bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice
Authors: Bhargavan Biju , Woollard Shawna M. , McMillan Jo Ellyn , Kanmogne Georgette D. 
Published: November 2021

Abstract
Background
Neurocognitive impairment is present in 50% of HIV-infected individuals and is often associated with Alzheimer’s Disease (AD)-like brain pathologies, including increased amyloid-beta (Aβ) and Tau hyperphosphorylation. Here, we aimed to determine whether HIV-1 infection causes AD-like pathologies in an HIV/AIDS humanized mouse model, and whether the CCR5 antagonist maraviroc alters HIV-induced pathologies.

Methods
NOD/scid–IL-2Rγcnull mice engrafted with human blood leukocytes were infected with HIV-1, left untreated or treated with maraviroc (120 mg/kg twice/day). Human cells in animal’s blood were quantified weekly by flow cytometry. Animals were sacrificed at week-3 post-infection; blood and tissues viral loads were quantified using p24 antigen ELISA, RNAscope, and qPCR. Human (HLA-DR+) cells, Aβ-42, phospho-Tau, neuronal markers (MAP 2, NeuN, neurofilament-L), gamma-secretase activating protein (GSAP), and blood-brain barrier (BBB) tight junction (TJ) proteins expression and transcription were quantified in brain tissues by immunohistochemistry, immunofluorescence, immunoblotting, and qPCR. Plasma Aβ-42, Aβ-42 cellular uptake, release and transendothelial transport were quantified by ELISA.

Results
HIV-1 significantly decreased human (h)CD4+ T-cells and hCD4/hCD8 ratios; decreased the expression of BBB TJ proteins claudin-5, ZO-1, ZO-2; and increased HLA-DR+ cells in brain tissues. Significantly, HIV-infected animals showed increased plasma and brain Aβ-42 and phospho-Tau (threonine181, threonine231, serine396, serine199), associated with transcriptional upregulation of GSAP, an enzyme that catalyzes Aβ formation, and loss of MAP 2, NeuN, and neurofilament-L. Maraviroc treatment significantly reduced blood and brain viral loads, prevented HIV-induced loss of neuronal markers and TJ proteins; decreased HLA-DR+ cells infiltration in brain tissues, significantly reduced HIV-induced increase in Aβ-42, GSAP, and phospho-Tau. Maraviroc also reduced Aβ retention and increased Aβ release in human macrophages; decreased the receptor for advanced glycation end products (RAGE) and increased low-density lipoprotein receptor–related protein-1 (LRP1) expression in human brain endothelial cells. Maraviroc induced Aβ transendothelial transport, which was blocked by LRP1 antagonist but not RAGE antagonist.

Conclusions
Maraviroc significantly reduced HIV-induced amyloidogenesis, GSAP, phospho-Tau, neurodegeneration, BBB alterations, and leukocytes infiltration into the CNS. Maraviroc increased cellular Aβ efflux and transendothelial Aβ transport via LRP1 pathways. Thus, therapeutically targeting CCR5 could reduce viremia, preserve the BBB and neurons, increased brain Aβ efflux, and reduce AD-like neuropathologies.
Bevacizumab confers significant improvements in survival for ovarian cancer patients with low miR-25 expression and high miR-142 expression
Authors: Li Jun , Yue Huiran , Li Wenzhi , Zhu Guohua , Zhu Tingting , Chen Ruifang , Lu Xin 
Published: November 2021

Abstract
Background
Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients.

Methods
The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset.

Results
We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status.

Conclusion
In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.
Pediatric eosinophilic esophagitis: a review for the clinician
Authors: Barni Simona , Arasi Stefania , Mastrorilli Carla , Pecoraro Luca , Giovannini Mattia , Mori Francesca , Liotti Lucia , Saretta Francesca , Castagnoli Riccardo , Caminiti Lucia , Cianferoni Antonella , Novembre Elio 
Published: November 2021

AbstractEosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms.EoE can occur at any age and has different clinical manifestations depending on the age onset.To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis.According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis.A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment.This review will provide a practical guide to assist pediatricians treating children with EoE.Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.
Neighborhood disadvantage and individual-level life stressors in relation to breast cancer incidence in US Black women
Authors: Barber Lauren E. , Zirpoli Gary R. , Cozier Yvette C. , Rosenberg Lynn , Petrick Jessica L. , Bertrand Kimberly A. , Palmer Julie R. 
Published: November 2021

Abstract
Background
Research on psychosocial stress and risk of breast cancer has produced conflicting results. Few studies have assessed this relation by breast cancer subtype or specifically among Black women, who experience unique chronic stressors.

Methods
We used prospective data from the Black Women’s Health Study, an ongoing cohort study of 59,000 US Black women, to assess neighborhood- and individual-level psychosocial factors in relation to risk of breast cancer. We used factor analysis to derive two neighborhood score variables after linking participant addresses to US Census data (2000 and 2010) on education, employment, income and poverty, female-headed households, and Black race for all households in each residential block group. We used Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for established breast cancer risk factors.

Results
During follow-up from 1995 to 2017, there were 2167 incident invasive breast cancer cases (1259 estrogen receptor positive (ER +); 687 ER negative (ER−)). For ER− breast cancer, HRs were 1.26 (95% CI 1.00–1.58) for women living in the highest quartile of neighborhood disadvantage relative to women in the lowest quartile, and 1.24 (95% CI 0.98–1.57) for lowest versus highest quartile of neighborhood socioeconomic status (SES). For ER+ breast cancer, living in the lowest quartile of neighborhood SES was associated with a reduced risk of ER+ breast cancer (HR = 0.83, 95% CI 0.70–0.98). With respect to individual-level factors, childhood sexual abuse (sexual assault ≥ 4 times vs. no abuse: HR = 1.35, 95% CI 1.01–1.79) and marital status (married/living together vs. single: HR = 1.29, 95% CI 1.08–1.53) were associated with higher risk of ER+, but not ER− breast cancer.

Conclusion
Neighborhood disadvantage and lower neighborhood SES were associated with an approximately 25% increased risk of ER− breast cancer in this large cohort of Black women, even after control for multiple behaviors and lifestyle factors. Further research is need to understand the underlying reasons for these associations. Possible contributing factors are biologic responses to the chronic stress/distress experienced by individuals who reside in neighborhoods characterized by high levels of noise, crime and unemployment or the direct effects of environmental toxins.
Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
Authors: Labrèche Cédrik , Cook David P. , Abou-Hamad John , Pascoal Julia , Pryce Benjamin R. , Al-Zahrani Khalid N. , Sabourin Luc A. 
Published: November 2021

Abstract
Background
Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression.

Methods
Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines.

Results
Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling.

Conclusion
Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.
COVID-19 vaccine preferences among university students in Hong Kong: a discrete choice experiment
Authors: Li Xue , Chong Man Yui , Chan Ching Yui , Chan Vindy Wing Sum , Tong Xinning 
Published: November 2021

Abstract
Objective
To promote public health and resume university activities, COVID-19 vaccination has been mandated from an increasing number of universities worldwide. The objective of the study is to understand the factors that impact preference and willingness to take the vaccine among university students in Hong Kong universities utilizing an online questionnaire. The findings will be imperative for health education and the success of the vaccination program.

Results
We conducted a discrete choice experiment survey among university students in Hong Kong and applied conditional logit regression to estimate their vaccine preference and the weight of each attribute. Regression results showed adverse reactions, efficacy, origin of the vaccine, required number of doses and out-of-pocket price are significant determinants for the choice of vaccine, ranked from the most to least important. Similar preference weighting results were observed after adjusting age, sex, monthly household income, studying medical-related subjects and recent influenza vaccination. Safety, efficacy and origin of the vaccine are key drivers for vaccination decisions among young adults in Hong Kong. Health education and communication focused on these factors are urgently needed to overcome vaccine hesitancy and improve the vaccine uptake.
Multiocular organoids from human induced pluripotent stem cells displayed retinal, corneal, and retinal pigment epithelium lineages
Authors: Isla-Magrané Helena , Veiga Anna , García-Arumí José , Duarri Anna 
Published: November 2021

Abstract
Background
Recently, great efforts have been made to design protocols for obtaining ocular cells from human stem cells to model diseases or for regenerative purposes. Current protocols generally focus on isolating retinal cells, retinal pigment epithelium (RPE), or corneal cells and fail to recapitulate the complexity of the tissue during eye development. Here, the generation of more advanced in vitro multiocular organoids from human induced pluripotent stem cells (hiPSCs) is demonstrated.

Methods
A 2-step method was established to first obtain self-organized multizone ocular progenitor cells (mzOPCs) from 2D hiPSC cultures within three weeks. Then, after the cells were manually isolated and grown in suspension, 3D multiocular organoids were generated to model important cellular features of developing eyes.

Results
In the 2D culture, self-formed mzOPCs spanned the neuroectoderm, surface ectoderm, neural crest, and RPE, mimicking early stages of eye development. After lifting, mzOPCs developed into different 3D multiocular organoids composed of multiple cell lineages including RPE, retina, and cornea, and interactions between the different cell types and regions of the eye system were observed. Within these organoids, the retinal regions exhibited correct layering and contained all major retinal cell subtypes as well as retinal morphological cues, whereas the corneal regions closely resembled the transparent ocular-surface epithelium and contained of corneal, limbal, and conjunctival epithelial cells. The arrangement of RPE cells also formed organoids composed of polarized pigmented epithelial cells at the surface that were completely filled with collagen matrix.

Conclusions
This approach clearly demonstrated the advantages of the combined 2D-3D construction tissue model as it provided a more ocular native-like cellular environment than that of previous models. In this complex preparations, multiocular organoids may be used to model the crosstalk between different cell types in eye development and disease.

Graphical abstract
Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency
Authors: Sonoda Soichiro , Yoshimaru Koichiro , Yamaza Haruyoshi , Yuniartha Ratih , Matsuura Toshiharu , Yamauchi-Tomoda Erika , Murata Sara , Nishida Kento , Oda Yoshinao , Ohga Shouichi , Tajiri Tasturo , Taguchi Tomoaki , Yamaza Takayoshi 
Published: November 2021

Abstract
Background
Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent.

Methods
To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl4)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody.

Results
BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED.

Conclusion
These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.
Scattering strength at active volcanoes in Japan as inferred from the peak ratio analysis of teleseismic P waves
Authors: Ganefianto Gugi , Nakahara Hisashi , Nishimura Takeshi 
Published: November 2021

AbstractSmall-scale seismic velocity heterogeneity has been studied through the calculation of peak amplitude ratio as a means to quantify the strength of seismic wave scattering at volcanoes in Japan. This ratio is defined as the ratio of the maximum (peak) P wave energy in the transverse component seismogram envelope over that of the three-component sum seismogram envelope (transverse + radial + vertical). According to the previous study using Japan’s Hi-net seismometer network, the peak ratio is observed to be larger near the (active) quaternary volcanoes. However, these Hi-net stations are not positioned on the volcanoes themselves. This study systematically examines the peak ratios at 47 active volcanoes across Japan, using seismometers operated by the Japan Meteorological Agency (JMA). Analyses were performed at four frequency bands: 0.5–1, 1–2, 2–4, and 4–8 Hz. We found that the JMA stations yield higher peak ratios than the Hi-net stations. Their differences are statistically significant at the 99.9% confidence level in all frequency bands. We also examined the differences between the ground surface and borehole stations of the JMA network. The former shows larger peak ratios, and for most frequency bands, the differences are also statistically significant at the 99.9% confidence level. This suggests an intensification of small-scale medium heterogeneities especially at shallow depths at active volcanoes, and that scattering might have been enhanced at the very shallow parts.
Graphical Abstract
Inferior vena cava collapsibility index as a predictor of fluid responsiveness in sepsis-related acute circulatory failure
Authors: Nagi Ahmed Ibrahim , Shafik Azza Mohamed , Fatah Amr Mohamed Abdel , Selima Wessam Zaher , Hefny Amira Fathy 
Published: November 2021

Abstract
Background
Assessing fluid responsiveness is the key to successful resuscitation of critically-ill sepsis patients. The use of IVC variation is favored among the dynamic methods of fluid responsiveness assessment in the ICU because it is non-invasive and inexpensive; moreover, it does not demand a high level of training. The aim of this study is to determine the value of the IVC respiratory variability for predicting fluid responsiveness in spontaneously breathing sepsis patients with acute circulatory failure.

Results
In this prospective observational study, fifty-eight spontaneously breathing sepsis patients admitted in the ICU were enrolled after the approval of the departmental Research Ethical Committee, and the informed written consent had been taken from the patients. Ultrasonographic and echocardiographic parameters were measured “IVC parameters and stroke volume (SV)” with calculation of the inferior vena cava collapsibility index (IVCCI) and cardiac output. These values were obtained before (baseline) and after volume expansion with a fluid bolus. The study showed that twenty-nine patients (50%) were considered to be responders, with an increase in CO by 10% or more after fluid challenge. There was a significant difference between responders and non-responders in baseline IVCCI (p value < 0.001). There were no significant differences between responders and non-responders in terms of demographic and baseline clinical characteristics. Also, there was statistically significantly larger maximum (IVC max) and minimum (IVC min) inferior vena cava diameters before volume expansion in non-responders than in responders with p value 0.037 and 0.001 respectively. The suggested cut off value regarding baseline IVCCI to predict response to fluid infusion is 0.32 with a high chance of response above this figure (a sensitivity of 72.41% and a specificity of 82.76%).

Conclusions
Inferior vena cava collapsibility index assessment can be a sensitive and a good predictor of fluid responsiveness, being based on a safe and a non-invasive technique compared to other methods such as central venous pressure (CVP) measurement and pulmonary artery catheter insertion.
Dialing for Change: Organizing Call Center Workers in the 1990s
Authors: Goldman Debbie 
Published: November 2021

Abstract
This article contrasts two Communications Workers of America (CWA) strategic organizing campaigns at Sprint and Southwestern Bell wireless in the 1990s. In the first case, the NLRA failed to protect Sprint workers after their employer closed the call center to avoid a union election, despite a complaint filed by a Mexican union under labor provisions of the North American Free Trade Agreement. In the second case, the CWA's “bargain to organize” strategy neutralized Southwestern Bell's opposition, and 40,000 wireless workers chose CWA representation under a negotiated neutrality/card-check recognition process. This article demonstrates how neoliberal regulatory changes in the telecommunications sector in combination with weak labor laws fostered the decline in union representation in this vitally important and dynamic sector of the economy.