bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Stroma Interaction: Positive Feedback Regulation of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Expression and Matrix Metalloproteinase-Dependent Generation of Soluble EMMPRIN
Authors: Tang Yi , Kesavan Prabakaran , Nakada Marian T. , Yan Li 
Published: May 2022

Abstract
Matrix metalloproteinases (MMPs) are metal-dependent endopeptidases that play pivotal roles in tumor disease progression. In many solid tumors, MMPs are indeed produced by tumor stromal cells, rather than by tumor cells. This expression pattern is, at least in part, regulated by tumor-stroma interaction via tumor cell-associated extracellular matrix metalloproteinase inducer (EMMPRIN). In vitro, recombinant EMMPRIN dose-dependently stimulated MMP-1 production by primary human fibroblast cells. Interestingly, in addition to stimulating MMP expression, EMMPRIN also induced its own gene expression. To further explore this potential positive feedback regulatory mechanism, we generated human breast cancer cells expressing different levels of EMMPRIN. Coculture of EMMPRIN-positive tumor cells with fibroblast cells resulted in a concomitant stimulation of MMP-2, MMP-9, and EMMPRIN production. This induction was EMMPRIN dependent, was further enhanced by overexpression, and was reduced by antisense suppression of EMMPRIN expression in tumor cells. Increased expression of membrane-associated EMMPRIN was accompanied by an MMP-dependent generation of a soluble form of EMMPRIN representing a proteolytic cleavage product lacking the carboxyl terminus. On the basis of these findings, we propose a model in which tumor cell-associated EMMPRIN stimulates MMPs, as well as EMMPRIN expression in tumor stroma. Increased MMP activity in tumor local environment results in proteolytic cleavage of membrane-associated EMMPRIN, releasing soluble EMMPRIN. Soluble EMMPRIN in turn acts in a paracrine fashion on stroma cells that are both adjacent and distant to tumor sites to further stimulate the production of MMPs and additional EMMPRIN, which consequently contributes to tumor angiogenesis, tumor growth, and metastasis.
Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer
Authors: Chae Chang-Suk , Sandoval Tito A. , Hwang Sung-Min , Park Eun Sil , Giovanelli Paolo , Awasthi Deepika , Salvagno Camilla , Emmanuelli Alexander , Tan Chen , Chaudhary Vidyanath , Casado Julia , Kossenkov Andrew V. , Song Minkyung , Barrat Franck J. , Holcomb Kevin , Romero-Sandoval E. Alfonso , Zamarin Dmitriy , Pépin David , D'Andrea Alan D. , Färkkilä Anniina , Cubillos-Ruiz Juan R. 
Published: May 2022

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid enriched in the tumor microenvironment of immunosuppressive malignancies such as ovarian cancer. Although LPA enhances the tumorigenic attributes of cancer cells, the immunomodulatory activity of this phospholipid messenger remains largely unexplored. Here, we report that LPA operates as a negative regulator of type I interferon (IFN) responses in ovarian cancer. Ablation of the LPA-generating enzyme autotaxin (ATX) in ovarian cancer cells reprogrammed the tumor immune microenvironment, extended host survival, and improved the effects of therapies that elicit protective responses driven by type I IFN. Mechanistically, LPA sensing by dendritic cells triggered PGE2 biosynthesis that suppressed type I IFN signaling via autocrine EP4 engagement. Moreover, we identified an LPA-controlled, immune-derived gene signature associated with poor responses to combined PARP inhibition and PD-1 blockade in patients with ovarian cancer. Controlling LPA production or sensing in tumors may therefore be useful to improve cancer immunotherapies that rely on robust induction of type I IFN.

Significance:
This study uncovers that ATX–LPA is a central immunosuppressive pathway in the ovarian tumor microenvironment. Ablating this axis sensitizes ovarian cancer hosts to various immunotherapies by unleashing protective type I IFN responses. Understanding the immunoregulatory programs induced by LPA could lead to new biomarkers predicting resistance to immunotherapy in patients with cancer.
See related commentary by Conejo-Garcia and Curiel, p. 1841.
This article is highlighted in the In This Issue feature, p. 1825
Corrigendum: Measuring Uncertainty and Its Impact on the Economy
Authors: Carriero Andrea , Clark Todd E. , Marcellino Massimiliano 
Published: May 2022

Abstract
Carriero, Clark, and Marcellino (2018, CCM2018) used a large BVAR model with a factor structure to stochastic volatility to produce an estimate of time-varying macroeconomic and financial uncertainty and assess the effects of uncertainty on the economy. The results in CCM2018 were based on an estimation algorithm that has recently been shown to be incorrect by Bognanni (2022) and fixed by Carriero et al. (2022). In this corrigendum we use the algorithm correction of Carriero et al. (2022) to correct the estimates of CCM2018. Although the correction has some impact on the original results, the changes are small and the key findings of CCM2018 are upheld.
Spontaneous nocturnal erections and masturbation in captive male chimpanzees (Pan troglodytes)
Authors: Havercamp Kristin , Brindle Matilda , Sommer Volker , Hirata Satoshi 
Published: May 2022

Abstract
Nocturnal penile tumescence (NPT) has been reported for males of only a few mammalian species, including humans, albeit this scarcity might be an artefact of the difficulty of documenting it. We investigated NPT in 12 adult male chimpanzees living in an all-male group at Kumamoto Sanctuary, Japan. Recorded non-invasively with infrared video cameras across 72 nights (6 per individual), we observed NPT in two thirds of the individuals (8/12), with events in total. More than three quarters occurred during a transition from sleep to wakefulness, suggesting NPT may be associated with rapid eye movement sleep, similar to humans. Masturbation occurred in conjunction with NPT, including the likely consumption of ejaculate, in 4–6 individuals. While detailing nocturnal erections in chimpanzees may help us to better understand this robust physiological phenomenon in humans, further comparative research is necessary to reconstruct its phylogenetic history. At present, our findings support hypothetical functional explanations such as the facilitation of nocturnal emissions in order to increase ejaculate quality or an increase in tissue oxygenation to prevent erectile dysfunction.
Gold and aurostibite from the metaturbidite-hosted Au–Zn–Pb–Ag Hera deposit, southern Cobar Basin, central NSW, Australia: geochemical and textural evidence for gold remobilisation
Authors: Graham Ian T , McKinnon Adam , Lay Angela , Privat Karen , Schellen Khalid , Burrows Lachlan , Liepa Elizabeth , Quan Hongyan 
Published: May 2022

AbstractThe Devonian Hera metaturbidite-hosted polymetallic Au–Zn–Pb–Ag deposit of central NSW, Australia, contained a total undepleted resource of 3.6 Mt @ 3.3 g/t Au, 25 g/t Ag, 2.6% Pb and 3.8% Zn. The deposit comprises a number of distinctive lodes with each containing a distinctive ore and alteration/gangue mineralogy, though generally the sulfide ore comprises various mixtures of sphalerite, galena, chalcopyrite, pyrrhotite and relatively common visible gold–electrum. The North Pod and Far West lodes are distinctly Sb rich and contain a more diverse ore mineralogy with arsenopyrite, native silver, native antimony, gudmundite, tetrahedrite-(Fe), argentotetrahedrite-(Fe), acanthite, dyscrasite, nisbite and breithauptite. From analysis of 52,760 assays from across the deposit it was found that there was a very poor correlation between gold and each of Fe, Zn, S, Pb, Cu, As and Ag, whereas Ag correlated reasonably well with both Pb and Zn. Results from EPMA shows that gold varies widely in composition from host-rock associated gold (96 wt.% Au) through more intermediate compositions (88–73 wt.% Au) to electrum (46–27 wt.% Au), commonly associated with Sb-phases and containing significant Sb within the gold itself (1.05–2.58 wt.% Sb). From the Far West lense, aurostibite occurs as distinctive rims around gold. Although aurostibite associated with gold contains no silver, the gold itself contains constant moderate amounts (10.87–12.27 wt.% Ag). We suggest that the aurostibite and other Sb phases formed from a late-stage Sb-rich hydrothermal during low-temperature retrograde skarn alteration. There is abundant evidence for both chemical and physical remobilisation at Hera and this remobilisation is largely responsible for the spectrum of gold compositions observed. The source for these fluids may be an underlying magmatic body, evidence for which occurs as granite pegmatite dykes in various locations throughout the deposit. Furthermore, gold with a moderate to high Sb content may be indicative of a low temperature of formation.
Mitochondrial composition of and diffusion limiting factors of three social wasp genera Polistes, Ropalidia, and parapolybia (Hymenoptera: Vespidae)
Authors: Luo Li , Huang Pan , Chen Bin , Li Ting-Jing 
Published: May 2022

Abstract
Background
Social wasps Polistes, Ropalidia, and Parapolybia, belonging to the subfamily Polistinae, have obviously different distribution patterns, yet the factors leading to this difference remain unknown.

Results
The 17 newly sequenced mitogenomes of Polistes, Ropalidia, and Parapolybia contain 37 genes, and there are obvious differences among the compositions of the three genera. The monophyly of the genus Polistes and a monophyletic Ropalidiini: (Ropalidia + Parapolybia) are concordant with previous morphological analysis of the subfamily Polistinae. Our inferred divergence time demonstrates Polistes (at around 69 Ma) was diverged earlier than Ropalidia and Parapolybia (at around 61 Ma). The rearrangement of both trnY and trnL1 are shared by all the Polistinae. In addition, the unique rearrangement of TDRL derived at 69 Ma is detected in Polistes, and Ropalidia contains a Reversal which may derive at 61 Ma. Hereafter, the possibility is elaborated that Polistes originated in Aisa and then dispersed from Africa to South America, and Polistes and Ropalidia spread from Southeast Asia to Australia. At last, continental drift and Quaternary Ice Ages are inferred to be two main limiting factors in the current distributions of the three genera.

Conclusions
Obvious differences occur in the mitochondrial composition of Polistes, Ropalidia, and Parapolybia. According to the reconstructed time-calibrated framework, it is inquired that the continental drifts and the climate are mainly diffusion limiting factors of the three genera.
HPLC and high-throughput sequencing revealed higher tea-leaves quality, soil fertility and microbial community diversity in ancient tea plantations: compared with modern tea plantations
Authors: Yang Guangrong , Zhou Dapeng , Wan Renyuan , Wang Conglian , Xie Jin , Ma Cunqiang , Li Yongmei 
Published: May 2022

Abstract
Background
Ancient tea plantations with an age over 100 years still reserved at Mengku Town in Lincang Region of Yunan Province, China. However, the characteristic of soil chemicophysical properties and microbial ecosystem in the ancient tea plantations and their correlation with tea-leaves chemical components remained unclear. Tea-leaves chemical components including free amino acids, phenolic compounds and purine alkaloids collected from modern and ancient tea plantations in five geographic sites (i.e. Bingdao, Baqishan, Banuo, Dongguo and Jiulong) were determined by high performance liquid chromatography (HPLC), while their soil microbial community structure was analyzed by high-throughput sequencing, respectively. Additionally, soil microbial quantity and chemicophysical properties including pH, cation exchange capacity (CEC), soil organic matter (SOM), soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali-hydrolyzable nitrogen (AN), available phosphorous (AP) and available potassium (AK) were determined in modern and ancient tea plantations.

Results
Tea-leaves chemical components, soil chemicophysical properties and microbial community structures including bacterial and fungal community abundance and diversity evaluated by Chao 1 and Shannon varied with geographic location and tea plantation type. Ancient tea plantations were observed to possess significantly (P < 0.05) higher free amino acids, gallic acid, caffeine and epigallocatechin (EGC) in tea-leaves, as well as soil fertility. The bacterial community structure kept stable, while fungal community abundance and diversity significantly (P < 0.05) increased in ancient tea plantation because of higher soil fertility and lower pH. The long-term plantation in natural cultivation way might significantly (P < 0.05) improve the abundances of Nitrospirota, Methylomirabilota, Ascomycota and Mortierellomycota phyla.

Conclusions
Due to the natural cultivation way, the ancient tea plantations still maintained relatively higher soil fertility and soil microbial ecosystem, which contributed to the sustainable development of tea-leaves with higher quality.
Immunohistochemical identification and assessment of the location of leptin, visfatin and chemerin in the liver of men with different body mass index
Authors: Kasacka I. , Piotrowska Ż. , Domian N. , Lewandowska A. , Acewicz M. 
Published: May 2022

Abstract
Background
Adipokines such as leptin, visfatin and chemerin play a pivotal role not only in the pathogenesis of excessive weight gain but also impact on hepatic metabolism. However, alterations in the production of these peptides in the liver of overweight individuals have not been fully elucidated yet. The aim of the study was to evaluate changes in leptin, visfatin and chemerin biosynthesis in the liver of men with different BMI.

Methods
Fourteen adult men without symptoms from the digestive system were recruited. Research material consisted of liver samples. Study participants were divided into two groups: lean (BMI ≤ 25 kg/m2) and overweight subjects (BMI > 25 kg/m2). Paraffin liver sections were processed by immunohistochemistry for detection of leptin, visfatin and chemerin. Hepatic expression of leptin, visfatin and chemerin genes was determined by qRT-PCR method.

Results
Increased immunoreactivity for leptin and chemerin, and decreased immunoreaction for visfatin were observed in the liver of overweight men in comparison to lean subjects. Overweight subjects with hepatic steatosis displayed increased immunoreactivity for leptin and weaker immunoreaction against visfatin and chemerin in the liver, compared to individuals with normal organ structure. Expression of leptin and chemerin was enhanced in the liver of overweight individuals, with the highest expression observed in subjects with hepatic steatosis. Conversely, expression of visfatin in the male liver was decreased in overweight subjects and those with and liver steatosis.

Conclusions
The present study proves that the expression of leptin, visfatin and chemerin in the male liver is altered in overweight individuals. Our report also indicates the potential importance of these peptides in hepatic steatosis associated with overweight.
Improving individualized prescription in patients with multimorbidity through medication review
Authors: Molist-Brunet Núria , Sevilla-Sánchez Daniel , Puigoriol-Juvanteny Emma , Barneto-Soto Matilde , González-Bueno Javier , Espaulella-Panicot Joan 
Published: May 2022

Abstract
Background
Older patients tend to have multimorbidity, represented by multiple chronic diseases or geriatric conditions, which leads to a growing number of prescribed medications. As a result, pharmacological prescription has become a major concern because of the increased difficulties to ensure appropriate prescription in older adults. The study’s main objectives were to characterize a cohort of older adults with multimorbidity, carry out a medication review and compare the pharmacological data before and after the medication review globally and according to the frailty index.

Methods
This was a quasi-experimental (uncontrolled pre-post) study with a cohort of patients ≥ 65 years old with multimorbidity. Data were collected from June 2019 to October 2020. Variables assessed included demographic, clinical, and pharmacological data, degree of frailty (Frail-VIG index), medication regimen complexity index, anticholinergic and or sedative burden index, and monthly drug expenditure. Finally, a medication review was carried out by an interdisciplinary team (primary care team and a consultant team with a geriatrician and a clinical pharmacist) by applying the Patient-Centered Prescription model to align the treatment with care goals.

Results
Four hundred twenty-eight patients were recruited [66.6% women; mean age 85.5 (SD 7.67)]. The mean frail index was 0.39 (SD 0.13), corresponding with moderate frailty. Up to 90% of patients presented at least one inappropriate prescription, and the mean of inappropriate prescriptions per patient was 3.14 (SD 2.27). At the three-month follow-up [mortality of 17.7% (n = 76)], the mean chronic medications per patient decreased by 17.96%, varying from 8.13 (SD 3.87) to 6.67 (SD 3.72) (p < 0.001). The medication regimen complexity index decreased by 19.03%, from 31.0 (SD 16.2) to 25.1 (SD 15.1), and the drug burden index mean decreased by 8.40%, from 1.19 (SD 0.82) to 1.09 (SD 0.82) (p < 0.001). A decrease in polypharmacy, medication regimen complexity index, and drug burden index was more frequent among frail patients, especially those with severe frailty (p < 0.001).

Conclusions
An individualized medication review in frail older patients, applying the Patient-Centered Prescription model, decreases pharmacological parameters related to adverse drug effects, such as polypharmacy, therapeutical complexity, and anticholinergic and, or sedative burden. The benefits are for patients with frailty.
Continued effectiveness of COVID-19 vaccination among urban healthcare workers during delta variant predominance
Authors: Lan Fan-Yun , Sidossis Amalia , Iliaki Eirini , Buley Jane , Nathan Neetha , Bruno-Murtha Lou Ann , Kales Stefanos N. 
Published: May 2022

Abstract
Background
Data on COVID-19 vaccine effectiveness (VE) among healthcare workers (HCWs) during periods of delta variant predominance are limited.

Methods
We followed a population of urban Massachusetts HCWs (45% non-White) subject to epidemiologic surveillance. We accounted for covariates such as demographics and community background infection incidence, as well as information bias regarding COVID-19 diagnosis and vaccination status.

Results
During the study period (December 16, 2020 to September 30, 2021), 4615 HCWs contributed to a total of 1,152,486 person-days at risk (excluding 309 HCWs with prior infection) and had a COVID-19 incidence rate of 5.2/10,000 (114 infections out of 219,842 person-days) for unvaccinated person-days and 0.6/10,000 (49 infections out of 830,084 person-days) for fully vaccinated person-days, resulting in an adjusted VE of 82.3% (95% CI 75.1–87.4%). For the secondary analysis limited to the period of delta variant predominance in Massachusetts (i.e., July 1 to September 30, 2021), we observed an adjusted VE of 76.5% (95% CI 40.9–90.6%). Independently, we found no re-infection among those with prior COVID-19, contributing to 74,557 re-infection-free person-days, adding to the evidence base for the robustness of naturally acquired immunity.

Conclusions
We found a VE of 76.5% against the delta variant. Our work also provides further evidence of naturally acquired immunity.
The severity of portal hypertension by a non-invasive assessment: acoustic structure quantification analysis of liver parenchyma
Authors: Cai Wen-Bin , Yin Ji-Kai , Li Qiao-ying , Yang Yi-Lin , Duan Yun-You , Zhang Li 
Published: May 2022

Abstract
Background
Acoustic structure quantification (ASQ) has been applied to evaluate liver histologic changes by analyzing the speckle pattern seen on B-mode ultrasound. We aimed to assess the severity of portal hypertension (PHT) through hepatic ultrasonography.

Methods
Sixty patients diagnosed with PHT and underwent surgical treatment with portosystemic shunts were enrolled. Portal pressure (PP) was measured intraoperatively. Patients were divided into subgroups according to the severity of gastroesophageal varices and Child–Pugh class. Three difference ratio (Cm2) values on ASQ histogram mode were analyzed for their relationships with PP, degree of gastroesophageal varices and Child–Pugh liver function. Thirty healthy volunteers matched with the patients for gender and age were enrolled as controls. Comparisons among groups and correlation of the parameters with PP were analyzed. Area under the receive operating characteristic curve was used to evaluate the predicting value of ASQ parameters.

Results
In the patients, the ASQ parameters peak Cm2 (Cm2max), mean Cm2 (Cm2mean) and the highest occurred Cm2 value of the obtained red curve (RmaxCm2) were all greatly increased (P < 0.0001, P < 0.0001, P = 0.027). Multiple comparisons indicated that, regardless of Child–Pugh class and degree of gastroesophageal varices, the patients had significantly increased Cm2max and Cm2mean compared with the controls (all P < 0.0001). No differences among subgroups were observed. Cm2max was significantly statistically correlated with PP (r = 0.3505, P < 0.01), degree of varices (r = 0.4998, P < 0.0001). Youden’s index for Cm2max with a cut-off value of 140.3 for predicting the presence of PHT, gastroesophageal varices and liver function equal to or worse than Child–Pugh class B were 0.8, 0.91 and 0.84, respectively.

Conclusions
ASQ analysis of ultrasonographic images may have a role in the evaluation of the severity of PHT by detecting liver histologic changes in the speckle pattern caused by cirrhosis.
miR-107 is involved in the regulation of NEDD9-mediated invasion and metastasis in breast cancer
Authors: Zhou Jiamin , Sun Xianglin , Zhang Xinyu , Yang Huan , Jiang Zhenglin , Luo Qianqian , Liu Yifei , Wang Guohua 
Published: May 2022

Abstract
Background
As a metastasis-related protein, NEDD9 has been reported in breast cancer (BC) metastasis research. However, there are few studies on the upstream regulators of NEDD9, especially involving the potential role of miRNAs. The purpose of this study was to explain whether miR-107 potentially regulates NEDD9, which may lead to invasion and metastasis of BC.

Methods
MCF-7 and MDA-MB-231 cells were transduced with lentiviruses to construct stably transduced cells with miR-107 overexpression, miR-107 silencing or empty vectors. A luciferase reporter assay was performed to verify the binding of miR-107 and NEDD9. The scratch test and Transwell assay were used to measure cell migration and invasion ability, respectively. For the study of metastasis in vivo, we injected MDA-MB-231 cells into the fat pad of nude mice to develop an orthotopic breast cancer model.

Results
We found that NEDD9 expression correlates with the prognosis of BC patients. In BC cell lines, NEDD9 was positively correlated with cell migration ability. Further research revealed that miR-107 inhibited NEDD9 expression by targeting the 3′-untranslated region of NEDD9. Overexpression of miR-107 suppressed the expression of NEDD9, thereby inhibiting the invasion, migration and proliferation of BC cells, but interference with miR-107 promoted the expression of NEDD9 as well as invasion, migration and proliferation. In an in vivo model, overexpression of miR-107 decreased the expression of NEDD9 and inhibited tumour growth, invasion and metastasis; however, these effects were reversed by inhibiting miR-107.

Conclusions
These findings indicated the potential role of miR-107 in regulating NEDD9 in the invasion, migration and proliferation of BC.