bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil Conversion to a Tumor-Killing Phenotype Underpins Effective Microbial Therapy
Authors: Yam Andrew O. , Bailey Jacqueline , Lin Francis , Jakovija Arnolda , Youlten Scott E. , Counoupas Claudio , Gunzer Matthias , Bald Tobias , Woodruff Trent M. , Triccas James A. , Goldstein Leonard D. , Gallego-Ortega David , Grey Shane T. , Chtanova Tatyana 
Published: February 2023

AbstractThe inflammatory microenvironment of solid tumors creates a protumorigenic milieu that resembles chronic inflammation akin to a subverted wound healing response. Here, we investigated the effect of converting the tumor microenvironment from a chronically inflamed state to one of acute microbial inflammation by injecting microbial bioparticles directly into tumors. Intratumoral microbial bioparticle injection led to rapid and dramatic changes in the tumor immune composition, the most striking of which was a substantial increase in the presence of activated neutrophils. In situ photoconversion and intravital microscopy indicated that tumor neutrophils transiently switched from sessile producers of VEGF to highly motile neutrophils that clustered to make neutrophil-rich domains in the tumor. The neutrophil clusters remodeled tumor tissue and repressed tumor growth. Single-cell transcriptional analysis of microbe-stimulated neutrophils showed a profound shift in gene expression towards heightened activation and antimicrobial effector function. Microbe-activated neutrophils also upregulated chemokines known to regulate neutrophil and CD8+ T-cell recruitment. Microbial therapy also boosted CD8+ T-cell function and enhanced the therapeutic benefit of checkpoint inhibitor therapy in tumor-bearing mice and provided protection in a model of tumor recurrence. These data indicate that one of the major effector mechanisms of microbial therapy is the conversion of tumor neutrophils from a wound healing to an acutely activated cytotoxic phenotype, highlighting a rationale for broader deployment of microbial therapy in the treatment of solid cancers.Significance:Intratumoral injection of microbial bioparticles stimulates neutrophil antitumor functions, suggesting pathways for optimizing efficacy of microbial therapies and paving the way for their broader utilization in the clinic.
Targeting Unc51-like Autophagy Activating Kinase 1 (ULK1) Overcomes Adaptive Drug Resistance in Acute Myelogenous Leukemia
Authors: Bhattacharya Seemana , Piya Sujan , Ma Huaxian , Sharma Priyanka , Zhang Qi , Baran Natalia , Ruvolo Vivian R. , McQueen Teresa , Davis R. Eric , Pourebrahim Rasoul , Konopleva Marina , Kantarjian Hagop , Cosford Nicholas D. P. , Andreeff Michael , Borthakur Gautam 
Published: February 2023

Abstract

Despite effective new therapies, adaptive resistance remains the main obstacle in acute myelogenous leukemia (AML) therapy. Autophagy induction is a key mechanism for adaptive resistance. Leukemic blasts at diagnosis express higher levels of the apical autophagy kinase ULK1 compared with normal hematopoietic cells. Exposure to chemotherapy and targeted agents upregulate ULK1, hence we hypothesize that developing ULK1 inhibitors may present the unique opportunity for clinical translation of autophagy inhibition. Accordingly, we demonstrate that ULK1 inhibition, by genetic and pharmacologic means, suppresses treatment-induced autophagy, overcomes adaptive drug-resistance, and synergizes with chemotherapy and emerging antileukemia agents like venetoclax (ABT-199). The study next aims at exploring the underlying mechanisms. Mechanistically, ULK1 inhibition downregulates MCL1 antiapoptotic gene, impairs mitochondrial function and downregulates components of the CD44-xCT system, resulting in impaired reactive oxygen species (ROS) mitigation, DNA damage, and apoptosis. For further validation, several mouse models of AML were generated. In these mouse models, ULK1 deficiency impaired leukemic cell homing and engraftment, delayed disease progression, and improved survival. Therefore, in the study, we validated our hypothesis and identified ULK1 as an important mediator of adaptive resistance to therapy and an ideal candidate for combination therapy in AML. Therefore, we propose ULK1 inhibition as a therapeutically relevant treatment option to overcome adaptive drug-resistance in AML.

Implications:
ULK1 drives a cell-intrinsic adaptive resistance in AML and targeting ULK1-mediated autophagy can synergize with existing and emerging AML therapies to overcome drug-resistance and induce apoptosis.
Female preferences for high vocal effort in singing mice
Authors: Burkhard Tracy Tran , Sachs E. Raney , Phelps Steven M. 
Published: February 2023

Abstract
Although vocalizations are essential to mammalian sociosexual behaviours, little is known about female preferences for male vocal displays in non-model mammalian species. Here, we characterized female preferences for the advertisement songs of male Alston’s singing mice (Scotinomys teguina). We developed procedures for inducing oestrus, using vaginal perforation as a morphological indicator of oestrus. We then broadcasted ‘high-effort’ and ‘low-effort’ songs recorded from wild-caught males to virgin laboratory-reared females, using a two-choice experiment. Our results indicate that females spent more time investigating speakers playing high-effort songs; surprisingly, this phonotactic response is independent of oestrus status. In wild singing mice, acoustic characteristics of high-effort male songs positively correlate with body condition. Our data suggest that females could use acoustic cues to select mates in good condition, thus providing preliminary support for adaptive mate choice hypotheses. More generally, our results support the hypothesis that elaborate Scotinomys song may be shaped by female choice.
Challenges and Opportunities in Communicating Weather and Climate Information to Rural Farming Communities in Central Zimbabwe
Authors: Makuvaro Veronica , Chitata Tavengwa , Tanyanyiwa Emmanuel , Zirebwa Solomon 
Published: February 2023

Abstract
Sustainability of rain-fed agriculture in semiarid regions is being threatened by climate variability and change. Weather and climate information (WCI) can be used to reduce the effects of this threat on agricultural production. WCI may be available, but is it readily accessible and communicated/disseminated efficiently to intended end users? Are stakeholders able to interpret the information to correctly inform decision-making? To answer these questions, in view of intermediate stakeholders (service providers to farmers), a study was carried out in two districts of the Midlands Province of Zimbabwe to identify the type and sources of WCI received by these stakeholders as well as constraints and opportunities to access, interpretation, and use of WCI. The study sample was drawn from the Midlands Provincial Drought Relief Committee, a link between the sources of WCI and the smallholder farmers. A questionnaire pretested for clarity and checked for internal consistency of themes using the standardized Cronbach’s alpha was used to collect data. Descriptive statistics were generated using SPSS (version 20.0). Findings were that WCI was sometimes not readily available or was received late. Approximately 36% of the intermediate stakeholders (service providers) passed on WCI to farmers in its original form, from the main source the Meteorological Services Department. It was also unfortunate to discover that 36% of the respondents had challenges interpreting WCI. Impediments to the use of WCI by farmers included scientific information not aligning with indigenous information, which is better understood by farmers, and lack of trust in WCI. It is imperative to improve access to WCI and to train stakeholders on interpretation and dissemination of WCI.

Significance Statement
Weather and climate information—if accurate, accessible, provided in a timely manner, and well understood—can be helpful in the farm decision-making process. Its usefulness is becoming more important with increased climatic variability and change. This paper highlights the challenges and opportunities for service providers in communicating and disseminating WCI. We believe that findings from the study will give direction to efficient utilization of the information by the various end users, for which smallholder farmers are the majority in most developing countries.
Efficacy of CT Value Along Portal Vein for Preoperative Prediction of Portal Vein Resection in Pancreatic Head Cancer
Authors: Ochiai Shigeto , Chiba Naokazu , Gunji Takahiro , Kobayashi Toshimichi , Sano Toru , Tomita Koichi , Shigoka Masatoshi , Tabuchi Satoshi , Hidaka Eiji , Wakiya Midori , Nakatsugawa Munehide , Kawachi Shigeyuki 
Published: February 2023

Background It is important for surgeons to determine whether combined portal vein (PV) resection (PVR) is necessary before surgery. The present study aimed to determine the ability of computed tomography (CT) value along the PV in predicting the necessity for concomitant PVR. Methods A total of 107 consecutive patients who underwent pancreaticoduodenectomy (PD) for invasive ductal carcinoma of the pancreatic head at our institute between September 2007 and September 2020 were reviewed retrospectively. Univariate analysis to predict PVR was performed with preoperative radiological valuables acquired by Synapse Vincent. The resected specimen near the PV or the PV notch was analyzed by histopathological findings. Results Only the CT value of the PV was independently associated with PVR (Mann-Whitney U test; P = .045, logistic regression test; P = .039). The outer boundary of the PV was unclear in the cases without pathological PV invasion and PVR due to the development of smooth muscle in the outer membrane of the PV and the proliferation of collagen fibers. The elastic fibers were arranged regularly in the notch portion of the PV in cases wherein PVR was not performed. Discussion The CT value along the PV was independently associated with PVR and is the only predictor of PVR. These results were very useful in predicting PVR preoperatively and were histopathologically supportive.
Angioembolization May Improve Survival in Patients With Severe Hepatic Injuries
Authors: Rozycki Grace F. , Sakran Joseph V. , Manukyan Mariuxi C. , Feliciano David V. , Radisic Amanda , You Bin , Hu Fang , Wooster Meghan , Noll Kathy , Haut Elliott R. 
Published: February 2023

Introduction Although reports on angioembolization (AE) show favorable results for severe hepatic trauma, information is lacking on its benefit in the management and mechanisms of injury (MOI). This study examined patient outcomes with severe hepatic injuries to determine the association of in-hospital mortality with AE. The hypothesis is that AE is associated with increased survival in severe hepatic injuries. Methods Demographics, age, sex, MOI, shock index (SI), ≥6 units packed red blood cells (PRBCs) per hospital length of stay (LOS), intensive care unit LOS, injury severity score (ISS), and AE were collected. The primary outcome was in-hospital mortality. Patients were stratified into groups according to MOI, AE, and operative vs non-operative management. Multivariable logistic regression determined the independent association of mortality with AE vs no AE and operative vs nonoperative management and modeled the odds of mortality controlling for MOI, AE vs no AE, age and ISS groups, SI >.9, and ≥6 units PRBCs/LOS. Results From 2013 to 2018, 2462 patients (1744 blunt; 718 penetrating) were treated for severe hepatic injuries. AE was used in only 21% of patients. Mortality rates increased with higher ISS and age. AE was associated with mortality when compared to patients who did not undergo AE. The strongest associations with mortality were ISS ≥25, transfusion ≥ 6 units PRBCs/LOS, and age ≥65 years. Conclusions AE is underutilized in severe hepatic trauma. AE may be a valuable adjunct in the treatment of severe hepatic injuries especially in older patients and those needing exploratory laparotomy.
Validity of Atherosclerotic Calcified Lesions Observed on Low-Dose Computed Tomography and Cardio-Ankle Vascular Index as Surrogate Markers of Atherosclerosis Progression
Authors: Homma Satoki , Kato Kiyoe 
Published: February 2023

The significance of atherosclerotic calcified lesions observed on low-dose computed tomography (LDCT) performed during general checkups was investigated. The coronary arteries (CA), ascending aorta and aortic arch (AAAA), descending thoracic aorta (DTA), and abdominal aorta (AA) were examined. Semiquantitative calcified index analysis of the DTA and AA in terms of atherosclerosis risk factors and cardio-ankle vascular index (CAVI) measurements was also performed. We included 1594 participants (mean age: 59.2 years; range: 31–91 years). The prevalence of calcified lesions was 71.0%, 66.6%, 57.2%, and 37.9% in the AA, CA, AAAA, and DTA, respectively. Age-related advances in calcification among participants with no major risk factors, revealed that calcification appeared earliest in the AA, followed by the CA, AAAA, and DTA. Participants with calcified lesions in all arteries had a significantly greater CAVI than those without calcification. The CAVI was negatively correlated with low-density lipoprotein cholesterol levels, particularly in participants without calcified lesions in the DTA. Calcified lesions on LDCT could indicate the end stage of atherosclerotic lesions. The CAVI can be used to assess atherosclerotic changes at all stages of disease progression. A combination of LDCT and CAVI could be used as a routine non-invasive assessment of atherosclerosis.
First Nations Peoples in the forensic mental health system in New South Wales: Characteristics and rates of criminal charges post-release
Authors: Dean Kimberlie , Lyons Georgia , Johnson Anina , McEntyre Elizabeth 
Published: February 2023

Background: It is well established that First Nations Peoples in Australia are overrepresented within the criminal justice system. However, First Nations Peoples appear to be comparatively underrepresented in the forensic mental health system, and little is known about their outcomes once released from secure care. Objective: To compare the characteristics and rates of repeat criminal justice contact for a criminal charge of First Nations and non-First Nations forensic patients in New South Wales. Methods: Data on the sample were extracted from the New South Wales Mental Health Review Tribunal paper and electronic files matched to the Bureau of Crime Statistics and Research Reoffending Database. Characteristics of First Nations and non-First Nations patients were compared using univariate logistic regression analysis. Univariate and multivariate Cox proportional hazard regression was used to determine predictors of post-release criminal charges. Results: Key differences in the sociodemographic, clinical and forensic characteristics of First Nations compared with non-First Nations forensic patients were identified. The time to first criminal justice contact following release was significantly shorter for First Nations forensic patients ( p < 0.01). Conclusion: The findings of this study confirm that First Nations forensic patients have distinct and complex needs that are apparent at entry to the forensic mental health system and that their poorer criminal justice contact rates following release from secure care indicate that these needs are not being adequately met either during treatment or once in the community. Responses to these study findings must consider the complex and continuing impact of colonisation on First Nations Peoples, as well as the need for solutions to be culturally safe.
Update on headaches associated with physical exertion
Authors: González-Quintanilla Vicente , Madera Jorge , Pascual Julio 
Published: February 2023

Background Headaches associated with physical exertion include headache precipitated by coughing or other Valsalva maneuvers, headache brought on by prolonged physical exercise, sexual headaches and cardiac cephalalgia. Objective To review and update the clinical characteristics, etiologies, pathophysiology and management of these headaches related to exertion. Methods In depth review of the publications, both in PubMed and in the main textbooks, of the different headaches induced by physical exercise. Results Cough, exercise and sexual headaches can be primary or secondary; therefore, complementary studies are mandatory to rule out structural lesions. However, clinical characteristics, such as an old age and response to indomethacin for cough headache or being a young male and response to beta-blockers for exercise and sexual headaches, plus a normal examination are suggestive of a primary etiology. Etiology for secondary varieties, as posterior fossa lesions for cough headache or vascular malformations for exercise and sexual headaches, are also different. Finally, headache as a distant manifestation of myocardial ischemia, also known as “cardiac cephalalgia”, appears at exertion in around two-thirds of cases and typically lasts less than 30 minutes and is relieved by nitroglycerine. Conclusions Primary and secondary cough headache can usually be suspected based on clinical characteristics and separated from exercise and sexual headaches, which share many aspects. Cardiac cephalalgia is not necessarily an exertional headache and should be considered in adult patients with short lasting headaches and patent vascular risk factors.
Retinal vessel dynamics analysis as a surrogate marker for raised intracranial pressure in patients with suspected idiopathic intracranial hypertension
Authors: Hagen Snorre Malm , Wibroe Elisabeth Arnberg , Korsbæk Johanne Juhl , Andersen Mikkel Schou , Nielsen Asger Bjørnær , Nortvig Mathias Just , Beier Dagmar , Poulsen Frantz Rom , Jensen Rigmor Højland , Hamann Steffen 
Published: February 2023

Introduction Retinal vessel dynamics analysis has proven to be a viable, non-invasive surrogate marker for increased intracranial pressure. We aimed to test this method in patients with suspected idiopathic intracranial hypertension. Methods Patients with suspected idiopathic intracranial hypertension were prospectively enrolled for hand-held fundus-videography during diagnostic lumbar puncture. After extracting optic disc images, peripapillary arteriole-to-venule-ratios were measured using machine-learning algorithms with manual identification control. A general linear model was applied to arteriole-to-venule-ratios and corresponding lumbar opening pressures to estimate cerebrospinal fluid pressure. Results Twenty-five patients were included with a significant difference in arteriole-to-venule-ratio between patients with ( n = 17) and without ( n = 8) idiopathic intracranial hypertension (0.78 ± 0.10 vs 0.90 ± 0.08, p = 0.006). Arteriole-to-venule-ratio correlated inversely with lumbar opening pressure (slope regression estimate −0.0043 (95% CI −0.0073 to −0.0023), p = 0.002) and the association was stronger when lumbar opening pressure exceeded 15 mm Hg (20 cm H2O) (slope regression estimate −0.0080 (95% CI −0.0123 to −0.0039), p < 0.001). Estimated cerebrospinal fluid pressure predicted increased lumbar opening pressure >20 mm Hg (27 cm H2O) with 78% sensitivity and 92% specificity (AUC 0.81, p = 0.02). A stand-alone arteriole-to-venule-ratio measurement predicting lumbar opening pressure >20 mm Hg (27 cm H2O) was inferior with a 48% sensitivity and 92% specificity (AUC 0.73, p = 0.002). Conclusion Retinal vessel dynamics analysis with the described model for estimating cerebrospinal fluid pressure is a promising non-invasive method with a high sensitivity and specificity for detecting elevated intracranial pressure at follow-up assessments of patients with confirmed idiopathic intracranial hypertension if initial lumbar opening pressure and arteriole-to-venule-ratio data are available.
Update on primary headache associated with sexual activity and primary thunderclap headache
Authors: Lin Po-Tso , Chen Shih-Pin , Wang Shuu-Jiun 
Published: February 2023

Background This narrative review aims to provide an update on primary headache associated with sexual activity and primary thunderclap headache. Methods We conducted a literature search on PubMed with the keywords “headache associated with sexual activity”, “sexual headache”, “orgasmic cephalalgia”, and “coital cephalalgia” in addition to “thunderclap headache” to assess the appropriateness of all published articles in this review. Results Primary headache associated with sexual activity is a “primary” headache precipitated by sexual activity, which occurs as sexual excitement increases (progressive at onset), or manifests as an abrupt and intense headache upon orgasm (thunderclap at onset) or combines these above two features. Primary headache associated with sexual activity is diagnosed after a thorough investigation, including appropriate neuroimaging studies, to exclude life-threatening secondary causes such as subarachnoid hemorrhage. According to the criteria of the third edition of the International Classification of Headache Disorders, primary thunderclap headache is also a diagnosis by exclusion. The pathophysiology of primary headache associated with sexual activity and primary thunderclap headache remains incompletely understood. Treatment may not be necessary for all patients since some patients with primary headache associated with sexual activity and primary thunderclap headache have a self-limiting course. Conclusion A comprehensive neuroimaging study is needed for distinguishing primary headache associated with sexual activity or primary thunderclap headache from secondary causes. Primary headache associated with sexual activity and primary thunderclap headache are self-limited diseases and the prognoses are good, but some patients with primary headache associated with sexual activity may have a prolonged course.