistic values of CXC chemokines as clinical biomarkers and therapeutic targets in PDAC have not been fully clarified.

Methods
The altered expression, interaction network, and clinical data of CXC chemokines in patients with PDAC were analyzed by the data from the Gene Expression Omnibus and the Tumor Cancer Genome Atlas.

Results
CXCL5 transcriptional level was significantly elevated in PDAC tissues. A significant correlation was found between the expression of CXC1/3/5/8 and the pathological stage of PDAC patients. The PDAC patients with low transcriptional levels of CXCL5/9/10/11/17 were associated with a significantly better prognosis. The functions of differentially expressed CXC chemokines are primarily related to the chemokine signaling pathway, cytokine-cytokine receptor interaction, and viral protein interaction with cytokine and cytokine receptor. RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the SRC family of tyrosine kinases, mitogen-activated protein kinases, CDK5, PRKCQ, ROCK1, ITK, IKBKE, JAK3, and NTRK2 are CXC chemokine targets.

Conclusions
The results indicated that CXC chemokines might serve as therapeutic targets and prognostic biomarkers in PDAC.
Diagnostic Categories and Key Features for Pathological Diagnosis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Samples of Pancreatic Lesions
Authors: Naito Yoshiki , Notohara Kenji , Omori Yuko , Aishima Shinichi , Itoi Takao , Ohike Nobuyuki , Okabe Yoshinobu , Kojima Motohiro , Tajiri Takuma , Tanaka Mariko , Tsuneki Masayuki , Nakagohri Toshio , Norose Tomoko , Hirabayashi Kenichi , Fukumura Yuki , Mitsuhashi Tomoko , Yamaguchi Hiroshi , Fukushima Noriyoshi , Furukawa Toru 
Published: April 2023

Objectives
This study aimed to establish a reliable and reproducible categorized diagnostic classification system with identification of key features to achieve accurate pathological diagnosis of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) samples of pancreatic lesions.

Methods
Twelve pathologists examined virtual whole-slide images of EUS-FNAB samples obtained from 80 patients according to proposed diagnostic categories and key features for diagnosis. Fleiss κ was used to assess the concordance.

Results
A hierarchical diagnostic system consisting of the following 6 diagnostic categories was proposed: inadequate, nonneoplasm, indeterminate, ductal carcinoma, nonductal neoplasm, and unclassified neoplasm. Adopting these categories, the average κ value of participants was 0.677 (substantial agreement). Among these categories, ductal carcinoma and nonductal neoplasm showed high κ values of 0.866 and 0.837, respectively, which indicated the almost perfect agreement. Key features identified for diagnosing ductal carcinoma were necrosis in low-power appearance; structural atypia/abnormalities recognized by irregular glandular contours, including cribriform and nonuniform shapes; cellular atypia, including enlarged nuclei, irregular nuclear contours, and foamy gland changes; and haphazard glandular arrangement and stromal desmoplasia.

Conclusions
The proposed hierarchical diagnostic classification system was proved to be useful for achieving reliable and reproducible diagnosis of EUS-FNAB specimens of pancreatic lesions based on evaluated histological features.
Reconstruction of Thumb Defects using the Second Dorsal Metacarpal Artery Flap with Two Pivot Points
Authors: Zhang Wenlong , Liu Linfeng , Lu Yun , Liu Yingnan , Zhuang Yongqing , Chen Chao 
Published: April 2023

Background:
This study aimed to introduce reconstruction of thumb defects using the second dorsal metacarpal artery (DMA) flap with two pivot points.

Methods:
A retrospective study was conducted with 43 patients (group A) underwent thumb reconstruction using the second DMA flap with two pivot points from Jul 2012 to May 2019. For comparison, we reviewed another cohort of 34 patients (group B) undergoing thumb reconstruction using the first DMA flap. Flap sensation and donor site morbidity were assessed.

Results:
In group A, the mean 2PD was 8.7 mm (range, 6 to 12 mm) and 9.7 mm (range, 7 to 12 mm) on the innervated and non-innervated flaps at the final follow-up, with a significant difference (P = 0.012). In group B, the mean 2PD of the flaps was 7.4 mm (range, 6 to 10 mm). By comparison, group B presented better discriminatory sensation than innervated flaps with double pivot points (P = 0.002). Based on the VAS, the mean score of scar pain and cosmetic appearance of the donor site were 0.1 (0 to 3) and 0.4 (0 to 2) in group A, and 0.5 (0 to 3) and 1.0 (0 to 4) in group B. By comparison, group A presented lower incidence of scar pain (P=0.020) and better cosmetic appearance of the donor site (P=0.019).

Conclusions:
The second DMA flap with two pivot points has a long vascular pedicle, which allows the flap to repair thumb defects. It is associated with low donor site morbidity but suboptimal sensory recovery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
High-Risk Sexual Activities and Condom Use Patterns During Group Sex Among Men Who Have Sex With Men in Melbourne, Australia
Authors: Lew Chen , Fairley Christopher K. , Tran Julien , Phillips Tiffany R. , Maddaford Kate , Chen Marcus Y. , Bradshaw Catriona S. , Chow Eric P. F. 
Published: April 2023

Background:Few studies have examined the types of sexual activities and condom use during group sex among men who have sex with men (MSM). This study aimed to examine sexual activities and condom use during group sex.Setting:A cross-sectional survey among MSM attending a sexual health clinic in Melbourne, Australia, between May 2019 and March 2020.Method:Participants were asked whether they had engaged in group sex (sex involving more than 2 participants) within the past 3 months, the number of people involved, the sexual activities they engaged in, and their condom use during the most recent group sex.Results:More than a quarter (26.8%, 287 of 1071) had engaged in group sex in the past 3 months, and the median number of people involved was 3 (interquartile range 3–4), including the participant. Fellatio was the most common activity in group sex (94.4%, 271 of 287), followed by kissing (85.7%, 246 of 287) and anal sex (79.8%, 229 of 287). The proportion of men who always used condoms and changed condoms between partners was 27.0% (48 of 178) for insertive and 32.3% (52 of 161) for receptive anal sex. Compared with men not taking pre-exposure prophylaxis (PrEP), men living with HIV (adjusted odds ratio [aOR]: 2.35; 95% confidence interval [CI]: 1.20 to 4.59) and men taking PrEP (aOR: 3.07; 95% CI: 2.21 to 4.26) had higher odds of engaging in group sex after adjusting for confounders.Conclusion:Two-thirds of MSM either did not use condoms or did not change condoms between partners during group sex, which may increase sexually transmitted infection transmission between partners.
Hybrid Autologous Costal Cartilage Grafting for Augmentation Rhinoplasty in Asian Patients
Authors: Fu Xiujun , Yin Chuang , Liang Yimin , Zhou Renpeng , Wang Danru , Wang Chen 
Published: April 2023

Background:
Autologous costal cartilage has been used for augmentation rhinoplasty in Asia for many years. This study aimed to assess the effectiveness and safety of hybrid grafting of costal cartilage for dorsal augmentation, septal reconstruction, and tip augmentation for Asian patients.

Methods:
A surgical technique was introduced and patients having rhinoplasty using this technique from April 2020 to March 2021 were retrospectively studied. In this technique, costal cartilage was meticulously carved or diced and grafted in various ways mainly based on the anatomic characteristics of nasal skin and subcutaneous soft tissues as well as bone and cartilage framework. The surgical outcomes, patient satisfaction, and complications retrieved from the documented medical records were reviewed and analyzed.

Results:
Twenty-five patients having rhinoplasty with the proposed technique were followed up from 6 months to 12 months. As for cosmetic outcomes, 21 patients were graded as good, 3 patients were graded as fair, and only 1 patient was graded as poor. Those patients who were not graded as good had over-rotated tips, insufficient dorsal augmentation, or asymmetry of nostrils and soft tissue contracture. The overall patient satisfaction was as high as 96.0%. Local infection occurred in 1 patient and hematoma was not observed. Warping and visibility of costal cartilage were not observed in any patients. Slight displacement of diced cartilages was found in 2 patients near the radix 1 week postoperatively.

Conclusions:
Hybrid autologous costal cartilage grafts can be used for both tip refinement and dorsal augmentation for East Asian patients and achieve an outcome of a natural-looking nose with minimal complications.

Level of Evidence:
Level IV.
Microglia at the scene of the crime: what their transcriptomics reveal about brain health
Authors: Arutyunov Artem , Klein Robyn S. 
Published: April 2023

Purpose of review
Microglia, which arise from primitive myeloid precursors that enter the central nervous system (CNS) during early development, are the first responders to any perturbance of homeostasis. Although their activation has become synonymous with neurologic disease, it remains unclear whether microglial responses are the cause of or response to neuropathology. Here, we review new insights in the roles of microglia during CNS health and disease, including preclinical studies that transcriptionally profile microglia to define their functional states.

Recent findings
Converging evidence suggests that innate immune activation of microglia is associated with overlapping alterations in their gene expression profiles regardless of the trigger. Thus, recent studies examining neuroprotective microglial responses during infections and aging mirror those observed during chronic neurologic diseases, including neurodegeneration and stroke. Many of these insights derive from studies of microglial transcriptomes and function in preclinical models, some of which have been validated in human samples. During immune activation, microglia dismantle their homeostatic functions and transition into subsets capable of antigen presentation, phagocytosis of debris, and management of lipid homeostasis. These subsets can be identified during both normal and aberrant microglial responses, the latter of which may persist long-term. The loss of neuroprotective microglia, which maintain a variety of essential CNS functions, may therefore, in part, underlie the development of neurodegenerative diseases.

Summary
Microglia exhibit a high level of plasticity, transforming into numerous subsets as they respond to innate immune triggers. Chronic loss of microglial homeostatic functions may underlie the development of diseases with pathological forgetting.
Solitalea agri sp. nov., a new member of the genus Solitalea isolated from rhizospheric soil of a jujube tree
Authors: Huq Md. Amdadul , Lee Sun-Young , Moon BoKyung , Choi Changsun , Moon Sung-Kwon , Akter Shahina 
Published: April 2023

A Gram-stain negative, aerobic, rod-shaped and creamy pink-coloured bacterium, designated MAHUQ-68T, was isolated from rhizospheric soil of a jujube tree. Colonies grew at 10–40 °C (optimum, 28 °C), pH 6.0–9.0 (optimum pH, 7.0) and in the presence of 0–1.5 % NaCl (optimum 0–0.5 %). Positive for both catalase and oxidase activity. Strain MAHUQ-68T hydrolysed casein, starch, aesculin and l-tyrosine. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-68T clustered together within the genus

Solitalea

. The closest members were

Solitalea longa

HR-AVT (98.8 % sequence similarity),

Solitalea canadensis

DSM 3403T (96.9 %) and

Solitalea koreensis

R2A36-4T (94.0 %). The genome of strain MAHUQ-68 T was 4 250 173 bp long with 68 scaffolds and 3 570 protein-coding genes. The genomic DNA G+C content of the type strain was 38.0 mol%. The average nucleotide identity and in silico DNA–DNA hybridization values between strain MAHUQ-68T and its closest relatives were 72.0–81.4% and 19.8–24.3 %, respectively. The major cellular fatty acids were iso-C15 : 0 and summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c). The main respiratory quinone was menaquinone-7. The polar lipids comprised phosphatidylethanolamine, an unidentified aminolipid and four unidentified lipids. Based on these data, strain MAHUQ-68T represents a novel species in the genus

Solitalea

, for which the name Solitalea agri sp. nov. is proposed. The type strain is MAHUQ-68T (=KACC 22249T=CGMCC 1.19062T).
Cardiac gene therapy with PDE2A limits remodeling and arrhythmias in mouse models of heart failure induced by catecholamines
Authors: Kamel Rima , Bourcier Aurélia , Margaria Jean Piero , Varin Audrey , Hivonnait Agnès , Mercier-Nomé Françoise , Mika Delphine , Ghigo Alessandra , Charpentier Flavien , Algalarrondo Vincent , Hirsch Emilio , Fischmeister Rodolphe , Vandecasteele Grégoire , Leroy Jérôme 
Published: April 2023

ABSTRACTBACKGROUNDConstitutive cardiac PDE2 activation was shown to protect against contractile dysfunction and arrhythmia in heart failure (HF). However, it remains unknown whether an acute elevation of PDE2 is efficient to prevent maladaptive remodeling and arrhythmia. In this study we tested whether increasing acutely PDE2A activity in preclinical models of HF using cardiac PDE2 gene transfer could be of therapeutic value.METHODS AND RESULTSC57BL/6 male mice were injected with serotype 9 adeno-associated viruses (AAV9) encoding for PDE2A, or luciferase (LUC). Cardiac function assessed by echocardiography unveiled neither structural change nor dysfunction consecutive to PDE2A overexpression while AAV9 inoculation led to a ≈10-fold rise of PDE2A protein levels. Two weeks after AAV9 injections, mice were implanted with osmotic minipumps delivering NaCl or isoproterenol (Iso) (60 mg/kg/day) or Iso and phenylephrine (Iso+Phe, 30 mg/kg/day each) for 2 weeks. In LUC mice, chronic infusion with Iso increased left ventricular (LV) weight over body weight ratio, promoted fibrosis and decreased ejection fraction, but animals overexpressing PDE2A were protected towards these deleterious effects. Similarly, concomitant treatment with Iso+Phe promoted LV contractile dysfunction, fibrosis and apoptosis in LUC mice, while PDE2A overexpression limited these adverse outcomes. Furthermore, inotropic responses to Iso of ventricular cardiomyocytes isolated from Iso+Phe-LUC mice loaded with 1 µmol/L Fura-2AM and stimulated at 1 Hz to record calcium transients and sarcomere shortening were dampened. Chronic treatment with catecholamines favoured spontaneous calcium waves upon β-AR stimulation at the cellular level and promoted susceptibility to ventricular arrhythmiasin vivoevoked by catheter-mediated ventricular pacing after Iso and atropine injection. However, these adverse effects were blunted by the cardiac gene therapy with PDE2A.CONCLUSIONGene therapy with PDE2A limits cardiac adverse left ventricle remodeling and dysfunction induced by catecholamines as well as ventricular arrhythmias, providing evidence that acutely increasing PDE2A activity could prevent progression towards HF.
Genetic risk of late-onset Alzheimer’s disease is associated with longitudinal loss of functional brain network segregation in middle-aged cognitively healthy individuals: The PREVENT-Dementia Study
Authors: Deng Feng , Ritchie Karen , Muniz-Terrera Graciela , Malhotra Paresh , Ritchie Craig W. , Lawlor Brian , Naci Lorina 
Published: April 2023

AbstractIt is well acknowledged that the pathological processes of Alzheimer’s disease (AD) start decades before clinical manifestations, but early indicators of AD in midlife remain unclear. Functional segregation of brain networks has recently emerged as a key indicator of brain health. In this study, we investigated the vulnerability of intrinsic brain networks to loss of functional segregation during healthy adult lifespan and in cognitively healthy midlife individuals at risk of late-onset AD, and the association between segregation loss and cognition in midlife. Network segregation was measured using the participation coefficient metric within a graph-theoretic framework. In a healthy adult lifespan cohort (18-88 years, N=652), linear relationships of network segregation with age and cortical grey matter volume (GMV) were assessed using multiple regression models. In a cognitively healthy midlife cohort (40-59 years, N=210), associations between network segregation and established risk factors for AD were examined cross-sectionally and longitudinally (over 2 years). Across the healthy adult lifespan, global network segregation was positively associated with GMV and negatively associated with age, replicating previous findings. Three high-order networks [default mode (DMN), frontal-parietal control, and salience] and two sensorimotor networks (visual and motor) showed prominent age-related changes in functional segregation throughout adulthood. At midlife, cross-sectionally, cognitively healthy apolipoprotein (APOE) ε4 carriers had higher global segregation than non-carriers. The DMN was the only individual network to show such an effect ofAPOEgenotype. Higher global and DMN segregation was associated with better episodic and relational memory. Critically,APOEε4 carriers, but not non-carriers, showed a significant longitudinal loss of segregation in the DMN over 2 years. Overall, our findings suggest that functional network segregation constitutes a novel and early substrate for the impact of the genetic AD risk on the brain in midlife and thus have implications for the early detection and intervention in AD.
Membrane-penetrating peptide from the translocation region ofBordetellaAdenylate Cyclase Toxin prevents toxin cytotoxicity on target cells
Authors: Amuategi Jone , Alonso Rocío , de la Arada Igor , Ostolaza Helena 
Published: April 2023

ABSTRACTAdenylate cyclase toxin (ACT) is one of the main virulence factors ofBordetella pertussis, with crucial role in colonization of human respiratory tract. ACT toxicity on target phagocytes results from translocation of its adenylate cyclase domain and production of high cAMP levels and from pore formation. Recently, we unveiled in ACT four cholesterol-recognition motifs involved in specific interaction with membrane cholesterol, which might stabilize membrane topology of critical helices for ACT activity. Here we explore an amphipathic peptide corresponding to ACT residues 454 to 487 containing one of such CRAC motifs. We show that P454-487 penetrates into DOPC vesicles as a long and tilted α-helix, while in cholesterol presence experiments conformational changes that critically depend on the CRAC Phe-485 residue. Moreover, P454-487 is capable of blocking ACT toxicity on cells by outcompeting with the full-length toxin for membrane binding. We anticipate P454-487 may have potential clinical applicability in controllingBordetellainfection.
Magnetic actuation of otoliths allows behavioral and brain-wide neuronal exploration of vestibulo-motor processing in larval zebrafish
Authors: Beiza-Canelo Natalia , Moulle Hippolyte , Pujol Thomas , Panier Thomas , Migault Geoffrey , Le Goc Guillaume , Tapie Pierre , Desprat Nicolas , Straka Hans , Debrégeas Georges , Bormuth Volker 
Published: April 2023

AbstractThe vestibular system in the inner ear plays a central role in sensorimotor control by informing the brain about the orientation and acceleration of the head. However, most experiments in neurophysiology are performed using head-fixed configurations, depriving animals of vestibular inputs. To overcome this limitation, we decorated the utricular otolith of the vestibular system in larval zebrafish with paramagnetic nanoparticles. This procedure effectively endowed the animal with magneto-sensitive capacities: applied magnetic field gradients induced forces on the otoliths resulting in robust behavioral responses comparable to that evoked by rotating the animal by up to 25°. We recorded the whole-brain neuronal response to this fictive motion stimulation using light-sheet functional imaging. Experiments performed in unilaterally injected fish revealed the activation of a commissural inhibition between the brain hemispheres. This magnetic-based stimulation technique for larval zebrafish opens new perspectives to functionally dissect the neural circuits underlying vestibular processing and to develop multisensory virtual environments, including vestibular feedback.HighlightsAfter injecting a ferrofluid into the inner ear of a larval zebrafish, the ear-stones can be actuated via magnetic forces.This method allows one to elicit vestibular-like behavioral responses without impairing physiological inner ear functions.It is compatible with brain-scale functional imaging and thus offers a promising avenue to investigate the neural underpinnings of vestibular-driven behaviors.eTOCFerrofluid injection into zebrafish inner ear allows magnetic manipulation of ear-stones to evoke vestibular responses in static animals. This in vivo method is compatible with brain-scale imaging, offering a promising approach to investigate neural mechanisms underlying vestibular-driven behaviors.