bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel selective leukocyte depletion human whole blood model reveals the specific roles of monocytes and granulocytes in the cytokine response to Escherichia coli
Authors: Fageräng Beatrice , Lau Corinna , Mc Adam Karin Ekholt , Schjalm Camilla , Christiansen Dorte , Garred Peter , Nilsson Per H , Mollnes Tom Eirik 
Published: December 2023

Abstract
The lepirudin-based human whole blood model is a well-established ex vivo system to characterize inflammatory responses. However, the contribution of individual cell populations to cytokine release has not been investigated. Thus, we modified the model by selectively removing leukocyte subpopulations to elucidate their contribution to the inflammatory response. Lepirudin-anticoagulated whole blood was depleted from monocytes or granulocytes using StraightFrom Whole Blood MicroBeads. Reconstituted blood was incubated with Escherichia coli (108/mL) for 2 hours at 37 °C. CD11b, CD62P, and CD63 were detected by flow cytometry. Complement (C3bc, sC5b-9) and platelet activation (platelet factor 4, NAP-2) were measured by enzyme-linked immunosorbent assay. Cytokines were quantified by multiplex assay. A significant (P &lt; 0.05) specific depletion of the monocyte (mean = 86%; 95% confidence interval = 71%–92%) and granulocyte (mean = 97%; 95% confidence interval = 96%–98%) population was obtained. Background activation induced by the depletion protocol was negligible for complement (C3bc and sC5b-9), leukocytes (CD11b), and platelets (NAP-2). Upon Escherichia coli incubation, release of 10 of the 24 cytokines was solely dependent on monocytes (interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-17A, interferon-γ, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-1α, and fibroblast growth factor–basic), whereas 8 were dependent on both monocytes and granulocytes (IL-1ra, IL-6, IL-8, IL-9, IL-10, macrophage inflammatory protein-1β, tumor necrosis factor, and eotaxin). Six cytokines were not monocyte or granulocyte dependent, of which platelet-derived growth factor and RANTES were mainly platelet dependent. We document an effective model for selective depletion of leukocyte subpopulations from whole blood, without causing background activation, allowing in-depth cellular characterization. The results are in accordance with monocytes playing a major role in cytokine release and expand our knowledge of the significant role of granulocytes in the response to E. coli.
AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation
Authors: Källberg Eva , Mehmeti-Ajradini Meliha , Björk Gunnarsdottir Frida , Göransson Marcus , Bergenfelz Caroline , Allaoui Fredriksson Roni , Hagerling Catharina , Johansson Martin E , Welinder Charlotte , Jirström Karin , Leandersson Karin 
Published: December 2023

Abstract
The autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and is necessary for maintaining immunological self-tolerance. Extrathymic AIRE expression is rare, and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study, we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor-associated neutrophils (TANs), and to a lesser extent to tumor-associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and cathepsin G. Here, we propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.
A roadmap to establishing global oncology as a priority initiative within a National Cancer Institute–designated cancer center
Authors: Van Loon Katherine , Breithaupt Lindsay , Ng Dianna , DeBoer Rebecca J , Buckle Geoffrey C , Bialous Stella , Hiatt Robert A , Volberding Paul , Hermiston Michelle L , Ashworth Alan 
Published: December 2023

Abstract
As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute–designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings.
Successful management of portal hypertension with splenomegaly and cavernous transformation of the portal vein: a rare case report
Authors: Sharjeel Simrah , Abdullah Muhammad 
Published: December 2023

Abstract
Portal hypertension, often stemming from liver cirrhosis or vascular anomalies, can result in cavernous transformation of the portal vein, a rare condition associated with biliary obstruction, variceal hemorrhage, and splenomegaly. This case report details a unique occurrence of portal hypertension, splenomegaly, and cavernous transformation of the portal vein successfully managed through splenectomy and spleno-renal shunt. A 30-year-old female with a history of portal hypertension, portal gastropathy, and splenomegaly presented with left upper quadrant abdominal pain. She had previously undergone esophageal variceal ligation and required intermittent blood transfusions. Additional complications included easy bruising, heavy menstrual bleeding, and a prior episode of hematemesis. Clinical assessment confirmed splenomegaly, while a CT scan confirmed the diagnosis. A tailored surgical approach was chosen, leading to splenectomy and spleno-renal shunt.
Simultaneous stoma closure and type IV parastomal hernia repair after botulinum toxin and progressive pneumoperitoneum
Authors: Correia Penélope , Pereira Ana Marta , Matos Maria Leonor , Rodrigues Catarina Santos , Guimarães Marta , Nora Mário 
Published: December 2023

AbstractSurgery is the only treatment for parastomal hernia (PH). When possible, stoma closure is the best way to manage this type of hernia, however, whether to perform it in a single approach with abdominal wall reconstruction (AWR) is still debatable. A 58-year-old woman with a type IV PH with loss of domain was submitted to preoperative optimization [botulinum toxin type A and progressive pneumoperitoneum (PPP)], followed by simultaneous stoma closure and AWR. Hospital discharge was on the eighth day with no complications. Six months later, no clinical evidence of recurrence or other complication was observed. Large PHs are technically challenging. Stoma closure and simultaneous AWR increase surgical risk. Preoperative optimization with a combination of adjuvants (including PPP) is feasible in PH and may overcome technical complexity, even though patient selection remains the key when choosing a PH repair with synchronous stoma closure.
An Ancestral Major Histocompatibility Complex Organization in Cartilaginous Fish: Reconstructing MHC Origin and Evolution
Authors: Veríssimo Ana , Castro L Filipe C , Muñoz-Mérida Antonio , Almeida Tereza , Gaigher Arnaud , Neves Fabiana , Flajnik Martin F , Ohta Yuko 
Published: December 2023

Abstract
Cartilaginous fish (sharks, rays, and chimeras) comprise the oldest living jawed vertebrates with a mammalian-like adaptive immune system based on immunoglobulins (Ig), T-cell receptors (TCRs), and the major histocompatibility complex (MHC). Here, we show that the cartilaginous fish “adaptive MHC” is highly regimented and compact, containing (i) a classical MHC class Ia (MHC-Ia) region containing antigen processing (antigen peptide transporters and immunoproteasome) and presenting (MHC-Ia) genes, (ii) an MHC class II (MHC-II) region (with alpha and beta genes) with linkage to beta-2-microglobulin (β2m) and bromodomain-containing 2, (iii) nonclassical MHC class Ib (MHC-Ib) regions with 450 million-year-old lineages, and (iv) a complement C4 associated with the MHC-Ia region. No MHC-Ib genes were found outside of the elasmobranch MHC. Our data suggest that both MHC-I and MHC-II genes arose after the second round of whole-genome duplication (2R) on a human chromosome (huchr) 6 precursor. Further analysis of MHC paralogous regions across early branching taxa from all jawed vertebrate lineages revealed that Ig/TCR genes likely arose on a precursor of the huchr9/12/14 MHC paralog. The β2m gene is linked to the Ig/TCR genes in some vertebrates suggesting that it was present at 1R, perhaps as the donor of C1 domain to the primordial MHC gene. In sum, extant cartilaginous fish exhibit a conserved and prototypical MHC genomic organization with features found in various vertebrates, reflecting the ancestral arrangement for the jawed vertebrates.
CRISPR-Cas immunity is repressed by the LysR-type transcriptional regulator PigU
Authors: Smith Leah M , Hampton Hannah G , Yevstigneyeva Mariya S , Mahler Marina , Paquet Zacharie S M , Fineran Peter C 
Published: December 2023

Abstract
Bacteria protect themselves from infection by bacteriophages (phages) using different defence systems, such as CRISPR-Cas. Although CRISPR-Cas provides phage resistance, fitness costs are incurred, such as through autoimmunity. CRISPR-Cas regulation can optimise defence and minimise these costs. We recently developed a genome-wide functional genomics approach (SorTn-seq) for high-throughput discovery of regulators of bacterial gene expression. Here, we applied SorTn-seq to identify loci influencing expression of the two type III-A Serratia CRISPR arrays. Multiple genes affected CRISPR expression, including those involved in outer membrane and lipopolysaccharide synthesis. By comparing loci affecting type III CRISPR arrays and cas operon expression, we identified PigU (LrhA) as a repressor that co-ordinately controls both arrays and cas genes. By repressing type III-A CRISPR-Cas expression, PigU shuts off CRISPR-Cas interference against plasmids and phages. PigU also represses interference and CRISPR adaptation by the type I-F system, which is also present in Serratia. RNA sequencing demonstrated that PigU is a global regulator that controls secondary metabolite production and motility, in addition to CRISPR-Cas immunity. Increased PigU also resulted in elevated expression of three Serratia prophages, indicating their likely induction upon sensing PigU-induced cellular changes. In summary, PigU is a major regulator of CRISPR-Cas immunity in Serratia.
Not Only Meningitis but Also Epiglottitis: An Emerging Clinical Presentation of Invasive Meningococcal Disease
Authors: Deghmane Ala-Eddine , Taha Samy , Taha Muhamed-Kheir 
Published: December 2023

Abstract
The rebound of invasive meningococcal disease cases in France since the fall of 2022 was accompanied by an increase in adult epiglottitis. These cases were provoked mainly by isolates of serogroup W belonging to the clonal complex 11 of Neisseria meningitidis. Awareness and surveillance should be reinforced.
Mathematical Explanations: An Analysis Via Formal Proofs and Conceptual Complexity
Authors: Poggiolesi Francesca 
Published: December 2023

Abstract
This paper studies internal (or intra-)mathematical explanations, namely those proofs of mathematical theorems that seem to explain the theorem they prove. The goal of the paper is a rigorous analysis of these explanations. This will be done in two steps. First, we will show how to move from informal proofs of mathematical theorems to a formal presentation that involves proof trees, together with a decomposition of their elements; secondly we will show that those mathematical proofs that are regarded as having explanatory power all display an increase of conceptual complexity from the assumptions to the conclusion.
Calcium regulation of the Arabidopsis Na+/K+ transporter HKT1;1 improves seed germination under salt stress
Authors: Chandran Ancy E J , Finkler Aliza , Hait Tom Aharon , Kiere Yvonne , David Sivan , Pasmanik-Chor Metsada , Shkolnik Doron 
Published: December 2023

Abstract
Calcium is known to improve seed-germination rates under salt stress. We investigated the involvement of calcium ions (Ca2+) in regulating HIGH-AFFINITY K+ TRANSPORTER 1 (HKT1; 1), which encodes a Na+/K+ transporter, and its post-translational regulator TYPE 2C PROTEIN PHOSPHATASE 49 (PP2C49), in germinating Arabidopsis (Arabidopsis thaliana) seedlings. Germination rates of hkt1 mutant seeds under salt stress remained unchanged by CaCl2 treatment in wild-type Arabidopsis, whereas pp2c49 mutant seeds displayed improved salt-stress tolerance in the absence of CaCl2 supplementation. Analysis of HKT1;1 and PP2C49 promoter activity revealed that CaCl2 treatment results in radicle-focused expression of HKT1;1 and reduction of the native radicle-exclusive expression of PP2C49. Ion-content analysis indicated that CaCl2 treatment improves K+ retention in germinating wild-type seedlings under salt stress, but not in hkt1 seedlings. Transgenic seedlings designed to exclusively express HKT1;1 in the radicle during germination displayed higher germination rates under salt stress than the wild type in the absence of CaCl2 treatment. Transcriptome analysis of germinating seedlings treated with CaCl2, NaCl, or both revealed 118 upregulated and 94 downregulated genes as responsive to the combined treatment. Bioinformatics analysis of the upstream sequences of CaCl2–NaCl-treatment-responsive upregulated genes revealed the abscisic acid response element CACGTGTC, a potential CaM-binding transcription activator-binding motif, as most prominent. Our findings suggest a key role for Ca2+ in mediating salt-stress responses during germination by regulating genes that function to maintain Na+ and K+ homeostasis, which is vital for seed germination under salt stress.
Noise in Expectations: Evidence from Analyst Forecasts
Authors: de Silva Tim , Thesmar David 
Published: December 2023

Abstract
Analyst forecasts outperform econometric forecasts in the short run but underperform in the long run. We decompose these differences in forecasting accuracy into analysts’ information advantage, forecast bias, and forecast noise. We find that noise and bias strongly increase with forecast horizon, while analysts’ information advantage decays rapidly. A noise increase with horizon generates a mechanical reversal in the sign of the error-revision (Coibion-Gorodnichenko) regression coefficient at longer horizons, independently of over-/underreaction. A parsimonious model with bounded rationality and a noisy cognitive default matches the term structures of noise and bias jointly.
Evaluating blood culture collection practice in children hospitalized with acute illness at a tertiary hospital in Malawi
Authors: Mukhula Victoria Temwanani , Harawa Philliness Prisca , Phiri Chisomo , Khoswe Stanley , Mbale Emmie , Tigoi Caroline , Walson Judd L , Berkley James A , Bandsma Robert , Iroh Tam Pui-Ying , Voskuijl Wieger 
Published: December 2023

Abstract

Background
Blood culture collection practice in low-resource settings where routine blood culture collection is available has not been previously described.

Methodology
We conducted a secondary descriptive analysis of children aged 2–23 months enrolled in the Malawi Childhood Acute Illness and Nutrition (CHAIN) study, stratified by whether an admission blood culture had been undertaken and by nutritional status. Chi-square test was used to compare the differences between groups.

Results
A total of 347 children were included, of whom 161 (46%) had a blood culture collected. Children who had a blood culture collected, compared to those who did not, were more likely to present with sepsis (43% vs. 20%, p &lt; 0.001), gastroenteritis (43% vs. 26%, p &lt; 0.001), fever (86% vs. 73%, p = 0.004), and with poor feeding/weight loss (30% vs. 18%, p = 0.008). In addition, hospital stay in those who had a blood culture was, on average, 2 days longer (p = 0.019). No difference in mortality was observed between those who did and did not have a blood culture obtained.

Conclusion
Blood culture collection was more frequent in children with sepsis and gastroenteritis, but was not associated with mortality. In low-resource settings, developing criteria for blood culture based on risk factors rather than clinician judgement may better utilize the existing resources.
2021 European Resuscitation Council/European Society of Intensive Care Medicine Algorithm for Prognostication of Poor Neurological Outcome After Cardiac Arrest—Can Entry Criteria Be Broadened?*
Authors: Arctaedius Isabelle , Levin Helena , Larsson Melker , Friberg Hans , Cronberg Tobias , Nielsen Niklas , Moseby-Knappe Marion , Lybeck Anna 
Published: December 2023

OBJECTIVES:
To explore broadened entry criteria of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) algorithm for neuroprognostication including patients with ongoing sedation and Glasgow Coma Scale-Motor score (GCS-M) scores 4–5.

DESIGN:
Retrospective multicenter observational study.

SETTING:
Four ICUs, Skane, Sweden.

PATIENTS:
Postcardiac arrest patients managed at targeted temperature 36°C, 2014–2018. Neurologic outcome was assessed after 2–6 months according to the Cerebral Performance Category scale.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
In 794 included patients, median age was 69.5 years (interquartile range, 60.6–77.0 yr), 241 (30.4%) were female, 550 (69.3%) had an out-of-hospital cardiac arrest, and 314 (41.3%) had a shockable rhythm. Four hundred ninety-five patients were dead at follow-up, 330 of 495 died after a decision on withdrawal of life-sustaining therapies. At 72 hours after cardiac arrest 218 patients remained unconscious. The entry criteria of the original algorithm (GCS-M 1–3) was fulfilled by 163 patients and 115 patients with poor outcome were identified, with false positive rate (FPR) of 0% (95% CI, 0–79.4%) and sensitivity of 71.0% (95% CI, 63.6–77.4%). Inclusion of patients with ongoing sedation identified another 13 patients with poor outcome, generating FPR of 0% (95% CI, 0–65.8%) and sensitivity of 69.6% (95% CI, 62.6–75.8%). Inclusion of all unconscious patients (GCS-M 1–5), regardless of sedation, identified one additional patient, generating FPR of 0% (95% CI, 0–22.8) and sensitivity of 62.9% (95% CI, 56.1–69.2). The few patients with true negative prediction (patients with good outcome not fulfilling guideline criteria of a poor outcome) generated wide 95% CI for FPR.

CONCLUSION:
The 2021 ERC/ESICM algorithm for neuroprognostication predicted poor neurologic outcome with a FPR of 0%. Broadening inclusion criteria to include all unconscious patients regardless of ongoing sedation identified an additional small number of patients with poor outcome but did not affect the FPR. Results are limited by high rate of withdrawal of life-sustaining therapies and few patients with true negative prediction.
Smartphone sensor data estimate alcohol craving in a cohort of patients with alcohol-associated liver disease and alcohol use disorder
Authors: Wu Tiffany , Sherman Garrick , Giorgi Salvatore , Thanneeru Priya , Ungar Lyle H. , Kamath Patrick S. , Simonetto Douglas A. , Curtis Brenda L. , Shah Vijay H. 
Published: December 2023

Background:
Sensors within smartphones, such as accelerometer and location, can describe longitudinal markers of behavior as represented through devices in a method called digital phenotyping. This study aimed to assess the feasibility of digital phenotyping for patients with alcohol-associated liver disease and alcohol use disorder, determine correlations between smartphone data and alcohol craving, and establish power assessment for future studies to prognosticate clinical outcomes.

Methods:
A total of 24 individuals with alcohol-associated liver disease and alcohol use disorder were instructed to download the AWARE application to collect continuous sensor data and complete daily ecological momentary assessments on alcohol craving and mood for up to 30 days. Data from sensor streams were processed into features like accelerometer magnitude, number of calls, and location entropy, which were used for statistical analysis. We used repeated measures correlation for longitudinal data to evaluate associations between sensors and ecological momentary assessments and standard Pearson correlation to evaluate within-individual relationships between sensors and craving.

Results:
Alcohol craving significantly correlated with mood obtained from ecological momentary assessments. Across all sensors, features associated with craving were also significantly correlated with all moods (eg, loneliness and stress) except boredom. Individual-level analysis revealed significant relationships between craving and features of location entropy and average accelerometer magnitude.

Conclusions:
Smartphone sensors may serve as markers for alcohol craving and mood in alcohol-associated liver disease and alcohol use disorder. Findings suggest that location-based and accelerometer-based features may be associated with alcohol craving. However, data missingness and low participant retention remain challenges. Future studies are needed for further digital phenotyping of relapse risk and progression of liver disease.