bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripartum infection at cesarean delivery may be related to uterine rupture during a subsequent trial of labor
Authors: Yaniv Rina Tamir , Farladansky-Gershnabel Sivan , Gluska Hadar , Daykan Yair , Maor Gil Shechter , Schonman Ron , Biron-Shental Tal
Published: July 2022

Background: Uterine rupture or dehiscence during trial of labor after cesarean is a cause of great concern for both parturitions and physicians. Although the risk-factors for uterine rupture are well-established, surgical site infection in the first cesarian-section has not been investigated in depth.Aim: To evaluate the relation between peripartum infection after caesarean delivery to uterine dehiscence or rupture at the subsequent delivery.Methods: A retrospective case-control study. The study group included women with a prior caesarean delivery and proven dehiscence, or uterine rupture diagnosed during their subsequent delivery. The control group were women who had a successful vaginal birth after cesarean section without evidence of dehiscence or uterine rupture. We compared the rate of infection during the cesarean delivery between the two groups. Findings: A total of 168 women were included, 71 with uterine rupture or dehiscence and 97 with successful vaginal birth after cesarean section. The rate of peripartum infection at the first caesarean delivery was significantly higher in the study group compared to the control group (22.2% vs. 8.2%,p=0.013). Endometritis had the highest correlation to uterine rupture (9.8% vs. 0%,p=0.02)Discussion: Peripartum infection in the first caesarean delivery, may be an independent risk-factor for uterine rupture in a subsequent delivery. Compared to other infections, endometritis may pose the greatest risk for uterine rupture or dehiscence.Conclusion: when consulting with a patient on repeat cesarean section vs. trial of labor after cesarian, endometritis after the previous surgery should be included among the considerations, along with other traditional risk-factors.
Preparation of PET/PDMS/Collagen nanofibrous membrane embedded in a microfluidic device for cell culture
Authors: Eslam Houra Mobaleghol , Tabatabaei Seyed Nasrollah , Fayazbakhsh Farzaneh , Salami Seyed Alireza , Ghanbari Hossein
Published: July 2022

Electrospun nanofibers can be used as membranes for cell culture applications. In addition to their high performance and cost-effectiveness, nanofibers can be made from a variety of polymers and utilized in microfluidic devices as separators, filters, and for biological assessments. In this paper, we have employed a two-pump technique to prepare a hybrid nanofiber-based membrane with a biocompatible polyethylene terephthalate (PET), polydimethylsiloxane (PDMS), and collagen. The introduction of collagen creates a suitable substrate for cell attachment and decreased hydrophobicity. To sustain collagen on the fibers, the membranes were treated with glutaraldehyde vapor and then detoxified. The membrane integrity and structure were evaluated using SEM, AFM, contact angle analyzer, FT-IR, and tensile apparatus. In addition, cell attachment capabilities and cytocompatibility were examined using SEM and AlamarBlue, respectively. The membrane was cased in a PDMS-based microfluidic device consisting of upper and lower channels. Our findings suggest that the incorporation of PET and PDMS provides a superior bonding capability and prevents unwanted leakage. Then, Human Umbilical Vein Endothelial Cells (HUVECs) were cultured on both sides of the proposed membrane inside the device. To simulate the dynamic environment and induce cellular shear stress, the culture medium was flown through the channel and the conditions were kept overnight inside an incubator. Cellular staining (Acridine Orange and Propidium Iodide, as well as DAPI) and further evaluation of cellular adhesion suggest that cells were well attached and viable inside the microfluidic device. The proposed membrane can be employed in fabrication of various biological barriers on-a-chip for the purpose of screening drugs, examining the effects of nanomaterials, and creation of in-vitro disease models.
Integrated effect of fillers, monomers and bioactive ingredients on color stability of resin composites
Authors: Costa Mylena Proença , Jacomine Juliana Carvalho , Mosquim Victor , Santin Daniella Cristo , Agulhari Maria Angélica Silvério , Mondelli Rafael Francisco Lia , Honório Heitor Marques , Wang Linda
Published: July 2022

Objectives: Resin composites containing surface pre-reacted glass (S-PRG) were introduced to reduce demineralization and improve remineralization of the tooth structure. However, water diffusion within the material is necessary for its action, which can impair its overall physical-mechanical properties over time, including the color stability. This study aimed to evaluate the color stability and related degree of conversion (DC) of four resin composites.Materials and Methods: Discs (n=5/group) of microhybrid, nanofilled, nanohybrid, and S-PRG-based nanohybrid composites with two opacities were prepared. Color (CIELab and CIEDE2000) was evaluated after aging in grape juice. The DC was analyzed by using Fourier Transform Infrared Spectroscopy before and after photopolymerization. Data were statistically analyzed by using two-way analysis of variance and post-hoc least significant difference tests (P<.05).Results: In the color stabilityanalysis, the interaction between filler type and opacity was significant. S-PRG influenced color stability and DC.Conclusions: The nanohybrid resin composite presented favorable color stability and a greater DC, which is likely related to its organic content. S-PRG based nanohybrid resins require caution since its bioactive benefits depends on interaction with the environment that can be prone to impair color stability.Clinical Relevance: As color stability is mandatoryin specific regions, staining can jeopardize the esthetics of a resin composite. The use of nanohybrid composites with no or reduced BisGMA content and diluents may be more appropriate in these areas. Since materials containing S-PRG can offer relevant benefits, professionals need to balance their higher susceptibility to staining favoring other relevant properties.
Clinical Manifestations and Prognosis of Unexpected Uterine Sarcoma
Authors: Cheng Guangyan , Hu Yuanjing , Gong Yingying
Published: July 2022

Background
To investigate the clinical manifestations and treatment of unexpected uterine sarcoma (UUS) and thus to improve the preoperative diagnostic rate and to reduce the risk of unexpected tumor dissemination.
Methods
The study retrospectively analyzed 45 UUS patients and 21 patients of preoperatively diagnosed uterine sarcoma (PDUS). We used the χ2 and T tests to assess the incidence and clinical features of patients. The Kaplan-Meier method was used to calculated disease related survival.
Results
The incidence of UUS is (45/6625) 0.67%.The incidence of UUS in patients undergoing total hysterectomy was higher than that in patients undergoing tumor resection (P < 0.001); The age of UUS is younger than that of PDUS (P = 0.046); The differences in menopausal status and primary complaints between the two groups are not statistically significant (P > 0.05).PDUS group had more patients with Stage II and III sarcomas than that of UUS group(P < 0.001); Duration of symptoms in PDUS group was longer than that of UUS group( P = 0.033). The 5-year overall survival(OS) rate of UUS group(77.7%) is higher than that of PDUS group(46.3% ) (P < 0.001).
Conclusions
The incidence of UUS is low. UUS has younger age of onset, shorter history of disease, earlier clinical stage, and better prognosis.
Relations disentanglement, the potential risk assessment and source identification of heavy metals in the sediment of the Changzhao Reservoir, Zhejiang Province
Authors: Lu Yumiao , Zeng Yanyan , Wang Wei
Published: July 2022

Heavy metal contamination in the water body is a distinctly important issue for the water security of the reservoir. 114 sediment samples of Changzhao reservoir were collected to investigate the spatial (horizontal and vertical) distribution characteristics, risks assessment, and source identification of heavy metals. Results suggested that the concentrations of heavy metals at the surface layer sediment were 0.02-39726.14 mg/kg, which were slightly higher compared with that at the middle and bottom layer sediment. The concentration of Zn and Cu was significantly different in the sediment (P ≤ 0.01). The concentration of TOC in the sediment was mostly influenced by the pH and Cd in the sediment. The proportion of “uncontaminated to moderately contaminated” for Cd, Zn, and As in the surface layer was 84.21%, 47.37%, and 34.21%, which indicated that the quality of sediment was mostly impacted by Cd, Zn, and As. The agricultural non-point source pollution is dominant according to source identification method of APCS-MLR. Overall, this paper presents the distribution and conversion trends of heavy metals and provides the insights of the reservoir protection in the future work.
Classification of breast lesions on DCE-MRI Data Using Fine-tuned MobileNet
Authors: Meng Mingzhu , Zhang Ming , He Guangyuan , Shen Dong , Wang Long
Published: July 2022

Background
Early and rapid diagnosis of breast cancer is very important. Traditional method for detecting and diagnosing breast cancer may lead to a false positive or negative result. Presently, most of the deep learning models used in breast cancer detection prevents their use on mobile phones or low-configuration devices. This study intends to evaluate the capability of MobileNetV1 and MobileNetV2 and their fine-tuned models to differentiate malignant from benign lesions in breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Methods
The diagnostic efficiencies of MobileNetV1_False(V1_False), MobileNetV1_True (V1_True), MobileNetV2_False(V2_False) and MobileNetV2_True(V2_True) were tested and evaluated under the same program architecture and dataset (2124 images in benign group and 2226 images in malignant group). A relatively optimal model was selected (with the highest accuracy in the training set and test set), and two fine-tuning strategies (S0 and S1) were used to modify it. The accuracy (Ac) of different models in the training and test sets, as well as the precision (Pr), recall rate (Rc), f1 score(f1) and area under the receiver operating characteristic curve (AUC), were taken as the performance indicators.
Results
The Ac of V1_True (0.9815) was higher than those of V1_False (0.9749), V2_False (0.9672) and V2_True (0.9699). Overfitting were observed in all models. Pr, Rc, f1 and AUC of V1_True were 0.79,0.73,0.74 and 0.74, respectively, they were higher than those of V1_False (0.77,0.73,0.73 and 0.73), V2_False (0.74,0.65,0.66 and 0.65) and V2_True (0.76,0.67,0.68 and 0.67).
Conclusion
The MobileNetV1_True model can differentiate between benign and malignant breast lesions on breast DCE-MRI, and has the potential to be deployed on an embedded mobile platform. Future work is necessary to improve the generalization capability of the proposed method.
Energy - Growth Hypothesis: Testing Non-Linearity by considering Production Function Approach for Spanish Economy
Authors: Hassan Muhammad Shahid , Mahmood Haider , Yousaf Saba
Published: July 2022

Targeting output growth is among one the prime concern of any economy in both developing and developed worlds. Energy utilization and exports are important drivers that would help in boosting production activities in any economy. Therefore, beyond labor force and capital formation, exports and energy utilization can be among the important inputs for accelerating economic growth in any economy. This research is conducted to investigate the linear impact of exports and the non-linear effect of energy consumption on economic growth considering the production function approach in the Spanish economy. After considering the ARDL bounds test for a period from 1980–2019, the study provides evidence of inverted-U shaped effects of energy consumption on economic growth. The findings also expose that exports, labor force and capital formation significantly accelerate economic growth in Spain. These findings are consistent with the diagnostics applied in the study. This research proposes that energy consumption should not be increased beyond a certain threshold for reaping positive fruits for economic growth. Beyond that cutoff, it will become harmful to economic growth. Policy advisors may consider exports to target economic growth in Spain as it helps in expanding production activities in the Spanish economy.JEL Codes: O44; F62, C22
Signature of Sinking Streams on Calcarenite Rock Study Using Geophysical and Geochemical Investigation in Ayankulam Area, South Tamilnadu, India
Authors: A Antony Ravindran , A Antony Alosanai Promilton , J Vinoth Kingston , S Richard Abishek , K Aswin S , R Abinaya
Published: July 2022

Ayankulam is the trending one recently during the 2021 monsoon of India. Despite a large supply of water from the Nambiar canal for five days, the village's fabled well was unable to fill. When the district collector and IIT team came, they assessed the community and noted that the wells' geological makeup was classified as a karst formation (as per e-news sited in The New Indian Express dated 03/12/2021). There might be some sinking stream that might link this well. Karst topography of calcarenite rocks is the reason for groundwater movement beneath the subsurface for not filling the well. One of the most crucial elements of nature's water supplies is groundwater. Groundwater has to be explored more thoroughly since demand for it rises as the population grows. To determine the existence of usable groundwater for irrigation purposes in the study area Geophysical (Azimuthal square array method and Magnetotelluric method) and Geochemical investigations were done. The Azimuthal Square array method covers 360º coverage of subsurface resulting in fracture orientation of rock to determine the weak/strong zones in different rock types. The Magnetotelluric method scans the subsurface rock and provides information about Geological formation, Weak zone where water oozes out, depth and movement of groundwater. Water samples were collected in and around the “Sinking Stream” origin well and its associated open and tube wells from the study area. The combination of Square Array, MT, Water quality, and quantity study focuses on the Trapped Aquifer system of sinking streams in all water bodies and wells. The movement of groundwater seems to be increasing in Seashore areas such as Uvari and Karikovil are identified relating its water samples from deep bore wells quality and sinking stream water quality. The heavy rainfall and hydrostatic pressure of predominant rock on eroded Calcarenite lime formation create water “Dry fall out” resulting in Sinking streams in the Ayankulam area.
Drug Coated Balloon Improves Outcomes of Sub-optimal Supera Deployment in the Intermediate Term
Authors: Krishnan Prakash , Sharma Raman , Avadhani Sriya , Tarricone Arthur , Gee Allen , Farhan Serdar , Kamran Haroon , Kini Annapoorna , Sharma Samin
Published: July 2022

Background: Sub-Optimal deployment of Self expanding interwoven stents (Supera) has been shown to increase the rate of Clinically Driven Target Lesion Revascularization (CD-TLR). Meanwhile, drug eluting balloons (DCB) have been shown to reduce CD-TLR in the femoral-popliteal segment in de- novo and restenotic lesions. However, the clinical effects of adjunctive DCB in nominal, compressed, and elongated Supera has not been widely studied . Objectives: The purpose of this study is to assess the outcomes of clinically driven re-intervention, major amputations, and mortality in relation to the adjunctive use of DCB in different deployment conditions (nominal, compressed, elongated) of the Supera stent. Methods: Patient chart data was collected at a single center hospital between March 2015 to May 2020. All patients were adults (≥18 years old) and were treated with at least one (≥1) Supera stent. Deployment status was extrapolated from anonymized angiograms. The primary endpoint of this study was CD-TLR. Secondary endpoints included amputation and mortality rates associated with each deployment condition. Results: A total of 670 limbs were treated and patients were followed for 36 months. Nominal stent deployment was observed in 337 limbs, followed by elongated condition (n=176), then by compressed conditions (n=159). CD-TLR was observed most frequently with elongated deployment. Adjunctive drug coated balloon use showed a protective effect regardless of deployment status; O.R=0.44 (CI: 0.30-0.66, p<.05). Conclusions: Adjunctive DCB with Supera deployment was found to provide a protective effect in reintervention regardless of deployment status.
PAX9 regulates periodontal ligament stem cell-like differentiation of human induced pluripotent stem cells
Authors: Sugiura Risa , Hamano Sayuri , Tomokiyo Atsushi , Hasegawa Daigaku , Yoshida Shinichiro , Sugii Hideki , Fujino Shoko , Adachi Orie , Kadowaki Masataka , Yamashita Daiki , Maeda Hidefumi
Published: July 2022

Periodontal ligament stem cells (PDLSCs) play central roles in periodontal ligament (PDL) tissue homeostasis, repair, and regeneration. Previously, we established a protocol to differentiate human induced pluripotent stem cell-derived neural crest-like cells (iNCs) into PDLSC-like cells (iPDLSCs) using human PDL cell-derived extracellular matrix (ECM). However it remained unclear what factors principally regulate the differentiation of iNCs into iPDLSCs. In this study, we aimed to identify the transcription factor regulating production of human PDL cell-derived ECM, which is responsible for the generation of iPDLSCs. We cultured iNCs on two human PDL cell lines (HPDLC-3S and HPDLC-3U) and human dermal fibroblasts (HDF). iNCs cultured on HPDLC-3U showed higher iPDLSC-associated gene expression and mesenchymal differentiation capacity than cells cultured on HDF or HPDLC-3S. The transcription factor PAX9 was highly expressed in HPDLC-3U compared with HDF and HPDLC-3S. iNCs cultured on siPAX9-transfected HPDLC-3U displayed downregulation of iPDLSC-associated marker expression and adipocytic differentiation capacity relative to controls. Our findings suggest that PAX9 is one of the transcription factors regulating ECM production in human PDL cells, which is responsible for the differentiation of iNCs into iPDLSCs.
Hand Pose Estimation Based on Improved NSRM Network
Authors: Yang Shiqiang , He Duo , Li Qi , Wang Jinhua , Li Dexin
Published: July 2022

Hand pose estimation is the basis of dynamic gesture recognition. In vision-based hand pose estimation, the joints of the human hand are highly flexible, and problems such as local similarity and severe occlusion have great influence on the estimation of hand posture. In order to identify the complicated hand posture, the structural relationship between the hand nodes is established, more accurate hand pose estimation can be achieved through the improved Nonparametric Structure Regularization Machine (NSRM) in this paper. Based on the NSRM network, the backbone network is replaced by New High-Resolution Net (NHRNet), then the input and output channels of some convolutional layers are reduced. Finally, a public dataset is used to conduct the hand pose estimation experiments. The experimental results show that the optimized NSRM network has higher accuracy and faster recognition speed for hand pose estimation.
Contact tracing reveals community transmission of COVID-19 in New York City
Authors: Pei Sen , Kandula Sasikiran , Vega Jaime Cascante , Yang Wan , Foerster Steffen , Thompson Corinne , Baumgartner Jennifer , Ahuja Shama , Blaney Kathleen , Varma Jay , Long Theodore , Shaman Jeffrey
Published: July 2022

Understanding SARS-CoV-2 transmission within and among communities is critical for tailoring public health policies to local context. However, analysis of community transmission is challenging due to a lack of high-resolution surveillance and testing data. Here, using contact tracing records for 644,029 cases and their contacts in New York City during the second pandemic wave, we provide a detailed characterization of the operational performance of contact tracing and reconstruct exposure and transmission networks at individual and ZIP code scales. We find considerable heterogeneity in reported close contacts and secondary infections and evidence of extensive transmission across ZIP code areas. Our analysis reveals the spatial pattern of SARS-CoV-2 spread and communities that are tightly interconnected by exposure and transmission. We find that higher vaccination coverage and reduced numbers of visitors to points-of-interest are associated with fewer within- and cross-ZIP code transmission events, highlighting potential measures for curtailing SARS-CoV-2 spread in urban settings.
A 2D Fragment-Assisted Protein Mimetic Approach to Rescue α-Synuclein Aggregation Mediated Early and Post-Disease Parkinson’s Phenotypes
Authors: Kumar Sunil , Stillman Nicholas , Joseph Johnson , Ahmed Jemil , Dohoney Ryan , Ball Tyler , Thomas Alexandra , Fitch Tessa , Donnelly Courtney
Published: July 2022

We have developed a Oligopyridylamide (OP) based 2-Dimensional Fragment-Assisted Structure-based Technique (2D-FAST) to identify potent antagonists of α-Synuclein (αS) aggregation, a process central to Parkinson’s disease (PD). The 2D-FAST utilizes a fragment-based screening of large chemical space in OPs, which led to the identification of NS132 as an antagonist of the multiple facets of αS aggregation. We also identified a better cell permeability analog (NS163) without sacrificing activity. OPs rescue αS aggregation mediated PD phenotypes in muscle cells and dopaminergic (DA) neurons in C. elegans models. OPs prevent the progression of PD phenotypes in a novel post-disease onset PD model.
This is one of the first examples of a synthetic mimetic-based 2D-FAST to identify antagonists of toxic αS self-assembly. We envision that 2D-FAST will have tremendous potential as it is expandable for other oligoamide scaffolds and for a much larger chemical space to identify lead therapeutics for various diseases.
Frailty screening in major cardiac surgical patients. Which tool is better for predicting poor outcomes?
Authors: Tatis Myriel Lopez , Rivera Carlos Amorós , Rodríguez Francisco Javier López , García María Elena Arnaiz , Arévalo-Abascal Ramón Adolfo , Vicente María Teresa Merino , Santos José María González , Varela Ana María Barral
Published: July 2022

Objective
To analyse the relationship between the degree of frailty and the risk of presenting poor short-term outcomes.
Methods
observational cohort study of the population ≥ 70 years of age undergoing elective and high-priority major cardiac surgery at our hospital. A total of 232 consecutive patients were enrolled in Salamanca University Hospital from October 2017-December 2019 This cohort study of 232 patients prospectively compared the results of the FRAIL questionnaire and the Fried Phenotype Criteria (FPC) and retrospectively adapted these tools based on the characteristics and confounding factors found in our sample. The individual items comprising the multi-item scales were then independently analysed using logistic regressions.
Results
Frailty was associated with increased mortality, although the differences were not significant. Standardizing the FPC improved its ability to identify frail patients (p = 0.027). Scores with both original tools were associated with a prolonged postoperative stay (p ≤ 0.05). Additionally, a positive result on the FRAIL questionnaire was associated with a higher number of complications (p = 0.025). In our study, the predictive capacity emerged from specific items: grip strength, gait speed, illness, and resistance. We united these items with the severity of pulmonary hypertension to create a specific frailty scale for cardiac surgery, and the scores were significantly associated with a combined endpoint, containing death, prolonged stay, and/or presenting ≥ 3 complications (p = 0.011).
Conclusions
The results indicated that frailty determined by either of the original tools was associated with worse results after cardiac surgery. Likewise, milder degrees of frailty, which we call pre-frailty, can also anticipate poor outcomes, in some cases. Standardization of the FPC improved its predictive capacity. In our study, we designed a tool for cardiovascular patients that is predictive of poor postoperative outcomes. Adapting frailty tools is necessary to avoid confusion with cardiovascular disease.
Tunable sliding ferroelectricity and magnetoelectric coupling in two-dimensional multiferroic MnSe materials
Authors: Zhao Mingwen , Liu Kehan , Ma Xikui , Xu Shuoke , Li Yangyang
Published: July 2022

Sliding ferroelectricity (SFE) found in two-dimensional (2D) van der Waals (vdW) materials, such as BN and transition-metal dichalcogenides bilayers, open an avenue for 2D ferroelectric materials. The multiferroic coupling in 2D SFE materials is expected to bring about new concepts for spintronic memory devices. Here, using first-principles calculations, we demonstrate that the recently-synthesized MnSe multilayers [ACS Nano 15, 13794 (2021)] have large reversible out-of-plane electric polarization (~10.6 pC/m) and moderate interlayer sliding barriers superior to the existing 2D SFE materials. More interestingly, the intrinsic electric polarization is also accompanied by nonzero net magnetic moments whose direction is dependent on the electric polarization direction and thus can be switched by interlayer sliding. Additionally, both the SFE and magnetoelectric coupling can be effectively regulated by external strain and/or hole doping. Our findings suggest the potential of MnSe multilayers in 2D multiferroic and spintronic applications.
Silver lining to a climate crisis: multiple prospects for alleviating crop waterlogging under future climates
Authors: Liu Ke , Harrison Matthew , Yan Haoliang , Liu De Li , Meinke Holger , Hoogenboom Gerrit , Wang Bin , Peng Bin , Guan Kaiyu , Jaegermeyr Jonas , Wang Enli , Zhang Feng , Yin Xiaogang , Archontoulis Sotirios , Nie Lixiao , Badea Ana , Man Jianguo , Wallach D , Zhao Jin , Benjumea Ana , Zhang Yunbo , Wang Weilu , Fahad Shah , Tao Fulu , ZHANG Z , Rötter Reimund , Yuan Youlu , Zhu Min , Dai Panhong , Nie Jiangwen , Yang Yadong , Tian Xiaohai , Zhou Meixue
Published: July 2022

Extreme weather events threaten food security, yet global assessments of crop waterlogging are rare. Here, we make three important contributions to the literature. First, we develop a paradigm that distils common stress patterns across environments, genotypes and climate horizons. Second, we embed improved process-based understanding into a contemporary farming systems model to discern changes in global crop waterlogging under future climates. Third, we elicit viable systems adaptations to waterlogging. Using projections from 27 global circulation models, we show that yield penalties caused by waterlogging increased from 3–11% historically to 10–20% by 2080. Altering sowing time and adopting waterlogging tolerant genotypes reduced yield penalties by up to 18%, while earlier sowing of winter genotypes alleviated waterlogging risk by 8%. We show that future stress patterns caused by waterlogging are likely to be similar to those occurring historically, suggesting that adaptations for future climates could be successfully designed using current stress patterns.
Hsa_circ_0002980 prevents proliferation, migration, invasion, and epithelial-mesenchymal transition of liver cancer cells through microRNA-1303/cell adhesion molecule 2 axis
Authors: Chen Wenxiang , Li Yiming , He Jun , Wang Yu , Liang Junjie , Yu Qiangfeng , Zhou Jianyin
Published: July 2022

Background: Liver cancer (LC) is a hackneyed malignant tumor. And the dysregulation of circular RNA (circRNA) is relevant to the metastasis of LC. Hsa_circ_0002980 was unexpectedly found to be up-regulated in LC tissues, while its specific function remains unclear. Methods: Hsa_circ_0002980 expression was first confirmed by RT-qPCR. Then the impacts of circ_0002980 on the proliferation, metastasis, and EMT-related proteins of LC cells through clone formation, Flow cytometer, Transwell, and western blot. Besides, the relationship between circ_0002980 and miR-1303 or miR-1303 and CADM2 was analyzed by dual luciferase reporter assay, and the influences of these three genes on LC cell progression were determined through the rescued experiments.Results: Has_circ_0002980 expression was lowered in LC. And circ_0002980 overexpression had obvious inhibitory actions on the proliferation, migration, invasion, and EMT of LC cells. Besides, circ_0002980 specifically binds to miR-1303, the acceleration effect of miR-1303 overexpression on LC progression can be partially reversed by circ_0002980. Moreover, miR-1303 can also target CADM2, and CADM2-mediated prevention also could be attenuated by miR-1303 overexpression.Conclusions: In LC cells, circ_0002980 upregulation prevents cell proliferation, metastasis and EMT by affecting miR-1303/CADM2 axis. Therefore, we suggest that this axis may be a novel therapeutic target for LC.
Hetero-Diels-Alder Reaction Coupled with Semipinacol Rearrangement for the Biosynthesis of Structurally Diversified Notoamides
Authors: Liu Shuai , Xu Wenqiang , Cao Ming-Ming , Tang Man-Cheng , Chang Yao-Wen , Lei Xin-Xiang , Tang Hong-Yu , Yuan Chunmao , Yang Jun-Bo , Zuo Zhili , Zeng Ying , Shen Yuemao , Di Ying-Tong , Wu Yun-dong , Hao Xiaojiang
Published: July 2022

Fungal prenylated indole alkaloids are a group of biologically diverse natural products featuring a bicyclo[2.2.2]diazaoctane ring system and densely functionalized indole-derived units. However, the detailed mechanisms underlying the assembly of the 2H-pyran moiety and stereochemically diversified bicyclo[2.2.2]diazaoctane systems remain uncharacterized. Herein, we report that the spe gene cluster governs the biosynthesis of notoamide B and its congeners (1–6) in Aspergillus ochraceus. In particular, SpeE, a flavoprotein monooxygenase (FPMO), catalyzed the formation of the 2H-pyran moiety; SpeF and SpeG worked together to produce active unstable intermediates, the 17S-hydroxy-2R,3R-epoxide of notoamide E (16), followed by the sequential inverse electronically demanded hetero-Diels-Alder (IEDHDA) reaction and semipinacol rearrangement (SPR) to construct the bicyclo[2.2.2]diazaoctane core and spiro-oxindole moiety in 1–6. Furthermore, enzymatic and nonenzymatic HDA and SPR steps were distinguished via chemical computations and metabolite profile analysis.
Application of the 2-deoxyglucose scaffold as a new chiral probe for elucidation of the absolute configuration of secondary alcohols
Authors: Trocka Alicja , Szwarc-Karabyka Katarzyna , Makowiec Sławomir , Laskowski Tomasz
Published: July 2022

Herein, we present the application of 2-deoxy-D-glucose derivatives as chiral probes for elucidation of the absolute configuration of chiral secondary alcohols. The probes are attached to the studied molecules via glycosylation reaction and the resulting products are examined by a set of standard 2D NMR experiments. The absolute configuration of an oxymethine carbon atom binding the probe is established on a basis of a set of diagnostic dipolar couplings (NOEs/ROEs). These correlations may be considered diagnostic due to a pronounced lack of conformational freedom of the formed glycosidic linkage. While the chance for an observation of the diagnostic signals is the highest when the resulting glycoside in an α-anomer. 2-deoxy-D-glucose was selected as a probe of choice since is it known to strongly prefer the formation of α-glycosides
Comprehensive proteome and phosphoproteome analysis reveals the protein characterization of invasive ductal and lobular carcinoma with specific molecular subgroup
Authors: Yang Ganglong , Zuo Chenyang , Fu Fangmeng , Gao Xiao-Dong , Lin Yuxiang , Wen Piaopiao , Chen Wenyan , Zhang Chairui , Xiao Han , Jiang Meichen , Zhou Xiaoman , Fujita Morihisa
Published: July 2022

Background
Breast cancer is one of the most frequently occurring malignant cancers worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histological subtypes of breast cancer. The prognosis and survival of the two subtypes were significantly different even with specific molecular subgroup. In this study, we aimed to deeply explore molecular characteristics and the relationship between IDC and ILC subtypes in same molecular subgroup of breast cancer using comprehensive proteomics and phosphoproteomics analysis.
Methods
Cancer tissues and noncancerous adjacent tissues (NATs) with the luminal subtype (ER- and PR-positive, HER2-negative) were obtained from paired IDC and ILC patients respectively. Label-free quantitative proteomics and phosphoproteomics methods were used to detect differentially expressed proteins and the phosphorylation status between 10 paired breast cancer and NATs. Then, bioinformatics analysis was performed to explore the difference between IDC and ILC subtypes, including the difference in protein expression levels and the degree of phosphorylation. Meanwhile, Kinase-Substrate Enrichment Analysis (KSEA) revealed the activation difference of kinases and their substrates between IDC and ILC.
Results
A total of 5,044 high-confidence proteins and 3,808 phosphoproteins were identified from breast cancer tissues. The protein phosphorylation level in ILC tissues was higher than that in IDC tissues. From the quantitative analysis of 1259 proteins and 560 phosphoproteins with high patient coverage, Histone H1.10, Complement C4-B and Crk-like protein were found to be significantly differentially expressed in the two subtype tissues from the proteomics analysis. Moreover, the differences in protein expression of Septin-2, Septin-9, Heterogeneous nuclear ribonucleoprotein A1 and Kinectin and their phosphorylation clearly distinguished IDC from ILC. In addition, differentially expressed proteins and differentially expressed phosphoproteins in IDC were primarily related to energy metabolism and MAPK pathway, while ILC subtypes were more closely involved in the AMPK and p53/p21 pathways. Furthermore, the kinomes from IDC were primarily significantly activated in the CMGC (Cyclin-dependent kinases, Mitogen-activated protein kinases, Glycogen synthase kinases and CDK-like kinases) groups.
Conclusions
Our research provides insights into the molecular characterization of IDC and ILC and contributes to discovering novel targets for further drug development and targeted treatment.
Effects of Nanopillars and Surface Coating on Dynamic Traction Force
Authors: Pang Stella , Cheng Yijun
Published: July 2022

Extracellular matrix serves as a structural support for cells and provides biophysical and biochemical cues for cell migration. Topography, material, and surface energy can regulate cell migration behaviors. The responses of MC3T3-E1 cells, including migration speed, morphology, and spreading on various platform surfaces were investigated. Polydimethylsiloxane (PDMS) micropost sensing platforms with nanopillars, silicon oxide, and titanium oxide on top of the microposts were fabricated, and dynamic cell traction force during migration was monitored. The relationships between various platform surfaces, migration behaviors, and cell traction force were studied. Compared with flat PDMS surface, cells on silicon oxide and titanium oxide surfaces showed reduced mobility, less elongation, and larger cell area. On the other hand, cells on nanopillar surface showed more elongation, higher migration speed, and smaller cell area compared to cells on silicon oxide and titanium oxide surfaces. MC3T3-E1 cells on microposts with nanopillars exerted larger traction force than those on microposts without nanopillars, as well as having more extensions of filopodia and long protrusions. Understanding the relationships between platform surface condition, migration behavior, and cell traction force can potentially lead to better control of cell migration in biomaterials capable of promoting tissue repair and regeneration.
A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients. GEMCAD 1602 study
Authors: Español-Rego Marta , Fernandez-Martos Carlos , Elez Elena , Foguet Carles , Pedrosa Leire , Rodriguez Núria , Ruiz-Casado Ana , Pineda Estela , Cid Joan , Cabezon Raquel , Oliveres Helena , Lozano Miquel , Ginés Angels , Garcia-Criado Angeles , Ayuso Juan Ramon , Pages Mario , Cuatrecasas Miriam , Torres Ferran , Thomson Timothy , Cascante Marta , Benitez-Ribas Daniel , Maurel Joan
Published: July 2022

Background: Immune check-point blockade (ICB) has shown clinical benefit in mismatch repair-deficient/microsatellite instability high metastatic colorectal cancer (mCRC) but not in mismatch repair-proficient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination has the potential to achieve synergistic effects. Methods: This was a Phase I/II multicentric study with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor effects of Avelumab plus ADC vaccine in heavily pre-treated MSS mCRC patients. Primary objective was to determine the maximum tolerated dose and the efficacy of the combination. The primary end-point was 40% progression-free survival at 6 months with a 2 Simon Stage. Results: A total of 28 patients were screened and 19 pts were included. Combined therapy was safe and well tolerated. An interim analysis (Simon design first-stage) recommended early termination because only 2/19 (11%) patients were disease free at 6 months. Median PFS was 3.1 months [2.1 – 5.3 months] and overall survival was 12.2 months [3.2 – 23.2 months]. Stimulation of immune system was observed in vitro but not clinically. The evaluation of basal RNA-seq noted significant changes between pre and post-therapy liver biopsies related to lipid metabolism and transport, inflammation and oxidative stress pathways. Conclusions: The combination of Avelumab plus ADC vaccine is safe and well tolerated but exhibited modest clinical activity. Our study describes, for the first-time, a de novo post-therapy metabolic rewiring, that could represent novel immunotherapy-induced tumor vulnerabilities. Trial registration: ClinicalTrials.gov (NCT03152565)
BfmRS encodes a regulatory system involved in light signal transduction in the human pathogen Acinetobacter baumannii.
Authors: Mora Bárbara Perez , Giordano Rocío , Permingeat Valentín , Calderone Malena , Arana Natalia , Müller Gabriela , Rodriguez Ramiro E. , Krasauskas Renatas , Mussi María Alejandra
Published: July 2022

We have previously shown that Acinetobacter baumannii as well as other relevant clinical bacterial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, perceive and respond to light at 37°C, the normal temperature in mammal hosts. In this work, we present evidence indicating that the two-component system BfmRS transduces a light signal in A. baumannii at this temperature, showing selective involvement of the BfmR and BfmS components depending on the specific cellular process. In fact, both BfmR and BfmS participate in modulation of motility by light, while only BfmR is involved in light regulation of desiccation tolerance in this microorganism. Neither BfmR nor BfmS contain a photoreceptor domain and then most likely, the system is sensing light indirectly. Intriguingly, this system inhibits blsA expression at 37°C, explaining previous results indicating that BlsA only functions at moderate temperatures 1–3, and thus governing the response to light at 37°C. Overall, we provide experimental evidence on a new biological function of this multifaceted system that broadens our understanding of A. baumannii’s physiology and responses to light.
Novel transcriptomic events discovery in esophageal cancer via alignment-free protocol
Authors: Xue Wenhua , Li Lifeng , Shen Zhibo , Zhao Jie , Liu Kangdong , Chen Kuisheng
Published: July 2022

ABSTRACT
Background
The combination of epigenetics, genomic variation, and transcriptional regulatory variation determines the identity of cancer cells. The differences determining the phenotype are frequently represented in transcriptome expression differences or peptides and proteins with generated aberrant structures. As a result, RNA-seq data is a valuable resource for discovering pathogenic variations.

Methods
We use k-mer technology to comprehensively capture pathogenic variations, which overcomes the constraints of typical NGS analysis approaches that rely on reference sequences and the alignment process.

Results
In esophageal cancer patients, we discovered high-frequency variations from various places (introns, exons, intergenic regions, repeats) and forms (splicing, polyadenylation, fusion, etc.). We investigated the significance of overlooked events in typical transcriptomics pipelines as indicators for tumor prediction, prognosis, tumor neoantigen prediction, and their relationship with the immune microenvironment. Unannotated lincRNA, new splice variants, repetitive sequences, and pathogenic microbial RNA all help to explain the process of esophageal cancer, according to our findings.

Conclusion
We anticipate that our reference/mapping-free technique will assist differential RNA-seq analysis of tumor/normal sample sets, offering a broader network for significant cancer-related events.
Effect of measurement errors in consumption expenditure on catastrophic health spending in India
Authors: Mohanty Sanjay K , Sharma Santosh Kumar , Dwivedi Laxmikant , Saggurti Niranjan
Published: July 2022

BackgroundIndia’s National Sample Survey (NSS), through its annual multi-subject and multi-round surveys, collects reliable data on morbidity, health care, and health spending. It also collects data on household consumption expenditure through a single question, which is used to explain the economic gradient in health outcomes. Literature suggests that using a single question to measure consumption expenditure results in measurement errors. In this paper, we examine the effect of measurement errors of household consumption expenditure on estimates of catastrophic health expenditure in India.MethodData from the 68th round of the consumption survey, 2011-12, and the 71st round of the health survey, 2014, carried out by the National Sample Survey (NSS) were used in the analysis. The consumption survey canvassed a detailed schedule on consumption and interviewed 101,651 households, whereas the health survey interviewed 65,932 households in the country. Descriptive statistics, estimates of catastrophic health expenditure and logistic regression models were used in the analysis. ResultResults suggest that the NSS health survey under-estimated monthly per capita expenditure (MPCE) in India by 32%. The level of underestimation is significant across the states of the country. Without adjusting for the level of underestimation, the incidence of catastrophic health expenditure (CHE) was overestimated at least by 3% in India. The pattern was similar with respect to the intensity of CHE. Though the predictors of CHE are similar with both the methods, the predicted probabilities of incurring CHE were significantly higher in unadjusted estimates of CHE across household characteristics. ConclusionMonthly per capita consumption expenditure in NSS-based health surveys is underestimated. It is recommended that the future rounds of NSS-based health surveys should include disaggregated questions on consumption expenditure and researchers may need to adjust the consumption expenditure while using such information in estimating CHE.
Anaplasma marginale multistrain infection in bovines under natural conditions correlates with transovarial transmission and vector competence in Rhipicephalus microplus ticks
Authors: Fournière Sofía , Guillemi † -Eliana Carolina , Paoletta Martina Soledad , Sarmiento Néstor Fabián , Farber Marisa Diana
Published: July 2022

Background
Anaplasma marginale, a gram-negative obligate intracellular microorganism, infects erythrocytes of ruminants and other host species from tropical and subtropical world regions. This pathogen of importance for cattle production, is known to be transmitted mechanically and through hematophagous parasites, mainly by Rhipicephalus microplus ticks. Even though transovarial transmission of A. marginale has been previously reported in R. microplus ticks, there is no evidence of A. marginale transmission from the resulting unfed larvae to a susceptible host. The aim of the present study was to evaluate the transovarial transmission of A. marginale in the R. microplus tick under natural conditions and to study the vector competence of the infected hatched larvae.
Methods
Engorged female R. microplus ticks were sampled from A. marginale positive bovines from an enzootic area in Argentina, and larvae were obtained from a subgroup of these females. After identifying A. marginale in the females and their larvae, selected ticks collected from a single bovine were used. After spawn, hatched larvae were seeded on a susceptible healthy bovine and another subgroup of engorged R. microplus ticks were subjected to dissection to recover the salivary glands and ovaries for A. marginale identification. Anaplasma marginale was detected by PCR and molecularly characterized by means of cloning and sequence all msp1α fragments while genotyping.
Results
A. marginale was detected in naturally infected bovines, in different organs of engorged R. microplus females that were parasitizing them, and in the larvae obtained from these females. A. marginale infection of the susceptible bovine was corroborated both from DNA detection and from compatible structures in a blood smear. The characterization of A. marginale msp1α genotypes involved throughout the infection process provided relevant information about the dynamics of the transmission process.
Conclusions
The results demonstrate the transovarial transmission of A. marginale in R. microplus ticks under natural conditions and, through an experimental infection assay, the vector competence of the infected R. microplus larvae to transmit A. marginale to a susceptible bovine. The high genetic diversity of A. marginale in natural transmission settings seems to be one of the key factors for the transovarial transmission to occur.
Temperature Response of Metabolic Activity of an Antarctic Nematode
Authors: Robinson Colin M. , Hansen Lee D. , Xue Xia , Adams Byron J.
Published: July 2022

Because of climate change, the McMurdo Dry Valleys of Antarctica (MCM) have experienced increased summer temperatures and surface ice and snow melting events. In response to these environmental changes, some nematode species in the MCM have experienced steady population declines over the last three decades, but Plectus murrayi, a mesophilic nematode species, has responded with a steady increase in range and abundance. To determine how P. murrayi responds to increasing temperatures we measured metabolic heat and CO2 production rates and calculated O2 consumption rates as a function of temperature at 5°C intervals from 5 to 50°C. Heat, CO2 production, and O2 consumption rates increase approximately exponentially up to 40°C, a temperature never experienced in their polar habitat. Metabolic rates decline rapidly above 40°C and are irreversibly lost at 50°C due to thermal stress and mortality. Caenorhabditis elegans, a much more widespread nematode that is found in more temperate environments reaches peak metabolic heat rate at just 27°C, above which it experiences high mortality due to thermal stress. At temperatures from 10 to 40°C, P. murrayi produces about 6 times more CO2 than the O2 it consumes, a respiratory quotient indicative of either acetogenesis or de novo lipogenesis. No potential acetogenic microbes were identified in the P. murrayi microbiome. We, therefore, conclude that P. murrayi is producing increased CO2 as a byproduct of de novo lipogenesis. This phenomenon, in conjunction with increased summer temperatures in their polar habitat, will likely lead to increased CO2 production, population abundance, and range expansion.