bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Autophagy-Related Genes of Gastric Cancer Patients on Chemotherapy
Authors: Liu Xiaolong , Ma Bin , Chen Mali , Zhang Yaqing , Ma Zhen , Chen Hao 
Published: October 2021

Background: Chemotherapy resistance based on fluorouracil and cisplatin is one of the most encountered postoperative clinical problems in patients diagnosed with gastric cancer (GC), resulting in poor prognosis.Aim of the Study: This study aimed to combine autophagy-related genes (ARGs) to investigate the susceptibility patients with GC to postoperative chemotherapy.Methods: Based on The Cancer Genome Atlas (TCGA) database, gene expression data for GC patients undergoing chemotherapy were integrated and analyzed. Prognostic genes were screened based on univariate and multivariate analysis regression analysis. Subjects were divided into high-risk and low-risk groups according to the median risk score. Kaplan-Meier method was used to evaluate OS and DFS. The accuracy of the prediction was determined by the subject operating characteristic curve analysis. In addition, stratified analyses based on different clinical variables was performed to assess the correlation between risk scores and clinical variables. Quantitative real-time (qRT) PCR was used to verify the expression of CXCR4 in GC tissues and cell lines.Results: A total of nine ARGs related to the prognosis of chemotherapy patients were screened out. Compared with normal gastric mucosa cell, CXCR4 showed elevated expression in GC and was significantly associated with survival. Based on GEO and TCGA databases, the model accurately predicted DFS and OS after chemotherapy.Conclusion: This study established prognostic markers based on nine genes, predicting that ARGs are related to chemotherapy susceptibility of GC patients, which can provide better individualized treatment regimens for clinical practice.
Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV
Authors: Mbuya Wilbert , Held Kathrin , Mcharo Ruby D. , Haule Antelmo , Mhizde Jacklina , Mnkai Jonathan , Mahenge Anifrid , Mwakatima Maria , Sembo Margareth , Mwalongo Wolfram , Agrea Peter , Hoelscher Michael , Maboko Leonard , Saathoff Elmar , Geisenberger Otto , Rwegoshora France , Torres Liset , Koup Richard A. , Kroidl Arne , Chachage Mkunde , Geldmacher Christof 
Published: October 2021

BackgroundCervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses.MethodsThe 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and M.tb-PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay.ResultsOverall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and M.tb-PPD (p &lt; 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses.DiscussionDepletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.
Mechanical Properties of Barchip Polypropylene Fibre-reinforced Lightweight Concrete Made With Recycled Crushed Lightweight Expanded Clay Aggregate
Authors: Yew Ming Kun , Yew Ming Chian , Han Beh Jing , Saw Lip Huat , Lee Foo Wei , Lee Yee Ling 
Published: October 2021

Concrete is one of the broadly used construction materials in the construction industry. This research intends to recommend the replacement of conventional coarse aggregates with recycled lightweight expanded clay aggregate (LECA) which offers several advantages such as lightweight, low cost, and easy availability. Lightweight concrete (LWC) offers numerous benefits; therefore, many researchers are using lightweight aggregate to produce lightweight structural composites concrete to compensate heavy loads by reducing the concrete self-weight due to lower density of lightweight concrete, improving in thermal properties and fire resistance, saving the cost of transportation and handling of precast units in the site. Different percentages (0, 0.15, 0.30, and 0.45%) of volume fraction of barchip polypropylene (BPP) fibre have been incorporated to improve the mechanical properties of lightweight aggregate concrete (LWA) concrete. In this study, the mixture of crushed lightweight expanded clay aggregate (CLECA) and barchip polypropylene (BPP) fibre have been used to achieve compressive strength between 28 and 37 MPa at 28-days with an oven-dry density ranged between 1900 and 2000 kg/m3. It is found that the inclusion of BPP fibres at an optimum volume fraction concrete enhances the compressive strength, splitting tensile strength and modulus of rupture. The compressive strength of the lightweight aggregate concrete containing 0.45% volume fraction of BPP fibre (CLLWAC-BPP0.45%) had achieved the highest compressive strength of 37 MPa at 28-days with a significant increment of about 31% compared to plain concrete. Hence, the findings of this research showed that the development of eco-friendly lightweight structural composites can be used as an alternative solution for conventional lightweight concrete, infrastructure and marine fields application.
Treatment Guidelines for Rare, Early-Onset, Treatment-Resistant Epileptic Conditions: A Literature Review on Dravet Syndrome, Lennox-Gastaut Syndrome and CDKL5 Deficiency Disorder
Authors: Chin Richard F. , Mingorance Ana , Ruban-Fell Benjamin , Newell Isabelle , Evans Jenni , Vyas Kishan , Nortvedt Charlotte , Amin Sam 
Published: October 2021

Background: Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) and CDKL5 deficiency disorder (CDD) are rare epileptic conditions, characterised by drug-resistant seizures. Seizure management in these patients requires careful therapy selection. This targeted literature review (TLR) aimed to collate and synthesise information from country-specific and international treatment guidelines for DS, LGS and CDD.Methods: A TLR was performed between 25th January and 11th March 2021. Online rare diseases and guideline databases were manually searched in addition to websites of national health technology assessment bodies for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK and US, as defined by pre-specified eligibility criteria. Search terms, developed for each condition, were translated into local languages where appropriate. Descriptive analyses were performed to examine the geographical distribution of included guidelines; methodologies used to develop guidelines; cross-referencing of treatment recommendations made within other guidelines; patterns of treatment recommendations. An author map was created using R version 3.5.1, to visualise the extent of collaboration between authors.Results: Forty total guidelines were included, of which 29, 34 and 0 contained recommendations for DS, LGS and CDD, respectively (some provided recommendations for ≥1 condition). Most were country-specific, with guideline authors predominantly publishing in regional groups. Five guidelines were classified as “International” and displayed connections between author groups in the US, UK, France and Italy. Reported guideline development processes were lacking [43% (17 guidelines) had unclear/absent literature review methodologies] and those reported were variable, including both systematic and targeted literature reviews. Use of expert consultation was also variable. A high degree of heterogeneity was observed in the availability of treatment recommendations across disorders, with 271 and 190 recommendations for LGS and DS, respectively, and contradictory positive and negative treatment recommendations for several drugs in each indication [35% (11/31) and 22% (6/27) in LGS and DS, respectively].Conclusions: This review highlights the need for further high-quality international consensus-based treatment guidelines for LGS, DS, and particularly for CDD (for which no treatment guidelines were identified). Supra-national consensus guidance based on findings from a wider geographical range may improve resource allocation and establish an improved world-wide standard of care.
A Novel Nutrition-Based Nomogram to Predict Prognosis After Curative Resection of Gastric Cancer
Authors: Zheng Hui , Zhu Wenchao , Niu Zhongfeng , Li Hongsen , Zheng Yu , Liu Zhen , Yao Junlin , Lou Haizhou , Hu Hong , Gong Liu , Pan Hongming , Pan Qin 
Published: October 2021

Objective: We sought to investigate the prognostic significance of body composition and weight change during the first 6 months of adjuvant chemotherapy after R0 resection and develop novel nomograms to accurately predict relapse-free survival (RFS) and overall survival (OS).Methods: This retrospective study included 190 patients who underwent curative radical gastrectomy for gastric cancer and received adjuvant chemotherapy. The changes in weight and body composition including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed for 6 months. LASSO Cox regression and multivariate Cox regression were conducted to evaluate other clinical characteristics, which were used to construct a nomogram for the prediction of 3- and 5-year RFS and OS. The constructed nomogram was subjected to 1,000 resamples bootstrap for internal validation. The Concordance index (C-index) and time-dependent receiver operating characteristic (t-ROC) curves were used to evaluate and compare the discriminative abilities of the new nomograms, non-nutritional nomograms, and pTNM stage.Results: The median follow-up duration was 42.0 (25.2–55.1) months. Factors included in the newly-built nomogram for RFS were pT stage, pN stage, tumor site, tumor size, nerve invasion or not, surgery type, and change of L3SMI, while factors included in the nomogram for OS were pT stage, pN stage, tumor size, nerve invasion or not, surgery type, and change of L3SMI. The C-index and t-ROC indicated that our newly-built nomograms had greater potential to accurately predict prognosis than the non-nutritional nomograms and pTNM stage system. Besides, oral nutritional supplements can reduce the degree of weight and L3SMI loss.Conclusion: Change in skeletal muscle mass during adjuvant chemotherapy can be incorporated into predictive prognostic nomograms for RFS and OS in GC patients after radical resection. Dynamic changes in body composition and weight during adjuvant chemotherapy contribute to the early detection of poor outcomes.
Associations of Human Milk Oligosaccharides With Otitis Media and Lower and Upper Respiratory Tract Infections up to 2 Years: The Ulm SPATZ Health Study
Authors: Siziba Linda P. , Mank Marko , Stahl Bernd , Kurz Deborah , Gonsalves John , Blijenberg Bernadet , Rothenbacher Dietrich , Genuneit Jon 
Published: October 2021

Background: Human milk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years.Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose.Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression.Results: Absolute concentrations (median [min, max], in g/L) of 2′-fucosyllactose (2′-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p &gt; 0.0031).Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2′-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life.
Branched-Chain Amino Acids Catabolism Pathway Regulation Plays a Critical Role in the Improvement of Leukopenia Induced by Cyclophosphamide in 4T1 Tumor-Bearing Mice Treated With Lvjiaobuxue Granule
Authors: Tian Jun-sheng , Zhao Hui-liang , Gao Yao , Wang Qi , Xiang Huan , Xu Xiang-ping , Huang Sheng , Yan Dong-lan , Qin Xue-mei 
Published: October 2021

Background: Cyclophosphamide is a common tumor chemotherapy drug used to treat various cancers. However, the resulting immunosuppression leads to leukopenia, which is a serious limiting factor in clinical application. Therefore, the introduction of immunomodulators as adjuvant therapy may help to reduce the hematological side effects of cyclophosphamide. Lvjiaobuxue granule has been widely used in the clinical treatment of gynecological diseases such as anemia and irregular menstruation. Recently, it has been found to increase the function of white blood cells, but its mechanism of action is still unclear. We aimed to reveal the mechanisms of Lvjiaobuxue granule against acute leukopenia by an integrated strategy combining metabolomics with network pharmacology.Methods: Subcutaneously inoculated 4T1 breast cancer cells to prepare tumor-bearing mice, intraperitoneal injection of cyclophosphamide to establish a 4T1 tumor-bearing mice leukopenia animal model, using pharmacodynamic indicators, metabolomics, network pharmacology and molecular biology and other technical methods. To comprehensively and systematically elucidate the effect and mechanism of Lvjiaobuxue granule in improving cyclophosphamide-induced leukopenia in 4T1 tumor-bearing mice.Results: Lvjiaobuxue granule can improve the blood routine parameters and organ index levels of the leukopenia model of 4T1 tumor-bearing mice. Metabolomics studies revealed that 15 endogenous metabolites in the spleen of mice were considered as potential biomarkers of Lvjiaobuxue granule for their protective effect. Metabonomics and network pharmacology integrated analysis indicated that Lvjiaobuxue granule exerted the leukocyte elevation activity by inhibiting the branched-chain amino acids (BCAAs) degradation pathway and increasing the levels of valine, leucine and isoleucine. The results of molecular biology also showed that Lvjiaobuxue granule can significantly regulate the key enzymes in the catabolism of BCAAs, which further illustrates the importance of BCAAs in improving leukopenia.Conclusion: Lvjiaobuxue granule exerts obvious pharmacological effects on the leukopenia model of 4T1 tumor-bearing mice induced by cyclophosphamide, which could be mediated by regulating the branched-chain amino acid degradation pathway and the levels of valine, leucine and isoleucine.
An Effective Treatment of Perimenopausal Syndrome by Combining Two Traditional Prescriptions of Chinese Botanical Drugs
Authors: Lan Junjie , Wu Caiming , Liang Wen’na , Shen Jianying , Zhuo Zewei , Hu Liu , Ruan Luwei , Zhang Pengheng , Ye Xiangrong , Xu Leqin , Li Chengfu , Lin Shengyuan , Yang Chuanhui , Wu Siqi , Dong Yingjun , Ren Haixia , Huang Huiying , Gao Bizhen , Yao Hongwei , Lin Tianwei , Chen Xueqin , Li Candong 
Published: October 2021

Ethnopharmacological relevance: Two types of traditional Chinese formulas of botanical drugs are prescribed for treating perimenopausal syndrome (PMS), a disorder in middle-aged women during their transition to menopause. One is for treating PMS as kidney deficiency (KD) due to senescence and declining reproductive functions, and the other is for treating it as liver qi stagnation (LQS) in association with stress and anxiety. Despite the time-tested prescriptions, an objective attestation to the effectiveness of the traditional Chinese treatment of PMS is still to be established and the associated molecular mechanism is still to be investigated.Materials and methods: A model for PMS was generated from perimenopausal rats with chronic restraint stress (CRS). The effectiveness of traditional Chinese formulas of botanical drugs and a combination of two of the formulas was evaluated based on 1H NMR plasma metabolomic, as well as behavioral and physiological, indicators. To investigate whether the formulas contained ligands that could compensate for the declining level of estrogen, the primary cause of PMS, the ligand-based NMR technique of saturation transfer difference (STD) was employed to detect possible interacting molecules to estrogen receptors in the decoction.Results: Each prescription of the classical Chinese formula moderately attenuated the metabolomic state of the disease model. The best treatment strategy however was to combine two traditional Chinese formulas, each for a different etiology, to adjust the metabolomic state of the disease model to that of rats at a much younger age. In addition, this attenuation of the metabolomics of the disease model was by neither upregulating the estrogen level nor supplementing an estrogenic compound.Conclusion: Treatment of PMS with a traditional Chinese formula of botanical drugs targeting one of the two causes separately could ameliorate the disorder moderately. However, the best outcome was to treat the two causes simultaneously with a decoction that combined ingredients from two traditional prescriptions. The data also implicated a new paradigm for phytotherapy of PMS as the prescribed decoctions contained no interacting compound to modulate the activity of estrogen receptors, in contrast to the treatment strategy of hormone replacement therapy.
Pharmacokinetic Engineering of OX40-Blocking Anticalin Proteins Using Monomeric Plasma Half-Life Extension Domains
Authors: Siegemund Martin , Oak Prajakta , Hansbauer Eva-Maria , Allersdorfer Andrea , Utschick Karoline , Winter Alexandra , Grasmüller Christina , Galler Gunther , Mayer Jan-Peter , Weiche Benjamin , Prassler Josef , Kontermann Roland E. , Rothe Christine 
Published: October 2021

Anticalin® proteins have been proven as versatile clinical stage biotherapeutics. Due to their small size (∼20 kDa), they harbor a short intrinsic plasma half-life which can be extended, e.g., by fusion with IgG or Fc. However, for antagonism of co-immunostimulatory Tumor Necrosis Factor Receptor Superfamily (TNFRSF) members in therapy of autoimmune and inflammatory diseases, a monovalent, pharmacokinetically optimized Anticalin protein format that avoids receptor clustering and therefore potential activation is favored. We investigated the suitability of an affinity-improved streptococcal Albumin-Binding Domain (ABD) and the engineered Fab-selective Immunoglobulin-Binding Domain (IgBD) SpGC3Fab for plasma Half-Life Extension (HLE) of an OX40-specific Anticalin and bispecific Duocalin proteins, neutralizing OX40 and a second co-immunostimulatory TNFRSF member. The higher affinity of ABD fusion proteins to human serum albumin (HSA) and Mouse Serum Albumin (MSA), with a 4 to 5-order of magnitude lower KD compared with the binding affinity of IgBD fusions to human/mouse IgG, translated into longer terminal plasma half-lives (t1/2). Hence, the anti-OX40 Anticalin-ABD protein reached t1/2 values of ∼40 h in wild-type mice and 110 h in hSA/hFcRn double humanized mice, in contrast to ∼7 h observed for anti-OX40 Anticalin-IgBD in wild-type mice. The pharmacokinetics of an anti-OX40 Anticalin-Fc fusion protein was the longest in both models (t1/2 of 130 h and 146 h, respectively). Protein formats composed of two ABDs or IgBDs instead of one single HLE domain clearly showed longer presence in the circulation. Importantly, Anticalin-ABD and -IgBD fusions showed OX40 receptor binding and functional competition with OX40L-induced cellular reactivity in the presence of albumin or IgG, respectively. Our results suggest that fusion to ABD or IgBD can be a versatile platform to tune the plasma half-life of Anticalin proteins in response to therapeutic needs.