bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of Governance Factors Influencing Performance of Selected Smallholder Dairy Cooperatives in Zimbabwe
Authors: Matangaidze Rebecca , Rukuni Mandivamba , Musara Joseph P. , Chapwanya Aspinas , Nyamushamba Godfrey B.
Published: June 2022

Cooperatives are organizations owned and operated by individuals or groups that use its services. Marketing of milk is through dairy cooperatives where the milk collection centres are mandated to help integrating smallholder farmers into competitive markets. The study investigated governance structures of five smallholder dairy schemes purposively selected based on their agroecological regions in Zimbabwe, coded A, B, E (Region II), D (Region III) and C (Region IV). Qualitative data were collected using focus group discussions with 20 dairy cooperative members from each milk collection centre. Key informant interviews were conducted with chairpersons, management committee members and dairy value chain stakeholders such as dairy associations and processors. The SWOT analysis technique was employed to identify governance structures highlighting major strengths, weakness, opportunities and threats as a gateway to isolating strategies for enhancing centre performance. An analysis of implications of the governance structures on resource allocation decision by farmers was also performed. The study results show that poor governance mainly caused by incompetent boards and management committees was the major factor affecting performance. Other findings were that if good governance factors were in place, then cooperatives became proficient leading to their growth. Thus, cooperatives must adopt business models based on private sector partnerships to maximise on expertise and technical support. The schemes ought to take advantage of existing opportunities, especially policies that mitigate threats and improve product diversity, value addition and effective pricing strategies. To achieve these milestones, capacity building roadmaps ought to identify competent and efficient boards.
Effect of Pulse Current Treatment on Microstructure and Properties of 304 Stainless Steel Ultra-thin Strip after Rolling
Authors: Liu Qi , Fan Wanwan , Ren Zhongkai , Wang Tao , Huang Qingxue
Published: June 2022

The annealing process is usually used to recrystallize the cold-deformed 304 stainless steel ultra-thin strip, but the whole process requires high temperature and long time. Here, we use the method of loading pulse current instead of the traditional annealing process to process the cold-rolled ultra-thin strip. After the cold-rolled sample with a thickness of 0.035 mm and a width of 6mm was loaded with 25 W pulse current for 5 minutes, complete recrystallization occurred. At this time, the measured temperature was only 540℃, and the annealing process at the same temperature and time was used. The microstructure of the sample is still dominated by deformed crystals, and the difference between the two is significant. By studying the microstructure and mechanical properties after treatment, it is found that the pulse current can greatly improve the plastic deformation ability of the cold-rolled ultra-thin strip. The reason is that the electrical effect generated by the pulse current flowing through the sample promotes recrystallization and causes grain refinement. However, the pulse current power has a threshold value. When the loading current power is lower than the threshold value, the effect is not enough to make the sample fully recrystallize. In this range, the area of recrystallization increases with the increase of power, and the fine grain chain is generated from part of the grain boundary area and develops into a large area of recrystallization. When the threshold value is exceeded, the recrystallized grain will grow again, thereby affecting the mechanical properties of the sample. This discovery provides a new idea for the recrystallization process of cold-rolled 304 stainless steel ultra-thin strip.
The Utilization of Bariatric Surgery in Patients with and without Diabetes: Results from the Second Kuwait National Bariatric Surgery Database Report
Authors: Sabah Salman Al , Haddad Eliana Al
Published: June 2022

BackgroundDuring the year 2021, we were able to create the second Kuwait National Bariatric Surgery Database Report, which we used to extract data on the status and outcomes of patients presenting with type 2 diabetes mellitus (T2DM) undergoing bariatric-metabolic surgery in Kuwait. MethodsData was collected from seven public hospitals in Kuwait, and submitted to be merged in the National Registry. Cross-sectional analysis was then conducted. ResultsAll seven hospitals contributed to the submission of data. The rate of T2DM was 12.5% (607 patients), of which 69% were female. The mean age of patients with T2DM was higher than that of patients without (42 years vs 31.9 years). The overall BMI was slightly higher for patients with T2DM (mean 43.4kg/m2 vs 43.1kg/m2). The majority of patients with T2DM were in the BMI range 40.0-49.9kg/m2. Laparoscopic sleeve gastrectomy accounted for 79.0% of all procedures performed in non-diabetic patients and 79.7% of those performed in diabetic patients. When looking at surgical procedure distribution when classified according to starting BMI group in diabetic patients, it was interesting to see that, in Group 1 (BMI <35), sleeve gastrectomy only accounted for 47.2%, while in the larger BMI groups (>35), sleeve gastrectomy accounted for 82.6-83.2% of all procedures performed. When comparing post-op compilations between diabetic vs non-diabetic patients, the percentage of overall complications encountered did not show a significant difference (1.81% vs 2.10% ; p=0.602). When looking at cardiovascular complications, patients with diabetes tended to present with higher post-op cardiac complications compared to non-diabetics (p=0.000).ConclusionLaparoscopic sleeve gastrectomy was the most performed procedure in both diabetics and non diabetics alike. Patients with diabetes tended to present for surgery at an older age than those without. It was interesting, albeit possibly expected, to note that patients with diabetes presented with a higher percentage of a multitude of complications post-operatively, pointing towards the importance of post-operative care in diabetic patients that present for bariatric surgery.
Experimental observation of spin-split energy dispersion in high-mobility single-layer graphene/WSe heterostructures
Authors: Bid Aveek , Tiwari Priya , Jat Mohit Kumar , Udupa Adithi , Narang Deepa , Watanabe Kenji , Taniguchi Takashi , Sen Diptiman
Published: June 2022

In this letter, we report the experimental determination of the band structure of single-layer graphene (SLG) in the presence of strong proximity-induced spin-orbit coupling. We achieve this in high-mobility hBN-encapsulated SLG/WSe2 heterostructures through measurements of quantum oscillations. We observe clear spin-splitting of the graphene bands along with a substantial increase in the Fermi velocity. Using a theoretical model with realistic parameters to fit our experimental data, we uncover evidence of a bandgap opening and band inversion in the SLG. Further, we establish that the deviation of the low-energy band structure from pristine SLG is determined primarily by the valley-Zeeman SOC and Rashba SOC, with the Kane-Mele SOC being inconsequential. Despite robust theoretical predictions and observations of band-splitting, a quantitative measure of the spin-splitting of the valence and the conduction bands and the consequent low-energy dispersion relation in SLG was missing -- our combined experimental and theoretical study fills this lacuna.
Screening behaviors, demographics, and stage at diagnosis in the publicly funded Ontario Breast Cancer Screening Program.
Authors: Gold Nicholas , Christensen Rebecca A.G , Anderson Geoffrey M , Brooks Jennifer D.
Published: June 2022

Purpose. The Ontario Breast Screening Program (OBSP) offers free screening mammograms every two years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with adherence to OBSP and if women screened in OBSP have a lower stage at diagnosis than non-screened eligible women. Methods. We used the Ontario Cancer Registry (OCR) to identify 51,617 women, aged 50-74, diagnosed with breast cancer between 2010-2017. These women were assigned as screened (N=33,821) or non-screened (N=17,796) in OBSP. We used logistic regression to investigate the demographic characteristics associated with non-screening behaviour. We used multinomial regression to examine the association between screening status and stage at diagnosis.Results. Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds ratio (OR) of not being screened (OR: 0.76, 95%CI: 0.72-0.81). Women in low income (versus high income) communities were more likely not to be screened (OR: 1.35, 95%CI: 1.27-1.43). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed stage II (OR: 1.76, 95%CI: 1.68-1.85), III (OR: 2.73, 95%CI: 2.56-2.92), or IV (OR: 6.93, 95%CI: 6.24-7.69) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in-situ (DCIS) (OR: 0.90, 95%CI: 0.85-0.96). Conclusions. This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed at earlier stages, supporting the value of this initiative and those like it.
A Phase II Trial of the JAK-Inhibitor Ruxolitinib with Exemestane for Estrogen Receptor Positive, Aromatase Inhibitor Resistant, Advanced Breast Cancer
Authors: Makhlin Igor , McAndrew Nicholas , Wileyto E. , Clark Amy , Holmes Robin , Bottalico Lisa , Mesaros Clementina , Blair Ian , Jeschke Grace , Fox Kevin , Domchek Susan , Matro Jennifer , Bradbury Angela , Feldman Michael , Hexner Elizaabeth , Bromberg Jacqueline , DeMichele Angela
Published: June 2022

PURPOSE
Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor outcomes and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. We investigated the safety and efficacy of ruxolitinib, an oral selective inhibitor of JAK1/2, given with exemestane in patients with HR + metastatic breast cancer (MBC) after progression on a non-steroidal AI (NSAI) and whether inflammatory biomarkers predict response.
METHODS
Participants had HR + MBC that relapsed on or within two years of adjuvant NSAI or progressed on NSAI for MBC. The trial was a phase II Simon two-stage design; primary objectives were safety and efficacy. Ruxolitinib, at a starting dose of 25mg twice daily, and exemestane, 25mg daily, were given continuously in the first stage; Grade 3/4 toxicity in < 5/15 participants enabled stage 2. Primary tumor and serial blood samples were collected.
RESULTS
Twenty-five subjects were enrolled. The combination of ruxolitinib and exemestane was safe and tolerable, though anemia requiring transfusion was a frequent adverse event at the 25 mg dose, leading to a reduction in the starting dose of 15 mg twice daily in stage 2. The clinical benefit rate (CBR) in the overall study population was 24% (95% CI 9.4–45.1) with 6/25 patients demonstrating stable disease for ≥ 6 months. Median progression free survival was 2.8 months (95% CI 2.6–3.9). Exploratory biomarkers revealed a cohort with high levels of systemic inflammation: 60% harbored a high-risk IL-6 promoter genotype. Pharmacodynamic investigation demonstrated only a modest on-target inhibition of phosphorylated-STAT3 by ruxolitinib at the doses given.
CONCLUSION
Ruxolitinib combined with exemestane was feasible but lacked clinically meaningful efficacy, with only modest on-target inhibition in AI-resistant tumors when administered at a tolerable dose to a cohort of patients with high levels of systemic inflammation. These findings highlight the need for more potent and specific therapies targeting inflammation in endocrine-resistant breast cancer.
Geochemical characterization of late Jurassic – early Cretaceous age limestones from Gümüşhane (NE-Turkey): Identification of the source of organic matter and paleo-environment conditions
Authors: Eker Çiğdem Saydam , ARI Uğur Volkan
Published: June 2022

Samples from late Jurassic – early Cretaceous age Limestones in five different areas in the Gümüşhane region (NE-Turkey), were studied using TOC/Rock-Eval and some trace elements analysis, to evaluate them their organic material source, type, thermal maturity, and paleo-environment conditions. The studied carbonate rocks are characterized by 90 m thick in the Bağlarbaşı section, 420 m in the Gülaçar, 584 m in the Ünlüpınar, 375 m in the Mescitli, and 272 m in the Yuvacık. The carbonate rocks are generally represented by, from bottom to top, dolomite, oolitic, sparitic, sandy, micritic, clayey, and bituminous limestones. Average total organic carbon (TOC) values are 0.14, 0.16, 0.20, 0.12, and 0.20% in the Bağlarbaşı, Gülaçar, Ünlüpınar, Mescitli, and Yuvacık sections, respectively. Organic material in the limestones consists of Type II-III kerogen, indicating that a mixture of terrigenous higher plants – marine aquatic organisms was the main source. Average Tmax values and Tmax-based vitrinite reflectance values (Ro %) are calculated as 435 and 0.67, 444 and 0.83, 431 and 0.60, 442 and 0.79, and 437oC and 0.70 in the Bağlarbaşı, Gülaçar, Ünlüpınar, Mescitli, and Yuvacık sections, respectively indicating that the samples have generally reached thermal maturity. The limestones in the Gülaçar, Mescitli, and Yuvacık areas are probably well-drained rocks that were extracted and originated hydrocarbon efficiently from the limestone fractures. A non-marine – marine deposition environment for the carbonates is supported by organic sulfur values. V/Ni and Sr/Ba ratios indicate a stratified water column with high – low salinity and anoxic – oxic bottom water circumstances.
Isolation and characterization of an anti- proliferative polysaccharide from the North American fungus Echinodontium tinctorium
Authors: Zeb Mehreen , Li Wai Ming , Heiss Christian , Black Ian , Tackaberry Linda E. , Massicotte Hugues B. , Egger Keith N. , Reimer Kerry , Azadi Parastoo , Lee Chow H.
Published: June 2022

A novel polysaccharide EtGIPL1a was purified from fruiting bodies of Echinodontium tinctorium, a fungus unique to western North America. EtGIPL1a has an estimated weight average molecular weight of 275 kDa and is composed of glucose (54.3%), galactose (19.6%), mannose (11.1%), fucose (10.3%), glucuronic acid (4%), and rhamnose (0.6%). It has multiple glycosidic linkages, with 3-Glcp (28.9%), 6-Glcp (18.3%), 3,6-Glcp (13%), 4-GlcpA (9.2%), 6-Galp (3.9%), 2,6-Galp (2.6%), 3-Fucp (2.5%), 6-Manp (2.4%) being the most prominent, and unsubstituted glucose (15.3%), mannose (1.3%) and fucose (0.9%) as major terminal sugars. EtGIPL1a has a backbone containing mostly 3-substituted β-glucopyranose with 4-substituted glucopyranosyluronic acid. EtGIPL1a showed anti-proliferative activity against multiple cancer cell lines, with IC50 ranging from 50.6–1446 nM. Flow cytometry analyses confirmed that apoptosis induction is one mechanism for its anti-proliferative activity. EtGIPL1a should be further investigated for its potential anti-cancer activity in animal models, and for its possible utility in differentiation cancer therapy.
Ionically Complexed Nanoparticles for Heparin Oral Delivery
Authors: Subramaniam Bhagyashree , Leonick Nicole , Gade Verenya , Frey David , Zhang Fuming , Linhardt Robert J , Gross Richard
Published: June 2022

Ionically complexed nanoparticles were prepared from an anionic polysaccharide drug, heparin, entrapped by a positively charged chitosan polysaccharide. In this study, the encapsulation of heparin was studied to optimize properties needed for its oral drug delivery. Chitosan, used in a variety of biomedical applications, was selected as a cationic polymer for heparin encapsulation. These particles were prepared with a slightly positive charge and an appropriate size for oral drug delivery. The release profiles of these ionically complexed nanoparticles were improved by using FDA approved stabilizers, such as pluronic non-ionic surfactant and polyvinyl alcohol. These results obtained in vitro suggest that these stabilized, ionically complexed nanoparticles may be well-suited for the oral drug delivery of heparin into the gastrointestinal tract.
Cytotoxic effect of ApoL1r in bovine epithelial kidney cells as an alternative treatment for Trypanosoma spp. in cattle
Authors: Jaramillo-Delgado Ingrid Lorena , Agudelo-Florez Piedad , Ruiz-Buitrago Jhon Didier
Published: June 2022

ApoL 1 has been considered as a good alternative to Trypanosoma spp treatment but is also related to kidney cytotoxicity in some mammals. The cytotoxic effect of the recombinant ApoL1 (ApoL1r) protein on bovine renal epithelial cells was evaluated in vitro. This cytotoxic effect led to an up to 50% decrease in cell viability. These results were comparable to those obtained through positive damage control (MM8 at 200 and 250 ug/ml). It was determined that the ApoL1r protein could not be used in experimental animal models, specifically in cattle, due to the loss of cell viability that was generated.
Superficial capillary plexus vessel density/deep capillary plexus vessel density ratio in healthy eyes
Authors: Nam Ki-Yup , lee minwoo , Lee Kook-Hyung , Kim Jung-Yeul
Published: June 2022

Purpose: To identify factors differently affecting the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in healthy eyes using their vessel density (VD) ratio.Methods: Healthy eyes were enrolled. The ratio between the VD of SCP and DCP (SVD/DVD ratio) was calculated. Pearson correlation analyses were performed to identify the relationships between this ratio and other factors.Results: The mean SVD and DVD were 36.0 ± 5.9 and 37.4 ± 4.8 %, respectively, and the mean SVD/DVD ratio was 0.96 ± 0.12. The SVD was significantly correlated with the best-corrected visual aucity (BCVA) (coefficient = -0.338, P < 0.001), age (coefficient = -0.389, P < 0.001), and OCTA quality (coefficient = 0.593, P < 0.001). The DVD was significantly correlated with the BCVA (coefficient = -0.194, P = 0.004), age (coefficient = -0.247, P < 0.001), and OCTA quality (coefficient = 0.507, P < 0.001). Among various factors, age (coefficient = -0.274, P < 0.001), the BCVA (coefficient = -2.80, P < 0.001), axial length (coefficient = 0.198, P = 0.003), and OCTA quality (coefficient = 0.271, P < 0.001) were significantly correlated with the SVD/DVD ratio.Conclusions: Age, BCVA, axial length, and OCTA image quality were significantly correlated with the SVD/DVD ratio. Age, the BCVA, and OCTA quality were more strongly correlated with the SCP, and the axial length was more strongly correlated with the DCP.
Clinical outcome analysis of sequential transplantation of frozen-thawed embryo transfer cycle
Authors: Zhou Wenjing , Cheng Zhaojun , Wang Chong , Feng Ying
Published: June 2022

Research Question: What were the advantages or disadvantages of sequential transplantation compared with the other two strategies in freeze-thaw embryo transfer? Design: A total of 767 patients undergoing frozen-thawed embryo transfer from July 1, 2020, to June 30, 2021, were enrolled in this study. All patients were divided into three groups based on the age of embryos: group A consisted of 60 cases of sequential transplantation, group B consisted of 576 cases of early embryo transfer, while group C was the blastocyst transplantation group consisting of 131 cases. The clinical data, embryo status, and pregnancy outcome in the three groups were compared and analyzed.Results: The number of subsequent transplants and the number of embryos transferred in the sequential group were significantly higher than those in the other two groups (p < 0.05). The blastocyst group (group C) had the highest implantation rate, which was significantly different from the early embryo group (group B, 43.50% vs. 30.00%), but there was no significant difference in the other two groups (39.13% vs. 30.00%, 39.13 vs. 43.50%). The sequential transfer group had the highest rate of multiple births and spontaneous abortion among the three groups, but there was no statistical difference.Conclusion: Sequential transplantation may achieve a higher clinical pregnancy rate than traditional single transplantation by increasing the number of transplants and embryos in a single cycle. Still, it increases embryo waste and may increase the rate of early abortion. The basic situation of the patient should be integrated to decide on the type of embryo transplant.
LINC01956 promotes metastasis and M2 polarization of tumor-associated macrophages in glioblastoma via the FUS/β-catenin signaling pathway
Authors: Zhang Gong , Jin Fa , Lu Fengfei , Zhao Lihong , deng xubin
Published: June 2022

Long noncoding RNAs (lncRNAs) can drive cancer progression. Here, we studied the role of a novel lncRNA, LINC01956, in glioblastoma (GBM). The level of LINC01956 was elevated in GBM cell lines and tissues. LINC01956 downregulation suppressed the migration and proliferation of GBM cells both in vitro and in vivo. Silencing of LINC01956 also significantly suppressed the growth of patient-derived organoids. M2 polarization of macrophages induced by exosomes derived from glioma cells overexpressing LINC01956 further accelerated GBM progression. Mechanistically, we found that FUS interacted with both LINC01956 and β-catenin. LINC01956 bound to FUS and reduced its ubiquitination. LINC01956 evoked nuclear translocation of phosphorylated (p)-β-catenin by recruiting FUS. Furthermore, under hypoxic conditions, LINC01956 was regulated by HIF-1α. Taken together, our data revealed for the first time that LINC01956 exerts pro-tumor effects via FUS-dependent activation of the WNT/β-catenin signaling pathway.
Role of same-day sequential approach – ERCP guided biliary clearance followed by Laparoscopic Cholecystectomy – in the management of Choledocholithiasis with concomitant Cholelithiasis: Prospective interventional single-centre study
Authors: Tantia Mridul , Suryawanshi Pravin , Gandhi Ashish
Published: June 2022

Background:
Early laparoscopic cholecystectomy (LC) after endoscopic retrograde cholangio-pancreaticography (ERCP) is beneficial for patients with gall stone disease (GSD) and common bile duct (CBD) stones. However there are no clear guidelines for the optimal timing of surgical intervention. This study aimed to assess the feasibility and clinical outcomes of same-day sequential approach – ERCP followed by LC for management of choledocholithiasis and concomitant cholelithiasis.
Materials and Methods:
Between December 2017 and November 2019, 24 patients diagnosed with choledocholithiasis and concomitant cholelithiasis underwent ERCP guided biliary clearance followed by LC sequentially on the same day. ERCP was done in the endoscopy suite, and followed by LC in the operation theatre. Both the procedures were performed by same endoscopist-cum-laparoscopic surgeon proficient in advanced endoscopy and laparoscopy. Success rate, ERCP findings, operative findings, logistic issues and complications were recorded and analysed.
Results:
Technical success for ERCP and LC, both were 100%. No major complications like bleeding, perforation, pancreatitis or mortality were encountered post-ERCP. Rate of conversion to open cholecystectomy was 0%. Post-operative self-resolving minor bile leak was encountered in 1 patient (4.1%) who was managed conservatively. The mean time for ERCP and LC was 33.33 minutes and 80.4 minutes, respectively. The mean time interval between the two procedures was 51 minutes. The mean post procedure hospital stay was 3.7 days.
Conclusion:
This study demonstrates safe, effective and feasible same-day sequential approach - ERCP guided biliary clearance followed by LC - in selected patients with choledocholithiasis with concomitant cholelithiasis
PCR based methodology for gender identification in date palm (Phoenix dactylifera L.) of Gujarat, India
Authors: Jani Mansi , Patel Fenil , Abbas Haidar , Joshi Chaitanya , Joshi Madhvi
Published: June 2022

Date palm (Phoenix dactylifera L.) is important dioecious plant in which male and female sex flowers are on different plant. The gender identification of date palm is only possible after 4–8 years when flowers developed. The date palm fruits are produced only on female plants, therefore identification of gender in date palm plants is essential for selection of female plants at seedling stage and increasing production. Currently, there is no consistent methodology available for the sex determination in date palm. There are several DNA marker-based methods available but none can provide truthful results for date palm sex identification. Here we focused on PCR based sex determination of date palm with Glycerol-3 phosphate acetyl transferase (GPAT3) male specific primer and LOX5.1 as positive control. GPAT3 plays important role in male fertility. According to results GPAT3 amplification only occur in male date palm samples, not in female. So that, if result of PCR amplification produced two bands than male and if one band than it is female. We further validated these primers to 315 date palm samples of Kutch region of Gujarat. Out of which, from 304 samples, we can successfully identify gender of date palm with p-value of 0.809 which indicate that the technique is efficient to differentiate sex of date palm.
Dynamic Homogenization of Internal Strain via High-concentration Doping of Oxygen with Large Mobility
Authors: Song Yajing , Zhang Bozhao , Li Tianxin , Fu Xiaoqian , Zou Jiawei , Chen Yujie , Fang Yan , Zhang Qinghua , GU Lin , Lu Yiping , Yang Guang , Liu Suya , Wang Haifeng , Ding Jun , Yu Qian
Published: June 2022

Internal strain and its distribution in crystal lattice play important roles in tuning dislocation activities, which would affect the mechanical properties of materials consequently. Here, by combing integrated differential phase contrast, in situ transmission electron microscope characterizations and computer simulations, we revealed a way of homogenizing dislocation pinning by doping high concentration of oxygen atoms with high diffusion mobility into NiCoCr medium entropy alloy. The doping of massive oxygen atoms introduces high density of strong local pinning points for dislocation motion. Moreover, the oxygen interstitials can easily diffuse and move between different octahedral and tetrahedral sites in the distorted crystal lattice of NiCoCr alloy at even room temperature, based on which severe stress concentrations produced by dislocation tangling can be released and strong local dislocation pinning points can be re-built at other sites towards a uniform way, enabling the material with high strength and outstanding deformability. Our results indicate that the interstitial atoms may become highly mobile at even ambient temperature in complex multi-elements alloys with spreading lattice distortion, which may open a new branch of dislocation engineering.
Completely diverted tube ileostomy versus conventional loop ileostomy
Authors: Bulut Alisina , Attaallah Wafi
Published: June 2022

Purpose
Diverting ileostomies are commonly performed to prevent morbidity and mortality caused by colorecta lanastomotic leakage. However, many complications may develop due to loop ileostomy itself and its reversal. In this study, we aimed to compare the outcomes ofcompletely diverted tube ileostomy and conventional loopileostomy.
Methods
The study was designed prospectively, and operations were performed by the same surgeon at a single center. Completely diverted tube ileostomy with the rubber strip was performed in 20 consecutive patients and loop ileostomy was performed in the next 20 consecutive patients who needed diverting stoma. Theprimary outcome of the study is to compare the overall complication rates in both techniques. Length of hospital stay, achieving complete diversion, and length of time with a stoma were evaluated as secondary outcomes.
Results
There were no significant differences in the demographic characteristics between the two groups. Complete diversion was achieved in both groups. The number of patients who developed any kind ofcomplications during the observation period was significantly higher in the loopileostomy group in comparison with tube ileostomy group [13 (65%) vs 3 (15%)respectively, p = 0.002].Median time with stoma was significantly higherin loop ileostomy group compared to tube ileostomy group [270 days (56–443)vs 21 days (14–28) respectively, p < 0.001].
Conclusion
Completely diverted tube ileostomy is superior to loop ileostomy for reasons such as lack of need for reversal surgery and fewer complications.
Dimethyl Fumarate attenuates Di-(2-ethylhexyl) phthalate-induced Nephrotoxicity, Crosstalk between Nrf2 and NFκB Signaling Pathways
Authors: Ashari Sorour , Barghi Nasrin Ghassemi , Bagheri Abouzar
Published: June 2022

Introduction: Dimethyl fumarate (DMF), the methyl ester of fumaric acid, exhibited various pharmacological effects. The aim of this study was to clarify the potential nephroprotective effect of DMF against DEHP-induced nephrotoxicity. Methods: HEK-293 cells were exposed to different concentrations of DMF plus IC50 concentrations of monoethylhexyl phthalate (MEHP) to evaluate possible cytoprotective effect of DMF. For more evaluation, rats were divided into 7 groups (n=6 per group). Corn oil group, DEHP group (200 mg/kg dissolved in corn oil by gavage). DMF (15, 30, and 60 mg/kg) plus DEHP (200 mg/kg) groups, vitamin E (20 mg/kg) plus DEHP (200 mg/kg) group and DMF (60 mg/kg) alone (45 days). Results: DMF significantly decrease MEHP-induced cytotoxicity DMF improved BUN and creatinine levels compared to DEHP in a dose-dependent manner. Furthermore, DEHP-induced mitochondrial dysfunction was reduced by DMF. To determine the molecular signaling involved in the nephroprotective effects of DMF, the expression of the p65 nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) genes was measured by real-time PCR. p65NFκB and TNFα expression was increased, whereas Nrf2 and HO-1 expression was decreased in the DEHP group compared to the control group. These effects were reversed by using DMF. Conclusions: The findings of the current study revealed that DMF can act as a nephroprotective agent against kidney damage induced by DEHP partly through inhibiting NFκB and improving Nrf2 signaling pathways.
Rational Design and Development of Novel NAE inhibitors for the treatment of pancreatic cancer
Authors: Lu Cheng , Lu Peng , Gong Lei , Zhu Li-Juan , An Yuanyuan , Wang Yubin
Published: June 2022

Pancreatic cancer remains clinically challenging because of the lack of efficient targeted therapies and high aggressiveness. NEDD8 activating enzyme (NAE) plays a critical role in various cellular functions in cancers. Herein, we report the synthesis, optimization, and evaluation of a new series of pyrido[2,3-d]pyrimidin-7(8H)-one derivative as highly selective and efficacious NAE inhibitors, enabling rapid degradation of related substrates and potent inhibition of BxPC-3 cell proliferation. Moreover, western blot assays demonstrated that compound 51 could inhibit NAE activity, resulting in apoptosis in BxPC-3 cells. Furthermore, compound 51 induced cell apoptosis in vitro and inhibited tumor growth in BxPC-3 xenograft models. Our work established that 51 was a highly potent and efficacious NAE inhibitor, representing an effective strategy and great potential as a new targeted therapy for pancreatic cancer.
Synthetic control of the surface area in nickel cobalt oxide for glucose detection via additive- assisted wet chemical method
Authors: Jang Kyu-bong , Park Kyoung Ryeol , Mo Chan Bin , Kim Seongtak , Jeon Jaeeun , Lim Sung-chul , Ahn Chisung , Han HyukSu , Kim Dongju , Kim Kang min , Mhin Sungwook
Published: June 2022

We investigated the effect of specific surface area on the electrochemical properties of NiCo2O4 (NCO) for glucose detection. NCO nanomaterials with controlled specific surface areas were prepared by additive-assisted hydrothermal synthesis, and self-assembled nanostructures with urchin-, pine-needle-, tremella-, and flower-like morphologies were obtained. The novelty of this method is the systematic control of chemical reaction routes assisted by the addition of different additives during synthesis, which results in the spontaneous formation of various morphologies without any difference in the crystal structure and chemical states of the constituent elements. Such morphological control of NCO nanomaterials leads to considerable changes in the electrochemical performance for glucose detection. Combined with materials characterization, the relationship between the specific surface area and the electrochemical performance is discussed for glucose detection. This work can provide scientific insights for tailoring the surface area of nanostructures, which determines their functionality for potential applications in glucose biosensors.
Characterization of Cassava brown streak virus proteins draw their sides during mixed infections and reveal P1 as a silencing suppressor
Authors: Pablo-Rodríguez José Luis , Bailey Andy M. , Foster Gary D.
Published: June 2022

Cassava brown streak disease (CBSD) is currently one of the major constraints on cassava production in Africa. CBSD is estimated to cause annual economic losses of over $100 million USD. CBSD is caused by at least two viral species: Cassava brown streak virus (CBSV) and the Uganda cassava brown streak virus (UCBSV). In field, CBSV and UCBSV occur in single and mixed infections with the potential to be found in mixed infections with other viruses. The interactions between CBSV and other viruses are poorly understood and many functions of CBSV genes are not fully characterised. In this study we analysed the interaction of CBSV with non-related viruses, for potential synergistic interactions, namely tobacco mosaic virus (TMV), and potato virus Y (PVY), both very well characterised for their infection and symptomatology in Nicotiana species. These interactions demonstrated to be synergistic with TMV and antagonistic with PVY. Then P1, P3, 6k1, CI, 6k2, VPg, NIa, NIb, Ham1-like and CP from CBSV were analysed separately, to determine which genes from CBSV were responsible for the direction of these interactions. For this analysis, transgenic lines expressing single CBSV genes were used, providing information about the importance of Ham1. Further functional analysis of these CBSV genes was carried out, analysing silencing suppression activity through agroinfiltration assays. This confirmed silencing suppression activity for the CBSV P1 protein and demonstrated that a functional LRRA domain is required for this activity.
Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating mTOR pathway in ossification of the posterior longitudinal ligament
Authors: Tang Yifan , Sun Yanqing , Zeng Junkai , Yuan Bo , Zhao Yin , Geng Xiangwu , Jia Lianshun , Zhou Shengyuan , Chen Xiongsheng
Published: June 2022

Background
Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease, of which the pathogenesis is still unclear, and there are no effective cure or prevention methods. Exosomal miRNA play an important role in osteogenesis of the ectopic bone. Therefore, we focused on the down-regulation miR-140-5p from OPLL cell-derived exosomes in order to explore the mechanism of exosomal miR-140-5p in inhibiting osteogenesis in OPLL.
Results
Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly down-regulated. The confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified exosomal miR-140-5p inhibited osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited the ectopic bone formation in mice assessed by micro-CT and immunohistochemistry.
Conclusions
We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.
Establishment of Cryogenic Constitutive Model for Ti-6Al-2Zr-1Mo-1V Titanium Alloy
Authors: LIU Kuo , Yu Qingbo , Gan Yongquan , Yang Yuebing , Zhang Yu , Wang Yongqing , Liu Haibo
Published: June 2022

Ti-6Al-2Zr-1Mo-1V (TA15) titanium alloy is widely used in aerospace and other key fields because of its excellent properties such as specific strength, specific stiffness, and corrosion resistance. TA15 titanium alloy has low thermal conductivity and high cutting temperature, which is a typical difficult-to-machine material. The cryogenic machining technology can effectively improve the problems of high cutting temperature and poor machining quality during the machining of titanium alloy. Many researchers have studied the constitutive model of TA15 titanium alloy in order to reveal the machining mechanism, but there has been no research on the cryogenic constitutive model of TA15 titanium alloy. In this paper, a series of tensile tests at low temperature were conducted with TA15 titanium alloy as the research target; The cryogenic constitutive model was established, and the accuracy of the cryogenic constitutive model was verified based on the unequal shear zone model. The test results show that the strength of TA15 titanium alloy increases and the plasticity decrease at low temperatures. the strengthened stage of TA15 titanium alloy was significantly shortened at − 196°C; The maximum error of shear force calculated by orthogonal cutting tests is less than 20% compared with that predicted by cryogenic constitutive model.
Aluminum induced oxidative mitochondrial DNA release mediated by HIF-1α-related pathway to activate NLRP3 inflammasome in astrocytes
Authors: Liu Ziyue , Hao Chenyu , Zhu Xiaoying , Song Yushuai , Hao Wudi , Wu Shengwen , Yang Jinghua , Lu Xiaobo , Jin Cuihong
Published: June 2022

Aluminum compounds are widely distributed in nature and applied frequently in daily life, which are considered as environmental pathogenic factor of neurodegenerative diseases. Previous studies have suggested that aluminum can cause neuroinflammation, but whether astrocytes could play an important role is still obscure. Here, the rat model of subchronic aluminum exposure was established by drinking water containing AlCl3 for 12 w. Primary astrocytes were isolated and treated with AlCl3. YC-1 was adopted as an inhibitor of HIF-1α in vitro experiments. In this study, aluminum exposure could activate astrocytes, decrease α-KGDH activity while increase SDH activity, which stabilized HIF-1α to enhance HIF-1α level and its colocalization with PKM2 in nucleus. Further, PKM2 was activated to phosphorylate C-Myc at Ser62 to prevent its degradation, which upregulated CLIC4 protein level to reduce mitochondrial membrane potential and OX-mt DNA was released. In the cytoplasm, OX-mt DNA could bind to and stimulate NLRP3 inflammasome, resulting in more IL-1β release to trigger neuroinflammation, and the intervention of YC-1 could rescue these impairments. That is, astrocytes play an important role in aluminum-induced neuroinflammation.
Healthier but Wasteful? Changing food loss and waste along global
food supply chains with healthier diets
Authors: Gatto Alessandro , Kuiper Marijke , Meijl Hans
Published: June 2022

Bridging economic and technical modelling of food loss and waste (FLW), we trace physical quantities of FLW along food supply chains (FSC) in a global economic model, building on a newly compiled FLW database. Imposing the EAT-Lancet diet provides changes in FLW magnitude, composition, and geographical location by 2030. By decreasing global food consumption FLW reduces along each stage of the FSC despite a shift to higher FLW foods. Shares of less-processed and plant-based FLW increase, improving reuse possibilities. While food trade decreases, high-income region (HIC) imports still generate substantial losses in low- and mid-income regions (LMIC) with limited scope for reuse. As import-embedded FLW is not captured in SDGs this eases HICs ability to meet SDG12.3, hampering LMICs. While the healthy diet generates less FLW, farm-level loss policies in LMIC need to be complemented by FLW reuse strategies to not let potential inputs for nutritious foods go to waste.
Effective natural inhibitors targeting IL-2 receptor by computational study
Authors: Hou Yuanyuan , Mou Yanhao , Xie Haoqun , Dou Gaojing , Ge Junliang , Zhong Sheng
Published: June 2022

Objective: This study aims to screen ideal lead compounds and potential candidate drugs with inhibitory effect on IL-2R from the drug library (ZINC database).Methods: Computer Aided virtual technology was used to identify the potential inhibitors of IL-2R. Libdock is used for structure based screening, followed by ADME (absorption, distribution, metabolism and excretion) and toxicity prediction. Molecular docking was performed to demonstrate the binding affinity mechanism between ligand and IL-2R. Molecular dynamics simulations were used to evaluate the stability of ligand receptor complexes.Results: Two effective natural compounds ZINC00044361247 and ZINC0028882432 were found in ZINC database to bind to IL-2R, showing high binding affinity. In addition, they were predicted to have low rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC00044361247 and ZINC0028882432 and IL-2R have more favorable potential energy and can exist stably in the natural environment.Conclusion: This study shows that ZINC00044361247 and ZINC0028882432 are ideal IL-2R targeted inhibitors. These compounds are safe potential drug candidates and are of great significance in inhibiting T cell-mediated immune response and allogeneic transplantation.
Prognostic Nomograms for Patients with Metastatic Gastric Cancer: A Large Population-Based Cohort Study and External Validation
Authors: Wang Zhengguang , Chen Mengding , Hou Huanan , Dao Qianze , Chen Ke
Published: June 2022

Purpose
This study aimed to identify the prognostic variables in patients with metastatic gastric cancer (MGC) and to establish a nomogram based on the number of organs for metastasis (NOM) to predict the survival of MGC patients.
Methods
Data of 3,909 patients (training cohort) were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database and that of 312 patients (validation cohort) were collected from two Chinese hospitals. Univariate and multivariate Cox regression analyses were performed to identify the significant prognostic variables. A predictive nomogram was built based on SEER cohort and validated in the Chinese cohort. The discrimination and calibration abilities were assessed by concordance index (C-index), calibration plot, and area under the (time-dependent receiver operating characteristic) curve (AUC).
Results
Race, surgery, chemotherapy, radiotherapy, tumor grade, number of organs affected by metastasis (NOM) were identified by univariate and multivariate Cox regression models. A predictive nomogram was constructed based on the SEER cohort. Excellent C-index, calibration plots, and AUC were obtained using the nomogram in the Chinese cohort. An online version was built based on the nomogram.
Conclusion
Our nomogram provides a reliable tool for predicting the prognosis of MGC patients.
Gene expression profiles associated with molecular subtypes and pathological response to neoadjuvant treatment in surgical breast cancer.
Authors: Baulies Sonia , Molina Miguel Ángel , Tresserra Francisco , Rodríguez Ignacio , Giménez-Capitán Ana , Ara Carmen , Fábregas Rafael
Published: June 2022

Purpose
The association between mRNA expression of 13 candidate genes in surgical breast cancer, molecular tumor subtypes and response to neoadjuvant chemotherapy has been investigated in order to identify potential markers with predictive and prognostic value.
Methods
Tumor pretreatment core biopsies of 92 breast cancer patients treated with neoadjuvant chemotherapy were submitted to gene expression profiling. Medians and percentiles of mRNA expression for each gene were calculated and correlated to molecular tumor subtype and pathological response.
Results
Positive-hormone receptor (HR) tumors showed significantly higher mRNA levels of AXL (p = 0.006), FGFR1 (p = 0.006), RAP80 (p = 0.007), GAS6 (p = 0.05), BTRCP (p = 0.003) and ZNF217 (p = 0.005). A significant association between gene expression and pathological complete response (pCR) was observed for four genes; AXL (p = 0.03), FGFR1 (p = 0.018), YAP (p = 0.023), BRCA1 (p = 0.027). Multivariate analysis identified low levels of AXL and BRCA1 mRNA as independent factors associated with pCR, with an OR 14.03 (CI95% 1.44-136.61) in AXL and 7.07 (CI95% 1.41–35.43) in BRCA1. The expression signature combining BRCA1 and AXL low levels associated with pCR in 100% of the cases (p < 0.001).
Conclusion
A two-gene mRNA expression signature including AXL and BRCA1 associates with pCR to neoadjuvant chemotherapy and can have predictive value.
Clinical observation of menopause hormone therapy in euthyroid and mild subclinical hypothyroidism postmenopausal women
Authors: Xu Wenxian , Huang Yizhou , Ma Linjuan , Chen Peiqiong , Li Saisai , Chu Ketan , Lan Yibing , Li Chunming , Song Yang , Ying Qian , Zhou Jianhong
Published: June 2022

Objective:
To evaluate the endocrine hormone and metabolic indexes in euthyroid and mild subclinical hypothyroidism postmenopausal women after menopause hormone therapy (MHT).
Methods:
A retrospective study was conducted including 587 postmenopausal women received MHT, whose median (25-75th percentile) age was 52.00 (49.00–54.00) years. According to the state of thyroid stimulating hormone (TSH) level at the initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After continuous oral MHT regimen used same potency of estradiol for 6–18 month cycles, serum endocrine hormone and metabolic indexes were reassessed.
Results:
Compared with baseline, serum TSH level in group I and II changed with significant difference, but all values were within the normal range, no significant difference was found of serum TSH level in group III. After treatment, all serum free triiodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index were decreased in group I with significant differences. All lipid and glucose parameters were found no significant differences in group III before and after treatment.
Conclusions:
MHT did not affect thyroid function in euthyroid and mild subclinical hypothyroidism women. MHT led to an improvement of lipid and glucose indicators in euthyroid women with low normal TSH range.