bluuebunny/crossref_metadata_2025_split huggingface dataset:
NetrinG1+ Cancer-Associated Fibroblasts Generate Unique Extracellular Vesicles that Support the Survival of Pancreatic Cancer Cells Under Nutritional Stress
Authors: Raghavan Kristopher S. , Francescone Ralph , Franco-Barraza Janusz , Gardiner Jaye C. , Vendramini-Costa Débora B. , Luong Tiffany , Pourmandi Narges , Andren Anthony , Kurimchak Alison , Ogier Charline , Campbell Paul M. , Duncan James S. , Lyssiotis Costas A. , Languino Lucia R. , Cukierman Edna 
Published: August 2022

It is projected that in 5 years, pancreatic cancer will become the second deadliest cancer in the United States. A unique aspect of pancreatic ductal adenocarcinoma (PDAC) is its stroma; rich in cancer-associated fibroblasts (CAFs) and a dense CAF-generated extracellular matrix (ECM). These pathogenic stroma CAF/ECM units cause the collapse of local blood vessels rendering the tumor microenvironment nutrient-poor. PDAC cells are able to survive this state of nutrient stress via support from CAF-secreted material, which includes small extracellular vesicles (sEV). The tumor-supportive CAFs possess a distinct phenotypic profile, compared with normal-like fibroblasts, expressing NetrinG1 (NetG1) at the plasma membrane, and active Integrin α5β1 localized to the multivesicular bodies; traits indicative of poor patient survival. We herein report that NetG1+ CAFs secrete sEVs that stimulate Akt-mediated survival in nutrient-deprived PDAC cells, protecting them from undergoing apoptosis. Furthermore, we show that NetG1 expression in CAFs is required for the prosurvival properties of sEVs. In addition, we report that the above-mentioned CAF markers are secreted in distinct subpopulations of EVs; with NetG1 being enriched in exomeres, and Integrin α5β1 being enriched in exosomes. Finally, we found that NetG1 and Integrin α5β1 were detected in sEVs collected from plasma of patients with PDAC, while their levels were significantly lower in plasma-derived sEVs of sex/age-matched healthy donors. The discovery of these tumor-supporting CAF-EVs elucidates novel avenues in tumor–stroma interactions and pathogenic stroma detection.Significance:Results from this study identified two unique types of tumor-supporting CAF EVs, with evidence of these being detected in patients. Thus, this study facilitates a novel avenue to further dissect the subtleties of the tumor–stroma interactions responsible for PDAC homeostasis and progression, as well as the possibility of establishing future means to detect and monitor dynamic stroma staging.
Targeting SIRT1 Rescues Age- and Obesity-Induced Microvascular Dysfunction in Ex Vivo Human Vessels
Authors: Mengozzi Alessandro , Costantino Sarah , Paneni Francesco , Duranti Emiliano , Nannipieri Monica , Mancini Rudj , Lai Michele , La Rocca Veronica , Puxeddu Ilaria , Antonioli Luca , Fornai Matteo , Ghionzoli Marco , Georgiopoulos Georgios , Ippolito Chiara , Bernardini Nunzia , Ruschitzka Frank , Pugliese Nicola Riccardo , Taddei Stefano , Virdis* Agostino , Masi Stefano 
Published: August 2022

Background:
Experimental evidence suggests a key role of SIRT1 (silent information regulator 1) in age- and metabolic-related vascular dysfunction. Whether these effects hold true in the human microvasculature is unknown. We aimed to investigate the SIRT1 role in very early stages of age- and obesity-related microvascular dysfunction in humans.

Methods:

Ninety-five subjects undergoing elective laparoscopic surgery were recruited and stratified based on their body mass index status (above or below 30 kg/m
2
) and age (above or below 40 years) in 4 groups: Young Nonobese, Young Obese, Old Nonobese, and Old Obese. We measured small resistance arteries’ endothelial function by pressurized micromyography before and after incubation with a SIRT1 agonist (SRT1720) and a mitochondria reactive oxygen species (mtROS) scavenger (MitoTEMPO). We assessed vascular levels of mtROS and nitric oxide availability by confocal microscopy and vascular gene expression of SIRT1 and mitochondrial proteins by qPCR. Chromatin immunoprecipitation assay was employed to investigate SIRT1-dependent epigenetic regulation of mitochondrial proteins.

Results:

Compared with Young Nonobese, obese and older patients showed lower vascular expression of SIRT1 and antioxidant proteins (FOXO3 [forkhead box protein O3] and SOD2) and higher expression of pro-oxidant and aging mitochondria proteins p66
Shc
and Arginase II. Old Obese, Young Obese and Old Nonobese groups endothelial dysfunction was rescued by SRT1720. The restoration was comparable to the one obtained with mitoTEMPO. These effects were explained by SIRT1-dependent chromatin changes leading to reduced p66
Shc
expression and upregulation of proteins involved in mitochondria respiratory chain.

Conclusions:

SIRT1 is a novel central modulator of the earliest microvascular damage induced by age and obesity. Through a complex epigenetic control mainly involving p66
Shc
and Arginase II, it influences mtROS levels, NO availability, and the expression of proteins of the mitochondria respiratory chain. Therapeutic modulation of SIRT1 restores obesity- and age-related endothelial dysfunction. Early targeting of SIRT1 might represent a crucial strategy to prevent age- and obesity-related microvascular dysfunction.
Exploring Group Differences in the Crossmodal Correspondences
Authors: Spence Charles 
Published: August 2022

Abstract
There has been a rapid growth of interest amongst researchers in the cross-modal correspondences in recent years. In part, this has resulted from the emerging realization of the important role that the correspondences can sometimes play in multisensory integration. In turn, this has led to an interest in the nature of any differences between individuals, or rather, between groups of individuals, in the strength and/or consensuality of cross-modal correspondences that may be observed in both neurotypically normal groups cross-culturally, developmentally, and across various special populations (including those who have lost a sense, as well as those with autistic tendencies). The hope is that our emerging understanding of such group differences may one day provide grounds for supporting the reality of the various different types of correspondence that have so far been proposed, namely structural, statistical, semantic, and hedonic (or emotionally mediated).
Continental Geometry’s Role in Shaping Wintertime Temperature Variance
Authors: Neumann Nicole K. , Lutsko Nicholas J. 
Published: August 2022

Abstract
The factors controlling the present-day pattern of temperature variance are poorly understood. In particular, it is unclear why the variance of wintertime near-surface temperatures on daily and synoptic time scales is roughly twice as high over North America as over Eurasia. In this study, continental geometry’s role in shaping regional wintertime temperature variance is investigated using idealized climate model simulations run with midlatitude continents of different shapes. An isolated, rectangular midlatitude continent suggests that in the absence of other geographic features, the highest temperature variance will be located in the northwest of the continent, roughly collocated with the region of largest meridional temperature gradients, and just north of the maximum near-surface wind speeds. Simulations with other geometries, mimicking key features of North America and Eurasia, investigate the impacts of continental length and width, sloping coastlines, and inland bodies of water on regional temperature variance. The largest effect comes from tapering the northwest corner of the continent, similar to Eurasia, which substantially reduces the maximum temperature variance. Narrower continents have smaller temperature variance in isolation, implying that the high variances over North America must be due to the nonlocal influence of stationary waves. Support for this hypothesis is provided by simulations with two midlatitude continents, which show how continental geometry and stationary waves can combine to shape regional temperature variance.

Significance Statement
Wintertime temperature variance over North America is roughly twice as high as over Eurasia, but the reasons for this are unknown. Here we use idealized climate model simulations to investigate how continental geometry shapes regional temperature variance. We find that the smaller variance over Eurasia is largely due to the tapering of its northwest coast, which weakens temperature gradients in the continental interior. Our simulations also suggest that in isolation a narrow continent, like North America, should have weak temperature variance, implying that stationary waves are responsible for the high variance over North America. Understanding the controls on regional temperature variance is important for interpreting present-day winter climates and how these will change in the future.
Pelvis and Trunk Energy Flow in Collegiate Softball Pitchers With and Without Upper Extremity Pain
Authors: Bordelon Nicole M. , Wasserberger Kyle W. , Downs-Talmage Jessica L. , Friesen Kenzie B. , Dugas Jeffrey R. , Oliver Gretchen D. 
Published: August 2022

Background: The softball pitch is a full-body motion, where efficient proximal to distal energy flow through the kinetic chain is said to reduce stress at the upper extremity. Although altered trunk kinematic parameters are associated with upper extremity pain in softball pitchers, further research is needed to determine whether differences exist in proximal energy flow between softball pitchers with and without pain. Hypothesis/Purpose: To examine pelvis and trunk energy flow during the acceleration phase of the pitch in collegiate softball pitchers with and without upper extremity pain. It was hypothesized that those with upper extremity pain would have less energy flowing into the proximal ends of the pelvis and trunk as well as less energy flowing out of the distal ends of the pelvis and trunk during the acceleration phase when compared with pitchers who did not have upper extremity pain. Study Design: Descriptive laboratory study. Methods: A total of 54 female National Collegiate Athletic Association Division I softball pitchers (age, 20.2 ± 2.0 years; height, 173.5 ± 6.9 cm; weight, 78.5 ± 11.5 kg) were assigned to pain (n = 17) and pain-free (n = 38) groups. Participants pitched 3 maximal effort rise-balls for a strike, and the average of the 3 trials was used for analysis. Kinematic data were collected at 100 Hz using an electromagnetic tracking system. A segment power analysis was performed to quantify energy flow for the pelvis and trunk. The Mann-Whitney U test was used to compare pelvis and trunk energy flow during the acceleration phase of the pitch as well as pitch velocity between collegiate softball pitchers with and without upper extremity pain. Results: No significant differences were found between pelvis and trunk energy flow during the acceleration phase or pitch velocity between collegiate softball pitchers with and without upper extremity pain (all P values >.057). Conclusion: Previous research determined that kinematic parameters differ between collegiate pitchers with and without upper extremity pain. However, the current study found no difference in pelvis and trunk energy flow or pitch velocity. Although altered kinematics in collegiate pitchers with upper extremity pain may serve as compensation patterns to maintain pitch velocity and proximal energy flow, future research is needed to confirm this postulation. Clinical Relevance: The lack of energy flow differences between upper extremity pain groups suggests that pitchers may adapt their biomechanics to maintain trunk and pelvis energy flow patterns. Coaches, athletes, and clinicians should know that movement adaptations can allow for maintained performance levels but may result in the presence of pain that may manifest in other deleterious and injury-susceptible biomechanics.
Sexual history of human monkeypox patients seen at a tertiary hospital in Bayelsa, Nigeria.
Authors: Ogoina Dimie , Yinka-Ogunleye Adesola 
Published: August 2022

Background: Human monkeypox (HMPX) is currently spreading outside endemic countries in Africa and the majority of those affected are gay and bisexual men within interconnected sexual networks. We investigated the sexual history of HMPX cases seen at a tertiary hospital in Bayelsa State during the 2017–2018 outbreak in Nigeria. Method: A cross-sectional study was conducted between 20 October 2017 and 2 January 2019 among adult confirmed/probable HMPX cases. A questionnaire was used to collect data on the sexual history of participants, including sexual contact in relation to the first symptom, and high-risk behaviours (HRB) such as a history of condomless casual sex, multiple sexual partners, and transactional sex. Results: Of 21 patients, 16 (76.2%) gave consent to participate in the study: age range of 22–43 years, 75% males, three (18.8%) HIV-1 positive, and 13 (81.2%) with genital ulcers. Nine (56.2%) of participants reported HRB, and all were male heterosexuals. Eight of the 16 participants (50%) reported having sex within a month before their first symptom, and five (62.5%) of this number reported HRB. There were two cases of sex with a partner with a non-genital rash, and a spouse who developed a vulval ulcer four days after sex with her husband. Conclusion: Our results support the role of sexual contact in the transmission of monkeypox among some confirmed cases from Nigeria. However, future elaborate studies are required to confirm if sexual behaviour and sexual transmission are associated with HMPX in Nigeria.
Effect of Gait-Specific Weight-Bearing Interventions on Physical Performance Among Subjects with Stroke: A Systematic Review and Meta-analysis
Authors: Ravichandran Hariharasudhan , Shetty Kshama Susheel , Janakiraman Balamurugan 
Published: August 2022

Background Postural instability, gait dysfunctions, and tendency to fall resulting from asymmetrical weight-bearing restrict balance and mobility functions among stroke survivors. Symmetrical weight-bearing is essential for restoring mobility functions following stroke. Strategies to improve symmetrical weight-bearing remain a challenge in stroke rehabilitation. Objective To explore the evidence regarding the effectiveness of weight-bearing interventions to improve physical performance among subjects with stroke. Methods Five databases, including PubMed, Cumulative Index for Nursing and Allied Health Literature, Physiotherapy Evidence Database (PEDro), Google Scholar, and OpenGrey, were screened for identifying published and unpublished studies from their inception and up to 2022. Studies investigating the effect of symmetrical weight-bearing interventions among stroke subjects using objective or self-reporting of physical function as an outcome tool were included. Ten articles with grade 1b level of evidence demonstrated an average PEDro score of 6.4. The risk of bias was moderate among the articles. Results Ten articles with 276 participants were included in this review. Meta-analysis performed using 9 articles report that gait-specific weight-bearing improved balance and gait velocity with an overall effect size of 1.35 (95% confidence interval: 0.88–1.81) and 0.66 (95% confidence interval: 0.20–1.13). However, the effect size of step length (0.51), cadence (0.26), and fall efficacy scale (0.21) indicates nonsignificant improvement. Conclusions This meta-analysis suggests that gait-specific weight-bearing strategies are effective in improving balance and speed of walking but did not improve other parameters of gait and risk of fall. These strategies could be used to improve the symmetrical weight-bearing of stroke subjects in rehabilitation settings who do not have access to technological assistance in rehabilitation.
The global inhomogeneity index assessed by electrical impedance tomography overestimates PEEP requirement in patients with ARDS: an observational study
Authors: Heines Serge J. H. , de Jongh Sebastiaan A. M. , Strauch Ulrich , van der Horst Iwan C. C. , van de Poll Marcel C. G. , Bergmans Dennis C. J. J. 
Published: August 2022

Abstract
Background
Electrical impedance tomography (EIT) visualises alveolar overdistension and alveolar collapse and enables optimisation of ventilator settings by using the best balance between alveolar overdistension and collapse (ODCL). Besides, the global inhomogeneity index (GI), measured by EIT, may also be of added value in determining PEEP. Optimal PEEP is often determined based on the best dynamic compliance without EIT at the bedside. This study aimed to assess the effect of a PEEP trial on ODCL, GI and dynamic compliance in patients with and without ARDS. Secondly, PEEP levels from “optimal PEEP” approaches by ODCL, GI and dynamic compliance are compared.

Methods
In 2015–2016, we included patients with ARDS using postoperative cardiothoracic surgery patients as a reference group. A PEEP trial was performed with four consecutive incremental followed by four decremental PEEP steps of 2 cmH2O. Primary outcomes at each step were GI, ODCL and best dynamic compliance. In addition, the agreement between ODCL, GI, and dynamic compliance was determined for the individual patient.

Results
Twenty-eight ARDS and 17 postoperative cardiothoracic surgery patients were included. The mean optimal PEEP, according to best compliance, was 10.3 (±2.9) cmH2O in ARDS compared to 9.8 (±2.5) cmH2O in cardiothoracic surgery patients. Optimal PEEP according to ODCL was 10.9 (±2.5) in ARDS and 9.6 (±1.6) in cardiothoracic surgery patients. Optimal PEEP according to GI was 17.1 (±3.9) in ARDS compared to 14.2 (±3.4) in cardiothoracic surgery patients.

Conclusions
Currently, no golden standard to titrate PEEP is available. We showed that when using the GI, PEEP requirements are higher compared to ODCL and best dynamic compliance during a PEEP trial in patients with and without ARDS.
Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting
Authors: Glasmeyer Laura , Mcharo Ruby Doryn , Torres Liset , Lennemann Tessa , Danstan Elizabeth , Mwinuka Nice , Judick Mona , Mueller William , Mbuya Wilbert , Hölscher Michael , Lellé Ralph , Geldmacher Christof , Kroidl Arne , France John Rwegoshora 
Published: August 2022

Abstract
Background
Worldwide 85% of cervical cancer (CC) related deaths occur in low- and middle-income countries. Sub-Saharan Africa is burdend by an overlapping high incidence of CC as well as HIV infection, a risk factor for HPV associated disease progression. Recent upscaling of CC screening activities increased the number of CC diagnoses in a previous unscreened population. The aim of the 2H study was to follow up on women with CC in the context of available health care services in Tanzania in relation to their HIV infection status.

Methods
This longitudinal observational cohort study included women with histological confirmed CC from Mbeya, Tanzania, between 2013–2019. All women were referred for CC staging and cancer-directed therapies (CDT), including surgery and/or radio-chemotherapy, or palliative care. Annual follow-up focused on successful linkage to CDT, interventions and survival. We assessed factors on compliance, used Kaplan–Meier-Survivor functions to evaluate survival time and poisson regression models to calculate incidence rate ratios on mortality (IRR) two years after diagnosis.

Results
Overall, 270 women with CC (123 HIV infected) were included. Staging information, available in 185 cases, showed 84.9% presented with advanced stage disease (FIGO ≥ IIB), no difference was seen in respect to HIV status. HIV-infected women were 12 years younger at the time of cancer diagnosis (median age 44.8 versus 56.4 years, p < 0.001). Median follow up period was 11.9 months (range 0.2–67.2). Survival information, available in 231 cases, demonstrated for women diagnosed in early-stage disease a median survival time of 38.3 months, in advanced-stage 16.0 months and late-stage disease 6.5 months after diagnosis. Of all women, 42% received CDT or palliative support. HIV co-infection and education were associated with higher health care compliance. CDT was significantly associated with lower 2-year mortality rates (IRR 0.62, p = 0.004). HIV coinfection did not impact mortality rates after diagnosis.

Conclusion
High numbers of advanced and late staged CC were diagnosed, compliance to CDT was low. A beneficial impact of CDT on CC mortality could be demonstrated for local health care services. This study indicates challenges for successful linkage and supports an effective scale up of cancer care and treatment facilities.
Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab
Authors: Glonnegger Hannah , Andresen Felicia , Kapp Friedrich , Malvestiti Stefano , Büchsel Martin , Zieger Barbara 
Published: August 2022

Abstract
Purpose
Real-world data and study data regarding therapy with Emicizumab in pediatric cohorts with haemophilia A is scarce. Especially, data on previously untreated pediatric patients (PUPs) and minimally treated patients (MTPs) are missing.

Methods
Thirteen pediatric patients with haemophilia A and treatment with Emicizumab were retrospectively evaluated for Annual Bleeding Rates (ABR) pre-and post-Emicizumab treatment. Safety data and data on management of minor surgery as well as laboratory results were collected. Additionally, we describe the clinical features of two PUPs and one MTP that are included in our cohort.

Results
Median age at initiation of Emicizumab was 5.3 (range: 0.26–17.5) years, three patients were younger than one year at initiation of treatment with Emicizumab. Median follow-up time on Emicizumab was 23.8 (range: 0.7–40) months. Total ABR (p = 0.009) as well as spontaneous (p = 0.018), traumatic (p = 0.018), and joint (p = 0.027) ABR reduced significantly post-Emicizumab transition. Safety profile was favourable as only one local site reaction occurred; no cessation of treatment was necessary. Surgery was successfully performed in three patients receiving rFVlla pre- and post-surgery. Emicizumab trough levels showed a median of 43.2 μg/ml (range: 23.9–56.8) after three doses of 3 mg/kg and 51.9 μg/ml (range: 30.4–75) at first follow-up with 1.5 mg/kg.

Conclusion
Emicizumab is safe and efficient in pediatric patients with and without inhibitors. More data on larger multicenter cohorts and especially on PUPs/MTPs are still needed.