bluuebunny/crossref_metadata_2025_split huggingface dataset:
25KDa branched polyethylenimine increases interferon-γ production in natural killer cells via improving translation efficiency
Authors: Ko Eun-Su , Choi Seung Hee , Lee Minwook , Park Kyung-Soon 
Published: May 2023

Abstract
Background
Ex vivo cultivation is a promising strategy for increasing the number of NK cells and enhancing their antitumor activity prior to clinical application. Recent studies show that stimulation with 25KDa branched polyethylenimine (25KbPEI) generates NK cells with enhanced antitumor activity. To better understand how 25KbPEI primes NK cells, we explored the mechanism underlying increase in production of IFN-γ.

Methods
Chemical priming was performed on NK-92MI cells by incubating them with 5 μg/ml of 25KbPEI. The production of IFN-γ was evaluated by RT-qPCR, ELISA, and Flow cytometry. By evaluating the effect of pharmacological inhibition of ERK/mTOR-eIF4E signaling pathways on IFN-γ translation, the function of these signaling pathways in IFN-γ translation was examined. To comprehend the level of 25KbPEI activity on immune-related components in NK cells, RNA sequencing and proteomics analyses were conducted.

Results
25KbPEI enhances the production of IFN-γ by NK cells without transcriptional activation. Activation of ERK and mTOR signaling pathways was found to be associated with 25KbPEI-mediated calcium influx in NK cells. The activation of ERK/mTOR signaling was linked to the phosphorylation of 4E-BP1, which resulted in the activation of translation initiation complex and subsequent IFN-γ translation. Analysis of RNA sequencing and proteomics data revealed that the activity of 25KbPEI to improve translation efficiency in NK cells could be extended to additional immune-related molecules.

Conclusions
This study provides substantial insight into the process by which 25KbPEI primes NK cells. Our data demonstrated that the 25KbPEI mediated activation of ERK/mTOR signaling and subsequent stimulation of eIF4E is the primary mechanism by which the chemical stimulates translation of IFN-γ in NK cells.
Qualitative assessment of providers’ experiences with a segmentation counseling tool for family planning in Niger
Authors: MacLachlan Ellen , Agali Balki Ibrahim , Maytan-Joneydi Amelia , Chaibou Sanoussi , Garba Souleymane Amadou , Halidou Illiassou Chaibou , Speizer Ilene S. , Nouhou Abdoul Moumouni 
Published: May 2023

Abstract
Introduction
This study examines experiences with a family planning segmentation counseling tool that is used during the provision of family planning services. Based on answers to a series of questions, women are segmented into one of five categories of family planning users and counseled based on their identified segment. This study aimed to qualitatively assess provider perspectives on implementation of the tool.

Methods
Semi-structured in-depth interviews took place in the Dosso region of Niger among 16 family planning providers who had been trained in segmentation and were currently using the segmentation tool. The facilities chosen for interviews were part of a larger mixed methods study assessing the impact of using the segmentation approach. Interview questions focused on training, supervision, how segmentation occurs at the health facility, how segmentation changes provider–client interactions, and any difficulties faced with implementation. Interviews were translated and transcribed into French and data were coded and thematically analyzed.

Results
All providers in the study reported positive outcomes associated with segmentation. While providers acknowledged that the segmentation approach added time to the clinic visit, they did see the benefit of this extra time in providing more meaningful interactions between clients and providers, leaving clients with a deeper understanding of family planning and of the different methods available. The implementation of the tool did not change other aspects of service delivery, except that a segmentation sheet was required to be filled in and kept in each patient’s file. Difficulties reported included translating the segmentation tool questions into local languages, training enough health care providers and avoiding stock outs of the segmentation sheets.

Conclusion
The segmentation process is of benefit to family planning clients in Niger and the scale-up of the strategy could bring higher quality services to women. If this approach is brought to scale the implementation challenges uncovered need to be addressed, especially adequate training. Further research is needed to determine if segmentation leads to changes in family planning use outcomes.
Psychosocial impacts of the COVID-19 pandemic from a cross-sectional Survey of people living with HIV in Washington, DC
Authors: Monroe Anne K. , Kulie Paige E. , Byrne Morgan E. , Wilbourn Brittany C. , Barth Shannon K. , Resnik Jenna B. , Huebner David M. , Horberg Michael A. , Castel Amanda D. , Greenberg Alan E. ,   the DC Cohort Executive Committee
Published: May 2023

AbstractBackgroundCOVID-19 has not only taken a staggering toll in terms of cases and lives lost, but also in its psychosocial effects. We assessed the psychosocial impacts of the COVID-19 pandemic in a large cohort of people with HIV (PWH) in Washington DC and evaluated the association of various demographic and clinical characteristics with psychosocial impacts.MethodsFrom October 2020 to December 2021, DC Cohort participants were invited to complete a survey capturing psychosocial outcomes influenced by the COVID-19 pandemic. Some demographic variables were also collected in the survey, and survey results were matched to additional demographic data and laboratory data from the DC Cohort database. Data analyses included descriptive statistics and multivariable logistic regression models to evaluate the association between demographic and clinical characteristics and psychosocial impacts, assessed individually and in overarching categories (financial/employment, mental health, decreased social connection, and substance use).ResultsOf 891 participants, the median age was 46 years old, 65% were male, and 76% were of non-Hispanic Black race/ethnicity. The most commonly reported psychosocial impact categories were mental health (78% of sample) and financial/employment (56% of sample). In our sample, older age was protective against all adverse psychosocial impacts. Additionally, those who were more educated reported fewer financial impacts but more mental health impacts, decreased social connection, and increased substance use. Males reported increased substance use compared with females.ConclusionsThe COVID-19 pandemic has had substantial psychosocial impacts on PWH, and resiliency may have helped shield older adults from some of these effects. As the pandemic continues, measures to aid groups vulnerable to these psychosocial impacts are critical to help ensure continued success towards healthy living with HIV.
On latches in biological systems: a comparative morphological and functional study of the retinaculum and the dens lock in Collembola
Authors: Rillich Birk , Oliveira Fábio G. L. 
Published: May 2023

AbstractBackgroundSpringtails have the ability to jump using morphological structures consisting of a catapult, the furca, and a latching system constructed with interaction of the retinaculum and the dens lock. The retinaculum engages in the furca at the dens lock in order to form a spring mechanism. They exhibit diversified morphological traits that serve as adaptations to a variety of terrestrial strata and aquatic surface environments. This comparative morphofunctional study centered on the retinaculum and the furcular region of the dens lock aims to describe the morphological variation between taxa and provide insights into the functional dynamics of the latching mechanism at work in the jumping apparatus. Using SEM, µCT and cLSM, we compared representatives of Collembola taxa, Poduromorpha (Neanura muscorumandPodura aquatica), Symphypleona (Dicyrtomina ornata) and Neelipleona (Megalothorax minimus), and examined extracts of the environment in which they were collected.ResultsA retinaculum is absent inN. muscorum, although vestigial muscles were found. Abdominal musculature varies significantly, being more abundant in springtails with clear segmentation (N. muscorumandP. aquatica), and reduced in springtails with fused segmentation (D. ornataandM. minimus). The M.a-ret varies as regards architecture and point of connection with the ramus, which is lateral inP. aquaticaand median in the other species studied. The number of teeth in the retinaculum ramus also varies between three inM. minimusand four in the other species. The dens lock of all species studied has two locks and two furrows.ConclusionsThe retinaculum and dens lock interact in a key-lock relationship. The latching and unlatching mechanism from the retinaculum and dens lock appear to be similar in all the taxa examined, occurring by muscle force. This leads us to question the hypothesis that hemolymph pressure may be a force generator in jumping. We offer a reconstruction of the ground pattern of the retinaculum and dens lock and, in addition, an explanation of their functioning and the interaction between them. Finally, we frame the interaction between the retinaculum and the dens lock as a latch in a biological system, a mechanism which functions by force of physical contact.
Metastases to the kidney from primary lung cancer : clinicopathological analysis of six cases in a single center
Authors: Lian Hui , Pan Xinyu , Hong Bo , Min Jie , Huang Fengbo 
Published: May 2023

Abstract
Objectives
Cancer metastasis to the kidney is a rare event. We retrospectively analyzed clinicopathologic characteristics in 6 cases of diagnosed renal metastases from primary lung cancer. We also provide clinical follow-up data and brief review of the literature.

Methods
Immunohistochemistry was used to evaluate the expression of TTF-1, NapsinA, CK7, CK(AE1/AE3), P63, P40, CgA, PAX-8, GATA3 and Ki-67 in primary tumor and metastases. Additionally, the clinical characteristics, imaging features, diagnosis, and treatment were analyzed.

Results
With the help of immunohistochemistry and combined clinical history, we found four cases were lung adenocarcinomas, one case was lung squamous cell carcinoma, and the other case was lung small cell carcinoma metastases to the kidney.The patients were all male by gender and had a mean age of 62 years, and metastasis to the left kidney were more universal. Most of the tumors histological grade originating from the lung were poorly-moderately differentiated, and the time to metastasis to the kidney was relatively short for squamous lung cancer and small cell lung cancer, while the time to metastasis for lung adenocarcinoma was related to its degree of differentiation. Overall, we found the prognosis of lung cancer patients with renal metastases were poor especially with multi-site metastases.

Conclusions
Distinguishing primary and secondary tumors of the kidney is essential to guide treatment and prevent unnecessary surgery, so clinical information, radiology, histological correlation of the primary tumor, and immunohistochemical findings help the pathologist determine correct diagnosis.
Study design and protocol of a stepped wedge cluster randomized trial using a practical implementation strategy as a model for hypertension-HIV integration — the MAP-IT trial
Authors: Aifah Angela A. , Hade Erinn M. , Colvin Calvin , Henry Daniel , Mishra Shivani , Rakhra Ashlin , Onakomaiya Deborah , Ekanem Anyiekere , Shedul Gabriel , Bansal Geetha P. , Lew Daphne , Kanneh Nafesa , Osagie Samuel , Udoh Ememobong , Okon Esther , Iwelunmor Juliet , Attah Angela , Ogedegbe Gbenga , Ojji Dike 
Published: May 2023

Abstract
Background
As people living with HIV (PLWH) experience earlier and more pronounced onset of noncommunicable diseases (NCDs), advancing integrated care networks and models in low-resource-high-need settings is critical. Leveraging current health system initiatives and addressing gaps in treatment for PLWH, we report our approach using a late-stage (T4) implementation research study to test the adoption and sustainability of a proven-effective implementation strategy which has been minimally applied in low-resource settings for the integration of hypertension control into HIV treatment. We detail our protocol for the Managing Hypertension Among People Living with HIV: an Integrated Model (MAP-IT) trial, which uses a stepped wedge cluster randomized trial (SW-CRT) design to evaluate the effectiveness of practice facilitation on the adoption of a hypertension treatment program for PLWH receiving care at primary healthcare centers (PHCs) in Akwa Ibom State, Nigeria.

Design
In partnership with the Nigerian Federal Ministry of Health (FMOH) and community organizations, the MAP-IT trial takes place in 30 PHCs. The i-PARiHS framework guided pre-implementation needs assessment. The RE-AIM framework will guide post-implementation activities to evaluate the effect of practice facilitation on the adoption, implementation fidelity, and sustainability of a hypertension program, as well as blood pressure (BP) control. Using a SW-CRT design, PHCs sequentially crossover from the hypertension program only (usual care) to hypertension plus practice facilitation (experimental condition). PHCs will recruit and enroll an average of 28–32 patients to reach a maximum of 960 PLWH participants with uncontrolled hypertension who will be followed longitudinally for BP outcomes.

Discussion
Given the need for integrated NCD-HIV care platforms in low-resource settings, MAP-IT will underscore the challenges and opportunities for integrating hypertension treatment into HIV care, particularly concerning adoption and sustainability. The evaluation of our integration approach will also highlight the potential impact of a health systems strengthening approach on BP control among PLWH.

Trial registration
Clinicaltrials.gov (NCT05031819). Registered on 2nd September 2021.
Development and validation of a radiomics model of magnetic resonance for predicting liver metastasis in resectable pancreatic ductal adenocarcinoma patients
Authors: Huang Yuzhou , Zhou Shurui , Luo Yanji , Zou Jinmao , Li Yaqing , Chen Shaojie , Gao Ming , Huang Kaihong , Lian Guoda 
Published: May 2023

Abstract
Background
Nearly one fourth of patients with pancreatic ductal adenocarcinoma (PDAC) occur to liver metastasis after surgery, and liver metastasis is a risk factor for prognosis for those patients with surgery therapy. However, there is no effective way to predict liver metastasis post-operation.

Method
Clinical data and preoperative magnetic resonance imaging (MRI) of PDAC patients diagnosed between July 2010 and July 2020 were retrospectively collected from three hospital centers in China. The significant MRI radiomics features or clinicopathological characteristics were used to establish a model to predict liver metastasis in the development and validation cohort.

Results
A total of 204 PDAC patients from three hospital centers were divided randomly (7:3) into development and validation cohort. Due to poor predictive value of clinical features, MRI radiomics model had similar receiver operating characteristics curve (ROC) value to clinical-radiomics combing model in development cohort (0.878 vs. 0.880, p = 0.897) but better ROC in validation dataset (0.815 vs. 0.732, p = 0.022). Radiomics model got a sensitivity of 0.872/0.750 and a specificity of 0.760/0.822 to predict liver metastasis in development and validation cohort, respectively. Among 54 patients randomly selected with post-operation specimens, fibrosis markers (α-smooth muscle actin) staining was shown to promote radiomics model with ROC value from 0.772 to 0.923 (p = 0.049) to predict liver metastasis.

Conclusion
This study developed and validated an MRI-based radiomics model and showed a good performance in predicting liver metastasis in resectable PDAC patients.
MiR-217 regulates autophagy through OPG/RANKL/RANK in giant cell tumors
Authors: Meng Chenyang , Jiang Boyong , Liu Wanlin , Wang Lianjuan , Zhao Zhenqun , Bai Rui , Zhao Yan 
Published: May 2023

Abstract
Background
Increasing evidence suggests that microRNAs (miRNAs) play a crucial role in cancer development and progression. Our previous study showed remarkably lower levels of miR-217 in GCT cells and tissues, and miR-217 re-expression inhibited the occurrence and development of GCT in vitro; however, the associated mechanisms remain unknown. Thus, this study aimed to explore the mechanisms underlying the proliferation inhibitory effect of miR-217 in GCT cells.

Methods
The proliferative potential of the GCT cells was measured with an MTT assay and BrdU straining. Changes in GCT cell migration and invasion was assessed by a transwell assay. Finally, Western blot and RT-PCR assays were employed to evaluate OPG/RANKL/RANK signaling pathway-related protein expression.

Results
The excessive upregulation of miR-217 markedly suppressed GCT cell proliferation and tumorigenesis both in vitro and in vivo. miR-217 overexpression could inhibit the OPG/RANKL/RANK signaling pathway in vitro and in vivo. Furthermore, ALP activity was significantly decreased in GCT cells following miR-217 treatment. Importantly, miR-217 could inhibit autophagy-related protein expression and autophagosome/autolysosome formation in GCT cells and tissues.

Conclusion
These results suggest that miR-217 upregulation could inhibit the occurrence and development of GCT by blocking autophagy. These findings offer an effective therapeutic target to improve the survival rates of patients with CGT in the future.
Total hip arthroplasty for failed internal fixation of femoral neck fracture: a retrospective study with 2–14 years’ follow-up of 345 patients
Authors: Lu Hanpeng , Zhu Niu , Ling Tingxian , Cao Jian , Xu Hong , Zhou Kai , Zhao Enze , Zhou Zongke 
Published: May 2023

Abstract
Objectives
The purpose of this study was to analyze mid- to long-term outcomes of total hip arthroplasty (THA) following failed internal fixation of femoral neck fracture.

Methods
This study retrospectively analyzed 345 patients with femoral neck fracture who underwent THA after failure of internal fixation at our hospital between January, 2003 and December, 2019. Patients older than 55 years (n = 175) and patients no older than 55 years (n = 170) were compared in terms of complications and survival rates during follow-up, which lasted a mean of 6 years.

Results
The two age groups showed similarly low incidence of complications and similarly long periods of survival without revision surgery. Only three younger patients and two older patients underwent revision surgery during follow-up. The two groups showed similarly high survival rates at the end of follow-up (> 93%). Younger patients showed significantly bettter Harris hip score at last follow-up (90.2 vs. 88.1 points, p < 0.001) without clinically significant difference, but they required THA significantly earlier after internal fixation (4.4 vs. 6.8 years, p < 0.001).

Conclusions
THA after failed internal fixation of femoral neck fracture is a well tolerated and effective procedure in older and younger patients.
Novel computational biology modeling system can accurately forecast response to neoadjuvant therapy in early breast cancer
Authors: Peterson Joseph R. , Cole John A. , Pfeiffer John R. , Norris Gregory H. , Zhang Yuhan , Lopez-Ramos Dorys , Pandey Tushar , Biancalana Matthew , Esslinger Hope R. , Antony Anuja K. , Takiar Vinita 
Published: May 2023

Abstract
Background
Generalizable population-based studies are unable to account for individual tumor heterogeneity that contributes to variability in a patient’s response to physician-chosen therapy. Although molecular characterization of tumors has advanced precision medicine, in early-stage and locally advanced breast cancer patients, predicting a patient’s response to neoadjuvant therapy (NAT) remains a gap in current clinical practice. Here, we perform a study in an independent cohort of early-stage and locally advanced breast cancer patients to forecast tumor response to NAT and assess the stability of a previously validated biophysical simulation platform.

Methods
A single-blinded study was performed using a retrospective database from a single institution (9/2014–12/2020). Patients included: ≥ 18 years with breast cancer who completed NAT, with pre-treatment dynamic contrast enhanced magnetic resonance imaging. Demographics, chemotherapy, baseline (pre-treatment) MRI and pathologic data were input into the TumorScope Predict (TS) biophysical simulation platform to generate predictions. Primary outcomes included predictions of pathological complete response (pCR) versus residual disease (RD) and final volume for each tumor. For validation, post-NAT predicted pCR and tumor volumes were compared to actual pathological assessment and MRI-assessed volumes. Predicted pCR was pre-defined as residual tumor volume ≤ 0.01 cm3 (≥ 99.9% reduction).

Results
The cohort consisted of eighty patients; 36 Caucasian and 40 African American. Most tumors were high-grade (54.4% grade 3) invasive ductal carcinomas (90.0%). Receptor subtypes included hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+, 30%), HR+/HER2− (35%), HR−/HER2+ (12.5%) and triple negative breast cancer (TNBC, 22.5%). Simulated tumor volume was significantly correlated with post-treatment radiographic MRI calculated volumes (r = 0.53, p = 1.3 × 10–7, mean absolute error of 6.57%). TS prediction of pCR compared favorably to pathological assessment (pCR: TS n = 28; Path n = 27; RD: TS n = 52; Path n = 53), for an overall accuracy of 91.2% (95% CI: 82.8% – 96.4%; Clopper–Pearson interval). Five-year risk of recurrence demonstrated similar prognostic performance between TS predictions (Hazard ratio (HR): − 1.99; 95% CI [− 3.96, − 0.02]; p = 0.043) and clinically assessed pCR (HR: − 1.76; 95% CI [− 3.75, 0.23]; p = 0.054).

Conclusion
We demonstrated TS ability to simulate and model tumor in vivo conditions in silico and forecast volume response to NAT across breast tumor subtypes.
High-throughput deep learning variant effect prediction with Sequence UNET
Authors: Dunham Alistair S. , Beltrao Pedro , AlQuraishi Mohammed 
Published: May 2023

AbstractUnderstanding coding mutations is important for many applications in biology and medicine but the vast mutation space makes comprehensive experimental characterisation impossible. Current predictors are often computationally intensive and difficult to scale, including recent deep learning models. We introduce Sequence UNET, a highly scalable deep learning architecture that classifies and predicts variant frequency from sequence alone using multi-scale representations from a fully convolutional compression/expansion architecture. It achieves comparable pathogenicity prediction to recent methods. We demonstrate scalability by analysing 8.3B variants in 904,134 proteins detected through large-scale proteomics. Sequence UNET runs on modest hardware with a simple Python package.