bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics
Authors: Hu Lingyu , Wang Xiaoguang , Song Zhengwei , Chen Fei , Wu Bin 
Published: November 2024

Abstract
Background
Pancreatic cancer is known for its poor prognosis and resistance to conventional therapies, largely due to the presence of cancer stem cells (CSCs) and aggressive angiogenesis. Effectively targeting these CSCs and associated angiogenic pathways is crucial for effective treatment. This study leverages single-cell multi-omics to explore a novel therapeutic approach involving Chimeric Antigen Receptor (CAR) macrophages engineered to target the c-Met protein on pancreatic CSCs.

Methods
We employed single-cell RNA sequencing to analyze pancreatic cancer tissue, identifying c-Met as a key marker of CSCs. CAR macrophages were engineered using a lentiviral system to express a c-Met-specific receptor. The phagocytic efficiency of these CAR macrophages against pancreatic CSCs was assessed in vitro, along with their ability to inhibit angiogenesis. The in vivo efficacy of CAR macrophages was evaluated in a mouse model of pancreatic cancer.

Results
CAR macrophages demonstrated high specificity for c-Met + CSCs, significantly enhancing phagocytosis and reducing the secretion of angiogenic factors such as VEGFA, FGF2, and ANGPT. In vivo, these macrophages significantly suppressed tumor growth and angiogenesis, prolonging survival in pancreatic cancer-bearing mice.

Conclusion
CAR macrophages targeting c-Met represent a promising therapeutic strategy for pancreatic cancer, offering targeted elimination of CSCs and disruption of tumor angiogenesis. This study highlights the potential of single-cell multi-omics in guiding the development of precision immunotherapies.
The miR-1269a/PCDHGA9/CXCR4/β-catenin pathway promotes colorectal cancer invasion and metastasis
Authors: Mei Haitao , Luo Qingshan , Weng Junyong , Hao Jialing , Cai Jinfeng , Zhou Runkai , Bian Ce , Ye Yingzi , Luo Shengzheng , Wen Yugang 
Published: November 2024

Abstract

Background
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. This research focuses on investigating the impact and underlying molecular mechanisms of protocadherin gamma subfamily A, 9 (PCDHGA9) on the invasion and metastasis of CRC, aiming to identify more precise molecular markers for the diagnosis and prognosis of CRC.

Methods
PCDHGA9 expression was detected using quantitative real-time quantitative polymerase chain reaction (RT-qPCR) in 63 pairs of colorectal cancer tissues. Differential gene expression from high-throughput sequencing was analyzed using ingenuity pathway analysis (IPA) to explore the biological functions of PCDHGA9 and its potential regulated genes. Bioinformatics tools were employed to explore potential upstream regulatory microRNAs of PCDHGA9. Dual-luciferase assays were performed to demonstrate the regulation between PCDHGA9 and miR-1269a. Protein mass spectrometry suggested an interaction between PCDHGA9 and HOXA1. JASPAR predicted that HOXA1 may act as a transcription factor of CXCR4. Coimmunoprecipitation, dual-luciferase assays, and nuclear–cytoplasmic fractionation experiments confirmed the molecular mechanism involving PCDHGA9, CXCR4, HOXA1, and β-catenin. Transwell, wound healing, and western blot assays were conducted to confirm the impact of PCDHGA9, miR-1269a, and CXCR4 on the invasion, metastasis, and epithelial–mesenchymal transition (EMT) functions of CRC cells in in vitro experiments. A whole-body fluorescence imaging system was used to evaluate the combined impact of miR-1269a and PCDHGA9 on the invasion and metastasis of CRC in in vivo experiments.

Results
The expression of PCDHGA9 was found to be lower in CRC tissues compared with their corresponding adjacent tissues. Low expression of PCDHGA9 potentially correlated with worse prognosis and increased chances of invasion and metastasis in CRC. miR-1269a was highly expressed in CRC tissues and acted as a negative regulator for PCDHGA9, promoting invasion, migration, and EMT of CRC cells. PCDHGA9’s interaction with HOXA1 downregulated CXCR4, a transcription factor, leading to accumulation of β-catenin and further promoting invasion, migration, and EMT of CRC cells.

Conclusions
PCDHGA9, acting as a tumor suppressor, is downregulated by miR-1269a. The low level of PCDHGA9 activates the Wnt/β-catenin pathway by releasing its interaction with HOXA1, promoting the expression of CXCR4, and causing invasion, migration, and EMT in CRC.

Graphical Abstract
Epidemiology of healthcare-associated bloodstream infection in South African neonatal units
Authors: Dramowski Angela , Bolton Larisse , Bekker Adrie , Engelbrecht Arnoldus , Erasmus Louisa , Fataar Aaqilah , Geldenhuys Chandre , Kunneke Marlize , Roux Dave Le , Connell Natasha O’ , Reddy Kessendri , Rhoda Natasha , Tooke Lloyd , Wates Mark , Wessels Thandi , van Schalkwyk Cari , Whitelaw Andrew 
Published: November 2024

Abstract
Background
Reports of healthcare-associated bloodstream infection (HA-BSI) epidemiology in African neonatal units are limited.

Methods
We conducted a cross-sectional study (2017–2018) in nine neonatal units in the Western Cape Province, South Africa, including central, regional and district hospitals (416 beds) using laboratory and clinical records. Patient demographics, HA-BSI rates, pathogen spectrum, and hospital outcomes and empiric antibiotic coverage rates were determined.

Results
Over two years, 23,748 neonates were admitted with unit occupancy rates ranging from 79 to 93%. 485 HA-BSI episodes occurred, with median onset at 11 (IQR 7–24) days of life. Most HA-BSI episodes (348; 72%) affected very low birth weight neonates (< 1500 g). The overall HA-BSI rate was 2.0/1000 patient days. The highest HA-BSI rate was observed at the central unit with onsite surgery (3.8/1000 patient days). Crude HA-BSI mortality was 31.8% (154/485) with two-thirds of deaths occurring within three days of BSI onset. Higher mortality was observed for Gram-negative/fungal BSI compared to Gram-positive BSI (RR 1.5; 95%CI 1.1-2.0; p = 0.01) and very preterm neonates (gestation < 32 weeks) versus ≥ 32 weeks (RR 1.5; 95%CI 1.1–2.1; p = 0.01). Mean estimated empiric antibiotic coverage rates varied by unit type: 66–79% for piperacillin-tazobactam plus amikacin, 60–76% for meropenem and 84–92% for meropenem plus vancomycin.

Conclusion
Most HA-BSI events affected preterm neonates at the central hospital with onsite surgery. One-third of patients with HA-BSI died, with highest mortality in preterm infants and Gram-negative/fungal BSI. Empiric antibiotic regimens provide moderate coverage of circulating pathogens but require annual review given increasing carbapenem resistance rates.
Nephrology providers’ perspective and use of mortality prognostic tools in dialysis patients
Authors: Bergeron Jennifer , Marchese Christina , Jensen Colton , Meagher Sean , Kennedy Amanda G. , Tompkins Bradley , Cheung Katharine L. 
Published: November 2024

Abstract
Background
Mortality prognostic tools exist to aid in shared decision making with kidney failure patients but are underutilized. This study aimed to elucidate nephrology providers’ practice patterns and understand barriers to prognostic tool use.

Methods
Nephrology providers (8 physicians and 2 nurse practitioners) at an academic medical center underwent semi-structured interviews regarding their experience and perspective on the utility of mortality prognostic tools. Common themes were identified independently by 2 reviewers using grounded theory. Three six-month mortality prognostic tools were applied to the 279 prevalent dialysis patients that the interviewed providers care for. The C statistic was calculated for each tool via logistic regression and subsequent ROC analysis. Nephrology providers reviewed the performance of the prognostication tools in their own patient population. A post interview reassessed perspectives and any change in attitudes regarding the tools.

Results
Nephrology providers did not use these mortality prognostic tools in their practice. Key barriers identified were provider concern that the tools were not generalizable to their patients, providers’ trust in their own clinical judgement over that of a prognostic tool, time constraints, and lack of knowledge about the data behind these tools. When re-interviewed with the results of the three prognostic tools in their patients, providers thought the tools performed as expected, but still did not intend to use the tools in their practice. They reported that these tools are good for populations, but not individual patients. The providers preferred to use clinical gestalt for prognostication.

Conclusion
Although several well validated prognostic tools are available for predicting mortality, the nephrology providers studied do not use them in routine practice, even after an educational intervention. Other approaches should be explored to help incorporate prognostication in shared-decision-making for patients receiving dialysis.
Detecting sleep and physical activity changes across the perinatal period using wearable technology
Authors: Claydon Elizabeth A. , Lilly Christa L. , Caswell Erin D. , Quinn Dawna C. , Rowan Shon P. 
Published: November 2024

Abstract
Background
Pregnant women may not experience disruptions in sleep duration throughout the course of pregnancy, however, their sleep quality is dramatically impaired. Sleep quality deteriorates throughout pregnancy, reaching its lowest in the third trimester. The purpose of this study was to understand the change in sleep patterns across the perinatal period, as well as the impact of physical activity on sleep.

Methods
A total of 18 physically active women trying to conceive wore a WHOOP strap (a fitness monitor) across the perinatal period. Daily behavior changes were tracked including time awake, hours in deep sleep, physical activity, and time in moderate to vigorous physical activity.

Results
Women maintained overall physical activity levels during and after pregnancy and averaged 20.70 min of physical activity and 6.97 h of sleep per day. Total time in awake hours increased postpartum. Moderate-vigorous physical activity minutes improved deep sleep hours overall (Est. = 0.003 h, p < 0.0001) and during pregnancy (Est. = 0.00001 h, p = 0.0004). Similar effects were found for all activity minutes, although in post pregnancy the moderating impact of activity minutes no longer maintained significance (p = 0.09).\.

Conclusions
Wearable technology, including fitness monitors such as WHOOP straps offer a convenient and less invasive way to track sleep and physical activity during the perinatal period. The findings of this study indicate a positive connection between sleep and engaging in moderate to vigorous activity and any activity throughout the perinatal period. These results may help inform clinical and practical recommendations for physical activity to improve sleep outcomes for pregnant women.
Puberty and NeuroDevelopment in adolescents (PANDA): a study protocol
Authors: Bray Katherine O. , Durbin Olivia , Hartanto Stephanie , Khetan Muskan , Liontos Daniel , Manuele Sarah J. , Zwaan Isabel , Ganella Despina , Herting Megan M. , Kim Jee Hyun , O’Connell Michele , Pozzi Elena , Schwartz Orli , Seal Marc , Simmons Julian , Vijayakumar Nandita , Whittle Sarah 
Published: November 2024

Abstract
Background
Biopsychosocial changes during adolescence are thought to confer risk for emotion dysregulation, and in particular, anxiety disorders. However, there are substantial gaps in our knowledge about the biological mechanisms underlying anxiety during adolescence, and whether this contributes to the higher prevalence in females. The Puberty and NeuroDevelopment in Adolescents (PANDA) study aims to examine links between biological (sex hormones, cortisol) and social environmental factors and brain function during adolescence, with a focus on key processes (emotion regulation, fear learning) identified as relevant for the development of anxiety disorders.

Methods
PANDA is a cross-sectional study with an observational design that aims to recruit a total of 175 adolescents aged 11-16 (majority female) and their parents/guardians, from the community. Brain function will be examined using magnetic resonance imaging (MRI), including functional MRI tasks of emotion regulation and fear learning. Hormones will be measured from hair (i.e., cortisol) and weekly saliva samples (i.e., oestradiol, progesterone, five across a month in females). Questionnaires and semi-structured interviews will be used to assess mental health and social environmental factors such as parenting and adverse childhood experiences. An online study of 113 adolescents was also incorporated during the COVID-19 pandemic as a questionnaire-only sub-study.

Discussion
Strengths of this study include the collection of multiple saliva samples to assess variability in hormone levels, examination of the timing of adverse childhood experiences, inclusion of both maternal and paternal parental factors, exploration of mechanisms through the examination of brain structure and function, and multi-method, multi-informant collection of mental health symptoms. This study addresses important gaps in the literature and will enhance knowledge of the biological and environmental contributors to emotion dysregulation and anxiety in adolescents.
Breastfeeding support during the Covid-19 pandemic in England: analysis of a national survey
Authors: Quigley Maria A. , Harrison Sian , Levene Ilana , Buchanan Phyllis , McLeish Jenny , Alderdice Fiona 
Published: November 2024

Abstract
Background
Breastfeeding support interventions are associated with longer breastfeeding duration. Contemporary nationally representative data on breastfeeding support as reported by women in England is lacking. Using English national maternity survey data, we describe sources and modes of breastfeeding support as reported by women who gave birth in 2020; sources of support are compared with earlier maternity surveys (2014, 2016, 2018). We also explore the characteristics associated with source/mode of support in 2020 (n = 4,611).

Methods
Women who breastfed were asked about sources of breastfeeding support (midwife; other health professional; other formal breastfeeding support such as breastfeeding specialist, breastfeeding support group, peer supporter; and partner/friend/relative), how this help was given and whether they would have liked more help from a health professional with breastfeeding. Adjusted risk ratios (aRR) for the association between sociodemographic and pregnancy-related variables and each source/mode of support were estimated using modified Poisson regression.

Results
From 2014 to 2020 support from midwives and other health professionals declined (from 84.0% to 64.7%, and 61.6% to 15.5% respectively) whereas other formal breastfeeding support and informal support from partners/friends/relatives remained constant at 27–31% and 34–38% respectively. The proportion of women who wanted more help with breastfeeding increased from 30% in 2014–2018 to 46% in 2020. In 2020, women most likely to want more help with breastfeeding were nulliparous (aRR = 1.64, 95%CI:1.50–1.79), younger (aRR = 1.21, 95%CI:1.03–1.42) and of Pakistani ethnicity (aRR = 1.30, 95%CI:1.06–1.60). Receiving breastfeeding support over the phone (35%) was more common than via video call (13%) or text message (5%); these percentages varied according to socio-demographic and pregnancy-related factors.

Conclusions
Breastfeeding support has declined in recent years, and did not meet the needs of many women during the pandemic. Planning for a future emergency should include adequate provision of breastfeeding support particularly if staff are redeployed into other roles. The characteristics associated with support can inform service planning and delivery. Future research should use these factors to develop novel ideas for intervention, such as directly targeting partners or other informal networks with educational or psychosocial interventions.
Willingness of population health survey participants to provide personal health information and biological samples
Authors: Jaswal Harpreet , Ialomiteanu Anca , Hamilton Hayley , Rehm Jürgen , Wells Samantha , Shield Kevin D. 
Published: November 2024

Abstract
Background
Biological sample collection and data linkage can expand the utility of population health surveys. The present study investigates factors associated with population health survey respondents’ willingness to provide biological samples and personal health information.

Methods
Using data from the 2019 Centre for Addiction and Mental Health (CAMH) Monitor survey (n = 2,827), we examined participants’ willingness to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information. Associations of willingness to provide such information with socio-demographic, substance use, and mental health details were also examined. Question order effects were tested using a randomized trial.

Results
The proportion of respondents willing to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information were 19.9%, 36.2%, 82.1%, and 17%, respectively. Willingness significantly varied by age, race, employment, non-medical prescription opioid use (past year), cocaine use (lifetime), and psychological distress. Significant question order effects were observed. Respondents were more likely to be willing to provide a saliva sample when this question was asked first compared to first being asked for direct data linkage. Similarly, respondents were more likely to be willing to allow for probabilistic data linkage when this question was asked first compared to first being asked for a saliva sample.

Conclusion
A lack of willingness to provide biological samples or permit data linkage may lead to representivity issues in studies which rely on such information. The presence of question order effects suggests that the willingness of respondents can be increased through strategic ordering of survey structures.
Examining the changes in the prevalence of Hepatitis a in Türkiye: systematic review and metaanalysis
Authors: Karakaya Suzan Özge , Bektaş Murat , Altındiş Mustafa , Kaya Özge , Eroğlu Ayşe , Çetinkaya Özdemir Serap , Tecik Seda , Emecen Ahmet Naci , Çınar Nursan 
Published: November 2024

Abstract
Background
The incidence of Hepatitis A is increasing worldwide. Yearly classification of Hepatitis A Seroprevalence for different times in different regions of Türkiye allows indirect measurement of year-specific incidence rates of HAV infection and can be considered the best way to define Hepatitis A status. This study aimed to examine the change in the incidence of hepatitis A by systematically evaluating the available data on the seroprevalence of anti-HAV antibodies in the Turkish population.

Methods
Studies published between First January, 2000- 31 December 2023 that meet the inclusion criteria searched between 16.09.2023 and 31.01.2024 in nine databases (MEDLINE, Web of Science, PubMed, ScienceDirect, Scopus, Eric, CINAHL Complate, TR DİZİN, TÜBİTAK Ulakbim). Independently by two reviewers evaluated all titles and abstracts with consensus-based decision making. The Joanna Briggs Institution (JBI) Analytical Cross Sectional Studies and Prevelance Studies list were used in this study. Pooled prevalence was calculated using 95% confidence intervals. Heterogeneity between studies was assessed by Cochrane’s Q and I2. The random effect model was selected by Cochrane’s Q and I2. Funnel plots were used for publication bias. The data were analyzed via Jamovi 1.2.22.

Results
Data were extracted from 63 studies. Pooled prevalence was calculated using 95% confidence intervals. Funnel plots were used for publication bias. In this meta-analysis, data were obtained from all geographical regions of Türkiye, and the general prevalence of Hepatitis A in the population was found to be 53% [95% CI 0.47, 0.59; I2 = 99.94%]. In subgroup analysis conducted by year, the prevalence of hepatitis A was 45% [95% CI 0.22, 0.67; I2 = 99.8%] between 2002 and 2006, 52% [95% CI 0.39, 0.65; I2 = 99.54%] between 2007 and 2011, 60% [95% CI 0.49, 0.70; I2 = 99.9%] between 2012 and 2016, and 51% [95% CI 0.41, 0.61; I2 = 99.97%] as of 2017. Additionally, a systematic review revealed that vaccination, socioeconomic status, and sex may also affect HAV seroprevalence.

Conclusions
HAV seroprevalence in Türkiye; It was observed that it increased between 2002 and 2016 and decreased until today as of 2017. This systematic review provide a comprehensive overview of HAV virus epidemiology and identify key knowledge gaps, contributing crucial information for influencing factors.

Trial registration
PROSPERO ID = CRD42023464384.
What really makes residents tick or burn out? Insights from a National survey
Authors: Zloto Ofira , Henenfeld Maxim , Weinstein Orly 
Published: November 2024

Abstract
Background
To examine the satisfaction rates and burnout feelings amongst residents physicians in different specialties and to examine associated affecting factors.

Method
Clalit Health Services (CHS) is the largest health maintenance provider in Israel. A survey was designed by an interdisciplinary team with questions addressing residency and the balance between residency and personal life, as well as the balance between residency and personal life, and was sent to all residents of CHS via personal email from March to May 2022.

Results
Four hundred sixty seven residents completed the survey. The mean satisfaction rate from the residency was 7.4 (± 1.93, 2–10). The highest satisfaction rate from residency was amongst anesthetics, psychiatrists and ophthalmologists ( 8.6, 8.1 and 8.0, respectively) while the lowest was among general surgeons, oncologists, plastic surgeons and orthopedic surgeons (6.8, 6.8, 6.7, 6.1, respectively). There was no correlation between satisfaction rates and monthly working hours or number of overnight shifts. Seventy four percent feel frequent burnout due to high workload and 68% feel frequent burnout due to high number of administrative tasks. Seventy three percent chose the work environment in their department as most influential of their residency experience, 61% chose relations between attending physicians and residents as most significant, and 60% chose the education during the residency as most influential during their residency training.

Conclusions
Satisfaction rates from the residency training require improvement, with differences between the residencies. Number of working hours and number of overnight shifts did not correlate with the satisfaction rates. The factor that influences the most between satisfactory rate and less burnout is the relationship with colleagues and good training programs. Major efforts should be done to improve these factors.