bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pak2 Depletion Induces a Failure of Early Embryonic Development in Mice
Authors: Zeng Juan , Liu Nengqing , Yang Yinghong , Cheng Yi , Li Yuanshuai , Guo Xiaoxia , Luo Qian , Zhu Lifen , Guan Hongmei , Song Bing , Sun Xiaofang 
Published: September 2021

Abstract
Background: The quality of the early embryo is vital to embryonic development and implantation. As a highly conserved serine/threonine kinase, p21-activated kinase 2 (Pak2) participates in diverse biologic processes, especially in cytoskeleton remodeling and cell apoptosis. However, the role of Pak2 in preimplantation embryos remains unelucidated. Methods: In the present work, Pak2 was depleted using a specific small interfering RNA in early mouse embryos, validating the unique roles of Pak2 in spindle assembly and DNA repair during mice early embryonic development. We also employed immunoblotting, immunostaining, in vitro fertilization (IVF) and image quantification analyses to test the Pak2 knockdown on the embryonic development progression, spindle assembly, chromosome alignment, oxidative stress, DNA lesions and blastocyst cell apoptosis.Results: We found that Pak2 deletion significantly reduced blastocyst formation of early embryos. In addition, Pak2 depletion led to dramatically increased abnormal spindle assembly and chromosomal aberrations in the embryos. We noted the overproduction of reactive oxygen species (ROS) with Pak2 knockdown in embryos. Pak2 knockdown also resulted in the accumulation of phosphorylated γH2AX, indicative of increased embryonic DNA damage. Commensurate with this, a significantly augmented rate of blastocyst cell apoptosis was detected in Pak2-KD embryos compared to their controls. Conclusions: Collectively, our data suggest that Pak2 may serve as an important regulator of spindle assembly and DNA repair, and thus participate in the development of early mouse embryos.
Plasma levels of sPD-1 and PD-1 genetic variants are associated with hepatitis B infection and related liver disease progression
Authors: Huyen Pham Thi Minh , Dung Dang Thi Ngoc , Weiß Peter Johann , Giang Dao Phuong , Uyen Ngo Thi , Trung Ngo Tat , Velavan Thirumalaisamy P , Song Le Huu , Hoan Nghiem Xuan 
Published: September 2021

Abstract
Background

Programmed cell death-1 (PD-1) variants and circulating levels of soluble PD-1 are associated with susceptibility to malignant and infectious disease. This study aimed to examine the association of PD-1.5 and PD-1.9 variants, and plasma sPD-1 levels with HBV infection and disease progression.
Methods

The study cohort consists of HBV-infected adults (n = 513) stratified by clinical course, including chronic hepatitis B (CHB, n = 173), liver cirrhosis (LC, n = 134), hepatocellular carcinoma (HCC, n = 206), and matched healthy controls (HC, n = 196). The PD-1.5 (rs2227981 C/T) and PD-1.9 (rs2227982 C/T) genetic variants were genotyped by Sanger sequencing, and then sPD-1 levels were quantified by enzyme immunoassay.
Results

The plasma sPD-1 levels were significantly high among HBV patients. The highest plasma sPD-1 levels were observed in CHB patients, followed by the LC and HCC groups. In addition, the plasma sPD-1 levels correlated positively with liver inflammation (aspartate transaminase, AST: rho = 0.57, P < 0.0001 and alanine aminotransferase, ALT: rho = 0.57, P < 0.0001) and were positively correlated with liver fibrosis (AST to Platelet Ratio Index, APRI score: rho = 0.53, P < 0.0001). The PD-1.9 TT genotype was less frequent in CHB patients compared to LC, HCC and HCC + LC patients in both codominant and recessive models (P < 0.01) and was found to be a risk factor for HCC predisposition [HCC vs. non-HCC: OR = 2.0 (95% CI: 1.13–3.7), Padj=0.017]. The PD-1.5 CT genotype was associated with a reduced risk of acquiring HCC [OR = 0.6 (95%CI: 0.4–0.9), Padj=0.031].
Conclusion

Our study concludes that sPD-1 levels are associated with liver inflammation and progression of liver fibrosis and the PD-1.5 and PD-1.9 variants are associated with HBV infection and progression of liver disease.
A New Method to Evaluate the Combined Performance of Check Dams and Afforestation on Debris Flows Mitigation in a Dry-hot Valley
Authors: Lyu Liqun , Xu Mengzhen , Zhou Guanyu , Wang Zhaoyin 
Published: September 2021

Abstract
Debris flows in waterways can transport large amounts of sediment downstream, which can cause serious damage and economic losses. The vegetation cover in the valley of the Xiaojiang River in Yunnan Province, China—classified as a dry-hot valley—was significantly reduced by logging in the 1950s. Soil erosion intensified and 107 gullies developed, which led to debris flows along the 86 km length of the river. Jiangjia Gully is a tributary of the Xiaojiang River. Historically, debris flows have occurred frequently, blocking the Xiaojiang River seven times between 1957 and 2000. Since 2000, the construction of check dams and afforestation have decreased the volume of debris flows in the three tributaries of Jiangjia Gully. However, different combinations of check dams and afforestation were adopted in the three tributaries of Jiangjia Gully, which has led to the different trends in debris flows behaviour. A new method was established to evaluate the mitigative effect of check dams and afforestation on debris flows. We found that the debris flow volume was proportional to the gravity energy of soil and rock on the gully bank and inversely proportional to the vegetation coverage in a dry-hot valley setting. The method revealed that under different gravity energy conditions, the implementation order of check dam construction and afforestation is important for debris flow mitigation.
Synthesis, Molecular Docking and Pharmacological Investigation of Heterocyclic Amine Derivatives as Potential Anticancer Agents
Authors: Sheikh Ahmed Sadiq , Nadeem Humaira , Alam Mahboob , Khan Muhammad Tariq , Khusro Ameer , Syed Akash , Malik Nadia Shamshad , Aslam Asif Mahmood , Aman Akhtar , Sahibzada Muhammad Umar 
Published: September 2021

Abstract
Cancer is life threatening disease that causes great damage to health worldwide. Studies shown that hypoxia is the major contributor to tumor and cancer development due to overexpression of carbonic anhydrase. To encounter such cells abnormalities, demanding new drugs or novel analogs of currently in use. Therefore, the search for new pharmacoactive moieties with considerable effective activity against such tumors and cancers is needed. The implication of heterocyclic amine and acetamide derivatives well known as chemotherapeutic agents. Heterocyclic amine morpholine was taken as principal products and its new derivatives were synthesized after being designed computationally via molecular docking. A series of some of its new synthetic analogs i.e heterocyclic amine derivatives 1(a-o) were successfully synthesized and screened for their anticancer and carbonic anhydrase inhibitory potential. Most of the compounds showed good results possessing reasonable carbonic anhydrase inhibitory activity particularly compounds 1c, 1d, 1h and 1i showed very reasonable carbonic anhydrase inhibitory activity whereas compound 1h showed maximum inhibition comparable to acetazolamide. Similarly, four of the synthesized compounds showed good anticancer activity particularly compound 1b, 1c, 1h, and 1i showed reasonable, whereas compound 1h have better IC50 value comparable to cisplatin when evaluated via in vitro MTT assay.
Research on the Measurement of Patent-intensive Industry Technology Lock-in from the Perspective of TML
Authors: Yang Wu , Sun Shiqiang , Gao Tengfei 
Published: September 2021

Abstract
[Purpose/Significance] As the core industry of technological innovation capabilities, patent-intensive industries, cultivating their rapid development is conducive to breaking the "technological lock-in" and realizing my country's independent innovation in the core technology field. [Method/Process] Based on the INNOJOY patent database, the wireless communication network patent was selected as the research object, and the subjective and objective weighting method and the growth rate cycle index synthesis method were used to measure the technical lock-in from the perspective of TML.[Results/Conclusions] (1) The technology lock-in index of the United States, Japan, and South Korea generally shows an upward trend, while the technology lock-in index of China has a trend of declining volatility, and the United States has the highest degree of lock-in in the field of wireless communication network technology, ranking first. Japan is in the second position, South Korea is in the third position, and China is in the fourth position; (2) The six core technologies identified belong to American companies. The public years are concentrated in 2017 and 2019, and the technical field is concentrated in H04W72/04 ( The same data transmission method and user equipment), H04W72/08 (signaling for proximity service and D2D discovery in LTE networks), and H04L1/00 (method to support channel allocation information for uplink and downlink channels) And device) these three core patents show that the current three core technologies are cutting-edge technologies in the field of wireless communication networks. The formation mechanism of technology lock-in was clarified, and measurement research was carried out to provide a theoretical basis and analysis method for cracking my country's "technology lock-in", and then to achieve the goal of "patent power."
Ten-year Follow-up of Sitagliptin Treatment in Type 2 Diabetes Mellitus Patients
Authors: Hattori Sachiko 
Published: September 2021

Abstract
Background: Early and effective intervention with a dipeptidyl peptidase 4 inhibitor (DPP4i) before the development of advanced atherosclerosis in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease (CVD) is reported to increase the chance of significant reductions in not only microvascular disease, but also CVD. Method: This study aimed to investigate whether sitagliptin is effective and tolerated for glycemic control and whether renoprotective effects and b-cell function are preserved for as long as ten years in Japanese patients with T2DM without a history of CVD. Results: The situation is equivalent to improving glycemic control as assessed by hemoglobin A1c both in a sitagliptin group (sitagliptin 50 mg as either monotherapy or combination therapy with other oral glucose-lowering drugs (n=17)) or a control group (placebo as either monotherapy or combination therapy with other glucose-lowering drugs (n=9)), while anti-inflammatory effects as assessed by high-sensitivity C-reactive peptide in the sitagliptin group were superior to those in the control group. In the sitagliptin group, the mean values of urinary albumin excretion measured as urinary albumin-to-creatinine ratio (ACR) were markedly decreased, but no changes in estimated glomerular filtration rate (eGFR) were seen throughout the study. Beta-cell function as evaluated by homeostatic model assessment of b-cell function (HOMA-β) values was reduced at baseline in both groups, improved significantly in the sitagliptin group, and continued unchanged in the control group during the study. Conclusion: This observation suggests that early intervention with sitagliptin in patients with T2DM may have long-lasting renoprotective and islet-protective effects. Trial registration: UMIN Clinical Registry (UMIN000038459). Registered 01November (Retrospectively registered), https://upload.umin.ac.jp/UMIN000038459
Relation Between Height Loss and Cardiovascular Disease: Data From Large Korean Cohort
Authors: Moon Jeonggeun , Oh Pyung Chun , Lee Kyounghoon , Jang Ho-Jun , Kim Tae-Hoon , Park Sang-Don , Kwon Sung Woo , Kong Min Gyu , Suh Jon , Kang Woong Chol 
Published: September 2021

Abstract
Question: What is the association between height loss and cardio-/cerebrovascular disease (CVD) incidence?Method: The data we obtained is a sample cohort data provided by NHIS from 2002 to 2015. The chi-square test and the Kruskal-Wallis test were used to see the group differences in demographic characteristics. To compute the primary and secondary outcomes, we used the Cox proportional-hazard model, Kaplan-Meier survival curve, and logistic regression.Results: The cumulative MACCE incidence rate was 3.6 % for Group 1, 4.5 % for Group 2, and 5.2 % for Group 3. Group 3 had a significantly higher incidence of MACCE than Group 1 (Group 1: hazard ratio [HR] = 1.46, 95 % confidence interval [CI] = 1.32-1.62; Group 2: HR = 1.27, 95 % CI = 1.17-1.37). In the model adjusted for age, sex, comorbidities, income level, body mass index, smoking, and drinking status, the MACCE risk was 1.25 times higher in Group 3 than Group 1 (95 % CI = 1.13-1.40).Conclusion: The degree of height loss was independently associated with CVD occurrences in the Korean population.
Petrophysical Core-Based Zonation of An Oil Field In The Bredasdorp Basin South Africa
Authors: Opuwari Mimonitu , Afolanyan Blessing , Mohammed Saeed , Amaechi Paschal Ogechukwu , Bareja Y , Chatterjee Tapas 
Published: September 2021

Abstract
This study aims to generate rock units based on core permeability and porosity of an oil field in the Bredasdorp Basin offshore South Africa. In this study, we identified and classified lithofacies based on sedimentology reports in conjunction with well logs. Lucia's petrophysical classification method is used to classify rocks into three classes. Results revealed three lithofacies as A(sandstone, coarse to medium-grained), B (fine to medium-grained sandstone), and C (carbonaceous claystone, finely laminated with siltstone). Lithofacies A is the best reservoir quality and corresponds to class 1, while lithofacies B and C correspond to class 2 and 3, which are good and poor reservoir quality rock, respectively. An integrated reservoir zonation for the rocks is based on four different zonation methods (Flow Zone indicator (FZI), Winland r35, Hydraulic conductivity (HC), and Stratigraphy modified Lorenz plot (SMLP)). Four flow zones were identified as high(HFZ), moderate (MFZ), Low (LFZ), and tight (TFZ), respectively. The HFZ is the best reservoir quality composed of a megaporous rock unit, with an average FZI value between 5 to 10µm, and HC from 40 to 120 mD/v3, ranked as very good. The most prolific flow units (HFZ and MFZ zones) form more than 75 % of each well's flow capacities. The TFZ is the most reduced rock quality composed of impervious and nanoporous rock. There appears to be a slight increase of illite in the tight and low zones that block pore throats, thereby decreasing permeability. Therefore, illite has a dominant effect on flow zones. Quartz is the dominant framework grain, and siderite is the dominant cement that affects flow zones. This study has demonstrated a robust approach to delineate flow units in an oilfield. A novel sandstone reservoir zonation classification criteria developed from this study can be applied to other datasets of sandstone reservoirs with confidence.
Use of Sildenafil and l-arginine in Preventing Neonatal Necrotizing Enterocolitis: An Experimental Model in Rats
Authors: Moreira Gabriela Araujo , Dias André Ivan Bradley dos Santos , Cadena Silvia Maria Suter Correia , Corrêa-Ferreira Marília Locatelli , Ioshii Sergio Ossamu , Fachin Camila Girardi 
Published: September 2021

Abstract
Necrotizing enterocolitis (NEC) has a 45% mortality in neonatal intensive care units. This paper aimed to evaluate the isolated and combined effects of sildenafil and l-arginine in intestinal wall and survival rates. Neonatal rats were fed formula milk and submitted to hypoxia under a 100% N2 atmosphere for 70 seconds. Then, animals were subjected to hypothermia (4ºC for 10 minutes), twice a day for three days. Forty neonatal rats were divided into five groups: negative control – not submitted to the protocol (n = 5), sildenafil group - NEC protocol (n = 9), l-arginine group - NEC protocol (n = 9), l-arginine and sildenafil group - NEC protocol (n = 9) and positive control - NEC protocol and intraperitoneal saline solution (n = 8). Jejunum and terminal ileus were removed for histopathologic and immunohistochemical Ki-67 analysis. Kruskal-Wallis test was used to analyze mortality, survival, body weight, intestinal injury score and Ki-67 proliferation index. All animals submitted to the protocol developed enterocolitis. Mortality rate was higher in group that received only l-arginine (p = 0.0293). The Ki-67 analysis showed a higher proliferative index in groups that received interventional drugs (p = 0.017). In conclusion, sildenafil and l-arginine were not effective to reduce intestinal injury.
Deep whole genome sequencing identifies recurrent genomic alterations in commonly-used breast cancer cell lines and patient derived xenograft models
Authors: Deng Niantao , Minoche Andre , Harvey Kate , Goga Andrei , Swarbrick Alex 
Published: September 2021

Abstract
BackgroundBreast cancer cell lines (BCCLs) and patient-derived xenografts (PDX) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Deep whole genome sequencing is the most sensitive and accurate method to detect single nucleotide variants and indels, gene copy number and structural events such as gene fusions. ResultsHere we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average ~ 60x coverage. We identify novel genomic alterations, including point mutations and genomic rearrangements at base-pair resolution, compared to previously available sequencing data. Through integrative analysis with publicly available functional screening data, we annotate new genomic features likely to be of biological significance. CSMD1 , previously identified as a tumor suppressor gene in various cancer types, including head and neck, lung and breast cancers, has been identified with deletion in 50% of our PDX models, suggesting an important role in aggressive breast cancers. ConclusionsOur WGS data provides a comprehensive genome sequencing resource of these models.
Association between diarrhea quantity and in-hospital mortality in intensive care unit patients: A retrospective cohort study
Authors: Yamamoto Ryohei , Yamazaki Hajime , Yamamoto Shungo , Ueta Yuna , Ueno Ryo , Yamamoto Yosuke 
Published: September 2021

Abstract
Background

Previous studies have shown that diarrhea is associated with increased mortality of patients in intensive care units (ICUs). However, these studies used dichotomized cutoff values, even if diarrhea was a continuous condition. This study aimed to assess the association between diarrhea quantity and mortality in ICU patients with newly developed diarrhea.
Methods

We conducted this single-center retrospective cohort study at the Kameda Medical Center ICU. We consecutively included all adult ICU patients with newly developed diarrhea in the ICU between January 2017 and December 2018. Newly developed diarrhea was defined based on a Bristol stool chart scale ≥ 6 and frequency of diarrhea ≥ 3 times per day. We excluded patients who already had diarrhea on the day of ICU admission among other criteria. We collected data on the quantity of diarrhea on the day when patients newly developed diarrhea. The primary outcome was in-hospital mortality. The risk ratio (RR) and 95% confidence interval (CI) for the association between the quantity of diarrhea and mortality were estimated using multivariable-modified Poisson regression models adjusted for the Charlson Comorbidity Index, sequential organ failure assessment score, and serum albumin levels.
Results

Among 231 participants, 68.4% (158/231) were men; the median age of the patients was 72 years. The median quantity of diarrhea was 401 g (interquartile range [IQR] 230‒645 g), and in-hospital mortality was 22.9% (53/231). More diarrhea at baseline was associated with higher in-hospital mortality; the unadjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.19). This association remained in the multivariable-adjusted analysis; the adjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.20).
Conclusions

A greater quantity of diarrhea was an independent risk factor for in-hospital mortality. The quantity of diarrhea may be an indicator of disease severity in ICU patients.
Identification of Adeno-Associated Virus Variants for Gene Transfer Into Human Neural Cell Types by Parallel Capsid Screening
Authors: Flitsch Lea Jessica , Börner Kathleen , Stüllein Christian , Ziegler Simon , Sonntag-Buck Vera , Semkova Vesselina , Yeung Si Wah Christina Au , Schlee Julia , Hajo Mohamad , Mathews Mona , Grimm Dirk , Brüstle Oliver 
Published: September 2021

Abstract
Human brain cells generated by in vitrocell programming provide exciting prospects for disease modeling, drug discovery and cell therapy. These applications frequently require efficient and clinically compliant tools for genetic modification of the cells. Recombinant Adeno-associated viruses (AAVs) fulfill these prerequisites for a number of reasons, including the availability of a myriad of AAV capsid variants with distinct cell type specificity (also called tropism). Here, weharnessed a customizable parallel screening approach to assessa panel of natural or synthetic AAV capsid variants for their efficacy in lineage-related human neural cell types.We identified common lead candidates suited for the transduction of directly converted,early-stage induced neural stem cells (iNSCs), induced pluripotent stem cell (iPSC)-derived later-stage, radial glia-like neuralprogenitors,as well as differentiated astrocytic and mixed neuroglial cultures.We then selected a subsetof these candidates for functional validation in iNSCs and iPSC-derived astrocytes, usingshRNA-induced downregulation of the citrate transporter SLC25A1 and overexpression of the transcription factor NGN2 for proofs-of-concept. Our study provides a comparative overview ofthe susceptibility of different human cell programming-derived brain cell types to AAV transduction and a critical discussionof the assets and limitations of the specific AAV capsidscreening approach.
Hospital variations during the first year of the COVID-19 pandemic in a referral hospital in a low-to-middle-income country: A large single-center cohort study
Authors: Dueñas-Castell Carmelo , Coronell Wilfrido , Borre-Naranjo Diana , Almanza Amilkar , Lora Leydis , Navarro Rafael , Rojas-Suarez Jose 
Published: September 2021

Abstract
Background

COVID-19 infection is characterized by its heterogeneity in clinical presentation. Hospital admission, intensive care unit (ICU) admission and mortality rates have shown wide variations throughout the months. Colombia experienced a high rate of COVID-19 infection, leading to significant morbidity and mortality. To date, there are only a few studies reporting peak variations. Therefore, we aimed to explore the potential reasons for epidemiological changes in COVID-19 with time.
Methods

This study was conducted at a tertiary referral center in Cartagena, Colombia, between March 7, 2020, and February 28, 2021. We included patients aged > 18 years with suspected or confirmed COVID-19. A diagnosis was made using the reverse-transcriptase polymerase chain reaction (RT-PCR) test. We extracted information from the Colombian National Surveillance System (SIVIGILA). We collected demographic data, such as age, sex, RT-PCR test results, and information on close contacts (awareness of the disease). We categorized the study period into two according to the two peaks defined in Colombia: the first period included weeks 10–35 (March 7–August 30, 2020), and the second period included weeks 36–60 (September 1, 2020-February 28, 2021). We adjusted the weekly overall mortality by covariates to identify potential changes during the pandemic.
Results

In total, 2761 COVID-19 patients were hospitalized at our institution. The most significant number of cases occurred in the first and second periods during week 21 (peak1: 121 patients) and week 50 (peak2: 128 patients), respectively.