bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant hysterectomy following primary chemoradiation for stage IB2 and IIA2 cervical cancer: a retrospective comparison of complications for open versus minimally invasive surgery
Authors: Miller Heather , Matsuo Koji , Roman Lynda D. , Yessaian Annie A. , Pham Huyen Q. , Hom Marianne , Castaneda Antonio , Pham Anthony , Ragab Omar , Muderspach Laila , Ciccone Marcia , Brunette Laurie L. 
Published: June 2021

Abstract
Background
Adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer has been shown to decrease local relapse rate. The objective of this study is to compare complications and recurrences between minimally invasive and open adjuvant hysterectomy for early stage cervical cancer.

Methods
Patients were identified who had undergone adjuvant hysterectomy following chemoradiation for 2009 FIGO stage IB2 and IIA2 cervical cancer from August 2006 to June 2018. Demographic information, treatment course, complications, recurrence data were retrospectively extracted from the medical record. Frequency of complications was compared with Fisher exact test or chi-square test as appropriate and inverse probability of treatment propensity score weighting was used to calculate the disease-free survival.

Results
Fifty-four patients met inclusion criteria with a median follow up time of 60.4 months (interquartile range 28.0–98.1 months). There were 24 (44%) open versus 30 (56%) minimally invasive hysterectomies performed. The overall grade 2 or worse complication rate was 43%. There were 8 (27%) patients with complications in the minimally invasive group compared to 4 (17%) in the open group (OR 1.82 (95% CI 0.5–7.0)). There were 9 vaginal cuff defects, dehiscences and/or fistulas in the minimally invasive group compared to 3 in the open group (OR 3.0 (95% CI 0.8–11.2)). There was no statistically significant difference between disease free survival and overall survival among the two groups, however there was a trend towards decreased disease-free survival in the minimally invasive group.

Conclusions
Among women undergoing adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer, there was no difference in complication rates between an open or minimally invasive surgical approach. However, the overall complication rate was high, including a high rate of vaginal cuff defect, dehiscence and/or fistulas. Our findings suggest that an adjuvant hysterectomy should be reserved for patients in which chemoradiation is not anticipated to successfully treat the primary tumor and, if performed, an open approach should be considered.
In vivo imaging of immediate early gene expression dynamics segregates neuronal ensemble of memories of dual events
Authors: Meenakshi P. , Kumar S. , Balaji J. 
Published: June 2021

AbstractIdentification of neurons undergoing plasticity in response to external stimuli is one of the pertinent problems in neuroscience. Immediate early genes (IEGs) are widely used as a marker for neuronal plasticity. Here, we model the dynamics of IEG expression as a consecutive, irreversible first-order reaction with a limiting substrate. First, we develop an analytical framework to show that such a model, together with two-photon in vivo imaging of IEG expression, can be used to identify distinct neuronal subsets representing multiple memories. Using the above combination, we show that the expression kinetics, rather than intensity threshold, can be used to identify neuronal ensembles responding to the presentation of two events in vivo. The analytical expression allowed us to segregate the neurons based on their temporal response to one specific behavioural event, thereby improving the ability to detect plasticity related neurons. We image the retrosplenial cortex (RSc) of cfos-GFP transgenic mice to follow the dynamics of cellular changes resulting from contextual fear conditioning behaviour, enabling us to establish a representation of context in RSc at the cellular scale following memory acquisition. Thus, we obtain a general method that distinguishes neurons that took part in multiple temporally separated events by measuring fluorescence of individual neurons in live mice.
Anti-tumor NAMPT inhibitor, KPT-9274, mediates gender-dependent murine anemia and nephrotoxicity by regulating SIRT3-mediated SOD deacetylation
Authors: Mitchell Shaneice , Zhang Pu , Cannon Matthew , Beaver Larry , Lehman Amy , Harrington Bonnie , Sampath Deepa , Byrd John C. , Lapalombella Rosa 
Published: June 2021

AbstractKPT-9274 is a phase 1 first-in-class dual PAK4/NAMPT inhibitor for solid tumor and non-Hodgkin’s lymphoma. It demonstrates pre-clinical efficacy toward a broad spectrum of acute myeloid leukemia (AML) subtypes by inhibiting NAMPT-dependent NAD+ production. NAMPT is the rate-limiting enzyme in the salvage metabolic pathway leading to NAD+ generation. Tumor cells which are deficient in de novo pathway enzyme NAPRT1 are addicted to NAMPT. In clinical trials, treatment with NAMPT inhibitors resulted in dose-limiting toxicities. In order to dissect the mechanism of toxicity, mice were treated with KPT-9274 and resulting toxicities were characterized histopathologically and biochemically. KPT-9274 treatment caused gender-dependent stomach and kidney injuries and anemia. Female mice treated with KPT-9274 had EPO deficiency and associated impaired erythropoiesis. KPT-9274 treatment suppressed SIRT3 expression and concomitantly upregulated acetyl-manganese superoxide dismutase (MnSOD) in IMCD3 cells, providing a mechanistic basis for observed kidney toxicity. Importantly, niacin supplementation mitigated KPT-9274-caused kidney injury and EPO deficiency without affecting its efficacy. Altogether, our study delineated the mechanism of KPT-9274-mediated toxicity and sheds light onto developing strategies to improve the tolerability of this important anti-AML inhibitor.
Bilateral sactosalphinx and congenital adrenal hyperplasia: case report on two rare conditions in two virgin girls
Authors: Scarpa Maria-Grazia , Iaquinto Marianna , Codrich Daniela , Schleef Jürgen 
Published: June 2021

Abstract
Background
Sactosalpinx means a collection of fluid (serum, blood or pus) in the fallopian tube. CAH (Congenital Adrenal Hyperplasia) is a typical 46XX DSD (Disorder of Sex Development) due to a steroidogenic enzymatic defect. Both conditions are rare and can lead to reduced fertility rate.

Case presentation
We describe two post-menarche virgin girls with CAH who were hospitalized for acute abdomen due to laparoscopically confirmed sactosalpinx. Case 1 recovered after conservative management, case 2 after a second-look and bilateral salpingectomy. The first case consisted of right sactosalpinx and previous peritonitis reported; the second one of bilateral symptomatic pyosalpinx and previous vaginal stenosis. Recurrent abdominal pain persisted at follow-up in Case 1: post-operative MRI (Magnetic Resonance Imaging) showed bilateral hydrosapinx that disappeared at a following ultrasound scan control. Follow-up was uneventful 36 months after surgery in Case 2, except for the surgical revision of the vaginal introitus.

Conclusions
CAH-sactosalpinx association is a very rare but not negligible event. We suggest a conservative approach for sactosalpinx if tubal and/or ovary torsion can be excluded. Pyosalpinx is more challenging to treat, but during pediatric age we suggest starting with a conservative approach, especially in patients with CAH who have a potential low fertility rate. Careful gynecological follow-up after menarche is recommended to rule out any further causes of infertility.
Single cell transcriptome atlas of mouse mammary epithelial cells across development
Authors: Pal Bhupinder , Chen Yunshun , Milevskiy Michael J. G. , Vaillant François , Prokopuk Lexie , Dawson Caleb A. , Capaldo Bianca D. , Song Xiaoyu , Jackling Felicity , Timpson Paul , Lindeman Geoffrey J. , Smyth Gordon K. , Visvader Jane E. 
Published: June 2021

Abstract
Background
Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty.

Methods
The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points.

Results
The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states.

Conclusions
This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.
Detection of Crimean-Congo hemorrhagic fever virus in blood-fed Hyalomma ticks collected from Mauritanian livestock
Authors: Schulz A. , Barry Y. , Stoek F. , Pickin M. J. , Ba A. , Chitimia-Dobler L. , Haki M. L. , Doumbia B. A. , Eisenbarth A. , Diambar A. , Bah M. Y. , Eiden M. , Groschup M. H. 
Published: June 2021

Abstract
Background
Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to the genus Orthonairovirus (Nairovididae) and is a (re)emerging tick-borne pathogen. It is endemic in most parts of Africa, Asia and southern Europe, and can cause severe hemorrhagic symptoms in humans, with high fatality rates (5–30%).

Methods
Hyalomma ticks were collected from four different livestock herds (cattle and camels) in Mauritania in 2018. The tick species were determined morphologically and confirmed molecularly by using the cytochrome oxidase 1 gene marker. For the detection of CCHFV, ticks were tested individually by one-step multiplex real-time reverse-transcriptase quantitative polymerase chain reaction. The small segment of all positive samples was sequenced to determine the CCHFV genotype.

Results
In total, 39 of the 1523 ticks (2.56%) collected from 63 cattles and 28 camels tested positive for CCHFV. Three Hyalomma species were identified. Hyalomma rufipes had the largest proportion of positivity (5.67%; 16/282), followed by Hyalomma dromedarii (1.89%; 23/1214). No Hyalomma impeltatum tested positive (0%; 0/21). Positive ticks were found in only six out of 91 host animals. Viral sequence analysis revealed the presence of two different CCHFV lineages (Africa I and Africa III).

Conclusions
In this study, 2.56% of Hyalomma ticks collected from camels and cattle in Mauritania tested positive for CCHFV. However, the true prevalence of CCHFV in unfed ticks may be lower, as a considerable number of ticks may have been passively infected during blood-feeding by co-feeding ticks or due to viremia of the host. The results indicate the need to track the actual area of circulation of this virus.

Graphical Abstract
Mathematical analysis of the effect of portal vein cells on biliary epithelial cell differentiation through the Delta-Notch signaling pathway
Authors: Yoshihara Masaharu , Nishino Teppei , Yadav Manoj Kumar , Kuno Akihiro , Nagata Takeshi , Ando Hiroyasu , Takahashi Satoru 
Published: June 2021

Abstract
Objective
The Delta-Notch signaling pathway induces fine-grained patterns of differentiation from initially homogeneous progenitor cells in many biological contexts, including Drosophila bristle formation, where mathematical modeling reportedly suggests the importance of production rate of the components of this signaling pathway. In contrast, the epithelial differentiation of bile ducts in the developing liver is unique in that it occurs around the portal vein cells, which express extremely high amounts of Delta ligands and act as a disturbance for the amount of Delta ligands in the field by affecting the expression levels of downstream target genes in the cells nearby. In the present study, we mathematically examined the dynamics of the Delta-Notch signaling pathway components in disturbance-driven biliary differentiation, using the model for fine-grained patterns of differentiation.

Results
A portal vein cell induced a high Notch signal in its neighboring cells, which corresponded to epithelial differentiation, depending on the production rates of Delta ligands and Notch receptors. In addition, this epithelial differentiation tended to occur in conditions where fine-grained patterning was reported to be lacking. These results highlighted the potential importance of the stability towards homogeneity determined by the production rates in Delta ligands and Notch receptors, in a disturbance-dependent epithelial differentiation.
Psychosocial burden of type 1 and 2 hereditary angioedema: a single-center Canadian cohort study
Authors: Hews-Girard Julia , Goodyear Marilyn Dawn 
Published: June 2021

Abstract
Background
Hereditary angioedema (HAE) is a rare but serious disorder associated with a multifaceted burden of illness including a high prevalence of psychiatric symptoms and impaired health-related quality of life (HRQoL). Despite recent efforts to clarify the psychosocial implications of HAE, important gaps still remain. The aim of this study was to characterize the psychosocial burden associated with HAE types 1 and 2.

Methods
Type 1 or 2 HAE patients (n  =  17), aged 19 years or older, completed the Depression, Anxiety, Stress Scale (DASS-21) and the DSM-5 cross cutting measures to identify psychiatric symptomatology, Angioedema Quality of Life Questionnaire (AE-QoL) and the Short-Form 36-Item Health Survey version 2 (SF-36v2) to assess disease-related and generic HRQoL respectively, and the Work Productivity and Activity Impairment Questionnaire (WPAI) to measure impact on work productivity and daily activities. Data analyses were conducted using SPSS statistical software (Version 25.0; IBM, Armonk, NY). Descriptive statistics were used to summarize continuous demographics and clinical characteristics and outcomes of interest while frequency distributions were used for categorical variables. T tests were used to compare SF-36v2 domain scores to Canadian norms and sex differences in scale scores.

Results
Depression [DASS-21 score  =  6.8  ±  10.2; n  =  12 (71%)] anxiety [DASS-21 score  =  6.2  ±  8.2; n  =  13 (76%)] and stress [DASS-21 score  =  10  ±  10.2; n  =  13 (76%)] were prevalent. Other psychiatric symptoms warranting inquiry included mania (n  =  14, 82.4%), anger (n  =  14, 82.4%), sleep disturbances (n  =  13, 76.5%), somatic symptoms (n  =  11, 64.7%) and impaired personality functioning (n  =  9, 52.9%). Mean AE-QoL score was 39  ±  18.2. Mean SF-36v2 domain scores were significantly lower than Canadian normative data for the entire sample (p  <  0.05). Impairment in work productivity was minimal; mean activity impairment was 20.6%  ±  21.1% [n  =  11 (64.7%)]. Female participants reported significantly greater HAE-related stress [DASS; t(15)  =  − 2.2, p  =  0.04], greater HAE-related fears [AEQoL; t(5.6)  =   − 2.7, p  =  0.04), and lower SF-36v2 domain scores than male patients.

Conclusions
Study findings offer specific, valuable insight into the psychosocial burden of HAE with the potential to improve clinical management of HAE. Best practices for effective management of HAE should include providing holistic care to address the psychosocial and mental health of HAE patients.
Double overexpression of miR-19a and miR-20a in induced pluripotent stem cell-derived mesenchymal stem cells effectively preserves the left ventricular function in dilated cardiomyopathic rat
Authors: Sheu Jiunn-Jye , Chai Han-Tan , Sung Pei-Hsun , Chiang John Y. , Huang Tien-Hung , Shao Pei-Lin , Wu Shun-Cheng , Yip Hon-Kan 
Published: June 2021

Abstract
Background
This study tested the hypothesis that double overexpression of miR-19a and miR-20a (dOex-mIRs) in human induced pluripotent stem cell (iPS)-derived mesenchymal stem cells (MSCs) effectively preserved left ventricular ejection fraction (LVEF) in dilated cardiomyopathy (DCM) (i.e., induced by doxorubicin) rat.

Methods and results
In vitro study was categorized into groups G1 (iPS-MSC), G2 (iPS-MSCdOex-mIRs), G3 (iPS-MSC + H2O2/100uM), and G4 (iPS-MSCdOex-mIRs + H2O2/100uM). The in vitro results showed the cell viability was significantly lower in G3 than in G1 and G2, and that was reversed in G4 but it showed no difference between G1/G2 at time points of 6 h/24 h/48 h, whereas the flow cytometry of intra-cellular/mitochondrial oxidative stress (DCFA/mitoSOX) and protein expressions of mitochondrial-damaged (cytosolic-cytochrome-C/DRP1/Cyclophilin-D), oxidative-stress (NOX-1/NOX2), apoptotic (cleaved-caspase-3/PARP), fibrotic (p-Smad3/TGF-ß), and autophagic (ratio of LC3B-II/LC3BI) biomarkers exhibited an opposite pattern of cell-proliferation rate (all p< 0.001). Adult-male SD rats (n=32) were equally divided into groups 1 (sham-operated control), 2 (DCM), 3 (DCM + iPS-MSCs/1.2 × 106 cells/administered by post-28 day’s DCM induction), and 4 (DCM + iPS-MSCdOex-mIRs/1.2 × 106 cells/administered by post-28 day’s DCM induction) and euthanized by day 60 after DCM induction. LV myocardium protein expressions of oxidative-stress signaling (p22-phox/NOX-1/NOX-2/ASK1/p-MMK4,7/p-JNK1,2/p-cJUN), upstream (TLR-4/MAL/MyD88/TRIF/TRAM/ TFRA6/IKKα/ß/NF-κB) and downstream (TNF-α/IL-1ß/MMP-9) inflammatory signalings, apoptotic (cleaved-PARP/mitochondrial-Bax), fibrotic (Smad3/TGF-ß), mitochondrial-damaged (cytosolic-cytochrome-C/DRP1/cyclophilin-D), and autophagic (beclin1/Atg5) biomarkers were highest in group 2, lowest in group 1 and significantly lower in group 4 than in group 3, whereas the LVEF exhibited an opposite pattern of oxidative stress (all p< 0.0001).

Conclusion
iPS-MSCdOex-mIRs therapy was superior to iPS-MSC therapy for preserving LV function in DCM rat.
Pooled estimate of vitamin D deficiency among pregnant women in India: a systematic review and meta-analysis
Authors: Jeyakumar Angeline , Shinde Vidhya , Ravindran Reshma 
Published: June 2021

Abstract
Background
Vitamin D deficiency among pregnant women is a public health concern globally. In India, individual studies report high prevalence. However, lack of national data masks the true burden. This work determined the pooled prevalence of vitamin D deficiency among pregnant women in India through a systematic review of literature and meta-analysis.

Methods
Three different search engines yielded 15 eligible articles. Study quality was assessed by 10 different criteria and summary of study quality was categorized as per Cochrane standards. Meta-analysis was performed to estimate pooled prevalence of vitamin D deficiency among healthy pregnant women and heterogeneity among selected studies. A sample of n = 4088 was used to study the pooled prevalence among pregnant women.

Results
The random effects combined estimate was 32.35% (95% CI, (12.58–117.48). High heterogeneity (tau2 = 0.39, I2 = 100%) and high risk of bias was observed among the selected studies. The test for overall effect was observed to be z = 2.54(P = 0.01).

Conclusion
Pooled estimate > 30% emphasizes the need for screening through antenatal care services and initiate preventive measures to address the deficiency.
α-Terpineol fumigation alleviates negative plant-soil feedbacks of Panax notoginseng via suppressing Ascomycota and enriching antagonistic bacteria
Authors: Ye Chen , Liu Yixiang , Zhang Junxing , Li Tianyao , Zhang Yijie , Guo Cunwu , Yang Min , He Xiahong , Zhu Youyong , Huang Huichuan , Zhu Shusheng 
Published: June 2021

AbstractThe accumulation of soil-borne pathogens is the main driving factor of negative plant-soil feedbacks (NPSFs), which seriously restricts the sustainable development of agriculture. Using natural volatile organic compounds (VOCs) from plants or microorganisms as biofumigants is an emerging strategy to alleviate NPSFs in an environmentally-friendly way. Here, we identified α-terpineol from the VOCs of pine needles, confirmed the ability of α-terpineol fumigation in alleviating the NPSF of Panax notoginseng via significantly reducing seed decay rate, and also deciphered the underlying mechanism by which the soil microbial community is modified. α-Terpineol fumigation could suppress culturable fungi but enrich bacteria in a dose-dependent manner. Network analysis with high-throughput sequencing data revealed that α-terpineol could distinctly modify both fungal and bacterial communities. In detail, α-terpineol significantly suppressed the relative abundance of Ascomycota from 64.04 to 32.26%, but enriched the relative abundance of Proteobacteria, Acidobacteria and Actinobacteria. Subnetwork analysis further demonstrated that α-terpineol could directly or indirectly suppress fungal pathogens and enrich plant growth-promoting rhizobacteria (PGPRs). In vitro fumigation and co-culture experiments with culturable isolates validated these findings. The antagonism between beneficial bacteria and pathogens, and the synergistic growth promotion among α-terpineol-enriched bacteria might be involved in soil microbial community assembly. In summary, α-terpineol fumigation could directly or indirectly modify the soil microbial community to alleviate NPSFs, especially by suppressing fungal pathogens and enriching beneficial bacteria. This study suggests that VOCs from natural products are worth developing as biofumigants due to their multiple functions in modifying the soil microbial community.