bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare, Social and Geographical Factors That Impact Surgical and Survival Outcomes in Penile Cancer
Authors: Angulo-Lozano Juan Carlos , Sanchez-Musi Luisa Fernanda , Garcia-Garcia Jose Antonio 
Published: May 2022

Abstract
Objectives
To analyze the level of access to healthcare, social and geographical factors that could predispose a negative surgical outcome and higher mortality rate in patients with penile cancer.
Methods
This is a retrospective cohort study. The study population (n = 93) are adult male patients with a diagnosis of penile cancer. Fisher’s exact test was performed to determine the association between the level of healthcare, social and geographical factors, and the outcomes for penile cancer.
Results
Patients without primary care access had a higher likeliness of having lymphovascular invasion at the time of diagnosis (OR = 37.5, P < .0001), a higher mortality rate at 24 months after diagnosis (OR = 19.2, P = .005), a lack of high-school diploma or equivalent (OR = 3.8, P = .049) and a higher likelihood of referral from a provincial hospital (OR = 10.1, P < .0001). Patients without a favorable surgical outcome (total resection of the penis) were more likely to have been referred from a provincial hospital (OR = 6.8, P < .0001) and to not have access to a primary care center (OR = 149.5, P < .0001), a tertiary care center (OR = 20.7, P = 0.003), and a high school diploma (OR = 7.9, P = 0.004).
Conclusions
The lack of access to primary care is strongly associated with vascular invasion at diagnosis, lower educational level, a referral from provincial zones, and a higher mortality rate at 24 months. Patients who did not have access to primary and tertiary care, a high school diploma, and were referred from the province were more likely to have a total resection of the penis.
Antagonism of the muscarinic acetylcholine type 1 receptor enhances mitochondrial membrane potential and expression of respiratory chain components via AMPK in human neuroblastoma SH-SY5Y cells and primary neurons
Authors: Naznin Farhana , Waise T.M. Zaved , Fernyhough Paul 
Published: May 2022

Abstract
Impairments in mitochondrial physiology play a role in the progression of multiple neurodegenerative conditions, including peripheral neuropathy in diabetes. Blockade of muscarinic acetylcholine type 1 receptor (M1R) with specific/selective antagonists prevented mitochondrial dysfunction and reversed nerve degeneration in in vitro and in vivo models of peripheral neuropathy. Specifically, in type 1 and type 2 models of diabetes, inhibition of M1R using pirenzepine or muscarinic toxin 7 (MT7) induced AMP-activated protein kinase (AMPK) activity in dorsal root ganglia (DRG) and prevented sensory abnormalities and distal nerve fiber loss. The human neuroblastoma SH-SY5Y cell line has been extensively used as an in vitro model system to study mechanisms of neurodegeneration in DRG neurons and other neuronal sub-types. Here, we tested the hypothesis that pirenzepine or MT7 enhance AMPK activity and via this pathway augment mitochondrial function in SH-SY5Y cells. M1R expression was confirmed by utilizing a fluorescent dye, ATTO590-labeled MT7, that exhibits great specificity for this receptor. M1R antagonist treatment in SH-SY5Y culture increased AMPK phosphorylation and mitochondrial protein expression (OXPHOS). Mitochondrial membrane potential (MMP) was augmented in pirenzepine and MT7 treated cultured SH-SY5Y cells and DRG neurons. Compound C or AMPK-specific siRNA suppressed pirenzepine or MT7-induced elevation of OXPHOS expression and MMP. Moreover, muscarinic antagonists induced hyperpolarization by activating the M-current and, thus, suppressed neuronal excitability. These results reveal that negative regulation of this M1R-dependent pathway could represent a potential therapeutic target to elevate AMPK activity, enhance mitochondrial function, suppress neuropathic pain and enhance nerve repair in peripheral neuropathy.
Clinical features and outcomes of patients with antineutrophil cytoplasmic antibody-positive systemic lupus erythematosus
Authors: wang ying , Yu Xiaoyang , Xie Xinfang , Li Huixian , Yang Wei , Liang Yu , Lu Wanhong 
Published: May 2022

Abstract
Objective: To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibodies (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China. Methods: We conducted a retrospective study of an ANCA-positive SLE cohort from 2012 to 2019. Clinical characteristics, laboratory data, renal histological features, and outcomes were analyzed. Patients diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal involvement, excluding those with SLE and ANCA-negative lupus nephritis (LN), were randomly selected as controls.Results: A total of 49 ANCA-positive LN patients were included in this study. The enrolled patients had a significantly lower estimated glomerular filtration rate (eGFR) than ANCA-negative LN patients and had a higher eGFR than AAV patients. SLE patients with MPO-ANCA had higher levels of serum creatinine (CREA) and blood urea nitrogen (BUN) than those with PR3-ANCA (CREA:156.5 µmol/L vs. 45.5 µmol/L, P = 0.005; BUN: 12.77 µmol/L vs 4.27 µmol/L, P = 0.005, respectively). ANCA titers positively correlated with serum complement levels in patients with SLE. ANCA-positive LN cases had a significantly higher percentage of tubulointerstitial fibrosis (84.6% vs. 14.3%, P < 0.001) and higher median glomerular chronicity index (2.1 vs. 0.9, P = 0.017) than ANCA-negative LN patients. During follow-up, there were significant differences in the proteinuria remission rates between the two matched groups when using propensity scoring (P = 0.008).Conclusion: ANCA-positive SLE patients may have worse baseline renal function (especially those with MPO-ANCA positivity) and lower protein remission rates. During the follow-up period, a decrease in ANCA titer seems to correlate with renal function improvement. ANCA titers should be regularly monitored throughout the follow-up period of SLE patients, especially when there is renal involvement.
Hot Jupiters are not as lonely as we thought
Authors: Wang Songhu , Wu Dong-Hong , Rice Malena 
Published: May 2022

Abstract
The first discovered extrasolar worlds -- giant, ``hot Jupiter'' planets orbiting remarkably close to their parent stars -- came as a surprise to solar-system-centric models of planet formation, prompting the development of new theories to produce these unexpected planets. The striking dearth of observed nearby planetary companions to hot Jupiters (~2%) has been widely quoted as evidence in support of high-eccentricity tidal migration: a framework in which hot Jupiters form further out in their natal protoplanetary disks before being thrown inward, stripping systems of any close-in planetary companions. By contrast, we demonstrate through a search for transit timing variations across the full four-year Kepler dataset that at minimum 13% of hot Jupiters have a nearby planetary companion. This subset of hot Jupiters must have a quiescent formation history such that they were able to retain nearby companions. We also demonstrate a ubiquity of nearby planetary companions to warm Jupiters, indicating that warm Jupiters typically form quiescently. We conclude with a new paradigm for the formation of short-period gas giants that is consistent with all current lines of evidence, in which >13% of hot Jupiters form in situ and the other <87% undergo high-eccentricity migration.
Metastatic clear-cell renal cell carcinoma: a frequent NOTCH1 mutation predictive of response to anti-NOTCH1 treatment
Authors: Bui Thi oanh , Bouchtaoui Morad El , Gapihan Guillaume , Dao Van Tu , Paris Justine , Leboeuf Christophe , Soussan Michael , Villarese Patrick , Ziol Marianne , Glabeke Emmanuel , Le Thi Huong , Feugeas Jean-Paul , Janin Anne , Bousquet Guilhem 
Published: May 2022

Abstract
Background
Despite some improvement in the prognosis of metastatic clear-cell renal cell carcinoma (ccRCC), the identification of new therapeutic targets is essential. Up to now, only limited genomic data has been obtained from metastatic samples.
Methods
We aimed to characterize metastatic ccRCC by way of whole-genome analyses of metastatic formalin-fixed samples, using OncoScan® technology. We identified a frequent, unexpected pL1575P NOTCH1 mutation which we set out to characterize for translational purposes. We thus implemented patient-derived xenografts from metastatic samples of human ccRCC to explore its clinical significance .
Results
We showed that pL1575P NOTCH1 mutation was an activating mutation, leading to the expression of NOTCH1-intracellular domain-active fragments in both cancer cells and tumor endothelial cells, suggesting a trans-differentiation of cancer cells into tumor micro-vessels. We demonstrated that this mutation could be used as a predictive biomarker of response to CB-103, a specific NOTCH1-ICD inhibitor. One striking result was the considerable anti-angiogenic effect, coherent with the presence of NOTCH1 mutation in tumor micro-vessels.
Conclusions
We identified a frequent, unexpected pL1575P_c4724T_C NOTCH1 mutation as a new biomarker for ccRCC metastases, predictive of response to the CB103 NOTCH1-intracellular domain inhibitor. This opens the way for further clinical trials among patients with metastatic RCCs.
Nestin as a marker of unipotent epithelial progenitor cell differentiation into outer root sheath keratinocytes in embryonic and adult hair follicles
Authors: Baba Yuta , Onishi-Sakamoto Saki , Ide Kaori , Nishifuji Koji 
Published: May 2022

Abstract
Nestin is an intermediate filament protein transiently expressed in neural stem/progenitor cells. We previously demonstrated that outer root sheath (ORS) keratinocytes of adult hair follicles (HFs) in mice descend from nestin-expressing cells, despite being an epithelial cell lineage. This study aimed to define the exact stage when nestin-expressing ORS stem/precursor cells or their descendants appear during HF morphogenesis and in adult HFs. Using Nes-Cre/CAG-CAT-EGFP mice, in which enhanced green fluorescent protein (EGFP) is expressed following Cre-based recombination driven by the nestin promoter, we found that EGFP+ cells appeared in the epithelial layer of embryonic HFs as early as the peg stage. EGFP+ cells in hair pegs were positive for keratin 5, but not vimentin, Sox2, Sox10, or S100 alpha 6. Tracing of tamoxifen-induced EGFP+ cells in postnatal Nes-CreERT2/CAG-CAT-EGFP mice revealed labeling of some isthmus HF epithelial cells in the first anagen stage. EGFP+ cells in adult HFs were not immunolabeled for keratin 15, an HF multipotent stem cell marker. However, when hairs were depilated to induce the anagen stage after tamoxifen injection, the majority of ORS keratinocytes in depilation-induced anagen HFs expressed EGFP. Our findings indicate that nestin-expressing unipotent progenitor cells capable of differentiating into ORS keratinocytes are present in both the HF primordia and adult HFs.
Long noncoding RNA LIPH-4 promotes esophageal squamous cell carcinoma progression by regulating the miR-216b/IGF2BP2 axis
Authors: Xiao Yuhang , Tang Jinming , Yang Desong , Zhang Baihua , Wu Jie , Wu Zhining , Liao Qianjin , Wang Hui , Wang Wenxiang , Su Min 
Published: May 2022

Abstract
IntroductionEsophageal squamous cell carcinoma (ESCC) represents a major malignancy with poor clinical outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of multiple cancers. However, how lncRNAs are involved in ESCC is currently undefined.MethodsLIPH-4 levels in ESCC tissue specimens and cells were assessed by qRT-PCR. The biological function of LIPH-4 was examined in cell and animal studies, applying CCK-8, EdU, colony formation and flow cytometry assays as well as xenograft model experiments. The underlying mechanisms of action of LIPH-4 were explored through bioinformatics, luciferase reporter assay, RNA-immunoprecipitation assay and immunoblot.ResultsWe identified a novel lncRNA, LIPH-4, which showed elevated amounts in ESCC tissues and positive correlations with increased tumor size and poor prognosis in ESCC patients. Functional studies showed that LIPH-4 promoted the growth, mediated cell cycle progression and inhibited apoptosis in ESCC cells in vitro, and promoted tumor growth in mice. In terms of mechanism, LIPH-4 could bind to miR-216b and act as a competing endogenous RNA (ceRNA) to induce the expression of miR-216's target gene IGF2BP2. LIPH-4 played an oncogenic role in ESCC through the miR-216b/IGF2BP2 axis.ConclusionsThis study suggested that LIPH-4 functions as a novel oncogenic lncRNA by acting as a ceRNA for miR-216b to regulate IGF2BP2, indicating LIPH-4 likely constitutes a prognostic biomarker and therapeutic target in ESCC.
Prenatal diagnosis of a rare case report of 45,X/46,X,dic(X) and literature review
Authors: Wang Ting , Lun Miao-Xu , Chen Han-biao , Du Qian-yi , Zheng Lai-ping , Zhong Yin-huan , Lu Jian , Guo Li 
Published: May 2022

Abstract
Objective
We present a prenatal case of 45,X/46,dic(X) with two asymmetric chromosome arms.
Methods
Single nucleotide polymorphism array(SNP-array),fluorescence in situ hybridization(FISH) and conventional cytogenetic analysis were performed for verification.
Results
The conventional G-banding analysis revealed a mosaic karyotype of mos 45,X/46,X,dic (X;X) (p11.2;q10) and the C-banding analysis showed that the derivative X chromosome had two darkly stained bands near the centromere.Two green signals and single green signal (X chromosome cetromere) were observed simultaneously in the metaphases and interphases FISH confirmation test,which indicated a mosaicism for X chromosome in the uncultured amniocytes.The SNP-array results revealed two copy-number-loss on the X chromosome.One was a 54.3Mb deletion in Xp22.33-p11.22 including 414 genes.Another was a mosaic deletion in Xp11.22-q28.
Conclusion
A combination of molecular and cytogenetic techniques should be employed to provide adequate genetic counseling to mosaic Turner sydrome patients for avoiding misdiagnosis.
Sedimentary record of historic seismicity in a small, southern Oregon lake
Authors: (Ross) Ann E. Morey , Shapley Mark D. , Gavin Daniel G. , Nelson Alan R. , Goldfinger Chris 
Published: May 2022

Abstract

We compare disturbances from the historic portion of the sedimentary record from Lower Squaw Lake, Oregon, to the historic record of events from the region to (1) determine if the lake records Cascadia megathrust earthquakes, and (2) if sediment deposits can be differentiated by disturbance type. We use the sedimentological characteristics and geochemically inferred provenance of the deposits (labeled A-J) from the historic portion (post 1650 CE) of the record to discriminate between types of deposits. We show that earthquake-triggered deposits are complex and flood deposits are simpler but vary depending on flood characteristics. Disturbance deposit J dates close to 1700 CE (1680–1780 CE) through multiple approaches. This deposit suspected to result from the magnitude (M) 8.8–9.2 1700 CE Cascadia megathrust earthquake is composed of unusually well-sorted, normally graded, medium-grained silt derived from distal rocks in the upper watershed. The silt grades upward, increasing in organic content forming a long, organic-rich tail. Load structures of silt into the organic-rich sediment below suggest rapid deposition. In contrast, a deposit attributed to the ~ M7.0 1873 CE intraplate earthquake is a normally graded, medium-grained, watershed-sourced silt overlain by a thinner organic tail and preceded by a deposit interpreted as a local wall failure. These results suggest that inland lakes can be sensitive recorders of earthquakes, and that it is possible to discriminate between plate margin and other types of earthquakes, and floods.
Managing environmental impacts of water and energy use by a multipurpose cropping pattern optimization
Authors: Sedighkia Mahdi , Fathi Zeynab 
Published: May 2022

Abstract
The present study proposes a multipurpose cropping pattern optimization to minimize the environmental impacts of water and energy use on agriculture through the income–energy–river ecosystem nexus approach in different hydrological conditions. The following three main purposes are considered in the optimization model: (1) mitigating greenhouse gas emissions due to farming by considering minimization of agricultural energy consumption; (2) mitigating environmental impacts on the river ecosystem by considering it as the main source for supplying irrigation demand in the case study and (3) maximizing farmers’ income. Field studies are carried out in the case study for recording energy inputs to assess average energy use, irrigation demand, production yield and other required parameters for the selected crops. The fuzzy physical habitat simulation is utilized to develop an environmental impact function in the river ecosystem. Based on the results of the case study, the optimization model is able to balance energy use, impacts on the river ecosystem and farmers’ income. However, its performance is not best in terms of all the defined purposes. The results indicate that more than 50% of the initial income is provided, while energy use is mitigated by more than 70% on average. Furthermore, the river ecosystem is protected properly.
Glaucoma: Biological Mechanism and its Clinical Translation
Authors: Durán-Cristiano Sandra C. 
Published: May 2022

Abstract:
Glaucoma is a common cause of visual loss and irreversible blindness,
affecting visual and life quality. Various mechanisms are involved in retinal ganglion cell
(RGC) apoptosis and functional and structural loss in the visual system. The prevalence
of glaucoma has increased in several countries. However, its early diagnosis has
contributed to prompt attention. Molecular and cellular biological mechanisms are
important for understanding the pathological process of glaucoma and new therapies.
Thus, this review discusses the factors involved in glaucoma, from basic science to
cellular and molecular events (e.g., mitochondrial dysfunction, endoplasmic reticulum
stress, glutamate excitotoxicity, the cholinergic system, and genetic and epigenetic
factors), which in recent years have been included in the development of new therapies,
management, and diagnosis of this disease.
Chitosan Modification-Enhanced Silencing Effect of Ad5-shPDGF-D
Vector in Breast Cancer Cell Line MDA-MB-231
Authors: Ekentok-Atıcı Ceyda , Akbuğa Jülide 
Published: May 2022

Background:
Gene therapeutics are being developed to treat metastatic breast tumors, which
are mostly resistant to conventional therapies. Targeting platelet-derived growth factor-D (PDGF-D) is
a viable approach because it is known to play roles in angiogenesis and tumor growth. The success of
gene therapy is largely dependent on delivery vectors, but both viral and nonviral delivery vectors have
their disadvantages. Evolving hybrid vectors are being used to overcome those disadvantages.

Objectives:
In this study, we aimed to prepare a recombinant adenovirus type-5 (Ad5)/chitosan hybrid
vector to deliver shPDGF-D in a breast cancer cell line by the noncovalent coating of the Ad5 surface
with chitosan, a natural polymer.

Methods:
The Ad5/chitosan hybrid vector was prepared by the noncovalent coating of the Ad5 surface
with different molecular weights (low and high) and different amounts of chitosan (12.5, 25, and 50
μg), and the effect of silencing PDGF-D was investigated in the MDA-MB-231 cell line.

Results:
In vitro characterization studies showed that the noncovalent chitosan coating increased the
size of the Ad5 particle and changed the surface charge from -16.53 mV to slightly neutral. In vitro cell
culture studies also showed that the addition of chitosan with both low (73.61%) and high (65.86%)
molecular weight increased the PDGF-D silencing efficiency of the Ad5 vector (42.44%) at 48 hours.
While low-molecular-weight chitosan had faster effects, high-molecular-weight chitosan provided a
more sustained effect in PDGF-D silencing.

Conclusion:
The results indicate that noncovalent chitosan modification may improve the therapeutic
effects of the Ad5 vector, offering the potential for further in vitro and in vivo experiments.
Palladium-Catalyzed Aminocarbonylation of Aryl Halides
Authors: Anilkumar Gopinathan , Abdulla Afsina Cheriya Mukkolakkal , Philip Rose Mary , Saranya Padinjare Veetil 
Published: May 2022

Abstract:
Palladium-catalyzed organic reactions are ubiquitous due to their high efficiency in
coupling reactions and have wide applications in synthetic chemistry. Their widespread use in
organic synthesis has been attributed to moderate conditions associated with reactions and tolerance
to different types of functional groups. Palladium-catalysts are extensively used in aminocarbonylation
of aryl halides for the synthesis of amides and have found a wide variety of
applications in pharmaceuticals, agrochemicals, petrochemicals, materials, polymers, etc. In this
review, we summarize the recent advances in the synthesis of amides via palladium-catalyzed
aminocarbonylation of aryl halides, and cover literature from 2010 to 2021
A Rare Case of Drug-induced Erectile Dysfunction with Adalimumab and
Certolizumab Solved after Switch to Ustekinumab in a Crohn's Disease
Patient
Authors: Hidalgo-Rios Samuel , Alonso-Moreno Marta , Iserte Jaime Torelló , Herrera-Justiniano Jose Manuel 
Published: May 2022

Background:
Crohn Disease (CD) is an intestinal inflammatory condition characterized
by a complex pathogenesis, with elevated levels of inflammatory cytokines. Adalimumab and certolizumab
are two biologic drugs inhibiting TNF-α.

Objective:
We report the first case of a probable relationship, according to Naranjo causality assessment
score, between two consecutive treatments with TNF-α inhibitors and induced erectile
dysfunction (ED), that disappeared after switching to another biologic drug (ustekinumab).

Case Presentation:
This case report describes a possible and important association of two TNF-α
inhibitors (certolizumab and adalimumab) and ED in a male patient with CD, with resolution after
switching to Ustekinumab (anti-interleukin 12 and 23 biologic drug). A 65 years old man experienced
erectile dysfunction during treatment with an anti-TNF. The adverse effect disappeared after
discontinuation of the drug. All necessary urologic exams were carried out. Adalimumab was replaced
by certolizumab and sexual disfunction symptoms appeared again, improving typically at
the end of treatment periods and getting worse with each new dose.

Results:
Switching to ustekinumab lead to a resolution of the erectile dysfunction.

Conclusion:
We describe for the first time a sexual dysfunction possibly due to two similar anti
TNF drugs and its resolution after the switch to another similar but different drug, highlighting the
potential difference between biologic drugs.